BACKGROUND:The combination of doravirine and islatravir is under investigation as a fixed-dose, single-tablet regimen for the treatment of HIV-1. We aimed to assess the efficacy and safety of switching to doravirine (100 mg) and islatravir (0·25 mg) from bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV-1. METHODS:This phase 3, randomised, controlled, double-blind, non-inferiority trial was conducted at 49 research, community, and hospital-based clinics in six countries: Australia, Chile, Israel, Japan, the UK, and the USA. Adults aged 18 years or older with HIV-1, who were virologically suppressed (with a viral load of HIV-1 RNA <50 copies per mL) for at least 3 consecutive months on bictegravir, emtricitabine, and tenofovir alafenamide and had no history of treatment failure or known resistance to doravirine, were eligible for the study. Participants were randomly assigned, in a 2:1 ratio according to a computer-generated randomisation schedule with a block size of three, to switch to oral doravirine (100 mg) and islatravir (0·25 mg) or to continue bictegravir, emtricitabine, and tenofovir alafenamide, once daily. Participants, investigators, study staff, and sponsor personnel were masked to study treatment; sponsor personnel directly involved in this analysis were unmasked at week 48. The primary endpoint, which was assessed in all randomly assigned participants who received at least one dose of study treatment, was the percentage of participants with a viral load of 50 copies per mL or higher at week 48 according to the US Food and Drug Administration snapshot approach; non-inferiority would be concluded if the upper bound of the multiplicity-adjusted 95% CI for the treatment difference was less than 4%. The trial is registered at ClinicalTrials.gov, NCT05630755, and is ongoing but closed to enrolment. FINDINGS:Between Feb 17 and Nov 17, 2023, 585 individuals were screened, of whom 514 were randomly assigned and 513 treated: 342 participants were switched to doravirine (100 mg) and islatravir (0·25 mg) and 171 continued bictegravir, emtricitabine, and tenofovir alafenamide. The median age of the 513 participants was 47 years (IQR 37-58), 403 (79%) were assigned male and 110 (21%) were assigned female at birth, 158 (31%) were Black or African American, and 117 (23%) were Hispanic, Latino, or Latina. At week 48, doravirine and islatravir showed non-inferiority to bictegravir, emtricitabine, and tenofovir alafenamide (viral load ≥50 copies per mL in five [1·5%] of 342 vs one [0·6%] of 171 participants) with a treatment difference of 0·9% (multiplicity-adjusted 95% CI -1·9 to 2·9). The rates of adverse events (74·6% [255 of 342 participants] vs 71·3% [122 of 171 participants]; difference 3·2 [95% CI -4·7 to 11·6]), treatment-related adverse events (10·2% [35] vs 9·4% [16]; 0·9 [-5·1 to 6·0]), serious adverse events (4·4% [15] vs 6·4% [11]; -2·0 [-7·1 to 1·9]), and discontinuations due to adverse events (2·9% [ten] vs 1·8% [three]; 1·2 [-2·3 to 3·9]) were similar in the doravirine and islatravir group and the bictegravir, emtricitabine, and tenofovir alafenamide group, and no deaths were reported. INTERPRETATION:The combination of doravirine (100 mg) and islatravir (0·25 mg) has similar efficacy and safety profiles to bictegravir, emtricitabine, and tenofovir alafenamide, and could provide a two-drug, once daily, oral single-tablet option without an integrase strand-transfer inhibitor for adults who are virologically suppressed and want to switch to a different ART regimen. FUNDING:Merck Sharp & Dohme, a subsidiary of Merck & Co.

