Viral Suppression Research Articles

Pretreatment and acquired HIV drug resistance in Belize—results of nationally representative surveys, 2021–22

Abstract Background The rising prevalence of pretreatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitors threatens the effectiveness of ART. In response, the WHO recommends dolutegravir-based ART regimens due to their high genetic barrier to resistance and better treatment outcomes. This is expected to contribute to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 95% viral suppression in people on ART. Objectives To estimate the prevalence of PDR among adults initiating ART and assess viral suppression and acquired HIV drug resistance (ADR) among individuals receiving ART in Belize. Patients and methods Nationally representative cross-sectional PDR and ADR surveys were conducted between 2021 and 2022. Sixty-seven adults were included in the PDR survey, and 43 children and adolescents and 331 adults were included in the ADR survey. Demographic and clinic data and blood specimens were collected. HIV drug resistance (HIVDR) was predicted using the Stanford HIVdb tool. Results The prevalence of PDR to efavirenz or nevirapine in adults was 49.3% (95% CI 42.2%–56.4%) and was significantly higher in those with previous antiretroviral exposure (OR: 7.16; 95% CI 2.71–18.95; P = 0.002). Among children and adolescents receiving ART, 50.0% had viral suppression, with better rates for those receiving dolutegravir-based ART (OR: 5.31; 95% CI 3.02–9.34; P < 0.001). In adults, 79.6% achieved viral suppression. No resistance to integrase inhibitors was observed in those on dolutegravir-based ART. Conclusions Prioritizing dolutegravir-based ART is critical for achieving HIV epidemic control in Belize. Efforts should focus on retention in care and adherence support to prevent HIVDR.

Treatment of prehypertension among adults with HIV: a randomized clinical trial

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti. Design: An unblinded randomized clinical trial (enrolled April 2021–March 2022) with 12-month follow-up. Setting: GHESKIO Centres, Port-au-Prince, Haiti. Participants: Two hundred fifty adults with HIV with prehypertension (SBP 120–138 or DBP 80–89) not on medication, aged 18–65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease. Intervention: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg). Main outcome measure: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months. Results: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07–0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews. Conclusion: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension. Registration: Clinicaltrials.gov NCT04692467

Neighborhoods, Networks, and HIV Care Among Men Who Have Sex With Men: Proposal for a Longitudinal Study.

The majority of people living with HIV in the United States are men who have sex with men (MSM), with race- and ethnicity-based disparities in HIV rates and care continuum. In order to uncover the neighborhood- and network-involved pathways that produce HIV care outcome disparities, systematic, theory-based investigation of the specific and intersecting neighborhood and social network characteristics that relate to the HIV care continuum must be engaged. Using socioecological and intersectional conceptual frameworks, we aim to identify individual-, neighborhood-, and network-level characteristics associated with HIV care continuum outcomes (viral suppression, retention in care, and antiretroviral adherence) among MSM living with HIV in New York City. In the longitudinal cohort study, we assess 3 neighborhoods of potential influence (residential, social, and health care access activity spaces) using Google Earth. We investigate the influence of neighborhood composition (eg, concentrated poverty and racial segregation) and four neighborhood-level characteristics domains: (1) community violence, physical disorder, and social disorganization (eg, crime rates and housing vacancy); (2) alcohol and other drug use; (3) social norms (eg, homophobia and HIV stigma); and (4) community resources (eg, social services and public transit access). We test theoretical pathways of influence, including stress or coping, stigma or resilience, and access to resources, across the different neighborhoods in which MSM live, socialize, and receive HIV care. At each visit, we locate each participant's reported activity spaces (ie, neighborhoods of potential influence) and collect individual-level data on relevant covariates (including perceptions of or exposure to neighborhoods) and social network inventory data on the composition, social support, and perceived social norms. The outcomes are HIV viral suppression, retention in care, and antiretroviral adherence. These data are combined with an existing, extensive geospatial database of relevant area characteristics. Spatial analysis and multilevel modeling are used to test the main theory-driven hypotheses and capture independent neighborhood-level and network-level effects and changes over time. The study began enrollment in March 2019 and concluded visits in December 2023, with a total of 327 participants enrolled. The median age was 44.1 (SD 11.5) years. Almost all participants self-identified as cisgender men (n=313, 98.1%) and as gay, homosexual, or bisexual (n=301, 94.4%). Overall, 192 (60.1%) participants identified as non-Hispanic Black, and 81 (25.3%) identified as Hispanic. Most (n=201, 63%) reported at least occasional difficulty in meeting basic needs (eg, rent and food) in the past 6 months. The mean number of years living with HIV was 15.4 (SD 10.1). This study will have direct implications for the design of multilevel interventions, addressing factors at the neighborhood, network, and individual levels. Results may inform urban planning and program design to improve HIV care outcomes for MSM, particularly for Black and Latino MSM living in urban areas. PRR1-10.2196/64358.

