High Rates Of Virologic Suppression Research Articles

Effectiveness, safety and discontinuation rates of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in people with HIV using real-world data: a systematic review and meta-analysis.

The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is based on the results of robust clinical trials. To assess the effectiveness and safety of BIC/FTC/TAF in treatment-naïve (TN) and treatment-experienced (TE) people with HIV using available real-world cohort studies. Systematic review and meta-analysis of publications and communications identified via Boolean search in Medline, PubMed and Embase, and conference abstracts reporting retrospective real-world use of BIC/FTC/TAF, published until 31 January 2024. The primary endpoint was the proportion of TN and TE people with HIV with viral load (VL) < 50 copies/mL at 48 weeks while on treatment. Of the 38 identified publications and conference abstracts, for the present analysis we included 12 publications (comprising 792 TN and 6732 TE individuals). For the three publications including 507 TN participants reporting the primary outcome, VL suppression was 97% [95% confidence intervals (CI): 89-100]. For the nine publications including 4946 TE participants reporting the primary outcome, VL suppression was 95% (95% CI: 94-96), with suppression >93% in all studies. Total discontinuations at 48 weeks in TE individuals were 3% (95% CI: 2-5), 1% (95% CI: 0-2) due to side effects. A total of four publications with 151 TE individuals with previous presence of M184V substitution were identified, reporting a suppression rate at 48 weeks of 95% (95% CI: 88-100). Real-world studies demonstrate low discontinuation rates and high rates of virologic suppression in individuals treated with BIC/FTC/TAF, both TN and TE with and without previous detection of M184V substitution.

Effect of dolutegravir on ferritin, iron, and C-reactive protein among people living with HIV and co-infections.

Dolutegravir-based antiretroviral therapy (ART) is currently recommended as the preferred first-line ART in many resource-limited settings. However, little is known about the clinical experience of dolutegravir within a context of prevalent co-infections. To assess virological outcomes, and iron, ferritin and C-reactive protein (CRP) levels among people living with HIV (PLWH) and co-infections after initiating or re-initiating dolutegravir-based ART. This prospective study was conducted between August 2022 and August 2023. Study participants were recruited from an HIV opportunistic infection clinic. Screening for co-infections (syphilis, hepatitis B virus, cytomegalovirus and herpes simplex virus) was performed at baseline, prior to ART initiation. Plasma HIV viral load (VL), CRP, ferritin and iron levels were measured at baseline and at the 6-month follow-up period. A total of 100 participants (51 women and 49 men) were enrolled in this study. The median age of the participants was 39 years. The prevalence of co-infections was 30%. Prior to ART initiation, participants with co-infections had higher VL, CRP and ferritin, and lower iron levels, compared to those without co-infections (P < 0.001). Following 6 months of ART, CRP and ferritin levels decreased while iron levels increased, regardless of co-infection status. However, CRP and ferritin remained significantly higher in those with co-infections despite similar and high rates of virologic suppression in both groups. The presence of co-infections in PLWH is associated with higher VL and with chronic inflammation. Ferritin and CRP decreased on dolutegravir-based ART but remained higher in people with co-infections despite similar rates of virologic suppression.

Reasons, Efficacy and Safety of Switching to Dolutegravir-Based Regimens Among Virologically Suppressed PLWH: A Retrospective Cohort Study of 96 Weeks.

The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG. PLWH's basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA <50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96. 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/μL (IQR 420.5-758) to 642 cells/μL (IQR 466.5-854) at week 96 (p<0.0001). An improvement was observed in liver function (ALT: p<0.0001; AST: p<0.0001) and fasting glucose (p<0.0001). However, there was an elevation in creatinine (Cr) (p<0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p<0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen. This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.

Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B: A comprehensive review of phases II and III therapeutic agents.

Chronic hepatitis B virus (HBV) infection affects over 295 million people globally and an estimated 1.6 million people in the United States. It is associated with significant morbidity and mortality due to cirrhosis, liver failure, and liver cancer. Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression, which in turn has been associated with a decreased risk of liver complications. However, current antiviral regimens are limited by concerns with adverse effects, adherence, resistance, long-term treatment, and ongoing risk for liver events. Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen (HBsAg) loss and suppression of HBV DNA. Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B, including core/capsid inhibitors, entry inhibitors, RNA interference (siRNA/ASO), HBsAg inhibitors, Toll-like receptor agonists, checkpoint inhibitors, and therapeutic vaccines.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies

BackgroundAs the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years).MethodsWeek 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis.ResultsOf 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years.ConclusionsAmong individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities.Trial registration number: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials.

