BACKGROUND:People with HIV (PWH) with persistent viremia and adherence challenges to oral antiretroviral therapy (ART) can achieve viral suppression (VS) with long-acting cabotegravir/rilpivirine (LA-CAB/RPV). The US guidelines, however, recommend CAB/RPV only in limited situations. We projected the impact of delaying LA-CAB/RPV implementation while awaiting trial data. METHODS:Using a microsimulation model, we considered 2 approaches for PWH with persistent viremia and intermittent care engagement: daily first-line oral ART or LA-CAB/RPV, both with intensive-support-services (ISS) to maximize adherence. We evaluated 4 CAB/RPV implementation scenarios: (1) Current practice (1% on CAB/RPV); (2) hypothetical Immediate/Delayed complete implementation (100% CAB/RPV after 0-4 year); (3) 2 Post-trial implementation scenarios: Post-one-arm-trial implementation (1-year trial, 5% uptake/year thereafter), Post-randomized-trial implementation (3-year trial, 15% uptake/year thereafter; and (4) Immediate incomplete implementation (1%-20% uptake/year). Outcomes were virologically suppressed person-years (VSPY) and 5-yearmortality. Inputs included cohort size 33,600, initial CD4 count of 150/µL, 6-month-VS from observational data: 23% (oral ART), 65% (LA-CAB/RPV). RESULTS:Current practice projects 35 810 VSPY and 17 640 deaths at 5 years. Immediate complete implementation increases VSPY by 26 830 and averts 3980 deaths; Delayed complete implementation produces 5370 fewer VSPY and 800 more deaths/delayed year. Post-one-arm-trial implementation yields 1700 more VSPY and 330 fewer deaths than Current practice; Post-randomized-trial implementation yields 1280 more VSPY and 270 fewer deaths. Immediate incomplete implementation at 3% and 2% uptake/year is similar to Post-one-arm-trial implementation and Post-randomized-trial implementation. CONCLUSIONS:LA-CAB/RPV for US PWH with persistent viremia and intermittent care engagement would increase VS and decrease mortality. Increased LA-CAB/RPV implementation with ISS should be undertaken while awaiting trial results.

Importance:As the population of older people with HIV (PWH) in the US is growing, costs to Medicare are expected to rise substantially. Objectives:To project the number of Medicare beneficiaries aged 65 years or older receiving care for HIV in the US from 2026 to 2035 and the budget impact on Medicare. Design, Setting, and Participants:This economic evaluation used the Cardiovascular, HIV, Aging, Hearing Loss, Mental Health, and Dementia (CHARMED) simulation model to project the number of Medicare beneficiaries aged 65 years or older receiving care for HIV and associated costs from 2026 to 2035. The model was populated with age- and sex-stratified clinical data and costs derived from 2023 traditional Medicare claims and accounted for enrollment in Medicare Advantage, as well as health care inflation. Data analysis was conducted from September 2023 to May 2026. Main Outcomes and Measures:Number of Medicare beneficiaries aged 65 years or older receiving care for HIV and undiscounted costs to Medicare from 2026 to 2035. Results:The simulated cohort was informed by 111 600 PWH enrolled in Medicare at the start of 2026 (mean [SD] age, 70.9 [5.0] years; 77% male). The analysis found that 121 890 PWH would be enrolled in Medicare and in care by the end of 2026, including 60 390 PWH aged 65 to 69 years, 36 340 aged 70 to 74 years, 17 200 aged 75 to 79 years, and 7970 aged 80 years or older. By the end of 2035, this number would increase to 193 560, with increases in each age category (65-69 years: 70 490; 70-74 years: 62 820; 75-79 years: 38 290; 80 years and older: 21 960). Annual costs to Medicare for PWH aged 65 years or older and receiving care for HIV would increase from $10.9 billion by the end of 2026 to $27.3 billion by the end of 2035. Cumulative costs over 10 years were projected to be $187.2 billion, with 63% of cumulative costs due to antiretroviral therapy (ART). If ART costs are reduced by 60%, Medicare would save $70.3 billion over the next decade; projected savings due to the Inflation Reduction Act and generic ART would be $19.4 billion, accounting for the timing of onset and estimated reductions. Based on uncertainties in the number of Medicare beneficiaries and costs of care, sensitivity analyses found that cumulative costs would range from $103.3 billion to $267.5 billion over the next decade. Conclusions and Relevance:In this economic evaluation using microsimulation modeling, the number of Medicare beneficiaries aged 65 years or older receiving care for HIV was projected to increase substantially over the next decade, resulting in $187.2 billion in 10-year cumulative costs to Medicare. Reducing ART costs by 60% could lead to 38% lower overall Medicare spending for older Medicare beneficiaries with HIV.

