Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF).

IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study.

Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) more than 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair.

Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. Nine of 18 (50%) were female sex-at-birth, and 14 of 18 (78%) were black. Median (range) age was 20 years (13-27), time on ART was 18.3 years (8.0-25.5), and FCCS was 68 (53-80). HIV-DNA was detected in PBMCs from all participants. In CSF, two of 18 (11%, 95% CI: 1.4-34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13 of 18 (72%, 95% confidence interval: 47-90). Detectable HIV-DNA in CSF was associated with male sex-at-birth ( P  = 0.051), lower CD4 + cell count at enrollment ( P  = 0.016), and higher PBMC HIV pol -DNA copies ( P  = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection.

We found that a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies.

The treatment of HIV infection has been revolutionized in recent years thanks to the advent of dual antiretroviral regimens, administered orally or as long-acting injectable formulations. Here, we provide an update on the usefulness of therapeutic drug monitoring (TDM) of antiretroviral drugs to optimize the management of people with HIV (PWH) in the current scenario.

A MEDLINE PubMed search for articles published between January 2014 and January 2024 was completed matching the terms HIV, antiretrovirals and TDM. Moreover, additional studies were identified from the reference list of retrieved articles.

Available antiretroviral treatments achieve a response rate of 90%-95%, making the routine TDM of antiretroviral drugs of limited clinical value. However, there are still some important applications of TDM in selected clinical conditions, such as assessing patient compliance or suspected drug-drug interactions (DDIs). Indeed, we are increasingly having to deal with polypharmacy and DDIs in the context of an aging patient with comorbidities that may potentially alter the pharmacokinetics of antiretroviral drugs. Finally, the role of pharmacogenetics, which is closely related to TDM, in influencing both the disposition of antiretrovirals and the course of DDIs should also be considered.

A digital health technology's success or failure depends on how it is received by users.

We conducted a user experience (UX) evaluation among persons who used the Food and Drug Administration-approved Digital Health Feedback System incorporating ingestible sensors (ISs) to capture medication adherence, after they were prescribed oral pre-exposure prophylaxis (PrEP) to prevent HIV infection. We performed an association analysis with baseline participant characteristics, to see if "personas" associated with positive or negative UX emerged.

UX data were collected upon exit from a prospective intervention study of adults who were HIV negative, prescribed oral PrEP, and used the Digital Health Feedback System with IS-enabled tenofovir disoproxil fumarate plus emtricitabine (IS-Truvada). Baseline demographics; urine toxicology; and self-report questionnaires evaluating sleep (Pittsburgh Sleep Quality Index), self-efficacy, habitual self-control, HIV risk perception (Perceived Risk of HIV Scale 8-item), and depressive symptoms (Patient Health Questionnaire-8) were collected. Participants with ≥28 days in the study completed a Likert-scale UX questionnaire of 27 questions grouped into 4 domain categories: overall experience, ease of use, intention of future use, and perceived utility. Means and IQRs were computed for participant total and domain subscores, and linear regressions modeled baseline participant characteristics associated with UX responses. Demographic characteristics of responders versus nonresponders were compared using the Fisher exact and Wilcoxon rank-sum tests.

Overall, 71 participants were enrolled (age: mean 37.6, range 18-69 years; n=64, 90% male; n=55, 77% White; n=24, 34% Hispanic; n=68, 96% housed; and n=53, 75% employed). No demographic differences were observed in the 63 participants who used the intervention for ≥28 days. Participants who completed the questionnaire were more likely to be housed (52/53, 98% vs 8/10, 80%; P=.06) and less likely to have a positive urine toxicology (18/51, 35% vs 7/10, 70%; P=.08), particularly methamphetamine (4/51, 8% vs 4/10, 40%; P=.02), than noncompleters. Based on IQR values, ≥75% of participants had a favorable UX based on the total score (median 3.78, IQR 3.17-4.20), overall experience (median 4.00, IQR 3.50-4.50), ease of use (median 3.72, IQR 3.33-4.22), and perceived utility (median 3.72, IQR 3.22-4.25), and ≥50% had favorable intention of future use (median 3.80, IQR 2.80-4.40). Following multipredictor modeling, self-efficacy was significantly associated with the total score (0.822, 95% CI 0.405-1.240; P<.001) and all subscores (all P<.05). Persons with more depressive symptoms reported better perceived utility (P=.01). Poor sleep was associated with a worse overall experience (-0.07, 95% CI -0.133 to -0.006; P=.03).

The UX among persons using IS-enabled PrEP (IS-Truvada) to prevent HIV infection was positive. Association analysis of baseline participant characteristics linked higher self-efficacy with positive UX, more depressive symptoms with higher perceived utility, and poor sleep with negative UX.

