Faculty Bibliography

Lenacapavir (LEN), a twice-yearly injectable long-acting capsid inhibitor used in combination with an optimized background regimen, is indicated for heavily treatment-experienced adults with multi-drug-resistant HIV-1 infection. From the US Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort, 116 adults with HIV with ≥1 set of LEN injections were included [baseline viral load (VL) <200 copies/mL = 74; ≥200 copies/mL = 42]. Many (56%) simplified their regimen at LEN initiation and/or later, and 31% maintained all the antiretrovirals (ARVs) from their prior regimen throughout LEN use. Among those with a baseline VL <200 copies/mL, the cumulative probability (Kaplan-Meier) of maintaining suppression to <200 copies/mL was 92% [95% confidence interval (CI): 80, 96]. Among those with a baseline VL ≥200 copies/mL, the cumulative probability of achieving suppression was 73% (95% CI: 59, 86). Among 78 individuals who received ≥2 sets of LEN injections, 82% received all sets of injections on time or early (≤28 weeks after the prior set) and 18% received ≥1 set late (>28 weeks after the prior set). The median delay was 11 days past the injection window (interquartile range: 4, 118). At study end, 91% remained on a LEN-containing regimen. In this cohort representative of routine clinical care in the United States, factors other than virologic control may be driving the decision to start LEN (e.g., safety, tolerability, resistance, simplification). Most people experienced favorable virologic outcomes and good adherence to LEN, which may serve as an effective option for those who could benefit from a long-acting injectable agent from a novel ARV class.

INTRODUCTION/BACKGROUND:Although antiretroviral therapy (ART) has substantially improved treatment-related outcomes among people with HIV (PWH), individuals may still undergo ART regimen switches for clinical and non-clinical reasons. While prior studies have focused on virologic outcomes, contemporary data describing ART regimen switching in routine care in the US, especially among virologically suppressed PWH, are limited. In an evolving HIV treatment landscape, including expanding switch strategies, this study estimated the incidence of ART regimen switching among virologically suppressed PWH and characterized switch patterns. METHODS:This observational cohort study used prospectively collected, routine electronic health records data from the OPERA Cohort. Adult PWH who were active in care and on a complete ART regimen between July 1, 2024 and June 30, 2025 were eligible. An ART regimen switch was defined as any change in antiretroviral agent, excluding pharmacokinetic boosting agents. Incidence of ART regimen switching was assessed during this 1-year period, overall and among PWH who were virologically suppressed. PWH who underwent a switch were characterized. Pre- and post-suppressed switch regimens, as well as patterns of suppressed switching, were outlined. RESULTS:Among 73,078 PWH who were eligible, 8188 (11%) experienced ≥ 1 ART regimen switch during the 1-year study period. Of 68,147 individuals who were virologically suppressed to < 200 copies/ml during the study period, 6888 (10%) experienced ≥ 1 ART regimen switch while suppressed. The rate of suppressed switching was 14.5 per 100 person-years. Integrase inhibitors predominated both pre- and post-switch regimens. Overall, 51% of suppressed switches resulted in regimen simplification (lower pill count, fewer anchor agents, and/or transition to a complete long-acting injectable regimen). CONCLUSIONS:In this large, contemporary US cohort, ART regimen switching was somewhat common and most frequently occurred among virologically suppressed PWH. These real-world findings on the incidence and patterns of virologically suppressed switches provide insight into new trends in treatment optimization and the need for new therapeutic options.