Abstract 4137891: Treated HIV infection is not associated with carotid vascular inflammation or plaque progression as assessed by dynamic contrast magnetic resonance imaging

Background: Inflammation and immune dysregulation are thought to drive residual cardiovascular disease risk among persons living with HIV (PLWH) despite effective viral suppression with antiretroviral therapy (ART). Question: We investigated differences in carotid vascular inflammation and atherosclerosis in a longitudinal cohort of virally suppressed PLWH (n = 50; on stable ART with CD4 >250 cells/mm 3 , viral load <200 copies/mL for >6 months) and HIV-uninfected controls (n = 51) matched for age, sex, hypertension, diabetes, smoking, hyperlipidemia, and family history of premature coronary artery disease. Methods&Results: Participants were > 40 years old at enrollment, 8% female, and had a high prevalence of cardiovascular risk factors ( Table 1 ). Measures of carotid inflammation and capillary permeability ( K trans ), neovascularization ( V p ), and wall thickness were assessed at baseline, 1 year, and change over 1 year by dynamic contrast-enhanced magnetic resonance imaging. Both PLWH and controls demonstrated a reduction in systolic and diastolic blood pressures and total cholesterol over 1 year; however, the difference was not significant by HIV status. PLWH had a significant reduction in triglycerides compared with controls (-48.8 mg/dL vs 12.8 mg/dL; p = 0.026). HIV was not associated with baseline, follow-up, or change in markers of systemic inflammation assessed by plasma cytokines (C-reactive protein, interleukin-6, interleukin-1ß), nor vascular inflammation or plaque as assessed by K trans , V p , carotid wall thickness, or percent wall volume ( Tables 2 & 3 ). Conclusions: In contrast to other studies of chronically treated and virally suppressed PLWH, HIV infection was not associated with carotid inflammation or plaque.

Efficacy and safety of DTG plus 3TC for prophylaxis of perinatal transmission of HIV infection in pregnant women who have detectable viral load after 14 weeks of gestation: A pilot study (PREGNANCY)

Abstract Background The prevention of perinatal HIV transmission depends on the safe and effective use of antiretroviral therapy (ART). Simplifying treatment reduces drug exposure for both mother and child. We evaluated the safety and efficacy of DTG/3TC for antiretroviral-naïve pregnant women living with HIV (PWLHIV). Methods This proof-of-concept trial enrolled ART-naïve pregnant women over 15 years old with HIV infection and a gestational age between 14 and 28 weeks. Participants received a fixed-dose combination of DTG/3TC. Baseline HIV genotyping was performed. Participants were monitored at baseline, every 4 weeks, and at delivery. Infants were assessed at birth, 4 weeks, and 6 weeks of age. Outcomes included the proportion of women achieving an undetectable HIV-1 plasma viral load (<50 copies/mL) at delivery, therapy modification frequency, perinatal HIV transmission rate, and adverse events. Results Between January 2019 and March 2021, 20 women were enrolled. At baseline, the median CD4 cell count was 401.6 ± 113.6 cells/μL, increasing to 690.2 ± 266 cells/μL at delivery. Median viral load was 9,514 copies/mL. All women achieved an undetectable viral load after an average of 40 days. No cases of perinatal HIV transmission were detected. No therapy modifications were necessary during the study, and no adverse events were related to the ART. Conclusion In this pilot trial, DTG/3TC demonstrated safety and efficacy, with all participants achieving viral suppression before delivery. There were no cases of perinatal HIV transmission and no drug-related adverse events. DTG/3TC can be an option for initial treatment of drug-naïve PWLHIV.