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet regimen recommended for HIV-1 treatment. The safety and efficacy of B/F/TAF as initial therapy was established in two Phase 3 studies: 1489 (vs dolutegravir [DTG]/abacavir/lamivudine) and 1490 (vs DTG+F/TAF). After 144 weeks of randomized follow-up, an open-label extension evaluated B/F/TAF to 240 weeks. Of 634 participants randomized to B/F/TAF, 519 completed the double-blinded treatment, and 506/634 (80%) chose the 96-week open-label B/F/TAF extension, which was completed by 444/506 (88%) participants. Efficacy was based on the secondary outcome of the proportion of participants with HIV-1 RNA <50 copies/mL at Week 240 by missing=excluded and missing=failure methods. All 634 participants who were randomized to B/F/TAF and received at least one dose of B/F/TAF were included in efficacy and safety analyses. (Study 1489: ClinicalTrials.govNCT02607930; EudraCT 2015-004024-54. Study 1490: ClinicalTrials.govNCT02607956; EudraCT 2015-003988-10). Of those with available virologic data, 98.6% (95% CI [97.0%-99.5%], 426/432) maintained HIV-1 RNA <50 copies/mL at Week 240 (missing=excluded); when missing virologic data were considered as failure, 67.2% (95% CI [63.4%-70.8%], 426/634) maintained HIV-1 RNA <50 copies/mL. Mean (SD) change in CD4+ count from baseline was+338 (236.2) cells/μL. No treatment-emergent resistance to B/F/TAF was detected. Adverse events led to drug discontinuation in 1.6% (n=10/634) of participants (n=5 with events considered drug-related). No discontinuations were due to renal adverse events. Median (IQR) total cholesterol increased 21 (1,42) mg/dL from baseline; the change in total cholesterol:HDL was 0.1 (-0.5,0.6). Median (IQR) weight change from baseline was+6.1kg (2.0, 11.7) at Week 240. In Study 1489, hip and spine bone mineral density mean percent changes from baseline were ≤0.6%. Through 5 years of follow-up, B/F/TAF maintained high rates of virologic suppression with no treatment-emergent resistance and rare drug discontinuations due to adverse events. These results demonstrate the durability and safety of B/F/TAF in people with HIV. Gilead Sciences.

1267. Efficacy and Safety of Switching to DTG/3TC in Virologically Suppressed PLWH by Age, Including Those Aged ≥65 Years: Pooled Results from the TANGO and SALSA Studies

Abstract Background The proportion of older adults living with HIV is growing, increasing the focus of managing age-related comorbidities and polypharmacy while maintaining virologic suppression. DTG/3TC is an international guidelines–recommended 2-drug regimen demonstrating high and durable efficacy, high barrier to resistance, and good safety and tolerability. We present pooled TANGO and SALSA efficacy and safety results analyzed by age (&amp;lt; 50, ≥ 50 to &amp;lt; 65, and ≥ 65 years). Methods Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily DTG/3TC fixed-dose combination or continuing current antiretroviral regimen (CAR; TANGO: TAF-based; SALSA: NNRTI-/bPI-/INSTI-based) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and &amp;lt; 50 c/mL (Snapshot, ITT-E) and safety were analyzed by age. Results Of 1234 participants (DTG/3TC, n=615; CAR, n=619), 71% were aged &amp;lt; 50 years, 26% aged 50 to &amp;lt; 65 years, and 3% aged ≥ 65 years. At Week 48, in participants aged 50 to &amp;lt; 65 years, 1 (&amp;lt; 1%) and 3 (2%) participants in the DTG/3TC and CAR groups, respectively, had HIV-1 RNA ≥ 50 c/mL, comparable to results in the overall population (Table 1). No participants aged ≥65 years had HIV-1 RNA ≥ 50 c/mL. Proportions with HIV-1 RNA &amp;lt; 50 c/mL were high regardless of age group. Adjusted mean change from baseline in CD4+ cell count and CD4+/CD8+ ratio was also consistent with overall results regardless of age (&amp;lt; 50 vs ≥ 50 years). No participants in the DTG/3TC group had confirmed virologic withdrawal (CVW); 1 participant in the CAR group had CVW (aged &amp;lt; 50 years; no resistance detected). Proportions of participants with baseline non-ART medication use and comorbidities increased with age in both treatment groups (Table 2). Across all age groups, proportions of any AEs were similar between the DTG/3TC and CAR groups, with few AEs leading to withdrawal and higher proportions of drug-related AEs with DTG/3TC vs CAR; similar results were observed in the overall population. Conclusion Among PLWH, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile across all age groups, including those aged ≥65 years. As non-ART medication use and comorbidities increased with age, a well-tolerated 2-drug regimen may help older PLWH avoid drug interactions. Disclosures Manyu Prakash, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Richard Grove, MSc, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Brian R. Wynne, M.D., ViiV Healthcare: I am an employee|ViiV Healthcare: Stocks/Bonds Choy Man, BSc, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Jean A. van Wyk, MBChB, MFPM, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Clifford B. Jones, BSc MSc MB ChB, GSK: Stocks/Bonds|viiv healthcare: Employee Chinyere Okoli, MSc, DIP, ViiV Healthcare: I am an employee of ViiV healthcare|ViiV Healthcare: Stocks/Bonds Emilio Letang, MD, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Mounir Ait-Khaled, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Andrew Clark, MD, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds.