PURPOSE:The aim of this study was to evaluate the effectiveness of remdesivir among vulnerable patients hospitalized with a primary diagnosis of coronavirus disease 2019 (COVID-19). METHODS:In this retrospective study, data from the Premier Healthcare Database compiled from December 2021 to December 2024 were examined. Four cohorts were analyzed: overall (≥18 years of age), elderly (≥65 years of age), those with pneumonia due to COVID-19, and those with chronic obstructive pulmonary disease (COPD). Analyses were stratified by supplemental oxygen requirements upon admission. Patients treated with remdesivir within the first 2 days of hospitalization were matched to those not treated with remdesivir during hospitalization, using 1:1 propensity score matching without replacement. Outcomes of interest were 14- and 28-day all-cause inpatient mortality. RESULTS:A total of 220,677 patients met the eligibility criteria; of these, 123,388 (55.9%) were treated with remdesivir within the first 2 days of hospitalization. Overall, treatment with remdesivir was associated with significantly lower 14- and 28-day mortality rates compared to rates in patients who did not receive remdesivir (adjusted hazard ratio [95% CI], 0.76 [0.73-0.79] and 0.78 [0.75-0.81], respectively; P < 0.0001). Similar results were observed across all patient groups irrespective of supplemental oxygen requirements and across early (December 2021-December 2022) and later (January 2023-December 2024) Omicron periods. CONCLUSIONS:These results build on previous research highlighting the effectiveness of early treatment initiation with remdesivir in vulnerable patients hospitalized due to SARS-CoV-2 infection.

The occurrence of virological failure in a subset of individuals is an inevitable aspect of antiretroviral treatment, and historically has been primarily influenced by suboptimal adherence to oral therapies. The risk of selecting 1- or 2-class human immunodeficiency virus (HIV) drug resistance is influenced by the composition of the regimen, differing significantly depending on the intrinsic barrier to resistance of the regimen. HIV resistance emergence during treatment can be viewed as a regimen-related adverse effect that warrants equal consideration in clinical trials alongside virological and safety endpoints. Antiretroviral regimens demonstrating non-inferiority and showing similar rates of virological failure can nonetheless differ in terms of HIV emergent resistance. We propose the development of a systematic framework to categorize emergent HIV drug resistance in clinical trials. Standardizing the evaluation of resistance in clinical trials and its reporting to regulatory agencies will facilitate an improved understanding of regimen-specific resistance risks and better inform clinical decision making.

While once-daily single-tablet regimens (STRs) are recommended for most people with human immunodeficiency virus (HIV; PWH), some require complex antiretroviral (ARV) regimens due to resistance, contraindications, or drug-drug interactions. We characterized PWH who were virologically suppressed on complex regimens (VS on CR) in a U.S. cohort to inform treatment optimization as new switch options emerge. This retrospective study analyzed electronic medical records from the Trio Health HIV Network and genotypic resistance data from Labcorp. We included PWH ≥ 18 years who were virologically suppressed (viral load [VL] < 200 copies/mL) at complex regimen initiation between January 2016 and November 2023, with ≥6 months from last prescription and ≥1 year of follow-up. Complex regimens included ≥2 of 3 core ARV classes concomitantly, more than once-daily dosing, multi-tablet regimens (MTRs) not replaceable by STRs, or resistance to two ARV classes. Virologic failure (VF) was defined as VL ≥ 500 copies/mL or two consecutive VLs ≥ 200 copies/mL. PWH on ibalizumab, fostemsavir, or lenacapavir were excluded to reflect standard clinical practice. Of 43,236 PWH with ARV prescriptions, 3,320 (8%) were VS on CR. Among these, 69% were on MTRs, 43% used ≥2 core ARV classes, and 11% had resistance to two classes. The median age was 52 years, and 77% were male. Common comorbidities included obesity (69%), neuropsychiatric disorders (35%), and cardiovascular disease (33%). Regimens predominantly included protease inhibitors (77%), nucleoside reverse transcriptase inhibitors (75%), and integrase strand transfer inhibitors (57%). Over a median 2.2-year follow-up, 4% experienced VF. Approximately 8% of PWH on ART remain VS on CR, underscoring the need for education on regimen optimization and novel treatment options for those unable to simplify their therapy.