Fostemsavir (FTR) is a pre-attachment inhibitor that binds directly to viral gp120 preventing HIV interaction with the host immune cell. This unique mechanism may drive the robust CD4+ T-cell recovery seen in the BRIGHTE study. Here, we evaluate changes in immunologic parameters following addition of FTR to antiretroviral (ARV) regimens among virally suppressed immune non-responders (INRs) through 48 weeks. RECOVER (NCT05220358) is an ongoing, open-label clinical trial that enrolled adult INRs defined as those with HIV-1 RNA<50 copies/mL and CD4+ T-cell count< 350 cells/mm3 while on suppressive ARVs for ≥2 years. Participants added FTR to their baseline ARV regimen and were followed for 48 weeks. Co-primary endpoints are mean and median change in CD4+ T-cell count at Week 48 using pre-FTR mean and median CD4+ T-cell counts 96 weeks prior to study entry as controls. 48-week data from the first 23 participants are included in this interim analysis. 22% enrolled were women, 74% were aged≥50 years and 65% were non-white. At baseline, mean duration of HIV infection, ARV therapy and viral suppression were 24.5, 24.7, and 18.4 years respectively. Baseline mean and median CD4+ T-cell counts were 248 cells/mm3 and 252 cells/mm3. At Week 48, mean and median CD4+ T-cell count significantly increased by 40 cells/mm3 and 32 cells/mm3 compared to pre-FTR controls (p=0.021 for mean and 0.024 for median). This was accompanied by an increase in mean and median CD4+ percentage of 0.5% and 0.9% compared to pre-FTR controls (p=0.372 for mean and 0.176 for median). Mean change from baseline in CD4/CD8 ratio was +0.02 (p=0.12). At Week 48, the proportion with CD4+ T-cell count≥350 cells/mm3 was 24%. Through Week 48, 2 participants had confirmed HIV-1 RNA≥50 copies/mL, however resuppressed on FTR plus the baseline ARV regimen. Drug-related adverse events (AEs) occurred in 17% and led to discontinuation in 4%. There were no drug-related serious AEs. Data from this interim analysis demonstrates significant increases in CD4+ T-cell parameters after the addition of FTR among virally suppressed INRs through Week 48. Further studies in larger samples are needed to confirm these findings and understand the biological mechanisms which may mediate these effects. Charlotte-Paige M. Rolle, MD, MPH, Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|MSD: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support|ViiV Healthcare: Honoraria Federico Hinestrosa, MD, Gilead Sciences: Honoraria|MSD: Honoraria

BACKGROUND:Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 (HIV) exposure. METHODS:IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After ∼9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label comparator for 20 months. RESULTS:In total, 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). Overall, 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had ≥1 adverse event (AE). Most AEs were mild or moderate, with 1 AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV infections occurred in either group during the double-blind phase. CONCLUSIONS:Islatravir qm was generally well tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

Objectives We evaluated Mycoplasma genitalium (MG) positivity and co-infection with Chlamydia trachomatis (CT) and/or Neisseria gonorrhoeae (NG), based on results from a trial assessing clinical performance of the Cobas® Liat CT/NG/MG point-of-care test. Methods A prospective, US, multicenter, noninterventional study assessed MG positivity in prospective urine samples (male) and clinician-collected vaginal swabs (female) from symptomatic/asymptomatic patients aged ≥14 years attending various clinical settings. Participants were designated positive or negative for MG, CT, and NG based on combined results from three US Food and Drug Administration-approved assays and one laboratory-developed test. MG co-infection with CT and/or NG was assessed. Results Among 4818 evaluable participants, median age was 35.0 years (range: 15.0-81.0), 40.3% were symptomatic, and 51.6% were assigned female sex at birth. MG positivity was 9.6% overall (symptomatic participants: 11.6%; asymptomatic participants: 8.2%). Among 4811 participants with valid results for all analytes, 0.1% were positive for MG, CT, and NG, 1.0% were co-infected with MG/CT; and 0.3% were co-infected with MG/NG. Conclusions MG positivity was high and MG co-infection with CT was common. These findings improve understanding of MG prevalence and may help inform the targeting of MG screening to specific patient populations. Co-infection data support using multiplex testing to facilitate targeted treatment decisions.