Real-life experience with bictegravir/emtricitabine/tenofovir alafenamide in a large reference clinical centre.

The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is mainly based on robust, pivotal clinical trials. To provide data on clinical use of BIC/FTC/TAF in real life. This was an observational, retrospective and single-centre study. We included all adult, treatment-naive (TN) and treatment-experienced (TE) people living with HIV (PLWH) starting BIC/FTC/TAF from 8 June 2018. We evaluated effectiveness [on treatment (OT), modified intention-to-treat (mITT) and intention-to-treat (ITT)], tolerability and safety in those patients who reached 6 months of follow-up (M6). We included 1584 PLWH [213 TN (13%) and 1371 TE (87%)]. The median (IQR) follow-up was 16 (7-21) months, with 81% and 53% of PLWH reaching M6 and M12, respectively. By OT, mITT and ITT, HIV-RNA <50 copies/mL was 77%, 70% and 62% at M6 and 92%, 77% and 63% at M12 for TN PLWH and 94%, 89% and 83% at M6 and 93%, 85% and 78% at M12 for TE PLWH, respectively. In PLWH carrying an M184V/I substitution, OT RNA <50 copies/mL was 89.5% at M6. The median CD4 cell count increased from 329 to 511/μL in TN PLWH and from 630 to 683/μL in TE PLWH at M6. Of the total, 1148 (88%) PLWH continued on BIC/FTC/TAF at M6. The most frequent known reason for discontinuation was toxicity [42 (69%) cases]; only 7 cases were considered virological failures (0.6% of the total OT cohort at M6), with no emerging resistance substitutions. In real life, BIC/FTC/TAF showed high rates of virological suppression and also in PLWH carrying lamivudine/emtricitabine resistance substitutions. The tolerability and safety of BIC/FTC/TAF were good, with high persistence observed for patients on this regimen at M6.

Lenacapavir: a first-in-class HIV-1 capsid inhibitor.

This review summarizes available data for lenacapavir, an investigational first-in-class agent that disrupts functioning of HIV capsid protein across multiple steps in the viral life cycle. Lenacapavir demonstrated picomolar potency in vitro with no cross resistance to existing antiretroviral classes and potent antiviral activity in persons with HIV-1. In persons with HIV-1, there was no preexisting resistance to lenacapavir regardless of treatment history. Lenacapavir can be administered orally either daily or weekly and subcutaneously up to every 6 months. In heavily treatment-experienced persons with multidrug-resistant HIV-1 and in treatment-naive persons with HIV-1, lenacapavir in combination with other antiretroviral agents led to high rates of virologic suppression and was well tolerated. Ongoing studies are evaluating long-acting dosing of lenacapavir for treating HIV-1 in combination with other antiretrovirals and preventing HIV-1 as a single agent.

75. High Rates of Virologic Suppression with DTG/3TC in Newly Diagnosed Adults with HIV-1 Infection and Baseline Viral Load &amp;gt;500,000 c/mL: 48-Week Subgroup Analysis of the STAT Study

