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von Hofsten J, Zetterberg M. Risk Factors for Cytomegalovirus Retinitis in a National Survey in Sweden. Ocul Immunol Inflamm 2024; 32:485-492. [PMID: 36625562 DOI: 10.1080/09273948.2022.2154679] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/23/2022] [Accepted: 11/28/2022] [Indexed: 01/11/2023]
Abstract
PURPOSE To investigate predisposing immunosuppressive conditions causing cytomegalovirus retinitis (CMVr) and risk factors for delayed diagnosis in patients diagnosed between 2008 and 2018 in the Swedish population of 10 million. RESULTS Sixty-three consecutive patients (100 eyes) were diagnosed with CMVr. The most common immunosuppressive state predisposing for CMVr was hematopoietic stem cell transplant recipients (27%) and hematological malignancy (24%). Two patients (3.2%) had no other predisposing factor than diabetes mellitus (DM). Patients with delayed diagnosis (≤30 days) were older than those with earlier diagnosis, mean age 68.7 (±9.8) and 48.8 (±17.6), respectively, p = .001. Signs of intraocular inflammation (IOI) were seen in 42 (70%) of cases and more common in delayed than early diagnosis, 16 (89%) and 21 (60%) respectively (p = .03). CONCLUSION Delayed diagnosis was more common in older individuals with signs of IOI. DM may be a risk factor for CMVr, and clinical signs can be mistaken for diabetic retinopathy.
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Affiliation(s)
- Joanna von Hofsten
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Ophthalmology, Halland Hospital Halmstad, Halmstad, Sweden
| | - Madeleine Zetterberg
- Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
- Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, Sweden
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2
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Du K, Dong L, Zhang K, Guan M, Chen C, Xie L, Kong W, Li H, Zhang R, Zhou W, Wu H, Dong H, Wei W. Deep learning system for screening AIDS-related cytomegalovirus retinitis with ultra-wide-field fundus images. Heliyon 2024; 10:e30881. [PMID: 38803983 PMCID: PMC11128864 DOI: 10.1016/j.heliyon.2024.e30881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 05/03/2024] [Accepted: 05/07/2024] [Indexed: 05/29/2024] Open
Abstract
Background Ophthalmological screening for cytomegalovirus retinitis (CMVR) for HIV/AIDS patients is important to prevent lifelong blindness. Previous studies have shown good properties of automated CMVR screening using digital fundus images. However, the application of a deep learning (DL) system to CMVR with ultra-wide-field (UWF) fundus images has not been studied, and the feasibility and efficiency of this method are uncertain. Methods In this study, we developed, internally validated, externally validated, and prospectively validated a DL system to detect AIDS-related from UWF fundus images from different clinical datasets. We independently used the InceptionResnetV2 network to develop and internally validate a DL system for identifying active CMVR, inactive CMVR, and non-CMVR in 6960 UWF fundus images from 862 AIDS patients and validated the system in a prospective and an external validation data set using the area under the curve (AUC), accuracy, sensitivity, and specificity. A heat map identified the most important area (lesions) used by the DL system for differentiating CMVR. Results The DL system showed AUCs of 0.945 (95 % confidence interval [CI]: 0.929, 0.962), 0.964 (95 % CI: 0.870, 0.999) and 0.968 (95 % CI: 0.860, 1.000) for detecting active CMVR from non-CMVR and 0.923 (95 % CI: 0.908, 0.938), 0.902 (0.857, 0.948) and 0.884 (0.851, 0.917) for detecting active CMVR from non-CMVR in the internal cross-validation, external validation, and prospective validation, respectively. Deep learning performed promisingly in screening CMVR. It also showed the ability to differentiate active CMVR from non-CMVR and inactive CMVR as well as to identify active CMVR and inactive CMVR from non-CMVR (all AUCs in the three independent data sets >0.900). The heat maps successfully highlighted lesion locations. Conclusions Our UWF fundus image-based DL system showed reliable performance for screening AIDS-related CMVR showing its potential for screening CMVR in HIV/AIDS patients, especially in the absence of ophthalmic resources.
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Affiliation(s)
- Kuifang Du
- Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Li Dong
- Beijing Tongren Eye Centre, Beijing Key Laboratory of Intraocular Tumour Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Kai Zhang
- Chongqing Chang'an Industrial Group Co. Ltd, Chongqing, China
| | - Meilin Guan
- Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Chao Chen
- Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Lianyong Xie
- Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Wenjun Kong
- Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Heyan Li
- Beijing Tongren Eye Centre, Beijing Key Laboratory of Intraocular Tumour Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Ruiheng Zhang
- Beijing Tongren Eye Centre, Beijing Key Laboratory of Intraocular Tumour Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Wenda Zhou
- Beijing Tongren Eye Centre, Beijing Key Laboratory of Intraocular Tumour Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Haotian Wu
- Beijing Tongren Eye Centre, Beijing Key Laboratory of Intraocular Tumour Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Hongwei Dong
- Department of Ophthalmology, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Wenbin Wei
- Beijing Tongren Eye Centre, Beijing Key Laboratory of Intraocular Tumour Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Ong DSY, Chong GLM, Chemaly RF, Cremer OL. Comparative clinical manifestations and immune effects of cytomegalovirus infections following distinct types of immunosuppression. Clin Microbiol Infect 2022; 28:1335-1344. [PMID: 35709902 DOI: 10.1016/j.cmi.2022.05.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 05/23/2022] [Accepted: 05/30/2022] [Indexed: 11/16/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is a well-recognized complication of solid organ and hematopoietic cell transplantation. However, CMV infection also occurs in patients with human immunodeficiency virus (HIV) infection, previously immunocompetent intensive care unit (ICU) patients, and individuals on immunosuppressive medications for various underlying diseases. OBJECTIVES This review describes the comparative effects of CMV infection in distinct types of acquired immunosuppression. SOURCES Selected peer-reviewed publications on CMV infections published until December 2021. CONTENT CMV infection affects various organ systems through direct cytolytic mechanisms, but may also exert indirect effects by promoting pro-inflammatory and immunosuppressive responses. This has been well studied in transplant recipients, for whom antiviral prophylaxis and pre-emptive therapy have now become standard practice. These strategies not only prevent direct CMV disease manifestations, but also mitigate various immunopathological processes to reduce graft-versus-host disease, graft rejection, and the occurrence of secondary bacterial and fungal infections. The efficacy of neither prophylactic nor pre-emptive treatment of CMV infection has been demonstrated for patients with critical illness- or medication-induced immunosuppression. Many observational studies have shown an independent association between CMV reactivation and a prolonged duration of mechanical ventilation or increased mortality in the ICU. Furthermore, data suggest that CMV reactivation may increase pulmonary inflammation and prolong the duration of mechanical ventilation. IMPLICATIONS A large number of observational and experimental studies suggest attributable morbidity and mortality related to CMV infection, not only in transplant recipients and patients with HIV infection but also in patients with critically illness- or medication-induced immunosuppression. Adequately powered randomized controlled trials investigating the efficacy of prophylaxis or pre-emptive treatment of CMV infection in these patients are lacking, with a notable exception for transplant recipients.
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Affiliation(s)
- David S Y Ong
- Department of Medical Microbiology and Infection Control, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands; Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
| | - Ga-Lai M Chong
- Erasmus University Medical Center, Department of Medical Microbiology & Infectious Diseases, Rotterdam, the Netherlands
| | - Roy F Chemaly
- Department of Infectious Diseases, Infection Control, & Employee Health, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Olaf L Cremer
- Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
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4
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Griffiths P, Reeves M. Pathogenesis of human cytomegalovirus in the immunocompromised host. Nat Rev Microbiol 2021; 19:759-773. [PMID: 34168328 PMCID: PMC8223196 DOI: 10.1038/s41579-021-00582-z] [Citation(s) in RCA: 332] [Impact Index Per Article: 83.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2021] [Indexed: 12/16/2022]
Abstract
Human cytomegalovirus (HCMV) is a herpesvirus that infects ~60% of adults in developed countries and more than 90% in developing countries. Usually, it is controlled by a vigorous immune response so that infections are asymptomatic or symptoms are mild. However, if the immune system is compromised, HCMV can replicate to high levels and cause serious end organ disease. Substantial progress is being made in understanding the natural history and pathogenesis of HCMV infection and disease in the immunocompromised host. Serial measures of viral load defined the dynamics of HCMV replication and are now used routinely to allow intervention with antiviral drugs in individual patients. They are also used as pharmacodynamic read-outs to evaluate prototype vaccines that may protect against HCMV replication and to define immune correlates of this protection. This novel information is informing the design of randomized controlled trials of new antiviral drugs and vaccines currently under evaluation. In this Review, we discuss immune responses to HCMV and countermeasures deployed by the virus, the establishment of latency and reactivation from it, exogenous reinfection with additional strains, pathogenesis, development of end organ disease, indirect effects of infection, immune correlates of control of replication, current treatment strategies and the evaluation of novel vaccine candidates.
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Affiliation(s)
- Paul Griffiths
- Institute for Immunity and Transplantation, University College London, London, UK.
| | - Matthew Reeves
- grid.83440.3b0000000121901201Institute for Immunity and Transplantation, University College London, London, UK
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5
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Affiliation(s)
- Juliana Wons
- Berner Augenklinik Am Lindenhofspital, Bern, Switzerland
| | - John Kempen
- MCM Eye Unit, MyungSung Christian Medical Center (MCM) General Hospital and MyungSung Medical College, Addis Ababa, Ethiopia
- Department of Ophthalmology, Massachusetts Eye and Ear; and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
| | - Justus G. Garweg
- Berner Augenklinik Am Lindenhofspital, Bern, Switzerland
- Swiss Eye Institute and University of Bern, Bern, Switzerland
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6
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Sudharshan S, Nair N, Curi A, Banker A, Kempen JH. Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update. Indian J Ophthalmol 2020; 68:1787-1798. [PMID: 32823395 PMCID: PMC7690468 DOI: 10.4103/ijo.ijo_1248_20] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 06/13/2020] [Accepted: 06/24/2020] [Indexed: 12/11/2022] Open
Abstract
Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.