BACKGROUND:Doravirine/islatravir is an investigational regimen that is being studied for human immunodeficiency virus type 1 (HIV-1) treatment. METHODS:In this phase 3, double-blind, double-dummy trial (ClinicalTrials.gov NCT04233879), previously untreated adults with HIV-1 were randomized (1:1) and stratified by HIV-1 RNA (≤/>100 000 copies/mL) and CD4 count (</≥200 cells/µL) to doravirine/islatravir (100/0.75 mg) or bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg) orally once-daily (primary endpoint: percentage of participants with HIV-1 RNA <50 copies/mL at week 48; US Food and Drug Administration snapshot, 10% noninferiority margin). RESULTS:Overall, 597 participants were treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. Doravirine/islatravir was noninferior to bictegravir/emtricitabine/tenofovir alafenamide: 265 of 298 (88.9%) versus 264 of 299 (88.3%) had HIV-1 RNA <50 copies/mL (difference, 0.5%; 95% confidence interval [CI]: -4.7, 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference, -50; 95% CI: -79, -21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 × 109/L (difference, -0.20; 95% CI: -0.30, -0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with coronavirus disease 2019 being most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs that led to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria that required discontinuation for decreased CD4 and lymphocyte counts. CONCLUSIONS:Doravirine/islatravir (100/0.75 mg) once-daily was noninferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment. Due to decreases in CD4 and lymphocyte counts, development of this dose of doravirine/islatravir was stopped. CLINICAL TRIALS REGISTRATION:NCT04233879.

Increased weight has been observed among treatment-naïve-and-experienced people living with HIV initiating bictegravir (BIC) and dolutegravir (DTG). Here, we report changes in weight and body mass index (BMI) following switch to a BIC versus DTG-based regimen (DBR) through 144 weeks. This observational study collected demographics, clinical characteristics, weight, and BMI from virologically suppressed adults switched to BIC/emtricitabine/tenofovir alafenamide (TAF), emtricitabine/TAF plus DTG, DTG/abacavir/lamivudine, DTG/rilpivirine (RPV), and DTG/lamivudine 2 years prior to switch through 144 weeks post-switch. Linear spline models were fit to estimate and compare the trajectories of weight and BMI changes observed pre-and-post-switch. Adjusted piecewise linear mixed-effects models were fit to examine factors associated with weight and BMI change pre-and-post-switch. At week 144, switching to BIC/emtricitabine/TAF versus a DBR were both associated with lower annualized weight gain post-switch (-0.88 kg/year vs -0.39 kg/year respectively, P = .15). DTG plus emtricitabine/TAF switches had the highest annualized weight gain (0.68 kg/year, 95% confidence interval: -0.32, 1.65) whereas, DTG/RPV switches had the lowest annualized weight gain (-2.22 kg/year, 95% confidence interval: -3.69, -0.62) post-switch. DTG/RPV and BIC/emtricitabine/TAF switches were the only groups with significantly lower annualized weight gain post-switch at week 144. Baseline BMI < 18.5 kg/m2 was associated with the highest annualized weight gain post-switch, whereas switching from protease inhibitors and self-report of dieting were associated with the lowest annualized weight gain post-switch. At week 144, switching to a BIC versus DBR were both associated with lower annualized weight gain post-switch among a large and diverse cohort of treatment-experienced people living with HIV.