INTRODUCTION/BACKGROUND:Cabotegravir + rilpivirine long-acting (CAB+RPV LA) injectable was approved in the United States in 2021 for HIV-1 treatment in virologically suppressed (viral load [VL] <50 copies/mI individuals. In clinical trials, CAB+RPV LA was non-inferior to oral antiretroviral therapy (ART) regimens in virologically suppressed individuals. We compared real-world effectiveness between CAB+RPV LA and oral ART regimens and assessed predictors of confirmed virologic failure (CVF) on CAB+RPV LA. METHODS:cohort, ART-experienced, virologically suppressed adults with HIV switching to CAB+RPV LA or a new oral ART regimen between 21 January 2021 and 31 December 2022 were followed through 30 June 2023. CVF was defined as 2 VL ≥200 copies/ml or 1 VL ≥200 copies/ml + discontinuation. Logistic regression was used to assess CVF risk by regimen and CVF predictors among CAB+RPV LA users. RESULTS:During the study period, 1362 virologically suppressed adults switched to CAB+RPV LA, and 2783 switched to a new oral ART regimen (92% second-generation integrase inhibitor [INSTI]-based). Compared to oral ART users, CAB+RPV LA users were younger, on their prior regimen less time and more likely to switch from an INSTI; median CD4 counts at initiation were similar. At study end, 81% of CAB+RPV LA users and 80% of oral ART users were on their respective regimens. CVF risk with CAB+RPV LA did not statistically differ compared to oral ART (adjusted odds ratio: 0.64; 95% confidence interval [CI]: 0.34, 1.14). Among CAB+RPV LA users, only baseline CD4 predicted CVF; every 100 CD4 cells/µl increase was associated with 20% lower CVF risk (OR [95% CI]: 0.80 [0.64, 0.97]). CONCLUSIONS:In the United States, routine clinical care, CVF risk did not differ between a switch to CAB+RPV LA or new oral ART, with most individuals remaining on their regimens at study end. Lower CD4 count at initiation was the only predictor of CVF on CAB+RPV LA.

OBJECTIVE:To assess HBV monitoring, HBV reactivation and hepatitis flares during tenofovir interruptions among people with HIV and HBV. DESIGN/METHODS:Cohort study of electronic health records. METHODS:All tenofovir (tenofovir disoproxil fumarate, tenofovir alafenamide) interruptions among people with HIV and positive HBV surface antigen (HBsAg) or positive HBV core antibody (HBcAb) were categorized by reactivation risk (high: HBsAg+; moderate: HBsAg-/HBcAb+/surface antibody [HBsAb] negative; low: HBsAg-/HBcAb+/HBsAb+). Incidence rates of HBV reactivation and hepatitis flare were assessed with Poisson regression. RESULTS:Among 5343 individuals with HIV and HBV, there were 6252 tenofovir interruptions (11% high-, 19% moderate-, 69% low-risk). During the interruptions, HBV DNA/HBsAg testing was infrequent (high: 52%/25%; moderate: 8%/31%, low: 5%/28%), although ALT testing was performed during nearly all interruptions. The HBV reactivation rate was 9.59 per 100 person-years (95% confidence interval [CI]: 7.91, 11.64) during high-risk, 0.58 (0.36, 0.91) during moderate-risk, and 0.04 (0.02, 0.11) during low-risk interruptions. The HBV reactivation with hepatitis flare incidence rate was much lower, especially in the high-risk group (3.06 per 100 person-year; 95% CI: 2.19, 4.29). CONCLUSIONS:In this large US cohort of people with HIV and HBV, tenofovir interruptions were common and HBV monitoring was sub-optimal. HBV reactivation rates were highest among the high-risk group, but much lower among the moderate- and low-risk groups. However, some reactivations were likely missed due to low monitoring frequency. Primary and HIV care providers must incorporate HBV monitoring in their standard of care and proceed with caution if considering a tenofovir interruption for people with HIV and HBV.