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Affiliation(s)
| | - Nivedita Nair
- Department of Uveitis, Medical Research Foundation, Chennai, Tamil Nadu, India
| | - Andre Curi
- André Luiz Land Curi, National Institute of Infectious Diseases - INI/ Fiocruz, Brazil
- Clinical Research Laboratory of Infectious, Diseases in Ophthalmology - INI / Fiocruz, Brazil
| | - Alay Banker
- Banker's Retina Clinic and Laser Centre, Ahmedabad, Gujarat, India
| | - John H Kempen
- Department of Ophthalmology, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts, Ethiopia
- Schepens Eye Research Institute, Boston, Massachusetts, USA
- MCM Eye Unit, MyungSung Christian Medical Center (MCM) General Hospital and MyungSung Medical College, Addis Ababa, Ethiopia
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7
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Agrawal R, Gunasekeran DV, Xu Y, Leo YS, Ng OT, Wong CS, Testi I, Ding J, Banu I, Teoh SC. Clinical Features and CD4+ T Cells Count in AIDS Patients with CMV Retinitis: Correlation with Mortality. Ocul Immunol Inflamm 2020; 30:42-47. [PMID: 32644842 DOI: 10.1080/09273948.2020.1772312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
PURPOSE To explore the all-cause mortality in patients with acquired immune deficiency syndrome (AIDS) and Cytomegalovirus (CMV) retinitis. METHODS A retrospective cohort study of patients with CMV retinitis (CMVR) presented to a tertiary referral center in Singapore from January 1, 2004, through December 31, 2015. RESULTS A total of 144 patients were studied (87 survived, 11 lost to follow up, 46 died). Patients with bilateral CMVR and six-month follow up CD4 + T cell count < 50 cells/mm3 have shorter time to mortality, compared to patients with CD4 + T cell count > 50 cells/mm3 (p < .001) and unilateral disease (p = .043). Baseline CD4 + T cell count, size and zone of initial primary retinitis lesions, recurrences of retinitis, and timing of combined antiretroviral therapy (cART) are not significantly associated with mortality. CONCLUSION Bilateral ocular involvement and lack of immune recovery in patients with AIDS and CMVR are associated with shorter survival time.
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Affiliation(s)
- Rupesh Agrawal
- National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, Singapore.,Moorfields Eye Hospital, National Health Service Foundation Trust, London, UK
| | - Dinesh V Gunasekeran
- National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore, Singapore
| | - Yanping Xu
- Department of Ophthalmology, Ng Teng Fong Hospital, Singapore, Singapore
| | - Yee-Sin Leo
- National Centre for Infectious Disease, Tan Tock Seng Hospital, Singapore, Singapore.,Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore
| | - Oon T Ng
- National Centre for Infectious Disease, Tan Tock Seng Hospital, Singapore, Singapore
| | - Chen Seong Wong
- National Centre for Infectious Disease, Tan Tock Seng Hospital, Singapore, Singapore
| | - Ilaria Testi
- Moorfields Eye Hospital, National Health Service Foundation Trust, London, UK
| | - Jianbin Ding
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
| | - Imrana Banu
- National Centre for Infectious Disease, Tan Tock Seng Hospital, Singapore, Singapore
| | - Stephen C Teoh
- Eagle Eye Center, Gleneagles Hospital, Singapore, Singapore
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8
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Peters RPH, Kestelyn PG, Zierhut M, Kempen JH. The Changing Global Epidemic of HIV and Ocular Disease. Ocul Immunol Inflamm 2020; 28:1007-1014. [PMID: 32396027 DOI: 10.1080/09273948.2020.1751214] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Purpose: Overview of the evolving epidemiology of human immunodeficiency virus (HIV)-related ocular disease over time. Method: Narrative review. Results: HIV enhances susceptibility to opportunistic eye infections, has direct pathogenic effects, and places patients at risk of immune recovery inflammatory syndromes in previously infected eyes after starting highly-active antiretroviral therapy (HAART). Widespread availability of HAART has resulted in a decrease of infectious ocular conditions such as cytomegalovirus retinitis, toxoplasmic retinitis, squamous cell carcinoma of the conjunctiva, and microvascular retinopathy. However, large coexisting burdens of tuberculosis, herpesvirus infection and syphilis (among others) continue to contribute to the burden of ocular disease, especially in low-resource settings. Growing risks of cataract, retinopathy and retinal nerve fiber thinning can affect patients with chronic HIV on HAART; thought due to chronic inflammation and immune activation. Conclusion: The changing epidemic of ocular disease in HIV-infected patients warrants close monitoring and identification of interventions that can help reduce the imminent burden of disease.
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Affiliation(s)
- Remco P H Peters
- Foundation for Professional Development, Research Unit , East London, South Africa.,Faculty of Health Sciences, Department of Medical Microbiology, University of Pretoria , Pretoria, South Africa.,Department of Medical Microbiology, Maastricht University Medical Centre, CAPRHI School of Public Health & Primary Care , Maastricht, The Netherlands
| | | | - Manfred Zierhut
- Department of Ophthalmology, University of Tuebingen , Tübingen, Germany
| | - John H Kempen
- Department of Ophthalmology, Massachusetts Eye and Ear , Boston, Massachusetts, USA.,Department of Ophthalmology, Harvard Medical School , Boston, Massachusetts, USA.,MCM Eye Unit, MyungSung Christian Medical Center and MyungSung Medical School , Addis Ababa, Ethiopia
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9
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Qian Y, Che X, Jiang J, Wang Z. Mechanisms of Blood-Retinal Barrier Disruption by HIV-1. Curr HIV Res 2020; 17:26-32. [PMID: 30873925 DOI: 10.2174/1570162x17666190315163514] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2019] [Revised: 03/10/2019] [Accepted: 03/13/2019] [Indexed: 11/22/2022]
Abstract
It has been found that human immunodeficiency virus (HIV)-1 RNA or antigens can be detected in the intraocular tissues of HIV-1 patients even under effective highly active anti-retroviral therapy (HAART). In vivo, blood-retinal barrier (BRB) establishes a critical, physiological guardian against microbial invasion of the eye, but may be compromised in the presence of HIV-1. The envelope glycoprotein gp120 is exposed on the surface of the HIV envelope, essential for virus entry into cells by the attachment to specific cell surface receptors. The BRB disruption by glycoprotein gp120 has been widely recognized, which is toxic to human retinal epithelial cells (RPE) and umbilical vein endothelial cells (HUVEC). The present review elaborates on various mechanisms of BRB disruption induced by HIV gp120, which may represent potential targets for the prevention of ocular HIV complications in the future.
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Affiliation(s)
- Yiwen Qian
- Department of Ophthalmology, Huashan Hospital of Fudan University, Shanghai, China
| | - Xin Che
- Department of Ophthalmology, Huashan Hospital of Fudan University, Shanghai, China
| | - Jing Jiang
- Department of Ophthalmology, Huashan Hospital of Fudan University, Shanghai, China
| | - Zhiliang Wang
- Department of Ophthalmology, Huashan Hospital of Fudan University, Shanghai, China
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10
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Griffiths P. The direct and indirect consequences of cytomegalovirus infection and potential benefits of vaccination. Antiviral Res 2020; 176:104732. [PMID: 32081353 DOI: 10.1016/j.antiviral.2020.104732] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 01/27/2020] [Accepted: 01/31/2020] [Indexed: 12/25/2022]
Abstract
Active infection with cytomegalovirus (CMV) occurs in patients who are immunocompromised and may produce the high viral loads required to cause end-organ disease. Such patients have complex medical histories and many experienced physicians have speculated that CMV may, additionally, contribute to adverse clinical outcomes. In 1989, Dr Bob Rubin coined the term "indirect effects" to describe this potential relationship between virus and patient. Examples include accelerated atherosclerosis in patients after heart transplant or with underlying HIV infection, the number of days patients require ventilation after admission to intensive care units, the development of immunosenescence in the elderly and mortality in many groups of patients, including the general population. It is difficult to distinguish between CMV acting as causal contributor to such diverse pathology or simply having a benign bystander effect. However, recruitment of patients into placebo-controlled randomised trials of antiviral drugs with activity against CMV offers such a potential. This article describes the studies that have been conducted to date and emphasises that mortality after stem cell transplant (not attributed to CMV end-organ disease) has recently become the first proven indirect effect of CMV now that letermovir has significantly reduced non-relapse deaths. The implications for CMV vaccines are then discussed. Vaccines are already predicted to be highly cost-effective if they can reduce CMV end-organ disease. Health planners should now consider that cost effectiveness is likely to be enhanced further through reduction of the indirect effects of CMV. A prototype scheme for assessing this possibility is provided in order to stimulate discussion within the field. This article forms part of an online symposium on the prevention and therapy of DNA virus infections, dedicated to the memory of Mark Prichard.
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Affiliation(s)
- Paul Griffiths
- Institute for Immunity & Transplantation, Royal Free Campus, University College London, London, NW3 2PF, United Kingdom.
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11
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Baraniak I, Gomes AC, Sodi I, Langstone T, Rothwell E, Atkinson C, Pichon S, Piras-Douce F, Griffiths PD, Reeves MB. Seronegative patients vaccinated with cytomegalovirus gB-MF59 vaccine have evidence of neutralising antibody responses against gB early post-transplantation. EBioMedicine 2019; 50:45-54. [PMID: 31735553 PMCID: PMC6921368 DOI: 10.1016/j.ebiom.2019.11.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 11/06/2019] [Accepted: 11/06/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Human cytomegalovirus (HCMV) causes a ubiquitous infection which can pose a significant threat for immunocompromised individuals, such as those undergoing solid organ transplant (SOT). Arguably, the most successful vaccine studied to date is the recombinant glycoprotein-B (gB) with MF59 adjuvant which, in 3 Phase II trials, demonstrated 43-50% efficacy in preventing HCMV acquisition in seronegative healthy women or adolescents and reduction in virological parameters after SOT. However, the mechanism of vaccine protection in seronegative recipients remains undefined. METHODS We evaluated samples from the cohort of seronegative SOT patients enroled in the Phase II glycoprotein-B/MF59 vaccine trial who received organs from seropositive donors. Samples after SOT (0-90 days) were tested by real-time quantitative PCR for HCMV DNA. Anti-gB antibody levels were measured by ELISA. Neutralization was measured as a decrease in infectivity for fibroblast cell cultures revealed by expression of immediate-early antigens. FINDINGS Serological analyses revealed a more rapid increase in the humoral response against gB post transplant in vaccine recipients than in those randomised to receive placebo. Importantly, a number of patient sera displayed HCMV neutralising responses - neutralisation which was abrogated by pre-absorbing the sera with recombinant gB. INTERPRETATION We hypothesise that the vaccine primed the immune system of seronegative recipients which, when further challenged with virus at time of transplant, allowed the host to mount rapid immunological humoral responses even under conditions of T cell immune suppression during transplantation.