Abstract Background Screening for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) can be achieved rapidly (in approximately 20 minutes) with the cobas® CT/NG/MG test (assay not cleared by US FDA. Submission currently under review and subject to change per health authority feedback). This automated, qualitative, real-time PCR-based nucleic acid amplification test (NAAT) is for use on the cobas® liat® system. This study evaluated the test’s clinical performance using urogenital samples from symptomatic and asymptomatic patients. Methods This non-interventional, non-observational study used prospective clinician-collected and self-collected specimens (urine, and vaginal swabs, all in cobas® PCR Media) from symptomatic/asymptomatic patients ≥14 years old from 13 POC sites across the US. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of cobas liat CT/NG/MG were calculated with respect to patient infected status (PIS), as determined using results from three FDA-approved NAATs and one laboratory-developed test. Due to insufficient positive NG samples during the trial period, further testing used archived samples. Results The median (range) age of the study population (N=4,800) was 35.0 (15.0-81.0) years; 40.4% (n=1,941) were symptomatic and 51.9% (n=2,489) were assigned female at birth. The cobas CT/NG/MG nucleic acid test demonstrated good clinical performance (Table 1). Across all specimen types, specificity was >97% for each analyte. Sensitivity was ≥95%, except in female urine (CT 87.0%, NG 93.1%, MG 78.9%). Regardless of specimen type, PPV and NPV were ≥95% for CT and NG; PPV for MG was highest in male urine (92.7%) and NPV was >97.5% across analytes. Conclusions In a clinical setting, the cobas CT/NG/MG nucleic acid test showed good clinical performance for the detection of CT, NG, and MG in urogenital samples, in addition to providing a short turn-around time and centralized testing lab quality at the POC for both self- and clinician-collected samples.

Abstract Background In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) was noninferior compared to continuing a tenofovir alafenamide (TAF)-based regimen, however switching from bictegravir (BIC)/emtricitabine (F)/TAF was not evaluated. Here, we present efficacy and safety of switching to DTG/3TC compared with continuing B/F/TAF in virologically suppressed adults through 24 weeks. Methods DYAD (NCT04585737) is an ongoing, open-label clinical trial that randomized adults with HIV-1 RNA< 50 copies/mL and no prior virologic failure (2:1) to switch to once-daily fixed-dose DTG/3TC or remain on B/F/TAF. The primary endpoint is the proportion with HIV-1 RNA ≥ 50 c/mL at Week (W) 48 (FDA snapshot algorithm, ITT-E population). A planned W24 interim analysis assessed noninferiority with a 6% margin. Results Overall, 222 adults (16% women; 51% aged ≥50 years; 28% Black) were randomized. At W24, 3 (2%) participants on DTG/3TC and 3 (4%) on B/F/TAF had HIV-1 RNA ≥ 50 c/mL (adjusted treatment difference -2.1%, 95% confidence interval [-9.5%, 2.5%]) meeting noninferiority criteria. Through W24, 4 on DTG/3TC and 3 on B/F/TAF met confirmed virologic withdrawal (CVW) criteria and underwent resistance testing. 2/7 had treatment-emergent resistance. One B/F/TAF CVW developed M184M/I and G140G/S at W12; at study discontinuation (DC), HIV-1 RNA< 50 c/mL and the participant remained on B/F/TAF. One DTG/3TC CVW had no resistance on study genotype but underwent repeat genotypic testing outside the study (ordered by clinic provider) and had M184V at W12; at study DC, HIV-1 RNA< 50 c/mL on DTG/3TC and the participant was subsequently transitioned to DTG + darunavir/cobicistat (DRV/c). One non-CVW DTG/3TC participant developed M184V and K65R at W12 (genotype inadvertently collected at first episode of unconfirmed viremia); at study DC, HIV-1 RNA< 50 c/mL on DTG/3TC and the participant was subsequently transitioned to DTG+DRV/c. Drug-related adverse events (AEs) and withdrawals due to AEs occurred in 31 (21%) and 6 (4%) participants with DTG/3TC and 1 (1%) and 0 participants with B/F/TAF, respectively. Conclusion DYAD demonstrated noninferior efficacy of switching to DTG/3TC vs. continuing B/F/TAF at W24. Higher AE rates in the DTG/3TC arm are likely consistent with the open-label nature of this switch study. Disclosures Charlotte-Paige M. Rolle, MD, MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Federico Hinestrosa, MD, AbbVie: Honoraria|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|MSD: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Edwin DeJesus, MD, Gilead Sciences, Inc: Advisor/Consultant|Theratechnology: Advisor/Consultant|Theratechnology: Honoraria