Changes to inflammatory markers during 5 years of viral suppression and during viral blips in people with HIV initiating different integrase inhibitor based regimens

BackgroundHeightened levels of inflammatory markers are linked to increased morbidity/mortality in people with HIV (PWH) and often remain elevated after virologic suppression by antiretroviral therapy (ART). As new combinations of ART become available, an evaluation of their effects on immune activation and inflammation is warranted. Additionally, it remains unknown whether transient increases in viral load (“blips”) during ART are associated with increases in inflammation.MethodsWe utilized cryopreserved samples from treatment-naïve PWH enrolled in two Phase 3 clinical trials investigating the efficacy and safety of bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) or dolutegravir, abacavir, and lamivudine (DTG/ABC/3TC) or DTG + F/TAF over a 5-year window (GS-US-380-1489/1490). At week 144, participants were offered the option to switch to open label B/F/TAF for an additional 96 weeks. We measured levels of interleukin-6 (IL-6), C-reactive protein (hsCRP), D-dimer, soluble CD14 (sCD14), and tumor necrosis factor-α receptor 1 (TNFR1) from available baseline, week 24, 48, 144, and 240 samples (B/F/TAF, N=123; DTG/ABC/3TC, N=62; DTG+F/TAF, N=58). Additional samples from PWH who experienced a viral blip (n=44, defined as a single HIV-1 RNA >50c/mL) were also analyzed and paired with the most recent available suppressed sample before the blip. Longitudinal biomarker changes were assessed using a constrained mixed effects linear regression model adjusting for covariates.ResultsBaseline demographics and selected laboratory characteristics were similar across groups. Levels of D-dimer, sCD14, and TNFR1 decreased significantly from baseline in all treatment arms, with no significant differences between arms at any timepoint. Biomarker levels also remained stable following ART-switch at week 144. No significant changes in hsCRP or IL-6 were observed versus baseline in any arm at any timepoint. A significant association was observed between sCD14 and increasing viral load (p=0.022) in viral blips; D-dimer also increased with blips in the B/F/TAF arm.ConclusionsViral suppression was associated with reductions in most inflammatory markers in PWH, with no significant differences among the three ART regimens during the 144-week randomized period. These decreases were sustained after the open label switch to B/F/TAF. Viral blips were associated with increases in monocyte activation (sCD14). Further analysis is needed to confirm these findings and determine the potential impact on clinical outcomes.

A novel HIV triple broadly neutralizing antibody (bNAb) combination-based passive immunization of infant rhesus macaques achieves durable protective plasma neutralization levels and mediates anti-viral effector functions.

To eliminate vertical HIV transmission and achieve therapy-free viral suppression among children living with HIV, novel strategies beyond antiretroviral therapy (ART) are necessary. Our group previously identified a triple broadly neutralizing antibody (bNAb) combination comprising of 3BNC117, PGDM1400 and PGT151 that mediates robust in vitro neutralization and non-neutralizing effector functions against a cross-clade panel of simian human immunodeficiency viruses (SHIVs). In this study, we evaluated the safety, pharmacokinetics, and antiviral potency of this bNAb combination in infant rhesus macaques (RMs). We demonstrate that subcutaneous infusion of the triple bNAb regimen was well tolerated in pediatric monkeys and resulted in durable systemic and mucosal distribution. Plasma obtained from passively-immunized RMs demonstrated potent HIV-neutralizing and Fc-mediated antiviral effector functions. Finally, using the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker threshold of >200, which was recently identified as a surrogate endpoint for evaluation of the preventative efficacy of bNAbs against mucosal viral acquisition in human clinical trials, we demonstrated that our regimen has PT80>200 against a large panel of plasma and breast milk-derived HIV strains and cross-clade SHIV variants. This data will guide the development of combination bNAbs for eliminating vertical HIV transmission and for achieving ART-free viral suppression among children living with HIV.