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Affiliation(s)
- Ilona Baraniak
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom
| | - Ariane C Gomes
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom
| | - Isabella Sodi
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom
| | - Toby Langstone
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom
| | - Emily Rothwell
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom
| | - Claire Atkinson
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom
| | - Sylvie Pichon
- Clinical Development, Sanofi Pasteur, Marcy l'Etoile, France
| | | | - Paul D Griffiths
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom
| | - Matthew B Reeves
- Institute for Immunity and Transplantation, UCL, Royal Free Campus, London NW3 2PF, United Kingdom.
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12
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Ocieczek P, Barnacle JR, Gumulira J, Phiri S, Heller T, Grabska-Liberek I. Cytomegalovirus Retinitis Screening and Treatment in Human Immunodeficiency Virus Patients in Malawi: A Feasibility Study. Open Forum Infect Dis 2019; 6:ofz439. [PMID: 31723570 PMCID: PMC6834087 DOI: 10.1093/ofid/ofz439] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 11/04/2019] [Indexed: 11/13/2022] Open
Abstract
Background Cytomegalovirus retinitis is a treatable cause of blindness in people with human immunodeficiency virus (HIV) typically with CD4 counts <50 cells/mm3. Diagnosis is with indirect fundoscopy, and treatment is with intravitreal ganciclovir injections or systemic therapy. However, diagnosis and treatment are not widely available in Malawi, which has an adult HIV prevalence estimated at 10.6%. This study aimed to establish the prevalence of cytomegalovirus retinitis among people with HIV in Malawi and the feasibility of screening. Methods Patients with CD4 counts <200 cells/mm3 were examined from 2 HIV clinics in Lilongwe and the main government hospital. Data were collected on antiretroviral therapy, ocular symptoms, and visual acuity. Fundoscopy was performed to investigate for features of cytomegalovirus retinitis. Retinal photographs were reviewed by an ophthalmologist. Patients diagnosed with cytomegalovirus retinitis were offered weekly ganciclovir injections, because systemic treatment was not available. Results Five of the 102 people with HIV screened had cytomegalovirus retinitis (4.9%). All affected patients had CD4 counts <50 cells/mm3 (mean, 15 cells/mm3; range, 3-22 cells/mm3). Visual acuity was unhelpful in identifying those with cytomegalovirus retinitis. Symptomatically, only blurred vision was useful. Two patients consented to treatment, 1 of which improved but relapsed after defaulting. Conclusions Cytomegalovirus retinitis screening based on CD4 count is essential to early recognition because visual acuity and symptoms are unreliable. Cytomegalovirus retinitis is a significant yet neglected public health issue in Malawi. Oral valganciclovir is essential to reduce blindness and mortality in those diagnosed but is not yet available. Further screening and advocacy are needed.
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Affiliation(s)
- Paulina Ocieczek
- Department of Ophthalmology, Szpital Klinczny im. Prof. W. Orłowskiego, Warsaw, Poland
| | | | | | - Sam Phiri
- Lighthouse Trust, Lilongwe, Malawi.,Department of Global Health, University of Washington, Seattle, USA.,Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.,Department of Public Health, College of Medicine, School of Public Health and Family Medicine, University of Malawi, Malawi
| | | | - Iwona Grabska-Liberek
- Department of Ophthalmology, Szpital Klinczny im. Prof. W. Orłowskiego, Warsaw, Poland
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Zuhair M, Smit GSA, Wallis G, Jabbar F, Smith C, Devleesschauwer B, Griffiths P. Estimation of the worldwide seroprevalence of cytomegalovirus: A systematic review and meta-analysis. Rev Med Virol 2019; 29:e2034. [PMID: 30706584 DOI: 10.1002/rmv.2034] [Citation(s) in RCA: 517] [Impact Index Per Article: 86.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Cytomegalovirus (CMV) infection does not usually produce symptoms when it causes primary infection, reinfection, or reactivation because these three types of infection are all controlled by the normal immune system. However, CMV becomes an important pathogen in individuals whose immune system is immature or compromised, such as the unborn child. Several vaccines against CMV are currently in clinical trials that aim to induce immunity in seronegative individuals and/or to boost the immunity of those with prior natural infection (seropositives). To facilitate estimation of the burden of disease and the need for vaccines that induce de novo immune responses or that boost pre-existing immunity to CMV, we conducted a systematic survey of the published literature to describe the global seroprevalence of CMV IgG antibodies. We estimated a global CMV seroprevalence of 83% (95%UI: 78-88) in the general population, 86% (95%UI: 83-89) in women of childbearing age, and 86% (95%UI: 82-89) in donors of blood or organs. For each of these three groups, the highest seroprevalence was seen in the World Health Organisation (WHO) Eastern Mediterranean region 90% (95%UI: 85-94) and the lowest in WHO European region 66% (95%UI: 56-74). These estimates of the worldwide CMV distribution will help develop national and regional burden of disease models and inform future vaccine development efforts.
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Affiliation(s)
- Mohamed Zuhair
- Department of Virology, Royal Free NHS Foundation Trust, London, UK
| | - G Suzanne A Smit
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.,Instituut of Tropical Medicine (ITM), Antwerp, Belgium.,Institute of Health and Society (IRSS), Université Catholique de Louvain, Brussels, Belgium
| | - Gabriel Wallis
- Department of Virology, Royal Free NHS Foundation Trust, London, UK
| | - Faiz Jabbar
- Department of Virology, Royal Free NHS Foundation Trust, London, UK
| | - Colette Smith
- Institute for Global Health, University College London, London, UK
| | - Brecht Devleesschauwer
- Department of Public Health and Surveillance, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium
| | - Paul Griffiths
- Department of Virology, Royal Free NHS Foundation Trust, London, UK.,Institute for Global Health, University College London, London, UK
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Griffiths PD. Disruption of gastrointestinal integrity in patients with HIV infection. Rev Med Virol 2017; 27. [PMID: 28677223 DOI: 10.1002/rmv.1935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Elevated cytomegalovirus IgG antibody levels are associated with HIV-1 disease progression and immune activation. AIDS 2017; 31:807-813. [PMID: 28121712 DOI: 10.1097/qad.0000000000001412] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To assess the association between cytomegalovirus (CMV) IgG antibody levels, HIV disease progression, and immune activation markers. DESIGN A prospective cohort study was conducted among women enrolled in a trial that was designed to determine the effect of acyclovir on HIV disease progression in Rakai, Uganda. METHODS The primary endpoints were progression to a CD4 T-cell count less than 250 cells/μl, nontraumatic death, or initiation of antiretroviral therapy (ART). CD4 T-cell counts, HIV viral load, C-reactive protein (CRP), and soluble CD14 levels were assessed biannually for 24 months. CMV IgG antibodies were measured at baseline among all women and annually among a subset of women who initiated ART. RESULTS There were 300 HIV/CMV-coinfected participants who contributed a total of 426.4 person-years with a median follow-up time of 1.81 years. Compared with the lowest CMV IgG tertile group at baseline, the highest CMV IgG tertile group was associated with an increased risk to reach a primary endpoint independent of acyclovir use, age, CD4 T-cell count, and HIV viral load at baseline [adjusted hazard ratio = 1.59; (95% CI = 1.05-2.39); P = 0.027]. Among pre-ART visits (n = 1200), women in the highest baseline CMV IgG tertile had increasing annual rates of soluble CD14 and CRP levels, which was not observed for the low CMV IgG tertile group. Compared with pre-ART visits, CMV IgG antibody levels were higher post-ART initiation, and concurrent levels remained associated with soluble CD14 and CRP during suppressive ART (n = 88 person-visits). CONCLUSION The magnitude of the immune response to CMV was associated with HIV disease progression and immune activation in sub-Saharan Africa.
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Maidji E, Somsouk M, Rivera JM, Hunt PW, Stoddart CA. Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction. PLoS Pathog 2017; 13:e1006202. [PMID: 28241080 PMCID: PMC5328284 DOI: 10.1371/journal.ppat.1006202] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 01/26/2017] [Indexed: 01/25/2023] Open
Abstract
Although invasive cytomegalovirus (CMV) disease is uncommon in the era of antiretroviral therapy (ART), asymptomatic CMV coinfection is nearly ubiquitous in HIV infected individuals. While microbial translocation and gut epithelial barrier dysfunction may promote persistent immune activation in treated HIV infection, potentially contributing to morbidity and mortality, it has been unclear whether CMV replication in individuals with no symptoms of CMV disease might play a role in this process. We hypothesized that persistent CMV replication in the intestinal epithelium of HIV/CMV-coinfected individuals impairs gut epithelial barrier function. Using a combination of state-of-the-art in situ hybridization technology (RNAscope) and immunohistochemistry, we detected CMV DNA and proteins and evidence of intestinal damage in rectosigmoid samples from CMV-positive individuals with both untreated and ART-suppressed HIV infection. Two different model systems, primary human intestinal cells differentiated in vitro to form polarized monolayers and a humanized mouse model of human gut, together demonstrated that intestinal epithelial cells are fully permissive to CMV replication. Independent of HIV, CMV disrupted tight junctions of polarized intestinal cells, significantly reducing transepithelial electrical resistance, a measure of monolayer integrity, and enhancing transepithelial permeability. The effect of CMV infection on the intestinal epithelium is mediated, at least in part, by the CMV-induced proinflammatory cytokine IL-6. Furthermore, letermovir, a novel anti-CMV drug, dampened the effects of CMV on the epithelium. Together, our data strongly suggest that CMV can disrupt epithelial junctions, leading to bacterial translocation and chronic inflammation in the gut and that CMV could serve as a target for therapeutic intervention to prevent or treat gut epithelial barrier dysfunction during HIV infection.