BACKGROUND:cohort and investigate virologic outcomes among individuals who resumed treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). METHODS:We identified adults with HIV-1 who were active in care and on an oral ART regimen with ≥ 2 antiretrovirals, including ≥ 1 anchor agent, between 30JUN2021 and 31AUG2023. Individuals with ≥ 1 period of ≥ 45 days without any ART, based on supply from last prescription, were considered to have experienced a treatment interruption. Individuals who resumed treatment by 31AUG2023 were defined as having experienced a treatment interruption with resumption. Each interruption observed during the study period was described, allowing for multiple interruptions per person. Treatment interruptions, pre-interruption regimens, and post-interruption regimens were described. Among individuals who resumed treatment with B/F/TAF, virologic outcomes were investigated through 29FEB2024 using Kaplan-Meier methods. All analyses were repeated with treatment interruption definitions of ≥ 60 and ≥ 90 days. RESULTS:Of 76,883 people for whom a treatment interruption could be observed, 8,550 (11%) experienced ≥ 1 period of ≥ 45 days without any ART. By 31AUG2023, 4,163 (49%) individuals resumed treatment (mean: 1.25 per person) and were included in the study population. The median age was 44 years, 81% were male, 52% Black, 41% White, and 18% Hispanic. Median time since HIV diagnosis was 118 months. B/F/TAF was the most common pre- and post-interruption regimen (49% and 51%, respectively). The cumulative probability of achieving virologic suppression on B/F/TAF was 68% (95% CI: 57, 78) when the viral load measurement was ≥ 200 copies/mL at resumption. CONCLUSIONS:Treatment interruptions occurred in 11% of ART users in routine clinical care during the 26-month study period. Despite treatment interruption increasing the risk for viral rebound, most individuals who resumed treatment with B/F/TAF were able to achieve virologic suppression or avoid virologic failure.

BACKGROUND:Weight gain has been associated with the use of antiretrovirals in people with HIV, especially with integrase inhibitors or tenofovir alafenamide, and among women. In 2018, doravirine became the latest non-nucleoside reverse transcriptase inhibitor to be approved in the US. We assessed changes in weight over time among virologically suppressed individuals who switched to a regimen containing doravirine (DOR). METHODS:From the US-based OPERA cohort, treatment-experienced adults with HIV who switched to a DOR-containing regimen between 30AUG2018-30NOV2022 with a viral load < 50 copies/mL were included (followed through 31MAY2023). The study population was characterized and a linear mixed model was used to estimate rates of weight change on DOR. Results were stratified by sex, by patterns of efavirenz (EFV) and/or tenofovir disoproxil fumarate (TDF) use before/after switch to DOR, and by integrase inhibitor (INSTI) & tenofovir alafenamide (TAF) use combination (restricted to individuals who maintained the same combination before/after switch). RESULTS:Of 388 included individuals, 21% were women, 33% were Black, and 78% were obese or overweight at DOR switch. Overall, people who switched to DOR lost an average of 0.80 kg/year (95% CI: -1.32, -0.28). Both women and men experienced statistically significant weight loss; women (70% Black, 70% aged ≥ 40 years) lost weight at a rate of -1.67 kg/year (95% CI: -3.32, -0.02) and men at a rate of -0.60 kg/year (95% CI: -1.12, -0.08). When EFV and TDF were absent before and after switch to DOR, statistically significant weight loss was observed. Among those who had the same INSTI and TAF combination throughout and had any INSTI or TAF use, a statistically non-significant trend toward weight loss was observed. CONCLUSIONS:In one of the first real-world analyses of weight changes among virologically suppressed individuals who switched to a DOR-containing regimen in the US, DOR was associated with statistically significant weight loss. Patterns of use of other antiretrovirals did not fully explain the observed weight loss. These findings are clinically meaningful given that most individuals included were overweight or obese at switch to DOR and that women were predominantly of perimenopausal or menopausal age.