Active tuberculosis disease among people living with HIV on ART who completed tuberculosis preventive therapy at three public hospitals in Uganda.

Tuberculosis (TB) preventive therapy (TPT) reduces the incidence of TB among people living with the human immunodeficiency virus (PLHIV). However, despite an increase in TPT uptake, TB/HIV coinfection remains stagnant in Uganda especially in areas of increasing HIV incidence such as the Bunyoro sub-region. This study was a retrospective review records (antiretroviral therapy [ART] files) of PLHIV who were active on ART and completed TPT in 2019/2020 at three major hospitals in the Bunyoro sub-region, Uganda: Masindi General Hospital, Hoima Regional Referral Hospital, and Kiryandongo General Hospital. The sample size (987) for each facility was determined using a proportionate sampling method to ensure the study's power and precision. Factors independently associated with acquiring TB disease post TPT were determined using modified Poisson regression analysis. An adjusted prevalence risk ratio (aPRR) with corresponding 95% confidence intervals were reported. The participants' mean age was 38.23 (±11.70) and the majority were female (64.94%). Overall, 9.63% developed active TB disease post TPT completion. In the adjusted analysis, factors associated with active TB disease were a history of an unsuppressed viral load after TPT (aPRR 4.64 (2.85-7.56), p<0.001), opportunistic infections after TPT completion (aPRR 4.31 (aPRR 2.58-7.2), p<0.001), a history of TB active TB disease (aPRR 1.60 (1.06-2.41), p = 0.026), and chronic illness during or after TPT (aPRR 1.68 (1.03-2.73), p = 0.038). To reduce the development of TB disease post TPT thereby improving the effectiveness of TPT, ART adherence should be emphasized to resolve viral suppression and active management of chronic and opportunistic infections. Further clinical management consideration and research is needed for PLHIV who receive TPT but have a previous history of TB disease.

Impact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania.

We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among HIV-positive infants in Mozambique and Tanzania. This cluster-randomized trial allocated health facilities to intervention, providing PoC-testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month-18. We estimated incidence rate ratios adjusted for timing of HIV-detection (aIRR) and reported viral suppression <1000 copies/mL. Among 6602 neonates enrolled October 2019-September 2021, 125 were diagnosed HIV-positive by week 12. In the intervention arm, 38/69 (55.1%) were diagnosed at birth with 35 initiating ART within two days. In the control arm, 27/56 (48.2%) were retrospectively detected HIV-positive at birth, of whom 6/56 (10.7%) died or were lost to follow-up before testing. Median age at ART initiation was 6 (intervention) versus 33 days (control). Birth test-and-treat was not associated with a significant reduction in clinical outcomes up to month-18 [53 (76.8%) versus 48 (85.7%); aIRR 0.857; 95% CI 0.505-1.492], but showed a 68% relative reduction in 6-month mortality. Viral suppression was poor overall, but improved in the intervention group at month 18 (65.7% versus 29.6%; p=0.005). PoC test-and-treat at birth is feasible in resource-poor settings and resulted in clinically-relevant reduction of early infant mortality, though improved clinical outcomes were not sustained to month-18. Poor viral suppression may undermine early survival benefits, calling for better paediatric treatments and tailored adherence interventions.

Disparities in dolutegravir utilisation in children, adolescents and young adults (0-24 years) living with HIV. An analysis of the IeDEA Paediatric West African cohort.