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Affiliation(s)
- Ekaterina Maidji
- Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco, California, United States of America
| | - Ma Somsouk
- Division of Gastroenterology, Department of Medicine, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco, California, United States of America
| | - Jose M. Rivera
- Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco, California, United States of America
| | - Peter W. Hunt
- Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco, California, United States of America
| | - Cheryl A. Stoddart
- Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco, California, United States of America
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Oppenheim S. Prognosis in HIV and AIDS #213. J Palliat Med 2016; 19:1114-1115. [DOI: 10.1089/jpm.2016.0206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Choopong P, Vivittaworn K, Konlakij D, Thoongsuwan S, Pituksung A, Tesavibul N. Treatment outcomes of reduced-dose intravitreal ganciclovir for cytomegalovirus retinitis. BMC Infect Dis 2016; 16:164. [PMID: 27090644 PMCID: PMC4836083 DOI: 10.1186/s12879-016-1490-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 03/31/2016] [Indexed: 11/25/2022] Open
Abstract
Background Cytomegalovirus retinitis (CMVR) is one of the most common opportunistic infection in immunocompromised individuals. Intravitreal ganciclovir injection has been used successfully but no standard regimen was established. Risks of drug toxicity, endophthalmitis, and injection-related complications increased with number and frequency of injection. The aim of this study is to evaluate the outcomes of reduced-dose intravitreal ganciclovir (2 mg/0.04 mL) for the treatment of CMVR. Methods A prospective observational cohort study involving 67 eyes of 49 patients with CMVR was performed. Induction therapy involved intravenous ganciclovir (10 mg/kg/day) for 2 weeks unless contraindicated or patients refused. Patients were then treated with reduced-dose intravitreal ganciclovir every week for 4 weeks, and then every other week until the lesion healed. The patients’ demographic data were recorded, and vision parameters were examined every visit. Results Twenty eyes (29.9 %) presented with initial visual acuities less than 6/60. The majority of patients were diagnosed with CMVR in zones 1 or 2 (63 eyes, 94 %), and, at least, one quadrant of the retina was involved (56 eyes, 83.6 %). Forty-one eyes (61.2 %) completely resolved after treatment within the 6-month follow-up. There was no significant difference in healing time, whether or not patients received induction treatment with intravenous ganciclovir (111.00 ± 12.96 vs 105.00 ± 28.32 days, p = 0.8). Five eyes (12.2 %) of patients with healed CMVR had visual acuities less than 6/60. Conclusions Reduced-dose intravitreal ganciclovir is a safe and effective treatment option. It provides comparable results to other weekly regimens. Induction with intravenous ganciclovir is not crucial in a resolution of retinitis, although it may be necessary to reduce systemic cytomegalovirus loads and mortality rates. Trial registration The trial was registered with Thai Clinical Trials Registry (TCTR) on 16 March 2016 – TCTR20160316001.
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Affiliation(s)
- Pitipol Choopong
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
| | - Kamolporn Vivittaworn
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
| | - Duanphen Konlakij
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
| | - Somanus Thoongsuwan
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
| | - Auengporn Pituksung
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
| | - Nattaporn Tesavibul
- Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand
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Sittivarakul W, Benjhawaleemas T, Aui-Aree N, Jirarattanasopa P, Liabsuetrakul T. Incidence Rate and Risk Factors for Contralateral Eye Involvement among Patients with AIDS and Cytomegalovirus Retinitis Treated with Local Therapy. Ocul Immunol Inflamm 2015; 24:530-6. [PMID: 26327465 DOI: 10.3109/09273948.2015.1032307] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE To calculate the incidence of, and to identify the risk factors for developing contralateral eye involvement among patients with AIDS and unilateral cytomegalovirus retinitis (CMV retinitis), who were treated, in the era of highly-active antiretroviral therapy (HAART), with repetitive intravitreal ganciclovir injections. MATERIALS AND METHODS The clinical records of 119 patients were included. The main outcome measurement was the occurrence of contralateral eye involvement. RESULTS Over a mean follow-up period of 1.6 years, the overall incidence rate of contralateral involvement was 0.17/person-year. The cumulative incidence of contralateral involvement at 6 months and 1 year was 23.8% and 28.4%, respectively. Receiving HAART at the visit before the event was associated with a decreased risk of developing contralateral retinitis (hazard ratio [HR] = 0.26, P = 0.002). CONCLUSIONS The use of HAART, associated with subsequent immune recovery, significantly reduced the incidence of contralateral eye involvement by approximately 75% among patients in our setting.
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Affiliation(s)
- Wantanee Sittivarakul
- a Department of Ophthalmology, Faculty of Medicine , Prince of Songkla University , Hat Yai , Thailand and
| | - Thanyapat Benjhawaleemas
- a Department of Ophthalmology, Faculty of Medicine , Prince of Songkla University , Hat Yai , Thailand and
| | - Nipat Aui-Aree
- a Department of Ophthalmology, Faculty of Medicine , Prince of Songkla University , Hat Yai , Thailand and
| | - Pichai Jirarattanasopa
- a Department of Ophthalmology, Faculty of Medicine , Prince of Songkla University , Hat Yai , Thailand and
| | - Tippawan Liabsuetrakul
- b Epidemiology Unit, Faculty of Medicine , Prince of Songkla University , Hat Yai , Thailand
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Jabs DA, Ahuja A, Van Natta ML, Lyon AT, Yeh S, Danis R. Long-term Outcomes of Cytomegalovirus Retinitis in the Era of Modern Antiretroviral Therapy: Results from a United States Cohort. Ophthalmology 2015; 122:1452-63. [PMID: 25892019 DOI: 10.1016/j.ophtha.2015.02.033] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Revised: 02/20/2015] [Accepted: 02/23/2015] [Indexed: 12/18/2022] Open
Abstract
PURPOSE To describe the long-term outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS in the modern era of combination antiretroviral therapy. DESIGN Prospective, observational cohort study. PARTICIPANTS Patients with AIDS and CMV retinitis. METHODS Immune recovery, defined as a CD4+ T-cell count >100 cells/μl for ≥3 months. MAIN OUTCOME MEASURES Mortality, visual impairment (visual acuity <20/40), and blindness (visual acuity ≤20/200) on logarithmic visual acuity charts and loss of visual field on quantitative Goldmann perimetry. RESULTS Patients without immune recovery had a mortality of 44.4/100 person-years (PYs) and a median survival of 13.5 months after the diagnosis of CMV retinitis, whereas those with immune recovery had a mortality of 2.7/100 PYs (P < 0.001) and an estimated median survival of 27.0 years after the diagnosis of CMV retinitis. The rates of bilateral visual impairment and blindness were 0.9 and 0.4/100 PYs, respectively, and were similar between those with and without immune recovery. Among those with immune recovery, the rate of visual field loss was approximately 1% of the normal field per year, whereas among those without immune recovery it was approximately 7% of the normal field per year. CONCLUSIONS Among persons with CMV retinitis and AIDS, if there is immune recovery, long-term survival is likely, whereas if there is no immune recovery, the mortality rate is substantial. Although higher than the rates in the population not infected by human immunodeficiency virus, the rates of bilateral visual impairment and blindness are low, especially when compared with rates in the era before modern antiretroviral therapy.
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Affiliation(s)
- Douglas A Jabs
- Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Center for Clinical Trials, Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.
| | - Alka Ahuja
- Center for Clinical Trials, Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Mark L Van Natta
- Center for Clinical Trials, Department of Epidemiology, The Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
| | - Alice T Lyon
- Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Steven Yeh
- Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia
| | - Ronald Danis
- Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin
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Dunn JP. An overview of current and future treatment options for patients with cytomegalovirus retinitis. Expert Opin Orphan Drugs 2014. [DOI: 10.1517/21678707.2014.945906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Heiden D, Saranchuk P, Tun N, Audoin B, Cohn J, Durier N, Holland G, Drew WL, 't Hoen E. We urge WHO to act on cytomegalovirus retinitis. LANCET GLOBAL HEALTH 2014; 2:e76-7. [PMID: 25104662 DOI: 10.1016/s2214-109x(13)70174-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- David Heiden
- Seva Foundation and California Pacific Medical Center, Pacific Eye Associates, San Francisco, CA 94115, USA.
| | - Peter Saranchuk
- Southern Africa Medical Unit, Médecins Sans Frontières, Cape Town, South Africa
| | - NiNi Tun
- Medical Action Myanmar, Yangon, Myanmar
| | | | - Jen Cohn
- Médecins Sans Frontières Access Campaign, Geneva, Switzerland
| | - Nicolas Durier
- TREAT Asia, amfAR (The Foundation for AIDS Research), Bangkok, Thailand
| | - Gary Holland
- Department of Ophthamology, Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, CA, USA
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Griffiths P, Plotkin S, Mocarski E, Pass R, Schleiss M, Krause P, Bialek S. Desirability and feasibility of a vaccine against cytomegalovirus. Vaccine 2013; 31 Suppl 2:B197-203. [PMID: 23598482 PMCID: PMC5672921 DOI: 10.1016/j.vaccine.2012.10.074] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2012] [Revised: 10/10/2012] [Accepted: 10/19/2012] [Indexed: 12/25/2022]
Abstract
Publication of a report from the Institute of Medicine in 2000 showing that a vaccine against cytomegalovirus (CMV) would likely be cost saving was very influential and encouraged the clinical evaluation of candidate vaccines. The major objective of a CMV vaccination program would be to reduce disease caused by congenital CMV infection, which is the leading viral cause of sensorineural hearing loss and neurodevelopmental delay. CMV has challenges as a vaccine target because it is a herpesvirus, it persists lifelong despite host immunity, infected individuals can be reinfected with new strains, overt disease occurs in those with immature or impaired immune systems and persons with this infection do not usually report symptoms. Nevertheless, natural immunity against CMV provides some protection against infection and disease, natural history studies have defined the serological and molecular biological techniques needed for endpoints in future clinical trials of vaccines and CMV is not highly communicable, suggesting that it may not be necessary to achieve very high levels of population immunity through vaccination in order to affect transmission. Three phase 2 CMV vaccine studies have been completed in the last 3 years and all report encouraging outcomes. A key international meeting was organized by the Food and Drug Administration in January 2012 at which interested parties from regulatory bodies, industry and academia discussed and prioritised designs for phase 2 and phase 3 clinical trials. Vaccines able to prevent primary infection with CMV and to boost the immune response of those already infected are desirable. The major target populations for a CMV vaccine include women of childbearing age and adolescents. Toddlers represent another potential population, since an effect of vaccine in this age group could potentially decrease transmission to adults. In addition, prospective recipients of transplants and patients with AIDS would be expected to benefit.