BACKGROUND:Persistent virological non-suppression among people with HIV receiving tenofovir-lamivudine-dolutegravir (TLD) can result from poor adherence with or without resistance; however, genotypic resistance testing (GRT) is not recommended routinely in South Africa. We examined the clinical and economic effect of GRT for all South African adults diagnosed with persistent virological non-suppression on TLD. METHODS:In this modelling study, we used the previously validated Cost-Effectiveness of Preventing AIDS Complications-International microsimulation model to compare three strategies: (1) continued TLD (baseline); (2) immediate switch to tenofovir-lamivudine plus ritonavir-boosted darunavir; and (3) GRT prompting switch to tenofovir-lamivudine plus ritonavir-boosted darunavir for people with dolutegravir resistance or TLD continuation for people without dolutegravir resistance. We estimated that 2·3% and 28·5% of the baseline population have dolutegravir resistance and nucleoside reverse transcriptase inhibitor (NRTI) resistance, respectively. We also examined the effect of a low-cost, point-of-care urine tenofovir test in development to detect recent antiretroviral therapy use (84% sensitivity and 50% specificity), with GRT only when positive. Costs included GRT (US$157 per test), TLD ($45 per year), tenofovir-lamivudine plus ritonavir-boosted darunavir ($247 per year), and urine tenofovir testing ($2 per test). Outcomes included life-years, costs (provider perspective), and incremental cost-effectiveness ratios (ICERs; $ per disability-adjusted life-year [DALY]). We considered cost-effectiveness thresholds of less than $3310 per DALY (base case) and less than $1100 to $4250 per DALY. FINDINGS:Based on our model, we estimated that continued TLD results in 14·11 undiscounted life-years and costs $5380 discounted at 3%; GRT results in 14·36 life-years and costs $5860 (0·14 discounted DALYs averted; ICER $3500 per DALY). Immediate switch results in fewer DALYs averted and higher costs. GRT has an ICER of $3310 per DALY or less when baseline dolutegravir resistance prevalence is ≥2·5% or genotypic resistance test costs ≤$147 per test. Urine tenofovir testing to identify GRT eligibility results in an ICER of $2300 per DALY; the ICER would be less than $1100 per DALY if urine test specificity is 0·87 or greater and costs $2 per test or test specificity is higher than 0·98 and costs $10 per test or less. INTERPRETATION:GRT could increase life expectancy for people with HIV and persistent virological non-suppression on TLD in South Africa and could be cost-effective, especially at lower test costs. At current effectiveness and costs of tenofovir-lamivudine plus ritonavir-boosted darunavir, an immediate switch would not be preferred. FUNDING:National Institute of Allergy and Infectious Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the MGH Jerome and Celia Reich Endowed Scholar in HIV/AIDS Research Award.

Background:Intact proviral DNA (IPD) is a measure of the replication-competent HIV reservoir. Little is known about how IPD levels compare in people with HIV (PWH) who initiate antiretroviral therapy (ART) during acute HIV infection (AHI), chronic infection (CHI) or as HIV controllers (CON). Methods:Participants with sustained plasma HIV RNA < 50 copies/mL on ART had longitudinal measurements of intact, defective and total proviral DNA in blood samples. Results:Twenty-nine participants were evaluated: 14 CHI, 7 AHI and 8 CON. PWH-CON had lower IPD than PWH-AHI or PWH-CHI during ART. PWH-CON also had low intact and total provirus levels before initiating ART. During years 2-5 of ART, IPD decay half-life was 1.0 years in PWH-AHI, 1.6 years in PWH-CHI and 3.2 years in PWH-CON (P = .01 for PWH-CON vs PWH-AHI). Defective provirus levels did not decrease in PWH-AHI and PWH-CHI. Conclusions:During the initial years of ART, PWH treated during acute and chronic infection have decay in intact but not defective proviruses. PWH controllers have low intact and total provirus levels before and during ART, suggesting interactions between host and virus shape the proviral landscape. Variable proviral decay patterns in these populations provide insight into approaches to achieve ART-free HIV remission.