HIV prevention service delivery models that offer product choices, and the option to change preferences over time, may increase prevention coverage. Outpatient departments in sub-Saharan Africa diagnose a high proportion of new HIV infections, but are an understudied entry point to biomedical prevention.

Individually randomized trial of dynamic choice HIV prevention (DCP) intervention vs. standard-of-care (SOC) among individuals with current/anticipated HIV exposure risk at outpatient departments in rural Kenya and Uganda (SEARCH; NCT04810650).

Our DCP intervention included 1) product choice (oral preexposure prophylaxis [PrEP] or postexposure prophylaxis [PEP]) with an option to switch over time, 2) HIV provider- or self-testing, 3) service location choice (community vs. clinic-based), and 4) provider training on patient-centered care. Primary outcome was proportion of follow-up covered by PrEP/PEP over 48 weeks assessed via self-report.

We enrolled 403 participants (61% women; median 27 years, IQR 22-37). In the DCP arm, 86% ever chose PrEP, 15% ever chose PEP over 48 weeks; selection of HIV self-testing increased from 26 to 51% and of out-of-facility visits from 8 to 52%. Among 376 of 403 (93%) with outcomes ascertained, time covered by PrEP/PEP was higher in DCP (47.5%) vs. SOC (18.3%); difference = 29.2% (95% confidence interval: 22.7-35.7; P  < 0.001). Effects were similar among women and men (28.2 and 31.0% higher coverage in DCP, respectively) and larger during periods of self-reported HIV risk (DCP 64.9% vs. SOC 26.3%; difference = 38.6%; 95% confidence interval: 31.0-46.2; P  < 0.001).

A dynamic choice HIV prevention intervention resulted in two-fold greater time covered by biomedical prevention products compared to SOC in general outpatient departments in eastern Africa.

HIV pre-exposure prophylaxis (PrEP) use is limited among male sex workers, who are at exceptionally high-risk for HIV infection. We developed a theory-informed, two-pronged intervention ("PrEPare-for-Work") to optimize PrEP initiation and adherence among male sex workers, which was preliminarily evaluated in a two-stage pilot randomized controlled trial of 110 male sex workers in the US Northeast. Individuals randomized to the Stage 1 PrEPare-for-Work Case Management arm were three times as likely as those in the standard of care (SOC) arm to initiate PrEP (RR = 2.95, 95% CI = 1.57-5.57). Participants who initiated PrEP and were randomized to the Stage 2 PrEPare-for-Work Adherence Counseling arm had higher rates of prevention-effective adherence (measured via tenofovir in hair) compared to those in the SOC arm (RR = 1.7, 95% CI 0.64-4.77; 55.6% vs. 28.6%, respectively); though not statistically significant. Given the need and the promise of this pilot RCT, further efficacy testing is warranted and should be prioritized.

Antibody-based testing for emtricitabine (FTC), a critical component of pre-exposure prophylaxis and antiretroviral therapy, would provide low-cost detection for clinical monitoring to improve adherence. We developed a mAb (5D2) to FTC and demonstrated its high specificity and physiologically relevant linear range of detection in a competitive enzyme immunoassay. Thus, this mAb is a key reagent that will enable simple and low-cost lateral flow assays and enzyme immunoassays for adherence monitoring.

Tenofovir alafenamide (TAF) is increasingly used in HIV treatment, with or without agents that require pharmacologic boosters such as ritonavir/cobicistat. Boosters increase TAF levels, so the TAF dose is lowered in single-pill combinations. We hypothesized that individuals on dose-adjusted boosted TAF would have similar urine tenofovir (TFV) concentrations to those on unboosted TAF.

We collected urine samples from patients with HIV on TAF, with evidence of virologic suppression and high self-reported adherence at 2 San Francisco clinics from June 2019 to January 2020. We measured urine TFV levels by liquid chromatography/tandem mass spectrometry and used linear regression to compare natural log-transformed urine TFV levels for patients on boosted versus unboosted TAF.

Our analysis included 30 patients on unboosted TAF (25 mg daily TAF) and 15 on boosted TAF (12 on 10 mg daily TAF and 3 on 25 mg daily TAF). Patients on unboosted vs. boosted TAF had similar baseline age, weight, sex, and creatinine. In unadjusted univariate linear regression, there were no significant differences in urine TFV levels based on presence/absence of boosting after TAF dose reduction to 10 mg (geometric mean ratio 1.07; 95% confidence interval: 0.53 to 2.16). This finding was unchanged in adjusted analysis.

No significant differences in urine TFV levels were seen for patients on unboosted vs. boosted dose-reduced TAF. These results have important implications for our forthcoming point-of-care urine immunoassay for TAF, implying that separate adherence cutoffs will not be necessary for patients on boosters and dose-reduced TAF. A single POC TAF immunoassay will, thus, support monitoring on most TAF-based antiretroviral therapy.