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Durier N, Ananworanich J, Apornpong T, Ubolyam S, Kerr SJ, Mahanontharit A, Ferradini L, Ruxrungtham K, Avihingsanon A. Cytomegalovirus viremia in Thai HIV-infected patients on antiretroviral therapy: prevalence and associated mortality. Clin Infect Dis 2013; 57:147-55. [PMID: 23511301 DOI: 10.1093/cid/cit173] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Prevalence and risk factors of cytomegalovirus (CMV) viremia in patients infected with human immunodeficiency virus (HIV) starting antiretroviral therapy (ART) in developing countries are understudied. METHODS We measured CMV DNA in stored plasma specimens of 293 Thai HIV patients starting ART at CD4 counts <200 cells/mm(3). We examined Cox proportional hazard ratios (HRs) of 24 months mortality and new AIDS-defining illness (ADI). RESULTS Of 293 patients, 159 (54.3%) were male. The median age was 33 years. The median baseline CD4 count was 82 cells/mm(3), and the median HIV-1 RNA was 4.9 log10 copies/mL. In total, 273 (93.2%) patients started potent combination ART, and 20 (6.8%) started dual nucleoside reverse transcriptase inhibitor (NRTI) therapy. CMV DNA was detected in 77 of 293 patients (26.3%) at baseline, and 9 of 199 patients with available specimen (4.5%) after 6 months of ART. The median CMV DNA was 548 copies/mL (interquartile range [IQR], 129-3849) at baseline and 114 copies/mL (IQR, 75-1099) at 6 months. In univariate analysis, death was associated with baseline CDC stage C, hemoglobin <10 g/dL, lower CD4 count, and CMV viremia. In multivariate analysis, only CMV DNA >500 copies/mL was significantly associated with mortality (HR: 7.28; 95% CI, 1.32-40.29, P = .023). CD4 count was the only variable associated with new ADI (HR: 0.70 per 50 CD4 cells increase; 95% CI, .49-.997, P = .048). CONCLUSIONS In these Thai patients with advanced HIV disease, CMV viremia was frequent, and CMV DNA >500 copies/mL predicted increased mortality despite ART initiation. This calls for increased attention to screening of active CMV infection in advanced HIV patients in developing countries. Trials assessing preemptive anti-CMV therapy may be warranted.
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Affiliation(s)
- Nicolas Durier
- TREAT Asia, amfAR/The Foundation for AIDS Research, Klongtoey, Bangkok 10110, Thailand.
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Jabs DA, Ahuja A, Van Natta M, Dunn JP, Yeh S. Comparison of treatment regimens for cytomegalovirus retinitis in patients with AIDS in the era of highly active antiretroviral therapy. Ophthalmology 2013; 120:1262-70. [PMID: 23419804 DOI: 10.1016/j.ophtha.2012.11.023] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2012] [Revised: 11/09/2012] [Accepted: 11/13/2012] [Indexed: 12/12/2022] Open
Abstract
PURPOSE To describe the outcomes of different treatment approaches for cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART). DESIGN Prospective cohort study, the Longitudinal Study of the Ocular Complications of AIDS. PARTICIPANTS A total of 250 patients with CMV retinitis and a CD4+ T-cell count <100 cells/μl (n = 221) at enrollment or incident retinitis (n = 29) during cohort follow-up. METHODS The effects of systemic therapy (vs. intraocular therapy only) on systemic outcomes and the effect of intraocular therapies (ganciclovir implants, intravitreal injections) on ocular outcomes were evaluated. MAIN OUTCOME MEASURES Mortality, CMV dissemination, retinitis progression, and treatment side effects. RESULTS Regimens containing systemic anti-CMV therapy were associated with a 50% reduction in mortality (adjusted hazard ratio [HR], 0.5; 95% confidence interval [CI], 0.3-0.7; P = 0.006), a 90% reduction in new visceral CMV disease (adjusted HR, 0.1; 95% CI, 0.04-0.4; P = 0.004), and among those with unilateral CMV retinitis at presentation, an 80% reduction in second eye disease (adjusted HR, 0.2; 95% CI, 0.1-0.5; P = 0.0005) when compared with those using only intraocular therapy (implants or injections). Compared with systemic treatment only, regimens containing intravitreal injections had greater rates of retinitis progression (adjusted HR, 3.4; P = 0.004) and greater visual field loss (for loss of one half of the normal field, adjusted HR, 5.5; P < 0.01). Intravitreal implants were not significantly better than systemic therapy (adjusted HR for progression, 0.5; P = 0.26; adjusted HR for loss of one half of the visual field, 0.5; P = 0.45), but the sample size was small. Hematologic and renal side effect rates were similar between those groups with and without systemic anti-CMV therapy. The rate of endophthalmitis was 0.017 per eye-year (EY) (95% CI, 0.006-0.05) among those treated with intravitreal injections and 0.01 per EY (95% CI, 0.002-0.04) among those treated with an implant. CONCLUSIONS In the HAART era, systemic anti-CMV therapy, while there is immune compromise, seems to provide benefits in terms of longer survival and decreased CMV dissemination. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.
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Affiliation(s)
- Douglas A Jabs
- Department of Ophthalmology, the Mount Sinai School of Medicine, New York, New York 10029, USA.
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Nayudu SK, Balar B. Colorectal cancer screening in human immunodeficiency virus population: Are they at average risk? World J Gastrointest Oncol 2012; 4:259-264. [PMID: 23443303 PMCID: PMC3581851 DOI: 10.4251/wjgo.v4.i12.259] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Revised: 09/07/2012] [Accepted: 09/20/2012] [Indexed: 02/05/2023] Open
Abstract
AIM To evaluate if human immunodeficiency virus (HIV) population is getting adequate screening for colon cancer in the highly active anti-retroviral treatment (HAART) era with improved longevity, and the prevalence of polyps and adenomas in this population, when compared with the general population. METHODS We conducted retrospective chart review of average-risk HIV population for colon cancer attending our infectious disease clinic. Individuals who underwent diagnostic colonoscopy were excluded. We extracted various demographic, HIV disease-specific and colonoscopy data including histo-pathological reports in the last 10 years. Total population was divided into a study group, who underwent screening colonoscopy and a control group who did not. We analyzed data using standard statistical methods and software. RESULTS We found that 25% of average-risk HIV-infected population was screened for colon cancer using colonoscopy. There was no difference in gender and ethnic distribution between the groups. We found wider distribution of age (50-84 years with mean 56 years) in the control group when compared to (50-73 years with mean 58 years) the study group. However, there were 89% of subjects with well-controlled HIV disease measured by HIV RNA copies of < 75 in the study group when compared with 70% in the control group (P < 0.0001). We noticed polyp detection rate of 55% and adenoma detection rate of 32% in HIV population. CONCLUSION It is unclear whether HIV or HAART medications play a role in increased prevalence of adenomas. We suggest that when estimating the risk for colonic neoplasms, HIV population should be considered as a high-risk group and screened accordingly.
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Affiliation(s)
- Suresh Kumar Nayudu
- Suresh Kumar Nayudu, Bhavna Balar, Division of Gastroenterology, Department of Medicine, Bronx Lebanon Hospital Center, Affiliated with Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10457, United States
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Barrett L, Walmsley S. CMV retinopathy in the antiretroviral therapy era: prevention, diagnosis, and management. Curr Infect Dis Rep 2012; 14:435-44. [PMID: 22688820 DOI: 10.1007/s11908-012-0269-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Before the advent of antiretroviral therapy (ART), CMV retinitis was a common, debilitating opportunistic infection in the HIV-infected population. ART has had such a favorable impact on the prevention and management of CMV retinitis that it can be considered in some ways to be CMV therapy. Currently available CMV directed antiviral therapies are quite successful at limiting vision loss, but in resource limited settings there is still significant morbidity associated with the disease. This review summarizes the pathology, diagnosis, clinical course and treatment of retinitis in the pre-ART era to provide context for the contemporary clinical scenario, and highlights current management strategies. Important questions concerning host correlates of susceptibility and ideal therapy in the context of drug resistance are also briefly reviewed.
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Affiliation(s)
- Lisa Barrett
- Laboratory of Immunoregulation, National Institutes of Health, Bethesda, MD, USA
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Griffiths PD. Burden of disease associated with human cytomegalovirus and prospects for elimination by universal immunisation. THE LANCET. INFECTIOUS DISEASES 2012; 12:790-8. [PMID: 23017365 DOI: 10.1016/s1473-3099(12)70197-4] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Cytomegalovirus is the most frequent cause of intrauterine infection and the commonest infectious agent to affect allograft recipients, yet the virus is acknowledged rarely as an occupational hazard for women of childbearing age or as a nosocomial infection. The potential role of cytomegalovirus in hastening the death of patients with AIDS, elderly people, individuals admitted to intensive-care units, and the general population is not emphasised. Development of vaccines against this important human pathogen has been delayed by reluctance to initiate proof-of-concept studies, but after recent trials, protection is a distinct possibility. Cytomegalovirus deserves to be eliminated from selected populations by means of universal immunisation as soon as suitable vaccines become licensed. This action should control disease in neonates and transplant recipients and could provide substantial additional benefits if other disease associations prove to be causal.