BackgroundThe primary analysis of the STAT study demonstrated the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting through 24 weeks, with therapy adjustments for baseline resistance or hepatitis B virus (HBV) co-infection. Here we present secondary analyses through Week 48 of virologic outcomes in participants by baseline viral load (VL). MethodsSTAT is a single-arm study of treatment-naive adults with HIV-1 infection who initiated DTG/3TC ≤ 14 days after HIV-1 diagnosis without availability of screening/baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance < 30 mL/min/1.73 m2, then antiretroviral therapy (ART) was potentially adjusted and participants remained on study. Efficacy analyses included proportion of participants with HIV-1 RNA < 50 c/mL regardless of ART regimen at Week 48, among all participants (ITT-E missing = failure analysis) and among participants with available HIV-1 RNA data at Week 48 (observed analysis). ResultsOf 131 enrolled, DTG/3TC treatment was adjusted in 10 participants, and of those with available data (n=7), all (100%) achieved HIV-1 RNA < 50 c/mL at Week 48. At Week 48, 82% (107/131) of all participants (Figure 1) and 97% (107/110) of those with available data (Figure 2) achieved HIV-1 RNA < 50 c/mL. Of participants with baseline VL ≥ 500,000 c/mL, 89% (17/19) achieved HIV-1 RNA < 50 c/mL at Week 48; the remaining 2 withdrew from study. Of participants with baseline VL ≥ 1,000,000 c/mL, 90% (9/10) achieved HIV-1 RNA < 50 c/mL at Week 48 (Table); the remaining participant withdrew consent. Of the 17 participants with baseline VL ≥ 500,000 c/mL with available data through Week 48, 76% (13/17) achieved virologic suppression by Week 24. One participant with baseline VL ≥ 500,000 c/mL switched from DTG/3TC before the Week 48 assessment. Of the 9 participants with baseline VL ≥ 1,000,000 c/mL with available data through Week 48, most participants (8/9; 89%) were suppressed by Week 24.Figure 1. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: ITT-E missing = failure analysis. Figure 2. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: observed analysis. Table. Viral Load by Study Visit Among Participants with Baseline HIV-1 RNA ≥1,000,000 c/mL ConclusionThese data provide evidence for the efficacy and feasibility of using DTG/3TC as a first-line regimen in a test-and-treat setting, including among participants with very high baseline VL.Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Scientific Research Study Investigator, Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Tulika Singh, MD MS AAHIVS, Gilead (Grant/Research Support, Advisor or Review Panel member)ViiV (Grant/Research Support, Advisor or Review Panel member, Speaker's Bureau) Moti Ramgopal, MD FIDSA, Abbvie (Scientific Research Study Investigator, Speaker's Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker's Bureau) Dushyantha Jayaweera, MD, mrcog(uk), face, Gilead (Research Grant or Support)Janssen (Research Grant or Support)viiv (Research Grant or Support) Peter Leone, MD, viiv healthcare (Employee) Jessica Matthews, BS, ViiV Healthcare (Employee) Michael Cupo, Ph.D., GlaxoSmithKline (Employee) Mark Underwood, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kostas Angelis, PhD, GSK (Employee, Shareholder) Brian Wynne, MD, ViiV Healthcare (Employee, Shareholder, I have shares in GSK, the part owner of ViiV) Deanna Merrill, PharmD, MBA, AAHIVP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christopher T. Nguyen, MD, ViiV Healthcare (Employee) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Andrew Zolopa, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

HIV Treatment with the Two-Drug Regimen Dolutegravir Plus Lamivudine in Real-world Clinical Practice: A Systematic Literature Review.

The two-drug regimen dolutegravir plus lamivudine demonstrated durable efficacy for up to 3 years in phase III studies and a high barrier to resistance in treatment-naive and virologically suppressed people with HIV (PWH). This systematic literature review summarizes real-world evidence evaluating effectiveness and safety of dolutegravir plus lamivudine. We searched Ovid MEDLINE®, Embase®, PubMed, Cochrane library, and relevant international conference proceedings from 2013 to 2020. Qualitative synthesis of virologic suppression at Week 48, treatment-emergent resistance, discontinuation rates, and comorbidities was undertaken, with no statistical analyses conducted. Linked publications and potential for duplication in reporting of outcomes for cohorts and populations were identified, and the publication reporting the highest number of PWH receiving dolutegravir plus lamivudine was included in the analysis. Thirty-four studies reporting on cohorts of PWH not suspected to be linked or to include duplicate data receiving dolutegravir plus lamivudine were identified (N = 5017). Of 3744 virologically suppressed PWH who switched to dolutegravir plus lamivudine, 603 (16%) reported history of virologic failure. Nineteen studies included effectiveness data (n = 3558), four of which included data from treatment-naive PWH (n = 69). In studies with > 100 PWH, high rates of virologic suppression (Week 48, 97–100%) were maintained with dolutegravir plus lamivudine, with low rates of virologic failure (0–3.3 per 100 person-years of follow-up); one instance of emergent integrase strand transfer inhibitor resistance was reported in a complex treatment-experienced individual. Rates of discontinuation due to adverse events were low and consistent with previously observed trial data. Dolutegravir plus lamivudine minimally impacted renal function and had minimal impact on or improved lipid profiles and bone mineral density. This systematic review demonstrates that effectiveness and safety of dolutegravir plus lamivudine in clinical practice support data from randomized controlled trials with regard to high rates of virologic response, low rates of discontinuation, and a high barrier to resistance.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00522-7.

Clinical characteristics and outcomes of COVID-19 in people living with HIV in Belgium: A multicenter, retrospective cohort.