Background Doravirine and islatravir is an investigational, once -daily, single -tablet regimen with high antiviral potency, favourable safety and tolerability, and low propensity for resistance. We report week 48 results from a phase 3 trial evaluating switch from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (075 mg). Methods This phase 3, multicentre, randomised, active -controlled, open -label, non -inferiority trial was conducted at 77 research, community, and hospital -based clinics in 15 countries. Adults aged 18 years or older with fewer than 50 HIV -1 RNA copies per mL on any oral, two -drug or three -drug ART regimen for at least 3 months, and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer -generated randomisation schedule to switch to doravirine (100 mg) and islatravir (075 mg) or to continue their baseline ART regimen. Block randomisation was based on a block size of four, and randomisation was stratified by baseline regimen (ie, protease inhibitor, integrase inhibitor, or other). Participants in the doravirine and islatravir group were instructed to take one tablet at approximately the same time each day, and participants in the baseline ART group continued to take the medication according to the locally approved label. HIV -1 RNA and safety evaluations were done at baseline and weeks 4, 12, 24, 36, and 48. CD4 cell counts were measured at baseline, week 24, and week 48. The primary endpoint was proportion of participants with greater than or equal to 50 HIV -1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug) using the US Food and Drug Administration snapshot approach and prespecified non -inferiority margin of 4%. This study is registered with ClinicalTrials.gov (NCT04223778) and is completed. Findings Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (908%) participants (249 [371%] women and 423 [629%] men; median CD4 count of 678 cells per mu L [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (075 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021. At week 48, zero of 336 participants in the doravirine and islatravir group versus five (15%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV -1 RNA copies per mL (difference -15, 95% CI -34 to -03). The per -protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [104%] of 336 participants in the doravirine and islatravir group, 16 [48%] of 336 in the baseline ART group), infection rates were similar (113 [336%] in both groups), and discontinuations due to adverse events were low (seven [21%] vs one [03%]). 66 (196%) of 336 participants had treatment -related adverse events in the doravirine and islatravir group compared with 30 (89%) of 336 in the baseline ART group. In the islatravir and doravirine group, CD4 cell counts (mean change -303 cells per mu L) and total lymphocyte counts (mean change -026 x 10 9 /L) were decreased at 48 weeks. Interpretation Switching to single -tablet doravirine (100 mg) and islatravir (075 mg) maintained viral suppression up to week 48 and was non -inferior to antiretroviral combinations used in clinical practice for adults with HIV -1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once -daily doravirine (100 mg) and islatravir (075 mg). Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:Doravirine and islatravir is an investigational, once-daily, single-tablet regimen with high antiviral potency, favourable safety and tolerability, and low propensity for resistance. We report week 48 results from a phase 3 trial evaluating switch from stable, oral antiretroviral therapy (ART) to the fixed combination of doravirine (100 mg) and islatravir (0·75 mg). METHODS:This phase 3, multicentre, randomised, active-controlled, open-label, non-inferiority trial was conducted at 77 research, community, and hospital-based clinics in 15 countries. Adults aged 18 years or older with fewer than 50 HIV-1 RNA copies per mL on any oral, two-drug or three-drug ART regimen for at least 3 months, and no history of previous virological failure on any past or current regimen were randomly assigned (1:1) by a computer-generated randomisation schedule to switch to doravirine (100 mg) and islatravir (0·75 mg) or to continue their baseline ART regimen. Block randomisation was based on a block size of four, and