To evaluate long-term changes in weight and metabolic parameters in people with HIV-1 (PWH) initiating first-line antiretroviral therapy. Analysis of two Phase 3, randomized, double-blind, active-controlled trials (1489: NCT02607930; 1490: NCT02607956). PWH received bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)-based treatment (Study 1489: dolutegravir/abacavir/lamivudine [DTG/ABC/3TC]; Study 1490: DTG + F/TAF) for 144 weeks, followed by B/F/TAF (96-week open-label extension up to Week 240). Weight and metabolic parameters were assessed through Week 144 by randomized treatment assignment. Weight changes by baseline viral load and CD4 count were evaluated in PWH receiving B/F/TAF from baseline through Week 240. Multivariate modeling explored baseline factors associated with absolute weight and weight change through Week 240 and weight gain ≥ 10

BACKGROUND:With progressive accumulation of knowledge on SARS-CoV-2 infection clinical management, treatment guidelines recommended several options including remdesivir, a broad-spectrum antiviral. Given the evolving nature of coronavirus disease 2019, capturing the totality of scientific evidence from clinical trials and observational studies is critical to inform clinical decision making. We conducted a systematic literature review with meta-analysis to summarize the effectiveness of remdesivir among hospitalized adults. METHODS:We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining remdesivir efficacy. A rigorous double-reviewer approach was used for source identification, screening, data extraction and risk of bias assessment. A hierarchical random-effects model meta-analysis was used, with subgroup analyses for randomized controlled trials (RCTs) and real-world (RW) studies. RESULTS:From January 2019 to December 2023 >18 000 sources were screened, and 122 unique studies were identified, reporting on 25 174 participants in RCTs and 1 279 859 in RW studies. Remdesivir significantly increased survival in the overall population (odds ratio, 0.69 [95% confidence interval, .55-.86]; P = .001] across SARS-CoV-2 variants and disease severity levels: no supplemental oxygen (0.81 [.75-.88]), low-flow oxygen (0.71 [.64-.79]), high-flow oxygen (0.87 [.83-.91]), and invasive mechanical ventilation (0.78 [.68-.90]). Rehospitalization risk was significantly reduced in patients receiving remdesivir (odds ratio, 0.72 [95% confidence interval, .64-.81]). CONCLUSIONS:Our comprehensive systematic literature review, capturing the totality of evidence, showed a significant survival benefit among patients hospitalized for SARS-CoV-2 infection and receiving remdesivir, across all disease severity levels. To assure that healthcare providers are aware of and deploy evidence-based optimal care, recommendations should rely on both RCT and RW data.

OBJECTIVE:Treatment adherence remains critical in maintaining HIV RNA suppression on antiretroviral therapy. High genetic barrier regimens constructed with three long half-life agents may prevent resistance emergence and can be potentially started or restarted after antiretroviral treatment interruption. METHODS:Data from the TRIO US HIV cohort were used to identify adult people with HIV initiating a new ART regimen from January 2021 to November 2023 and describe prevalence of treatment interruptions (defined as ≥90 days without dispensed ART). Virologic outcomes were assessed among those restarting or switching to B/F/TAF after treatment interruption. RESULTS:Of 2710 people with HIV, 765 (28%) experienced treatment interruption. Compared to individuals without treatment interruptions, those with treatment interruptions had higher proportion of women (24 vs. 19%), Black race (50 vs. 35%), substance use (14 vs. 9%), CD4 + cell count less than 200 cells/mm 3 (15 vs. 8%) and lower proportion with commercial insurance (48 vs. 62%) or virologic suppression at initiation (76 vs. 85%). Among 379 who restarted or switched to B/F/TAF following treatment interruption, 245 (65%) were suppressed at restart; 137 (56%) had at least one viral load after treatment interruption, of whom 129 (94%) maintained suppression. Of 87 with unknown viral status at restart, 46 (53%) had at least one viral load during follow-up, of whom 44 (96%) achieved suppression. Among 47 viremic at restart, 27 (57%) had at least one viral load after treatment interruption. Of them, 70% were suppressed during follow-up. No integrase inhibitor resistance emergence was observed. CONCLUSION:High levels of suppression following treatment interruption may suggest B/F/TAF regimen forgiveness making it an appropriate choice for treatment switch or restart.