The aim of this study was to describe the clinical characteristics and outcomes of coronavirus disease 2019 (COVID‐19) among people living with HIV (PLWH) in Belgium. We performed a retrospective multicenter cohort analysis of PLWH with either laboratory‐confirmed, radiologically diagnosed, or clinically suspected COVID‐19 between February 15, 2020 and May 31, 2020. The primary endpoint was outcome of COVID‐19. Secondary endpoints included rate of hospitalization and length of hospital stay and rate of Intensive Care Unit (ICU) admission and mechanical ventilation. One hundred and one patients were included in this study. Patients were categorized as having either laboratory‐confirmed (n = 65), radiologically‐diagnosed (n = 3), or clinically suspected COVID‐19 (n = 33). The median age was 51.3 years (interquartile range [IQR] 41.3–57.3) and 44% were female. Ninety‐four percent of patients were virologically suppressed and 67% had a CD4+ cell count more than or equal to 500 cells/µl. Overall, 46% of patients required hospitalization and the median length of hospital stay was 6 days (IQR 3–15). Age more than or equal to 50 years, Black Sub‐Saharan African patients, and being on an integrase strand transfer inhibitor‐based regimen were associated with being hospitalized. ICU admission and mechanical ventilation was required for 15% and 10% of all patients respectively. Overall, 9% of patients died while 78 (77%) patients made a full recovery. HIV patients with COVID‐19 experienced a high degree of hospitalization despite having elevated CD4+ cell counts and a high rate of virologic suppression. Matched case‐control studies are warranted to measure the impact that HIV may have on patients with COVID‐19.

1028. Long-term Follow-up After a Switch to Bictegravir, Emtracitabine, Tenofovir Alafenamide from Dolutegravir, Abacavir, Lamivudine

BackgroundBictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) is a guidelines-recommended single-tablet regimen (STR) for people living with HIV-1 (PLWH). Week (W) 48 primary endpoint results of this phase 3 study switching to B/F/TAF from dolutegravir (DTG), abacavir (ABC) and lamivudine (3TC) established the safety and efficacy of B/F/TAF. Here we report outcomes from an open-label (OL) extension of B/F/TAF.MethodsAdults virologically suppressed on DTG, ABC, and 3TC were randomized 1:1 to switch to B/F/TAF once daily or continue their current regimen as a STR in a double blind (DB) manner. Unblinding occurred after the W48 primary endpoint, then participants received B/F/TAF in an OL extension while transitioning off the study. All participants who received B/F/TAF in the DB or OL phases are included in analyses. Efficacy was assessed as the proportion with HIV-1 RNA < 50 copies/mL at each study visit using missing=excluded (M=E) analysis, efficacy in in subgroups with pre-existing resistance was assessed using last observation carried forward. Safety was assessed by adverse events (AEs) and laboratory results.Results563 participants were randomized and treated (282 B/F/TAF, 281 ABC/DTG/3TC); 524 (93%) completed the DB phase and received OL B/F/TAF; a total of 547 participants received B/F/TAF in DB and/or OL phases: 11% women, 21% Black, median age 47 yrs (range 21, 71). The median duration of B/F/TAF was 96 weeks (IQR 49-119). HIV-1 RNA < 50 c/mL was maintained in 99-100% at all timepoints (M=E) through a maximum of 168 weeks, including high efficacy in those with archived resistance (Table 1). No participant developed resistance to B/F/TAF. Study drug-related AEs occurred in 7% on B/F/TAF; most were grade 1; the most common was headache (1.6%). 7 (1%) participants had an AE leading to premature study drug discontinuation, only 1, headache, occurred in the OL phase. Estimated GFR and lipids were mostly stable with slightly increased LDL at W96; weight changes are noted at W48 and W96. (Table 2).Table 1. Table 2. ConclusionExtended follow-up to the study of switching to B/F/TAF from DTG/ABC/3TC, demonstrates continued high rates of virologic suppression with no resistance and excellent safety and tolerability of B/F/TAF through a maximum of 168 weeks for treatment of PLWH.Disclosures Indira Brar, MD, Gilead (Speaker’s Bureau)janssen (Speaker’s Bureau)ViiV (Speaker’s Bureau) Peter Ruane, MD, AbbVie (Consultant, Grant/Research Support, Speaker’s Bureau)Bristol-Myers Squibb (Grant/Research Support)Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Shareholder, Speaker’s Bureau)Idenix (Consultant)Janssen (Grant/Research Support, Speaker’s Bureau)Viiv Healthcare (Grant/Research Support) Douglas Ward, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau)Merck (Advisor or Review Panel member)Viiv Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Jean-michel Molina, MD, PhD, Bristol-Myers Squibb (Advisor or Review Panel member)Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Janssen (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Teva (Advisor or Review Panel member)Viiv Healthcare (Advisor or Review Panel member) Anthony Mills, MD, Gilead (Grant/Research Support, Advisor or Review Panel member)Janssen Pharmaceutica (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Shionogi (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Advisor or Review Panel member) Mezgebe Berhe, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator) Cynthia Brinson, MD, Gilead (Advisor or Review Panel member, Speaker’s Bureau)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Moti Rampogal, MD, Gilead Sciences (Consultant, Research Grant or Support, Speaker’s Bureau)Janssen (Consultant, Research Grant or Support, Speaker’s Bureau)Merck (Consultant, Research Grant or Support)ViiV Healthcare (Consultant, Research Grant or Support, Speaker’s Bureau) Keith Henry, MD, Gilead (Research Grant or Support, Paid to institution)GSK/ViiV (Research Grant or Support, Paid to institution)Janssen (Research Grant or Support, Paid to institution)Merck (Research Grant or Support, Paid to institution) Hailin Huang, PhD, Gilead Sciences Inc. (Employee, Shareholder) Kristen Andreatta, MSc, Gilead Sciences (Employee, Shareholder) Hal Martin, MD, MPH, Gilead Sciences Inc. (Employee, Shareholder)