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Kempen JH, Sugar EA, Lyon AT, Lewis RA, Jabs DA, Heinemann MH, Dunn JP. Risk of cataract in persons with cytomegalovirus retinitis and the acquired immune deficiency syndrome. Ophthalmology 2012; 119:2343-50. [PMID: 22853972 DOI: 10.1016/j.ophtha.2012.05.044] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2011] [Revised: 05/24/2012] [Accepted: 05/24/2012] [Indexed: 11/17/2022] Open
Abstract
OBJECTIVE To evaluate cataract risk in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis and to identify risk factors. DESIGN Prospective cohort study. PARTICIPANTS Patients with AIDS and CMV retinitis. METHODS Patients 13 years of age and older were enrolled between 1998 and 2008. Demographic and clinical characteristics, slit-lamp biomicroscopy findings, and dilated ophthalmoscopy results were documented at quarterly visits. Cataract status was determined at the initial visit (prevalence) and at follow-up visits (incidence). MAIN OUTCOME MEASURES For cataract, a high grade of lens opacity by biomicroscopy to which best-corrected visual acuity worse than 20/40 was attributed. Eyes that had undergone cataract surgery before enrollment or between visits also were counted as having cataract. RESULTS Seven hundred twenty-nine eyes of 489 patients diagnosed with CMV retinitis were evaluated. Higher prevalence was observed for patients with bilateral versus unilateral CMV retinitis (adjusted odds ratio [aOR], 2.74; 95% confidence interval [CI], 1.76-4.26) and, among unilateral CMV retinitis cases, for eyes with retinitis versus without retinitis (15% vs. 1.4%; P<0.0001). The age-adjusted prevalence of cataract among CMV retinitis cases was higher than that in a population-based sample (P<0.0001). Cataract prevalence increased with age (aOR, 11.77; 95% CI, 2.28-60.65 for age ≥ 60 years vs. younger than 40 years) and longer duration of retinitis (aOR, 1.36; 95% CI, 1.20-1.54 per year). Among eyes with CMV retinitis initially free of cataract, the cataract incidence was 8.1%/eye-year (95% CI, 6.7%-10.0%). Prior retinal detachment was associated with higher cataract risk (if repaired with silicone oil: adjusted hazard ratio [aHR], 10.37; 95% CI, 6.51-16.52; otherwise: aHR, 2.90; 95% CI, 1.73-4.87). Large CMV retinitis lesions also were associated with higher risk of cataract (for involvement of 25-49% retinal area: aHR, 2.30; 95% CI, 1.51-3.50; for ≥ 50% involvement: aHR, 3.63; 95% CI, 2.18-6.04), each with respect to ≤ 24% involvement, as were anterior segment inflammation (aHR, 2.27; 95% CI, 1.59-3.25) and contralateral cataract (aHR, 2.52; 95% CI, 1.74-3.66). CONCLUSIONS Cytomegalovirus retinitis is associated with a high absolute and relative risk of cataract. Among several risk factors, large retinal lesion size and use of silicone oil in retinal detachment repair are potentially modifiable, albeit not in all cases. Cataract is likely to be an increasingly important cause of visual morbidity in this population.
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Affiliation(s)
- John H Kempen
- Department of Ophthalmology, and the Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
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Sugar EA, Jabs DA, Ahuja A, Thorne JE, Danis RP, Meinert CL. Incidence of cytomegalovirus retinitis in the era of highly active antiretroviral therapy. Am J Ophthalmol 2012; 153:1016-24.e5. [PMID: 22310076 DOI: 10.1016/j.ajo.2011.11.014] [Citation(s) in RCA: 75] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2011] [Revised: 11/14/2011] [Accepted: 11/14/2011] [Indexed: 10/14/2022]
Abstract
PURPOSE To estimate the incidence of cytomegalovirus (CMV) retinitis in the era of highly active antiretroviral therapy (HAART) and to characterize the factors associated with increased risk of CMV retinitis. DESIGN Prospective cohort study. METHODS A total of 1600 participants with acquired immunodeficiency syndrome (AIDS) but without CMV retinitis at enrollment who completed at least 1 follow-up visit in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) were seen every 6 months to obtain disease and treatment history, ophthalmic examination, and laboratory testing. Incidence of CMV retinitis and risk factors for incident CMV retinitis were assessed. RESULTS The incidence rate of CMV retinitis in individuals with AIDS was 0.36/100 person-years (PY) based upon 29 incident cases during 8134 PY of follow-up. The rate was higher for those with a CD4+ T cell count at the immediately prior visit below 50 cells/μL (3.89/100 PY, P < .01), whereas only 1 individual with a CD4+ T cell count of 50 to 99 cells/μL and 2 individuals with a CD4+ T cell count >100 cells/μL developed CMV retinitis. Having a CD4+ T cell count below 50 cells/μL at the clinical visit prior to CMV retinitis evaluation was the single most important risk factor (HR: 136, 95% CI: 30 to 605, P < .0001) for developing retinitis. CONCLUSIONS Patients with AIDS, especially those with severely compromised immune systems, remain at risk for developing CMV retinitis in the HAART era, although the incidence rate is reduced from that observed in the pre-HAART era.
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Oktavec KC, Nolan K, Brown DM, Dunn JP, Livingston AG, Thorne JE. Clinical outcomes in patients with cytomegalovirus retinitis treated with ganciclovir implant. Am J Ophthalmol 2012; 153:728-33, 733.e1-2. [PMID: 22265144 DOI: 10.1016/j.ajo.2011.09.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2011] [Revised: 09/09/2011] [Accepted: 09/11/2011] [Indexed: 11/27/2022]
Abstract
PURPOSE To describe the clinical outcomes of patients with cytomegalovirus (CMV) retinitis and AIDS treated with ganciclovir implant. DESIGN Retrospective cohort study. METHODS The charts of 115 patients (166 affected eyes) with CMV retinitis treated with ganciclovir implant in the Division of Ocular Immunology, Wilmer Eye Institute from April 1996 through November 2009 were reviewed. Ophthalmologic data collected included visual acuity, ocular complications, treatment, and presence of immune recovery. Kaplan-Meier analyses and Cox regression models were used to investigate relationships between potential risk factors and ocular outcomes. RESULTS At implantation, 55% of patients were prescribed highly active antiretroviral therapy (HAART), 21% were formerly on HAART, and 24% were HAART-naïve. One hundred sixty-six eyes received 257 ganciclovir implants. Fifty-seven of the implanted eyes were diagnosed with a total of 126 ocular complications after implant surgery (rate=0.19/eye-year [EY]), the 3 most common being cataract, vitreous hemorrhage, and retinal detachment. Despite these ocular complications, the development of severe vision loss (≥6 lines lost) was low (0.005/EY). Patients with immune recovery during follow-up were less likely to have ocular complications after implant surgery; however, only the risk reduction for retinal detachment achieved statistical significance (hazard ratio=0.29, 95% CI: 0.08, 0.98). CONCLUSIONS Our data suggest that ocular complications after implant surgery, including cataract, vitreous hemorrhage, and retinal detachment, were relatively common after ganciclovir implantation but severe vision loss after surgery was low. Presence of immune recovery may lessen the risk of postoperative ocular complications.
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Affiliation(s)
- Kathleen C Oktavec
- Department of Epidemiology, Center for Clinical Trials, the Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21287, USA
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Cade WT, Reeds DN, Overton ET, Herrero P, Waggoner AD, Davila-Roman VG, Lassa-Claxton S, Gropler RJ, Soto PF, Krauss MJ, Yarasheski KE, Peterson LR. Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis. Cardiovasc Diabetol 2011; 10:111. [PMID: 22151886 PMCID: PMC3258269 DOI: 10.1186/1475-2840-10-111] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2011] [Accepted: 12/08/2011] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND In the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV) and combination anti-retroviral therapy (cART) are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC. METHODS Prospective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET) imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs), and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs). Left ventricular function parameters were quantified using echocardiography. RESULTS Myocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic complications (HIV+: 9.2 ± 6.2 vs. HIV-: 10.4 ± 8.1 nmol/g/min/μU/mL) than men without metabolic complications (HIV+: 45.0 ± 33.3 vs. HIV-: 60.3 ± 53.0 nmol/g/min/μU/mL). Lower GLUT/INS was associated with lower myocardial relaxation velocity during early diastole (r = 0.39, p < 0.001). CONCLUSION Men with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for blunted myocardial glucose utilization per unit of insulin. TRIAL REGISTRATION NIH Clinical Trials NCT00656851.
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Affiliation(s)
- W Todd Cade
- Program in Physical Therapy, Washington University School of Medicine, 4444 Forest Park Boulevard, St, Louis, Missouri 63108, USA.
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Fielding K, Koba A, Grant AD, Charalambous S, Day J, Spak C, Wald A, Huang ML, Corey L, Churchyard GJ. Cytomegalovirus viremia as a risk factor for mortality prior to antiretroviral therapy among HIV-infected gold miners in South Africa. PLoS One 2011; 6:e25571. [PMID: 22022413 PMCID: PMC3192109 DOI: 10.1371/journal.pone.0025571] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2011] [Accepted: 09/07/2011] [Indexed: 11/28/2022] Open
Abstract
Background Cytomegalovirus (CMV) viremia has been shown to be an independent risk factor for increased mortality among HIV-infected individuals in the developing world. While CMV infection is nearly ubiquitous in resource-poor settings, few data are available on the role of subclinical CMV reactivation on HIV. Methods Using a cohort of mineworkers with stored plasma samples, we investigated the association between CMV DNA concentration and mortality prior to antiretroviral therapy availability. Results Among 1341 individuals (median CD4 count 345 cells/µl, 70% WHO stage 1 or 2, median follow-up 0.9 years), 70 (5.2%) had CMV viremia at baseline; 71 deaths occurred. In univariable analysis CMV viremia at baseline was associated with a three-fold increase in mortality (hazard ratio [HR] 3.37; 95% confidence intervals [CI] 1.60, 7.10). After adjustment for CD4 count, WHO stage and HIV viral load (N = 429 with complete data), the association was attenuated (HR 2.27; 95%CI 0.88, 5.83). Mortality increased with higher CMV viremia (≥1,000 copies/ml vs. no viremia, adjusted HR 3.65, 95%CI: 1.29, 10.41). Results were similar using time-updated CMV viremia. Conclusions High copy number, subclinical CMV viremia was an independent risk factor for mortality among male HIV-infected adults in South Africa with relatively early HIV disease. Studies to determine whether anti-CMV therapy to mitigate high copy number viremia would increase lifespan are warranted.
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Affiliation(s)
- Katherine Fielding
- Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom.