ImportanceNew data and new antiretroviral drugs and formulations continue to become available for the prevention and management of HIV infection.ObjectiveTo provide updated recommendations for HIV treatment and clinical management and HIV prevention.MethodsA panel of volunteer expert physician scientists were appointed to provide updated consensus recommendations for 2024. Relevant evidence in the literature since the last report was identified from PubMed and Embase searches (which initially yielded 3998 unique citations, of which 249 were considered relevant); from ongoing monitoring of the literature by the panel members; from data submitted by product manufacturers; and from studies presented at peer-reviewed scientific conferences between June 2022 and October 2024.FindingsAntiretroviral therapy continues to be recommended for all individuals with HIV. For most people with HIV, initial regimens composed of an integrase strand transfer inhibitor (InSTI), specifically bictegravir or dolutegravir, with 2 (and in some cases 1) nucleoside or nucleotide reverse transcriptase inhibitors are recommended. Recommendations are made for those with particular clinical circumstances, such as pregnancy and active opportunistic diseases, as well as for those unable to take InSTIs. Regimens may need to be changed for virologic failure, adverse effects, convenience, or cost, among other reasons. Long-acting injectable therapy is available for those who prefer not to take daily oral medications and for people struggling with adherence to daily therapy. Recommendations are provided for laboratory monitoring, management of substance use disorders and weight changes, as well as use of statins for cardiovascular disease prevention. For HIV prevention, oral (daily or intermittent) and injectable long-acting medications are effective options for people at increased likelihood of HIV exposure. Further, new tools for maintaining health and well-being among people with HIV, such as doxycycline postexposure prophylaxis to avert sexually transmitted infection, and strategies to treat substance use disorders, are recommended. Disparities in HIV acquisition and care access are discussed and solutions proposed.ConclusionsNew approaches for treating and preventing HIV offer additional tools to help end the HIV epidemic, but achieving this goal depends on addressing disparities and inequities in access to care.

Long-acting injectable cabotegravir plus rilpivirine (LA CAB/RPV) is currently US Food and Drug Administration approved and Human Immunodeficiency Virus (HIV) treatment guideline endorsed as a switch strategy for patients with HIV (PWH) who are virologically suppressed on oral antiretroviral therapy without a history of treatment failure. Recent changes to the International Antiviral Society-USA and US Department of Health and Human Services' Panel on Antiretroviral Guidelines recommend the consideration of LA CAB/RPV in select PWH with viremia who are unable to achieve suppression with oral antiretroviral therapy due to suboptimal medication adherence. In this article, we review the existing data on this off-label use of LA CAB/RPV, discuss the motivations and specific caveats implicit in the guideline change, and propose next steps in exploring this novel treatment in a vulnerable patient population.

Abstract Background Weight gain among persons with HIV (PWH) on integrase strand transfer inhibitors (INSTIs) is highly variable. Given the importance of the melanocortin-4 receptor (MC4R) in obesity, we examined associations between MC4R gene variants and weight gain following switch to INSTI-containing antiretroviral therapy (ART) among PWH in ACTG observational cohort studies A5001 and A5322. Methods Eligible participants switched to their first INSTI-containing ART from 2005-2018 and had available genetic and weight data. Imputed genotypes were from genome-wide data. Linear models assessed associations between MC4R variants and weight change, including 20 variants previously associated with weight/obesity in populations without HIV. Analyses adjusted for age, sex at birth, genetic principal components, time after switch, and body mass index, CD4 count and virologic control at switch; separate models were stratified by race/ethnicity, sex and baseline BMI category. Results Among 530 PWH, median age was 50 (IQR 42, 57) years, 29% were non-Hispanic Black, 22% were cis-gender female, 62% were overweight or obese at INSTI switch, and 73% switched from a protease inhibitor. INSTIs were raltegravir (62%), dolutegravir (21%), elvitegravir (17%), and bictegravir (1%). The switch regimen included tenofovir alafenamide (TAF) in 9%. Overall median weight gain after switch was 1.25 kg (IQR -1.2, 4.0). Of 20 MC4R variants previously associated with weight/obesity, three were nominally associated (p< 0.05) with weight change after switch in all participants or in subgroups. One (rs11873305) was associated with weight gain in all participants (p=0.01), and male (p=0.004) and White (p=0.02) subgroups. Of 507 additional MC4R variants, the lowest p-value among all participants was for rs56758444 (p=0.001). After Bonferroni correction, no variant was significant in MC4R or in exploratory genome-wide analysis. Conclusion Among PWH, MC4R variants were nominally associated with weight change after switch to INSTI-based ART. These findings are consistent with the known importance of melanocortins in appetite and weight, and suggest a neuroendocrine contribution to INSTI-related weight gain. Additional studies with newer INSTIs and TAF are needed. Disclosures Kristine M. Erlandson, MD MS, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|ViiV: Advisor/Consultant Sara H. Bares, MD, Gilead Sciences: Expert Testimony|Janssen: Grant/Research Support|ViiV Healthcare: Grant/Research Support Todd T. Brown, MD, PhD, EMD Serono: Advisor/Consultant|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Jordan Lake, MD, Merck: Advisor/Consultant|Theratechnologies: Advisor/Consultant Grace A. McComsey, MD, Gilead, Merck, GSK: Advisor/Consultant John R. Koethe, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Merck & Co.: Advisor/Consultant|Merck & Co.: Grant/Research Support