109. Preexisting Resistance and Week 48 Virologic Outcomes After Switching to B/F/TAF in African American Adults with HIV

BackgroundThe BRAAVE 2020 study is evaluating the safety and efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) among virologically suppressed Black adults with HIV. At Week (W) 24, 0.6% (2/328) on B/F/TAF vs 1.8% (3/165) who stayed on their baseline 3 drug regimen (SBR) had HIV-1 RNA ≥ 50 c/mL demonstrating noninferiority of B/F/TAF. Here, resistance analyses and virologic outcomes at W48 are described.MethodsEnrollment criteria permitted prior treatment failure, except on an INSTI-containing regimen, and allowed documented resistance to NNRTIs, PIs and/or NRTIs, except for K65R/E/N, ≥ 3 thymidine analog mutations (TAMs), or T69-insertions; primary INSTI resistance (-R) was excluded. Preexisting drug resistance was assessed with historical genotypes and proviral DNA genotyping. B/F/TAF outcomes were determined by last on-treatment HIV-1 RNA through W48.ResultsAltogether, 495 participants enrolled (B/F/TAF n=330, SBR n=165). Preexisting primary NRTI-R, NNRTI-R, and PI-R substitutions were observed in 14% (70/495), 21% (102/495), and 13% (62/495), respectively. M184V/I and TAMs were detected in 10% (51/495) and 7% (34/495), respectively. Primary INSTI-R was detected post-randomization in 2% (11/495); all continued on study and were included in efficacy analyses. At W24, 163 in the SBR group switched to B/F/TAF (SBR to B/F/TAF). W48 outcomes were determined for 489 participants who had ≥ 1 post-switch HIV-1 RNA measurement: 99% (324/327) in the B/F/TAF and 100% (162/162) in the SBR to B/F/TAF groups had HIV-1 RNA < 50 copies/mL at their last study visit, including 100% (68/68) with NRTI-R (50 of whom had archived M184V/I and post-switch data), and 100% (11/11) with INSTI-R (Table). No participant had treatment emergent resistance to study drugs.Table. BRAAVE 2020 Preexisting Resistance and Virologic Suppression at Week 48 (Last On-treatment Observation Carried Forward Analysis) ConclusionPreexisting resistance was common among virologically suppressed Black adults in BRAAVE 2020, notably M184V/I, TAMs, and NNRTI-R. High rates of virologic suppression were maintained through 48 weeks of B/F/TAF treatment and there were no failures with de novo resistance, indicating that B/F/TAF is an effective treatment option for virologically suppressed people with HIV with or without preexisting resistance to NNRTIs, PIs, or non-tenofovir NRTIs.DisclosuresKristen Andreatta, MSc, Gilead Sciences (Employee, Shareholder) Michelle L. D’Antoni, PhD, Gilead Sciences (Employee, Shareholder) Silvia Chang, Masters, Gilead Sciences (Employee, Shareholder) Aiyappa Parvangada, MS Computational Biology, Gilead Sciences (Employee) Christiana Blair, MS, Gilead Sciences (Employee, Shareholder) Sean E. Collins, MD, MS, Gilead Sciences (Employee) Kirsten L. White, PhD, Gilead Sciences, Inc. (Employee, Shareholder)

Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation.