We describe the 24-month incidence of Dolutegravir (DTG)-containing antiretroviral treatment (ART) initiation since its introduction in 2019 in West Africa. We included all patients aged 0-24 years on ART from nine clinics in Cote d Ivoire (n=4), Ghana, Nigeria, Mali, Benin, and Burkina Faso. Baseline varied by clinic and was defined as date of first DTG prescription; patients were followed up until database closure/death/loss to follow-up (LTFU, no visit 7 ≥ months), whichever came first. We computed the cumulative incidence function for DTG initiation; associated factors were explored in a shared frailty model, accounting for clinic heterogeneity. Since 2019, 3,350 patients were included; 47.2% were female;78.9% had been on ART ≥ 12 months. Median baseline age was 12.5 years (Interquartile range[IQR]: 8.4-15.8). Median follow-up was 14 months (IQR: 7-22). The overall cumulative incidence of DTG initiation reached 22.7% (95% Confidence Interval (CI): 21.3-24.2) and 56.4% (95% CI: 54.4-58.4) at 12 and 24 months, respectively. In univariate analyses, those aged <5 years and females were overall less likely to switch. Adjusted on ART line and available viral load (VL) at baseline, females >10 years were less likely to initiate DTG compared to males of the same age (adjusted Hazard Ratio [HR] among 10-14 years: 0.62, 95% CI: 0.54-0.72; among ≥ 15 years: 0.43, 95% CI: 0.36-0.50), as were those with detectable VL (> 50 copies/mL) compared to those in viral suppression (aHR: 0.86, 95% CI: 0.77-0.97) and those on protease inhibitors compared to those on non-nucleoside reverse-transcriptase inhibitors (aHR after 12 months of roll-out: 0.75, 95% CI: 0.65-0.86). Paediatric DTG uptake was incomplete and unequitable in West African settings: DTG use was least likely in children <5years, females ≥ 10 years and those with detectable viral load. Maintained monitoring and support of treatment practices is required to better ensure universal and equal uptake.

Effect of Mental Health Care Visits on HIV Care Outcomes.

To improve the quality of life for people living with HIV (PLWH), it is vital their treatment plans closely follow the HIV care continuum. However, many barriers, such as mental health disorders (MHD), can complicate treatment. Patients being treated for HIV with comorbid MHD are more likely to not be retained in care and maintain an unsuppressed viral load. As PLWH and people vulnerable to acquiring HIV are more commonly diagnosed with MHD in comparison to the general population, it is important that steps to mitigate the possible effects of MHD are addressed during treatment. This study examines how minimal mental health care in a safety-net hospital system in the U.S. South can show benefits in retaining patients throughout their treatment of HIV. The results showed that older individuals retained a higher level of viral suppression when they followed up regularly with a mental health care provider during treatment. In addition, regardless of age, the higher the number of mental health care visits a patient attended during treatment, the higher the likelihood of viral suppression. By incorporating mental health care into the HIV treatment plan, the patients who met at least one of these criteria had better treatment outcomes and progressed further along the HIV care continuum.

The burden of HIV-1 and HIV-2 epidemics in Ivory Coast.

Simian immunodeficiency viruses (SIV) infecting chimpanzees (SIVcpz) and sooty mangabeys (SIVsm) are, respectively, the biological precursors of human immunodeficiency viruses (HIV) Types 1 and 2. Former French colonies in West Africa are the regions where retroviruses first jumped from primates to humans. Ivory Coast is nowadays a country of over 29 million people, being 2% (580,000) persons living with HIV (PLWH). However, one-quarter remains undiagnosed. Heterosexual transmission is by far the most frequent mechanism of HIV acquisition and women exhibit higher rates of infection than men. Despite preventive measures, HIV infection in children throughout breastfeeding remains significant. The proportion of PLWH carrying HIV-1 is rising whereas conversely HIV-2 carriers are steadily declining. A nationwide survey conducted on earlier 2024 showed that a total of 188,880 PLWH were on follow-up. HIV-1 infection was found in 163,947, HIV-2 in 5,114, and coinfection in 3,182. HIV type was not reported for 7,500. Antiretroviral therapy with tenofovir, lamivudine, and dolutegravir is by far the most frequently prescribed regimen in Ivory Coast (n = 168,543). Viral suppression is recognized in 94.3% of treated PLWH, despite one-third acknowledging unwanted treatment interruptions after failure of stock supplies. Given shared transmission routes with HIV, coinfection with other human retroviruses such as Human T-lymphotropic virus type-1 (HTLV-1) and/or hepatitis viruses B, C, and delta are frequent in Ivory Coast. Coinfections remain largely undiagnosed and poorly managed. In summary, the HIV pandemic caused by both HIV-1 and HIV-2 is a major public health challenge in Ivory Coast, where strategies for expanding diagnosis, sustain antiretroviral treatment, and manage coinfections warrant further efforts.