Abstract Background With progressive understanding of the natural history of COVID-19 and accumulation of knowledge on clinical management, treatment guidelines recommended several options including remdesivir (RDV), a broad-spectrum antiviral. Given the evolving nature of COVID-19, it is critical to capture the totality of scientific evidence to inform clinical decision making. We conducted a systematic literature review (SLR) to summarize the mortality endpoint for RDV among hospitalized adults throughout COVID-19 eras and contrasted with evidence informing treatment recommendations in clinical guidelines. Methods We systematically searched MEDLINE, Embase and Cochrane Library databases for interventional and observational studies examining RDV efficacy. Clinical trial registries, Cochrane COVID-19 Study Register, and conference abstracts were hand-searched (Fig1). Case reports and case studies were excluded. A review of most recent RDV recommendations across guidelines was conducted. Results From Dec ’19 to Dec ’22, 123 relevant publications were identified. In ’23, the evidence grew significantly, with 70 new publications. In total, 193 publications were evaluated, and 122 unique studies were included. While early randomized clinical trials (RCT) and small sample size observational studies did not universally demonstrate a significant difference in mortality in all severity groups of RDV-treated patients, real-world studies with larger sample sizes showed a significant impact across disease severity levels, regardless of COVID-19 era (Table1). Guideline recommendations for COVID-19 treatment with RDV are based on early RCTs (Table2) and most have not been updated (Fig2). Conclusion Our comprehensive evaluation of scientific literature indicates that evidence of RDV impact on mortality in hospitalized COVID-19 patients continued to grow and cover full range of disease severity. Guideline recommendations have not evolved in parallel which may explain differing recommendations in certain subgroups (e.g. IMV/ECMO). To assure that providers in the hospital setting are aware of and deploy evidence-based optimal care for patients with COVID-19, recommendations should rely on current evidence, including real-world data. Disclosures Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Michele Bartoletti, MD, PhD, Advan pharma: Advisor/Consultant|Advan pharma: Honoraria|Biomereux: Honoraria|Gilead: Advisor/Consultant|Gilead: Honoraria|Infectopharma: Advisor/Consultant|Msd: Advisor/Consultant|Msd: Grant/Research Support|Msd: Honoraria|Pfizer: Honoraria Alpesh N. Amin, MD, MBA, Alexion: Advisor/Consultant|Aseptiscope: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Bayer: Advisor/Consultant|Dexcom: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Ferring: Advisor/Consultant|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Heartrite: Advisor/Consultant|Nova Nordisk: Advisor/Consultant|Pfizer: Advisor/Consultant|Renibus: Advisor/Consultant|Reprieve: Advisor/Consultant|Salix: Advisor/Consultant|Seres: Advisor/Consultant|Spero: Advisor/Consultant Yohei Doi, MD, PhD, bioMerieux: Lecture fees|Entasis: Grant/Research Support|Fujifilm: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|GSK: Advisor/Consultant|KANTO CHEMICAL CO.,INC.: Grant/Research Support|KANTO CHEMICAL CO.,INC.: Patent for genotyping kit|MeijiSeika Pharma: Advisor/Consultant|Moderna: Advisor/Consultant|MSD: Lecture fees|Pfizer: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant|Gilead: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Board Member Michael Roshon, MD/PhD, MD/PhD, Gilead: Honoraria Thomas F. Oppelt, PharmD, BCPS, Gilead Sciences, Inc: I am an employee of Gilead Sciences, Inc|Gilead Sciences, Inc: Stocks/Bonds (Public Company) Mel Chiang, Ph.D., Gilead Sciences: I am an employee of Gilead Sciences|Gilead Sciences: Stocks/Bonds (Public Company)