Background:The ability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) to maintain virologic suppression in participants with M184V and/or M184I resistance mutations from historical genotypic reports when switching from a tenofovir disoproxil fumarate–based or abacavir (ABC)-based regimen was investigated.Setting:Phase IIIb, 48-week, open-label, single-arm, multicenter, clinical trial (NCT02616029).Methods:Virologically suppressed adults with HIV and documented M184V/I on historical genotypic records switched to E/C/F/TAF from a tenofovir disoproxil fumarate–based or ABC-based regimen. The primary end point was HIV-1 RNA of <50 copies per milliliter at week 12 using pure virologic response (PVR). Secondary end points included HIV-1 RNA of <50 copies per milliliter at weeks 24/48 (PVR) and at weeks 12, 24, and 48 (Food and Drug Administration snapshot algorithm), and change in CD4+ count at weeks 12, 24, and 48.Results:M184V alone was reported in 82.8% of 64 participants; 9.4% and 7.8% had M184I and M184V/I, respectively, and 43.8% had archived M184V/I (baseline DNA). All (62/62 with available data, 100%, 95% confidence interval 94.2% to 100%) participants maintained PVR at weeks 12, 24, and 48. By Food and Drug Administration snapshot algorithm, one participant had HIV-1 RNA of ≥50 copies per milliliter (week 12); confirmatory HIV-1 RNA was <50 copies per milliliter. No significant changes were observed in CD4+ cell count. Drug-related adverse events (AEs) were reported by 10 (15.6%) participants. Six (9.4%) and 5 (7.8%) participants had grade 3–4 AEs or serious AEs, respectively (none drug related).Conclusions:The presence of the resistance mutations M184V/I did not jeopardize the efficacy of switching to E/C/F/TAF in virologically suppressed adults. High rates of virologic suppression were maintained throughout 48 weeks of therapy and treatment was well tolerated.

Zimbabwe's national third-line antiretroviral therapy program: Cohort description and treatment outcomes.

BackgroundIn 2015, Zimbabwe introduced third-line antiretroviral therapy (ART) through four designated treatment centers; three government clinics in Harare and Bulawayo, and Newlands Clinic (NC), operated by a private voluntary organization in Harare. We describe characteristics of patients receiving third line ART and analyzed treatment outcomes in this national programme as of 31 December 2018.MethodsWe described the population using proportions for categorical variables, and medians and interquartile ranges for continuous variables. Patients from NC, where data were more complete, were followed from the date of starting third-line ART until death, transfer, loss to follow up or 31 December 2018.ResultsA total of 209 patients had ever received third-line ART: 124 at NC and 85 from the three government clinics. HIV genotype results were available for 89 (72%) patients at NC and fourteen (16.5%) patients in the government clinics. Median duration of third line ART (years) in the government clinics was 2.3 (IQR:0.6–3.4), 1.3 (IQR: 0.7–1.7) and 1 (0.6–1.9). Of the 67 patients who received third line ART in the government clinics for at least six months, 53 (79%) had most recent viral load (VL) < 1000 copies/ml. Data on other treatment outcomes from government clinics were incomplete.From NC: a total of 109 (88%) patients were still in care, 13 (10.5%) had died and 2 (1.5%) were transferred. Median duration of third-line ART was 1.4 years (IQR: 0.6–2.8). Among the 111 NC patients who had received third-line ART for at least 6 months, 83 (75%) had a VL <50 copies/ml and 106 (95.5%) had a VL <1000 copies/ml.ConclusionOur findings demonstrate that, with comprehensive care, patients failing second-line ART can achieve high rates of virological suppression on third-line regimens. There is need to decentralize the provision of third-line ART in Zimbabwe. More needs to be done to improve completeness of data in the government clinics.

887. High Rates of Virologic Suppression Achieved in HIV-1–Infected Adults Rapidly Starting Antiretroviral Therapy (ART) with the Single-Tablet Regimen (STR) of Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (D/C/F/TAF) 800/150/200/10 mg Regardless of Baseline Disease Characteristics: Week 48 Subgroup Analyses From the Phase 3 DIAMOND Trial