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Tun N, London N, Kyaw MK, Smithuis F, Ford N, Margolis T, Drew WL, Lewallen S, Heiden D. CMV retinitis screening and treatment in a resource-poor setting: three-year experience from a primary care HIV/AIDS programme in Myanmar. J Int AIDS Soc 2011; 14:41. [PMID: 21843351 PMCID: PMC3163508 DOI: 10.1186/1758-2652-14-41] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2011] [Accepted: 08/15/2011] [Indexed: 11/10/2022] Open
Abstract
Background Cytomegalovirus retinitis is a neglected disease in resource-poor settings, in part because of the perceived complexity of care and because ophthalmologists are rarely accessible. In this paper, we describe a pilot programme of CMV retinitis management by non-ophthalmologists. The programme consists of systematic screening of all high-risk patients (CD4 <100 cells/mm3) by AIDS clinicians using indirect ophthalmoscopy, and treatment of all patients with active retinitis by intravitreal injection of ganciclovir. Prior to this programme, CMV retinitis was not routinely examined for, or treated, in Myanmar. Methods This is a retrospective descriptive study. Between November 2006 and July 2009, 17 primary care AIDS clinicians were trained in indirect ophthalmoscopy and diagnosis of CMV retinitis; eight were also trained in intravitreal injection. Evaluation of training by a variety of methods documented high clinical competence. Systematic screening of all high-risk patients (CD4 <100 cells/mm3) was carried out at five separate AIDS clinics throughout Myanmar. Results A total of 891 new patients (1782 eyes) were screened in the primary area (Yangon); the majority of patients were male (64.3%), median age was 32 years, and median CD4 cell count was 38 cells/mm3. CMV retinitis was diagnosed in 24% (211/891) of these patients. Bilateral disease was present in 36% of patients. Patients with active retinitis were treated with weekly intravitreal injection of ganciclovir, with patients typically receiving five to seven injections per eye. A total of 1296 injections were administered. Conclusions A strategy of management of CMV retinitis at the primary care level is feasible in resource-poor settings. With appropriate training and support, CMV retinitis can be diagnosed and treated by AIDS clinicians (non-ophthalmologists), just like other major opportunistic infections.
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Affiliation(s)
- Nini Tun
- California Pacific Medical Center, San Francisco, USA
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Scherrenburg J, Schellens IM, van Baarle D. Influence of HIV infection on cytomegalovirus-specific immunity: T-cell responses to pp65 and IE1 before and after HAART may reflect altered cytomegalovirus biology. Antivir Ther 2011; 16:565-75. [PMID: 21685544 DOI: 10.3851/imp1800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
BACKGROUND Data are inconclusive whether treatment with HAART induces functional recovery of HIV-specific T-cells. Since the introduction of HAART, a marked decrease of cytomegalovirus (CMV) disease - for which untreated HIV-infected individuals are at increased risk - is observed, suggesting that this treatment influences CMV-specific T-cell immunity. METHODS To study potential functional recovery of HIV- and CMV-specific T-cells, CD4(+) and CD8(+) T-cell responses were measured longitudinally after in vitro expansion using gag, pp65 and IE1 peptide pools, during HIV infection and after long-term HAART. RESULTS HIV-specific T-cell function, measured by interferon (IFN)-γ production, was low after initiation of HAART. Interestingly, the cytotoxic function - measured by CD107a expression - of these T-cells temporarily increased after start of treatment, suggesting some functional recovery. The pp65-specific CD8(+) T-cell responses tended to decrease during HIV infection, whereas pp65-specific CD4(+) T-cell responses decreased upon treatment with HAART. Both pp65-specific CD4(+) and CD8(+) T-cell responses were low after initiation of HAART compared to healthy controls. By contrast, IE1-specific CD4(+) T-cell responses increased during the course of HIV infection. After initiation of HAART, IE1-specific T-cell responses decreased, but IE1-specific CD8(+) T-cells seemed increased compared to healthy controls. CONCLUSIONS This study suggests that HIV-infection leads to an altered CMV biology, affecting pp65- and IE1-specific T-cell responses in a different way, which is not restored by treatment with long-term HAART.
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Affiliation(s)
- Jolanda Scherrenburg
- Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands
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Jabs DA. Cytomegalovirus retinitis and the acquired immunodeficiency syndrome--bench to bedside: LXVII Edward Jackson Memorial Lecture. Am J Ophthalmol 2011; 151:198-216.e1. [PMID: 21168815 PMCID: PMC3057105 DOI: 10.1016/j.ajo.2010.10.018] [Citation(s) in RCA: 96] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2010] [Revised: 10/08/2010] [Accepted: 10/11/2010] [Indexed: 11/29/2022]
Abstract
PURPOSE To update information on cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) and to integrate information on its pathogenesis and clinical outcomes. DESIGN Literature review. METHODS Selected articles from the medical literature, particularly large epidemiologic studies, including the Johns Hopkins Cytomegalovirus Retinitis Cohort Study, the Longitudinal Study of the Ocular Complications of AIDS, and the Cytomegalovirus Retinitis and Viral Resistance Study, were reviewed. Clinical information is discussed in light of knowledge on CMV, its pathogenesis, and its interactions with human immunodeficiency virus (HIV). RESULTS Cytomegalovirus uses several mechanisms to evade the immune system and establish latent infection in immunologically normal hosts. With immune deficiency, such as late-stage AIDS, CMV reactivates, is disseminated to the eye, and establishes a productive infection, resulting in retinal necrosis. HIV and CMV potentiate each other: CMV accelerates HIV disease, and CMV retinitis is associated with increased mortality. Randomized clinical trials have demonstrated the efficacy of treatments for CMV retinitis. Systemically administered treatment for CMV retinitis decreases AIDS mortality. Highly active antiretroviral therapy (HAART) effectively suppresses HIV replication, resulting in immune recovery, which, if sufficient, controls retinitis without anti-CMV therapy. Resistant CMV, detected in the blood, correlates with resistant virus in the eye and is associated with worse clinical outcomes, including mortality. Host factors, including host genetics and access to care, play a role in the development of CMV retinitis. CONCLUSIONS Clinical outcomes of CMV retinitis in patients with AIDS are dependent on characteristics of the virus and host and on HIV-CMV interactions.
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Affiliation(s)
- Douglas A Jabs
- Department of Ophthalmology, the Mount Sinai School of Medicine, New York, New York 10029, USA.
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Abstract
Cytomegalovirus (CMV) retinitis is the most common cause of vision loss in patients with acquired immunodeficiency syndrome (AIDS). CMV retinitis afflicted 25% to 42% of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, with most vision loss due to macula-involving retinitis or retinal detachment. The introduction of HAART significantly decreased the incidence and severity of CMV retinitis. Optimal treatment of CMV retinitis requires a thorough evaluation of the patient's immune status and an accurate classification of the retinal lesions. When retinitis is diagnosed, HAART therapy should be started or improved, and anti-CMV therapy with oral valganciclovir, intravenous ganciclovir, foscarnet, or cidofovir should be administered. Selected patients, especially those with zone 1 retinitis, may receive intravitreal drug injections or surgical implantation of a sustained-release ganciclovir reservoir. Effective anti-CMV therapy coupled with HAART significantly decreases the incidence of vision loss and improves patient survival. Immune recovery uveitis and retinal detachments are important causes of moderate to severe loss of vision. Compared with the early years of the AIDS epidemic, the treatment emphasis in the post- HAART era has changed from short-term control of retinitis to long-term preservation of vision. Developing countries face shortages of health care professionals and inadequate supplies of anti-CMV and anti-HIV medications. Intravitreal ganciclovir injections may be the most cost effective strategy to treat CMV retinitis in these areas.
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Affiliation(s)
- Michael W Stewart
- Department of Ophthalmology, Mayo School of Medicine, Jacksonville, FL, USA.
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Patil AJ, Sharma A, Kenney MC, Kuppermann BD. Valganciclovir in the treatment of cytomegalovirus retinitis in HIV-infected patients. Clin Ophthalmol 2010; 4:111-9. [PMID: 20234777 PMCID: PMC2835533 DOI: 10.2147/opth.s3248] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2010] [Indexed: 11/24/2022] Open
Abstract
Oral valganciclovir is a new and highly efficacious alternative to the chronic administration of ganciclovir in the treatment of cytomegalovirus (CMV) retinitis in HIV-infected patients. In addition to its excellent bioavailability and favorable pharmacokinetic profile, valganciclovir has also proved cost effective and is the most widely used drug in the armamentarium for the treatment of CMV retinitis. Valganciclovir is a prodrug of ganciclovir, the erstwhile commonly used therapy. In March 2001, the US Food and Drug Administration approved valganciclovir for the induction and maintenance treatment of CMV disease, including CMV retinitis. Valganciclvoir has compared favorably with both oral and intravenous treatments for induction and maintenance therapy with ganciclovir. The reduced pill burden and the ease of oral administration has helped avoid the risks associated with intravenous therapy. The most serious adverse event is neutropenia, which makes the patient susceptible to infections. In the current review, we have compiled all the available evidence-based information on valganciclovir.
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Affiliation(s)
- A Jayaprakash Patil
- Department of Ophthalmology, Gavin S Herbert Eye Institute,University of California, Irvine, Irvine, CA, USA
- Department of Ophthalmology, Summa Health System, Akron, OH, USA
- Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH, USA
| | - Ashish Sharma
- Department of Ophthalmology, Gavin S Herbert Eye Institute,University of California, Irvine, Irvine, CA, USA
- Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, FL, USA
| | - M Cristina Kenney
- Department of Ophthalmology, Gavin S Herbert Eye Institute,University of California, Irvine, Irvine, CA, USA
| | - Baruch D Kuppermann
- Department of Ophthalmology, Gavin S Herbert Eye Institute,University of California, Irvine, Irvine, CA, USA
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Jabs DA, Martin BK, Forman MS. Mortality associated with resistant cytomegalovirus among patients with cytomegalovirus retinitis and AIDS. Ophthalmology 2009; 117:128-132.e2. [PMID: 19818505 DOI: 10.1016/j.ophtha.2009.06.016] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2009] [Revised: 06/08/2009] [Accepted: 06/10/2009] [Indexed: 10/20/2022] Open
Abstract
OBJECTIVE To evaluate the effect of drug-resistant cytomegalovirus (CMV) on survival among patients with CMV retinitis. DESIGN Prospective cohort study during 1993 to 2003. PARTICIPANTS We included 266 patients with AIDS and newly diagnosed CMV retinitis treated with either ganciclovir or foscarnet. METHODS Data on ganciclovir and foscarnet resistance were obtained from blood and urine specimens collected at regular, predetermined intervals. The effect of resistant CMV on mortality was evaluated with a time-dependent Cox proportional hazard model. MAIN OUTCOME MEASURES Mortality. RESULTS The median survival of the entire cohort was 12.6 months. Analysis of risk factors for mortality demonstrated that resistant CMV was associated with an increased mortality (hazard ratio, 1.65; 95% confidence interval, 1.05-2.56; P = 0.032). Among the other parameters tested, only time since AIDS diagnosis was associated significantly with mortality, with a hazard ratio of 1.10 per year since AIDS diagnosis (P = 0.001). CONCLUSIONS Resistant CMV is associated with increased mortality among patients with AIDS being treated for CMV retinitis. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.