BACKGROUND:Patients on second-line protease inhibitor-based regimens in low-income and middle-income countries have high rates of nucleoside reverse transcriptase inhibitor (NRTI) resistance, but access to testing is scarce. We aimed to assess the efficacy of combination oral bictegravir, emtricitabine, and tenofovir alafenamide in this population. METHODS:In this open-label non-inferiority trial conducted in Port-au-Prince, Haiti, adults (aged 18 years or older) with viral suppression (HIV-1 RNA <200 copies per mL) on second-line regimens including ritonavir-boosted protease inhibitors and two NRTIs were randomised (1:1) using a computer-generated random-number list. Participants either switched from their current regimen to combination oral bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily (bictegravir group) or continued their current regimen (atazanavir 300 mg and ritonavir 100 mg once daily or lopinavir 400 mg and ritonavir 100 mg twice daily plus two NRTIs; boosted protease inhibitor group). The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 200 copies or more per mL at week 48, in accordance with the US Food and Drug Administration Snapshot algorithm. Primary and safety analyses were conducted in the intention-to-treat population, which included all participants who underwent randomisation and received at least one dose of study medication. The prespecified non-inferiority margin was 4%. The study is registered with ClinicalTrials.gov (NCT04311957). FINDINGS:Between Oct 23, 2020, and April 21, 2023, 444 people with HIV were screened for eligibility and 301 were randomly assigned to the bictegravir group (n=153) or to the boosted protease inhibitor group (n=148). The median age at enrolment was 49·5 years (IQR 43·6-56·2) in the bictegravir group and 48·0 (40·5-57·4) years in the boosted protease inhibitor group. 173 (57%) participants were women and 128 (43%) were men. All participants were Black. Enrolment was stopped early due to restricted access to the protease inhibitor-based regimen. At week 48, the proportion of participants with HIV-1 RNA of 200 copies per mL or more was 0·7% (one of 153 participants) in the bictegravir group and 4·1% (six of 148 participants) in the boosted protease inhibitor group (difference -3·4%, 95% CI -8·1 to 0·2), meeting non-inferiority criteria. Four participants in each group developed a new grade 3 or 4 adverse event, but no study drug was discontinued due to adverse events. INTERPRETATION:Switching adults with HIV and viral suppression on a second-line boosted protease inhibitor-based regimen to combination bictegravir, emtricitabine, and tenofovir alafenamide is non-inferior to continuing boosted protease inhibitor-based antiretroviral therapy. These findings support international treatment guideline recommendations to use second-generation integrase inhibitors for treatment-experienced patients. FUNDING:Gilead Sciences. TRANSLATION:For the French translation of the abstract see Supplementary Materials section.

This retrospective observational study evaluated the clinical use and treatment outcomes in virologically suppressed people with HIV (PWH) switching to either bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)-based regimens (single- and multi-tablet formulations (STR and MTR)). We analyzed electronic medical and dispensing records from Trio Health HIV Research Network for treatment-experienced PWH ≥ 18 years suppressed (viral load [VL] < 200 copies/mL) at switch to B/F/TAF, DTG STR (DTG/3TC, DTG/RPV, DTG/3TC/ABC) or most common DTG MTRs with VL at 12 months (+/-3) since switch between April 2019 and December 2024. Univariate comparisons: chi-square or t-test; characteristics associated with virologic suppression at 12 months: multivariable logistic regression [LR], controlling for age, gender, race, baseline CD4 count, regimen, and adherence (proportion days covered [PDC] ≥ 80