BackgroundRapid initiation of ART requires that clinicians start therapy prior to having baseline laboratory Results. High rates of virologic suppression and retention were reported in the DIAMOND trial. Efficacy and safety are presented, according to baseline disease characteristics.MethodsDIAMOND (ClinicalTrials.gov: NCT03227861), a phase 3, single-arm, open-label, prospective, multicenter study, assessed efficacy/safety of D/C/F/TAF in rapid initiation. Adults enrolled within 14 days of diagnosis and started D/C/F/TAF without baseline laboratory results; investigators reviewed results as they became available. Primary endpoint was virologic suppression (HIV-1 RNA < 50 copies[c]/mL; intent-to-treat (ITT); Food and Drug Administration [FDA] snapshot) at Week 48. Virologic suppression <50 c/mL and <200 c/mL were also assessed via an observed analysis, excluding patients with missing data.ResultsOverall, 109 patients were enrolled; 25% had HIV-1 RNA ≥100,000 c/mL and 21% had CD4+ < 200 cells/μL (Table 1). 21% of patients started therapy within 24 hours of diagnosis. At Week 48, 84%, and 88% of patients had HIV-1 RNA <50 c/mL and <200 c/mL (FDA snapshot), respectively. In the observed analysis, 96% and 100% of patients had HIV-1 RNA <50 c/mL and <200 c/mL, respectively, at Week 48. Earlier ART initiation, HIV-1 RNA <100,000 c/mL, and CD4+ >200 cells/μLwere associated with numerically higher virologic suppression rates (ITT-FDA snapshot; Table 2). No patient discontinued due to lack of efficacy or met protocol-defined virologic failure (PDVF) criteria. In the observed analysis, virologic suppression rates were consistent across all subgroups; all patients were suppressed <200 c/mL at Week 48. One patient discontinued due to an adverse event (AE); incidences of grade 3/4 (10%) and serious (9%) AEs were low, with no serious AEs related to study drug and no deaths.ConclusionIn the first phase 3 study of an STR in a rapid initiation model, no patients rapidly starting D/C/F/TAF discontinued therapy due to lack of efficacy or had PDVF through 48 weeks. High rates of virologic suppression were achieved and maintained with a variety of baseline characteristics, and treatment was safe and well tolerated, indicating D/C/F/TAF as a preferred ART option for patients rapidly starting treatment. Disclosures All Authors: No reported Disclosures.

2484. Patient Reported Outcomes After Switching to a 2-Drug Regimen of Dolutegravir + Rilpivirine: Week 148 Results from the Sword-1 and Sword-2 Studies

BackgroundThe SWORD-1 and SWORD-2 studies previously demonstrated that high rates of virologic suppression were maintained for 148 weeks after switching virologically suppressed HIV-1 infected adults from their current 3- or 4-drug antiretroviral regimen (CAR) to the 2-drug regimen (2DR) of dolutegravir + rilpivirine on Day 1 (Early Switch (ES) DTG+RPV group). This abstract reports the pooled SWORD-1/2 results of patient reported outcomes (PRO) measures through Week 148.MethodsHIV Treatment Satisfaction Questionnaire (HIVTSQ) and Symptom Distress Module (SDM) were secondary PRO endpoints in the SWORD trials. For HIVTSQ, high scores represent greater treatment satisfaction (range 0 to 60). SDM was assessed using the Symptom Bother Score with low values indicating less symptom bother (range 0 to 80). The EQ-5D-5L measure of general health status was assessed as an exploratory endpoint with maximum utility score of 1 to indicate perfect health. Change from Baseline in these endpoints was calculated for the ES subjects (over 148 weeks). Subjects randomized to CAR switched to DTG+RPV at Week 52 (Late Switch (LS) DTG+RPV group) and change from LS Baseline (i.e., last pre-switch assessment) was calculated (over 96 weeks).ResultsLow Symptom Bother (9.6 and 10.3) and high TSQ scores (54.4 and 54.3) were reported pre-switch in the ES and LS groups, respectively.ES subjects reported modest improvements from Baseline in both symptom burden and overall treatment satisfaction in all visits through Week 148 (Figures 1 and 2). Among the LS group, there was little change in symptom burden but similar improvement in treatment satisfaction. Pre-switch health status was high in ES and LS groups (EQ-5D mean utility: 0.96 and 0.94, respectively) and remained stable in both groups at all time points.ConclusionHigh treatment satisfaction and low symptom burden that were observed in patients under CAR were maintained long term after switching to DTG+RPV. These results corroborate DTG+RPV as a well-tolerated 2DR alternative treatment option in patients currently suppressed on other 3/4-drug regimens without previous virologic failure. Disclosures All authors: No reported disclosures.

Resistance Analysis of Bictegravir-Emtricitabine-Tenofovir Alafenamide in HIV-1 Treatment-Naive Patients through 48 Weeks.

In clinical studies GS-US-380-1489 (study 1489) and GS-US-380-1490 (study 1490), bictegravir-emtricitabine-tenofovir alafenamide (B-F-TAF), dolutegravir-abacavir-lamivudine (DTG-ABC-3TC), and dolutegravir plus emtricitabine-tenofovir alafenamide (DTG+F-TAF) treatment achieved high rates of virologic suppression in HIV-1 treatment-naive participants through week 48. Preexisting primary drug resistance was present at levels of 1.3% integrase strand transfer inhibitor resistance (INSTI-R), 2.7% nucleoside reverse transcriptase inhibitor resistance (NRTI-R), 14.1% nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R), and 3.5% protease inhibitor resistance (PI-R) in the 1,274 participants from these studies. These mutations did not affect treatment outcomes. Resistance analyses in 13 virologic failures found no emergent resistance to study drugs.