OBJECTIVES/OBJECTIVE:Fostemsavir is a novel attachment inhibitor used with other antiretrovirals in heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. Real-world immunological and virological responses were assessed in individuals starting fostemsavir in the OPERA cohort. METHODS:Among adults with HIV-1 starting fostemsavir between 2 July 2020 and 1 September 2022, 6-month and 12-month changes in CD4 T-cell count and CD4%, and maintenance/achievement of viral load (VL) <50 copies/mL were described and stratified by baseline VL (suppressed: <50 copies/mL; viraemic: ≥50 copies/mL) and CD4 count (high: ≥350 cells/μL; low: <350 cells/μL). RESULTS:Of 182 individuals starting fostemsavir, 64% were viraemic (34% low CD4, 30% high CD4) and 36% were suppressed (16% low CD4, 20% high CD4). The suppressed/low CD4 group had the largest median increases in CD4 count (6-month: 30 cells/μL [interquartile range {IQR} 9-66], 12-month: 66 cells/μL [IQR 17-125]), and CD4% (6-month: 1.0% [IQR -0.3-2.8], 12-month: 1.9% [IQR 1.3-3.9]). Regardless of baseline VL, those with a high baseline CD4 count experienced a greater variability in immunological response than those with low CD4 counts (12-month standard deviation range 172-231 cells/μL vs. 69-90 cells/μL). VL <50 copies/mL was maintained in most suppressed individuals; nearly half of the viraemic/high CD4 group and a third of the viraemic/low CD4 group achieved a VL <50 copies/mL at either timepoint. CONCLUSIONS:After 6 or 12 months of fostemsavir use, virological response was low in viraemic individuals, although most suppressed individuals did maintain suppression. While immunological response varied across individuals, virologically suppressed HTE individuals with low CD4 counts may benefit from immunological improvements with fostemsavir.

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA^®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016-2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m². Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death.

BACKGROUND:We evaluated the impact of the CHORUS™ app on adherence to the cabotegravir and rilpivirine long-acting injectable (CAB + RPV LAI) monthly injections schedule. METHODS:Healthcare centers (HCCs) were randomized to access CHORUS™ CAB + RPV LAI features (intervention) or not (control) from 01OCT2021-31JAN2022. Target window adherence (maintenance injections ≤7 days before/after target day) was assessed with multivariate logistic regression (generalized estimating equations). RESULTS:CAB + RPV LAI was administered to 188 and 79 individuals at intervention and control HCCs, respectively. Intervention was not associated with improved target window adherence (adjusted odds ratio: 0.61 [95% CI: 0.30-1.25]). However, app use was associated with increased odds of adherence compared to no app use among all intervention HCCs (2.98 [1.26-7.06]) and at smaller HCCs (3.58 [1.31-9.80]). CONCLUSIONS:While access to CHORUS™ CAB + RPV LAI features did not improve target window adherence, app use did, especially at smaller HCCs which may not have established LAI management procedures. TRIAL REGISTRATION/BACKGROUND:https://clinicaltrials.gov/show/NCT04863261.

We aimed to describe the prevalence, incidence, and predictors of HIV-associated wasting (HIVAW)/low weight among people with HIV (PWH) in the United States. We conducted an observational, clinical cohort analysis, utilizing prospectively collected electronic health record data obtained from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA^®) cohort. HIVAW/low weight included a wasting or low body-mass index (BMI)/underweight diagnosis (ICD codes and title search) or BMI <20 kg/m². Prevalence was estimated among adult PWH in care from 2012 to 2015 and 2016 to 2020. Incidence from January 1, 2016, to October 31, 2021, was estimated using univariate Poisson regression among eligible PWH without prior HIVAW/low weight. Demographic and clinical predictors of incident HIVAW/low weight were included in multivariable logistic regression models, stratified by antiretroviral therapy (ART) experience. The period prevalence of HIVAW/low weight was 12% in both 2012-2015 and 2016-2020. Among 67,119 PWH without any prior HIVAW/low weight, 7% experienced incident HIVAW/low weight a median 64 months from HIV diagnosis. In multivariable regression models, similar predictor patterns were observed among ART-naïve and ART-experienced PWH without any prior HIVAW/low weight: lower odds of HIVAW/low weight with older age, female sex, Black race, and Hispanic ethnicity and higher odds with Medicaid. Notably, there was a dose-response relationship between increasing Veterans Aging Cohort Study Mortality Index scores and incident HIVAW/low weight in both groups. Wasting/low weight remains a challenge for PWH and may be underappreciated by providers. Advanced HIV and comorbidities significantly predict incident HIVAW/low weight. Increasing awareness of HIVAW, especially among frailer PWH, could improve the care of affected PWH.