“I desire to have an HIV-free baby”: pregnant and breastfeeding mothers’ perceptions of Viral load testing and suppression in HIV care in southwestern Uganda

IntroductionViral suppression is a critical component for preventing mother-to-child transmission of HIV(MTCT). Mothers’ perceptions of viral load suppression is crucial in the attainment of successful outcomes in preventing mother to child transmission of HIV. We therefore aimed to explore the experiences and perceptions of women on viral suppression.MethodsThis was a qualitative sub-study embedded in a cluster-randomized trial (NCT04122144) designed to improve viral load outcomes among pregnant and breastfeeding mothers living with HIV in four level III/IV health facilities in South-western Uganda. Thirty-two in-depth interviews were conducted with pregnant and breastfeeding women with HIV from 1st March 2020 to 30th September 2020 to explore their understanding and interpretation of viral suppression. Interviews were audio-recorded, transcribed, and coded in Dedoose software for analysis.ResultsA total of 32 Women living with HIV were enrolled in this qualitative study. WLHIV explained viral suppression in the context of attaining good health and having HIV-free babies. Adherence to ART was presented as a key avenue to viral suppression. The level of engagement with providers was presented as a key attribute of attaining viral suppression. The participants narrated their experiences with viral load testing within the routine services. However, they revealed experiencing some proximate barriers to suppression including anticipated stigma, challenges with non-disclosure of HIV status, pregnancy distress, and distance to the health facility.ConclusionThe understanding and interpretation of viral suppression among pregnant and breastfeeding mothers living with HIV provides a basis for adopting behaviors leading to prevention of vertical transmission of HIV. Health care workers can support women by providing clear and culturally appropriate education about viral suppression, adherence strategies and creating a supportive and non-judgmental environment.

Rapid viral suppression using integrase inhibitors during acute HIV-1 infection.

Antiretroviral therapy (ART) is recommended for all individuals with HIV infection, including those with acute HIV-1 infection (AHI). While recommendations are similar to those for chronic infection, efficacy data regarding treatment of acute HIV is limited. This was a single arm, 96-week study of a once-daily integrase inhibitor (INSTI)-based regimen using elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF) in AHI. Primary endpoint was proportion of participants with HIV-1 RNA <200 copies/mL and <50 copies/mL by treatment weeks 24 and 48, respectively. We also examined time to viral suppression and weight gain after treatment initiation. Outcomes and characteristics were compared with a historical AHI cohort using a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen with efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF). Thirty-three participants with AHI were enrolled with 31 available for analyses. Most were African American (61%) and men who have sex with men (73%). Median age was 26 (IQR 22-42). Demographics were similar between the two AHI cohorts. By Week 24, 100% in the INSTI and 99% in the NNRTI cohort were <200 copies/mL; by Week 48, 100% in both cohorts were <50 copies/mL. Time to viral suppression was shorter in the INSTI cohort (median 54 versus 99 days). Mean weight change was similar with a 3.6 kg increase in the INSTI cohort and 2.4 kg in the NNRTI cohort at 96 weeks. INSTI-based ART during AHI resulted in rapid and sustained viral suppression. Over 96 weeks, weight increased in the INSTI-based cohort but was similar to weight increase in a historical NNRTI-based AHI cohort.

Examining the Accuracy of Self-Reported Antiretroviral Therapy Adherence Using a Visual Analog Scale Among Opioid-Dependent People Living with HIV.

Evidence indicates that regular assessment of antiretroviral therapy (ART) adherence is necessary to promote adherence and achieve viral suppression. Self-reported adherence using a visual analog scale (VAS) has been used extensively to measure ART adherence. However, less is known about the accuracy of the VAS for measuring ART adherence among opioid-dependent people living with HIV. In this study, we aimed to evaluate the accuracy of the VAS in measuring ART adherence in opioid-dependent people living with HIV who are enrolled in a methadone maintenance program (MMP). This study was conducted within a larger randomized controlled trial among opioid-dependent people living with HIV (N = 109) who were enrolled in an inner-city MMP. Self-reported VAS ART adherence data were compared to pharmacy refill data, which is a more objective measure. Self-reported VAS ratings and pharmacy refill behavior were significantly correlated at the 6-month post-intervention mark (r = 0.349, p = 0.006) but not at any other time point (i.e., pre-intervention, post-intervention, 3-months, and 9-months post-intervention). Based on the pharmacy refill data, participants did not consistently adhere to their ART medication but self-reported high adherence on the VAS. The self-report VAS may not be an accurate measure for assessing ART adherence among opioid-dependent persons living with HIV and enrolled in a MMP. Based on our findings, it may be more accurate to use pharmacy refill information or other objective measures to quantify ART adherence over extended periods for this patient population.

Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical development

IntroductionFor many therapeutic drugs, including antiretroviral drugs used to treat people living with HIV-1 (PLWH), we have little data on the potential effects on the developing human brain due to limited access to tissue and historical constraints on the inclusion of pregnant populations in clinical trials. Human induced pluripotent stem cells (iPSCs) offer a new avenue to gain insight on how drugs may impact human cell types representative of the developing central nervous system. To prevent vertical transmission of HIV and promote the health of pregnant PLWH, antiretroviral therapy must be initiated and/or maintained throughout pregnancy. However, many antiretroviral drugs are approved for widespread use following clinical testing only in non-pregnant populations and there may be limited information on potential teratogenicity until pregnancy outcomes are evaluated. The integrase strand transfer inhibitor dolutegravir (DTG) is a frontline antiretroviral drug that is effective in viral suppression of HIV but was previously reported to be associated with a slight increase in the risk for neural tube defects in one study, although this has not been replicated in other cohorts.MethodsTo directly investigate the potential impact of DTG on human cortical neurogenesis, we measured the effects of daily drug exposure on the early stages of corticogenesis in a human iPSC-based forebrain organoid model. We quantified organoid size and structure and analyzed gene and protein expression to evaluate the impact of several doses of DTG on organoid development.ResultsWe observed deficits in organoid structure and impaired neurogenesis in DTG-treated organoids compared to vehicle-treated control organoids after 20 or 40 days in culture. Our highest dose of DTG (10 μM) resulted in significantly smaller organoids with a reduced density of neural rosette structures compared to vehicle-treated controls. Mechanistically, RNA-sequencing and immunohistological analysis suggests dysregulated amino acid transport and activation of the integrated stress response in the DTG-treated organoids, and functionally, a small molecule integrated stress response inhibitor (ISRIB) could partially rescue increased expression of proteins related to cell cycle regulation.DiscussionTogether, these results illustrate the potential for human iPSC-based strategies to reveal biological processes during neurogenesis that may be affected by therapeutic drugs and provide complementary data in relevant human cell types to augment preclinical investigations of drug safety during pregnancy.

Predictors of Injection Visit Adherence in Those Receiving Injectable Cabotegravir/Rilpivirine.

There is limited data evaluating potential predictors of adherence to injection visits and the impact of late injections on viral suppression in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for the treatment of HIV. A retrospective cohort study was conducted among adult people with HIV (PWH) receiving LAI CAB/RPV for at least 6 months between May 2021 and August 2023. Data collected included demographics, office visit no-shows one year prior to switching to LAI CAB/RPV, injection visit no-shows, injections outside the dosing window, and virologic outcomes. Cox-proportional hazards regression was performed to evaluate predictors of no-show to injection visits or late injections. Included were 287 PWH with a median follow up time (IQR) of 450 days (344-548 days). Younger age [HR 0.97 (95%CI 0.95-0.98)] and ≥ 1 office visit no-show in the year prior to switch to LAI CAB/RPV [HR 2.03 (1.32-3.12]) were associated with having a no-show to an injection visit (32.1%). Male sex assigned at birth [HR 9.18 (1.26-66.9)] with a trend towards younger age [HR 0.98 (0.95-1.0)] were associated with having a late injection (15.3%). There was no relationship between late injections and having a detectable viral load or virologic failure (n=3) after switch to LAI CAB/RPV. Having office visit no-shows prior to switching to LAI CAB/RPV was associated with missed injection visits, and younger age was associated with both missed injection visits and late injections. Resources to reduce and manage missed injection appointments need to be considered when implementing LAI CAB/RPV.