Abstract Background Most clinical guidelines recommend treatment of patients hospitalized for COVID-19 with remdesivir (RDV), while adding a corticosteroid such as dexamethasone (DEX) is recommended among patients with hypoxemia. Since other corticosteroids (CORT) such as prednisone, prednisolone, methylprednisolone, and hydrocortisone can be used in place of dexamethasone or for other underlying conditions, we examined all-cause mortality in hospitalised COVID-19 patients initiating RDV+CORT vs. CORT monotherapy with information from the more recent COVID-19 era.Table 1:Baseline characteristics before and after matching Methods Using the PINC AI Healthcare database, adults hospitalised during the Omicron period (December 2021 to April 2023) with a primary discharge diagnosis of COVID-19 and flagged as “present-on-admission” and initiating RDV+CORT or CORT monotherapy in the first 2 days of hospitalisation (baseline period) were included. Patients were matched using 1:1 preferential within-hospital propensity matching. Cox Proportional Hazards Model was used to examine time to 14- and 28-day mortality.Figure 1:14- and 28-day mortality in patients hospitalized for COVID-19 receiving RDV+Corticosteroids or Corticosteroids monotherapy by supplemental oxygen requirements Results Among 151,215 COVID-19 hospitalised patients, 67,580 (45%) initiated RDV+CORT and 43,618 (29%) CORT monotherapy (24% DEX monotherapy; 5% non-DEX corticosteroid monotherapy) in the first 2 days of hospitalization. Of the latter, RDV was not added for 90% (n=39,286) of patients after the first two days of hospitalization. A total of 39,104 RDV+CORT patients were matched 1:1 to CORT monotherapy patients. Post-matching balance was achieved with 71% age 65+, 36% LFO, 16% HFO/NIV, and 2% IMV/ECMO at baseline (Table 1). After adjusting for baseline and clinical covariates, RDV+CORT had a significantly lower mortality risk compared to CORT monotherapy overall and across all supplemental oxygen requirements at 14 days and at 28 days (Figure 1). Similar results were obtained for RDV+DEX vs. DEX monotherapy (Figure 2).Figure 2:14- and 28-day mortality in patients hospitalized for COVID-19 receiving RDV+Dexamethasone vs. Dexamethasone monotherapy by supplemental oxygen requirements Conclusion The study highlights the important role of antiviral therapy with remdesivir in improving clinical outcomes in patients hospitalized with COVID-19, supporting the guidelines that recommend its use. The data also expose non-adherence to these guidelines, as corticosteroid monotherapy should rarely be used, especially in those who do not require supplemental oxygen. Disclosures Essy Mozaffari, PharmD, MPH, MBA, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Aastha Chandak, PhD, Gilead Sciences Inc.: My organization (Certara) was contracted by Gilead to conduct this study Robert L. Gottlieb, MD, AbbVie: Advisor/Consultant|AbCellera: Stocks/Bonds (Public Company)|AstraZeneca: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Gilead Sciences Inc.: Advisor/Consultant|Gilead Sciences Inc.: Honoraria|Gilead Sciences Inc.: travel support, gift-in-kind to his institution to facilitate an unrelated academic-sponsored clinical trial NCT03383419|GSK Pharmaceuticals: Advisor/Consultant|Johnson & Johnson: Advisor/Consultant|Pfizer: Honoraria|Regeneron: Grants or contracts to institution|Roche: Advisor/Consultant|Roivant Sciences (Kinevant Sciences): Grants or contracts to institution Chidinma Chima-Melton, MD, Gilead Sciences: Advisor/Consultant Mark Berry, PhD, Gilead Sciences, Inc.: Employee|Gilead Sciences, Inc.: Stocks/Bonds (Public Company) Thomas F. Oppelt, PharmD, BCPS, Gilead Sciences, Inc: I am an employee of Gilead Sciences, Inc|Gilead Sciences, Inc: Stocks/Bonds (Public Company) Jason F. Okulicz, MD, Gilead Sciences Inc.: Employee|Gilead Sciences Inc.: Stocks/Bonds (Public Company) Alpesh N. Amin, MD, MBA, Alexion: Advisor/Consultant|Aseptiscope: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Bayer: Advisor/Consultant|Dexcom: Advisor/Consultant|Eli Lilly: Advisor/Consultant|Ferring: Advisor/Consultant|Gilead: Advisor/Consultant|GSK: Advisor/Consultant|Heartrite: Advisor/Consultant|Nova Nordisk: Advisor/Consultant|Pfizer: Advisor/Consultant|Renibus: Advisor/Consultant|Reprieve: Advisor/Consultant|Salix: Advisor/Consultant|Seres: Advisor/Consultant|Spero: Advisor/Consultant