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Affiliation(s)
- Douglas A Jabs
- Department of Ophthalmology, The Johns Hopkins University School of
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Oppenheim S. Prognosis in HIV and AIDS #213. J Palliat Med 2009; 12:833-5. [PMID: 19719373 DOI: 10.1089/jpm.2009.9567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Chaudhary MA, Moreno S, Kumar RN, Nocea G, Elbasha E. Cost-effectiveness analysis of raltegravir in treatment-experienced HIV type 1-infected patients in Spain. AIDS Res Hum Retroviruses 2009; 25:679-89. [PMID: 19552590 DOI: 10.1089/aid.2008.0254] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Raltegravir, a novel HIV-1 integrase inhibitor, has superior efficacy with optimized background treatment (OBT) vs. placebo + OBT in treatment-experienced HIV-1 patients. This study assessed the long-term cost effectiveness of raltegravir from a Spanish National Healthcare System perspective. A cohort-state-transition model was used to estimate clinical and economic outcomes associated with raltegravir + OBT vs. OBT alone. Subjects were stratified into health states according to HIV RNA level, CD4 count, and opportunistic infection (OI) history, and could transition into different health states over time based on projected long-term efficacy. Each health state was associated with a distinct treatment cost and utility (QoL) score. Model inputs for mortality, resource utilization, unit costs, OI risk, and long-term durability of viral suppression were obtained from clinical trials, published studies, and database analyses. Model outcomes were reported as incremental cost-effectiveness ratios (ICERs) in 2007 Euros per quality-adjusted life-year (euro/QALY) gained. Costs and QALYs were discounted at 6% per year based on Spanish cost-effectiveness guidelines. Extensive sensitivity analyses were conducted. Five years of treatment with raltegravir + OBT resulted in an additional 4.5 years of undiscounted life expectancy vs. OBT alone. The ICER of raltegravir + OBT vs. OBT alone was euro22,908/QALY and euro31,431/QALY for 3- and 5-year use, respectively. Lower ICERs were observed with lower discount rates (3%) for costs and benefits, lower raltegravir price (20%), and shorter treatment duration (3 years). ICER was also sensitive to analytical time horizon and alternative sources of QoL scores. In treatment-experienced Spanish patients, raltegravir was projected to provide survival benefits and be cost effective.
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Affiliation(s)
| | | | | | | | - Elamin Elbasha
- Merck Research Laboratories, North Wales, Pennsylvania 19454
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Antinori A, Ammassari A, Torti C, Marconi P, Andreoni M, Angarano G, Bonora S, Castagna A, Cauda R, Clerici M, Monforte AD, De Luca A, Di Perri G, Galli M, Girardi E, Gori A, Lazzarin A, Lo Caputo S, Mazzotta F, Montella F, Mussini C, Perno CF, Puoti M, Rizzardini G, Rusconi S, Vullo V, Carosi G. Italian consensus statement on management of HIV-infected individuals with advanced disease naïve to antiretroviral therapy. Infection 2009; 37:270-82. [PMID: 19479193 DOI: 10.1007/s15010-008-8134-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2008] [Accepted: 09/10/2008] [Indexed: 01/11/2023]
Abstract
BACKGROUND Individuals with advanced HIV infection naïve to antiretroviral therapy represent a special population of patients frequently encountered in clinical practice. They are at high risk of disease progression and death, and their viroimmunologic response following the initiation of highly active antiretroviral therapy may be more incomplete or slower than that of other patients. Infection management in such patients can also be complicated by underlying conditions, comorbidities, and the need for concomitant medications. AIM To provide practical guidelines to those clinicians providing care to HIV-infected patients in terms of diagnostic assessment, monitoring, and treatment. CONCLUSIONS The principals of antiretroviral treatment in asymptomatic naïve patients with advanced HIV infection are the same as those applicable to the general population with asymptomatic HIV infection. Naïve patients with advanced HIV infection and a history of AIDS-defining illnesses urgently need antiretroviral treatment, with the choice of antiretroviral regimen and timetable based on such factors as concomitant treatment and prophylaxis, drug interactions, and potential concomitant drug toxicity. Finally, an adequate counseling program - both before and after HIV-testing - that includes aspects other than treatment adherence monitoring is a crucial step in disease management.
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Affiliation(s)
- A Antinori
- Istituto Nazionale Malattie Infettive Lazzaro Spallanzani IRCCS, via Portuense 292, 00149, Rome, Italy.
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The prognosis of CMV retinitis among patients with AIDS in Serbia. Biomed Pharmacother 2008; 62:443-7. [PMID: 18243635 DOI: 10.1016/j.biopha.2007.12.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2007] [Accepted: 12/11/2007] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) end-organ diseases, including CMV retinitis, are major opportunistic events in terminal AIDS patients. METHODS A retrospective study of 30 AIDS patients with CMV retinitis treated between 1997 and 2007 in Serbia was conducted to examine the prognosis and factors associated with survival. RESULTS Eighteen (60%) patients survived the mean follow-up period of 46.4+/-36 months. Patients' sex, mode of HIV transmission or previous AIDS diagnosis did not affect survival. Bilateral CMV retinitis predicted dissemination of CMV disease and poor prognosis (OR 7.8, 95% CI 1.3-47.0, P=0.012), but was not associated with blindness (P=0.33). Among patients treated with HAART and CMV therapy the probability of surviving 10 years was 70%, while in those on CMV therapy alone, the median survival was 10 months (log rank P=0.00). However, HAART itself was not sufficient to prevent blindness and the major predictor of blindness was a baseline CD4 cell count of less than 50/microL (OR 6.8, 95% CI 1.1-41.8, P=0.03). After CMV disease, most patients suffered other opportunistic events regardless of HAART introduction. CONCLUSION Even in the HAART era patients with advanced immunodeficiency and CMV retinitis may not escape from the high risk mortality group, while survivors commonly lose sight.
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Abstract
The authors describe CMV retinitis in resource-poor settings and suggest possibilities for management.
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Antiretroviral therapy in AIDS patients with CMV disease: impact on the survival and long-term treatment outcome. J Infect 2007; 56:40-3. [PMID: 18037166 DOI: 10.1016/j.jinf.2007.10.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2007] [Revised: 10/05/2007] [Accepted: 10/11/2007] [Indexed: 11/20/2022]
Abstract
OBJECTIVES To determine the impact of antiretroviral therapy (ART) on the long-term survival of AIDS patients with CMV disease and evaluate long-term outcomes of ART. METHODS A retrospective cohort study was conducted among HIV-infected patients with CMV disease in a medical school hospital during 1996-2005 and followed-up until June 2007. RESULTS There were 154 patients, mean age 34.5 years and 57.8% were male. Organ involvement of CMV disease included retina (94.8%), central nervous system, lungs, and gastrointestinal tract. Median CD4 cell count was 20 cells/mm(3) and 99 patients received ART. During median follow-up of 32 months (interquartile range 23-96), 29.2% of patients died. From Kaplan-Meier analysis, median survival is significantly longer in patients receiving ART (>116.2 vs. 21.6 months, log-rank test, p<0.001). From Cox's proportional hazard model, ART (HR 0.6, p<0.001) and previous opportunistic infections (HR 3.5, p=0.025) were negatively and positively associated with death, respectively. At median time of 69 months (interquartile range 34-101) in patients who received ART, 80.8% had HIV-1 RNA <50 copies/mL and median CD4 was 421 cells/mm(3). One patient had immune reconstitution syndrome at 3 months after initiation of ART and resulted in permanent vision loss. CONCLUSIONS ART significantly improves long-term survival of AIDS patients with CMV disease. Long-term virological and immunological outcomes are durable.
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Affiliation(s)
- Lucia Sobrin
- Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Boston, MA 02114, USA
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Thorne JE, Holbrook JT, Jabs DA, Kempen JH, Nichols C, Meinert CL. Effect of Cytomegalovirus Retinitis on the Risk of Visual Acuity Loss among Patients with AIDS. Ophthalmology 2007; 114:591-8. [PMID: 17123624 DOI: 10.1016/j.ophtha.2006.08.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2006] [Revised: 08/01/2006] [Accepted: 08/02/2006] [Indexed: 11/25/2022] Open
Abstract
PURPOSE To describe the prevalence and incidence of reduced visual acuity in eyes of patients with AIDS and without cytomegalovirus (CMV) retinitis at enrollment and estimate the proportion of incident vision loss attributable to new-onset CMV retinitis in this cohort. DESIGN Multicenter prospective observational study. PARTICIPANTS Three thousand fourteen eyes of 1507 patients with AIDS and without CMV retinitis at enrollment. METHODS Medical history, ophthalmologic examination, and laboratory testing collected at enrollment and at follow-up visits every 6 months thereafter. MAIN OUTCOME MEASURES Loss of visual acuity across the < or =20/50 and < or =20/200 thresholds and doubling of the visual angle; potential causes of this vision loss. RESULTS For eyes of patients without CMV retinitis at enrollment, the proportions with best-corrected visual acuity of < or =20/50 and of < or =20/200 were 3.9% and 1.8%, respectively. The incidence rates of vision loss to < or =20/50, < or =20/200, and to a doubling of the visual angle were 1.5/100 eye-year (EY), 0.8/100 EY, and 2.1/100 EY, respectively. Approximately 40% of the incident vision loss was attributable to CMV retinitis diagnosed during the follow-up period, and approximately 25% was attributable to cataract. CONCLUSIONS Although the development of CMV retinitis was the most common reason for visual acuity loss in eyes of our patients with AIDS, it accounted for less than half of the vision loss in our population (approximately 40%). Newly diagnosed cataract during the follow-up period accounted for a substantial amount of incident vision loss as well.
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Affiliation(s)
- Jennifer E Thorne
- Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Affiliation(s)
- Dhananjay Shukla
- Aravind Eye Hospital and Postgraduate Institute of Ophthalmology, Madurai, Tamil Nadu, India
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