A dual-purpose humanized mouse model for testing antiviral strategies against both SIV and HIV

Nonhuman primate (NHP) models employing simian/simian-human immunodeficiency viruses (SIV/SHIVs) played a major role in the study of HIV pathogenesis, latency, and cure studies in a preclinical setting. However, it took many years to arrive at the current effective triple drug ARV regimen against SIV due to the genetic differences with that of HIVs. Since new combinations of drugs will be used in the evolving HIV cure studies, a small animal model would be ideal to determine their efficacy against the commonly used SIVs such as SIVmac239 to triage ineffective drugs prior to their application in NHPs. We recently determined that humanized mice (hu-mice) with a transplanted human immune system are permissive to SIVmac strains in addition to HIVs. Based on this novel finding, here we evaluated the utility of this dual-purpose hu-mouse model to test different ART regimens against SIVmac239. Infected mice showing chronic viremia were treated with a combination anti-retroviral treatment (cART) regimen consisting of emtricitabine/elvitegravir/tenofovir disoproxil fumarate (FTC/EVG/TDF). Full viral suppression was seen for several weeks in SIVmac239-infected and treated mice similar to that seen with HIV-1 BaL virus used as a control. However, viral rebound was eventually observed in SIVmac239 infected mice during the treatment period, suggesting viral escape compared to HIV-1 BaL with which viral suppression was fully sustained. Next, a cART regimen consisting of emtricitabine/bictegravir/tenofovir alafenamide fumarate (FTC/BIC/TAF) was similarly evaluated. Our results showed that this ARV regimen was fully effective in rapidly suppressing both SIVmac239 and HIV-1 BaL. Complete viral suppression was maintained until treatment interruption after which viral loads rebounded. These findings highlight the utility of humanized mice for in vivo screening of new combinations of ARV compounds against various SIVs prior to employing them in NHPs. In addition to identifying new effective cART regimens against SIVs, this model would also be amenable to evaluating immunotherapeutic strategies using broadly neutralizing antibodies, LRAs and novel therapeutics in comparative cure studies of SIV and HIV.

Switch to Integrase Strand Transfer Inhibitors during the Menopausal Transition is Associated with Accelerated Body Composition Change in Women with HIV.

Integrase strand transfer inhibitors (INSTIs) and the menopausal transition have separately been associated with body composition changes in women with HIV (WWH), but their interaction is unknown. From 2006-2019, 1131 non-pregnant WWH with viral suppression [(419 who switched to INSTI (INSTI+); 712 who did not switch (INSTI-)] and 887 women without HIV (WWOH) from the Women's Interagency HIV Study were included. Mixed effect models were used to evaluate change in waist circumference (WC) and BMI by menopausal phase defined using anti-Müllerian hormone, a biomarker of ovarian reserve. During premenopause, WWH had increases in WC (INSTI+: 0.01cm per 6 month (mo); 95%CI:-0.29,0.32 and INSTI-: 0.22cm per 6mo;95%CI:-0.01,0.44) that were not statistically significantly different from WWOH; there was also little difference by INSTI status. In late perimenopause, INSTI+ had faster increases in WC (0.37cm per 6mo;95%CI:0.15,0.60) while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.06,0.34) compared to WWOH. In menopause, INSTI+ had faster increases peaking at 43mo then declining while INSTI- had smaller increases (0.14cm per 6mo;95%CI:-0.02,0.30). Compared to INSTI-, in late perimenopause, INSTI+ had 0.26 cm per 6mo (95%CI:0.02,0.50) faster linear increases in WC and in menopause, INSTI+ was associated with faster increases peaking at 41mo. BMI trajectories were similar to WC in late peri- and menopausal women. Switching to an INSTI-based regimen during late peri- and menopause is associated with faster increases in WC and BMI when compared to women who did not switch. Menopausal status should be considered when switching to an INSTI.

Beyond Viral Suppression—The Impact of Cumulative Violence on Health-Related Quality of Life Among a Cohort of Virally Suppressed Patients: Erratum

Beyond Viral Suppression—The Impact of Cumulative Violence on Health-Related Quality of Life Among a Cohort of Virally Suppressed Patients: Erratum