randomisation was stratified by baseline regimen (ie, protease inhibitor, integrase inhibitor, or other). Participants in the doravirine and islatravir group were instructed to take one tablet at approximately the same time each day, and participants in the baseline ART group continued to take the medication according to the locally approved label. HIV-1 RNA and safety evaluations were done at baseline and weeks 4, 12, 24, 36, and 48. CD4 cell counts were measured at baseline, week 24, and week 48. The primary endpoint was proportion of participants with greater than or equal to 50 HIV-1 RNA copies per mL at week 48 in the full analysis set (ie, all participants who received at least one dose of study drug) using the US Food and Drug Administration snapshot approach and prespecified non-inferiority margin of 4%. This study is registered with ClinicalTrials.gov (NCT04223778) and is completed. FINDINGS:Between Feb 18 and Oct 2, 2020, 740 individuals were screened for eligibility, of whom 672 (90·8%) participants (249 [37·1%] women and 423 [62·9%] men; median CD4 count of 678 cells per μL [IQR 496-868]) were randomly assigned to doravirine (100 mg) and islatravir (0·75 mg; n=336) or to continue baseline ART (n=336). The last follow-up visit occurred on Sept 8, 2021. At week 48, zero of 336 participants in the doravirine and islatravir group versus five (1·5%) of 336 participants in the baseline ART group had greater than or equal to 50 HIV-1 RNA copies per mL (difference -1·5, 95% CI -3·4 to -0·3). The per-protocol analysis showed consistent results. Headache was the most common adverse event in both groups (35 [10·4%] of 336 participants in the doravirine and islatravir group, 16 [4·8%] of 336 in the baseline ART group), infection rates were similar (113 [33·6%] in both groups), and discontinuations due to adverse events were low (seven [2·1%] vs one [0·3%]). 66 (19·6%) of 336 participants had treatment-related adverse events in the doravirine and islatravir group compared with 30 (8·9%) of 336 in the baseline ART group. In the islatravir and doravirine group, CD4 cell counts (mean change -30·3 cells per μL) and total lymphocyte counts (mean change -0·26 × 109/L) were decreased at 48 weeks. INTERPRETATION:Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral combinations used in clinical practice for adults with HIV-1; however, decreases in CD4 cell and total lymphocyte counts do not support further development of once-daily doravirine (100 mg) and islatravir (0·75 mg). FUNDING:Merck Sharp & Dohme, a subsidiary of Merck & Co.

Background Cohort studies suggest higher discontinuation rates with integrase strand transfer inhibitors (INSTIs) than are seen in clinical trials. We assessed discontinuations and adverse events (AEs) that were considered related to the initial INSTI in the first year following initiation among treatment-naïve people living with HIV (PLWH). Methods Newly diagnosed PLWH initiating raltegravir, elvitegravir/cobicistat, dolutegravir or bictegravir in combination with emtricitabine/tenofovir alafenamide or emtricitabine/tenofovir disoproxil fumarate between 10/2007 and 1/2020 at the Orlando Immunology Center were included. Unadjusted incidence rates (IRs) and incidence rate ratios (IRRs) were calculated for treatment-related discontinuations and AEs associated with the initial INSTI in the first year following initiation. Results Of 331 enrolled, 26 (8%) initiated raltegravir, 151 (46%) initiated elvitegravir/cobicistat, 74 (22%) initiated dolutegravir and 80 (24%) initiated bictegravir. Within the first year, treatment-related discontinuations occurred in 3 on elvitegravir/cobicistat (IR 0.02 per person-years (PPY)) and 5 on dolutegravir (IR 0.08 PPY); no treatment-related discontinuations occurred among those initiating raltegravir or bictegravir. Eleven treatment-related AEs occurred in 7 on raltegravir (IR 0.46 PPY), 100 treatment-related AEs occurred in 63 on elvitegravir/cobicistat (IR 0.72 PPY), 66 treatment-related AEs occurred in 37 on dolutegravir (IR 0.97 PPY) and 65 treatment-related AEs occurred in 34 on bictegravir (IR 0.88 PPY). Unadjusted IRRs did not reveal any significant difference between INSTIs in terms of early treatment-related discontinuations or AEs. Conclusions In our cohort, treatment-related AEs occurred in 43% initiating INSTIs but were responsible for early discontinuation in only 2% with no treatment-related discontinuations observed among those initiating RAL or BIC.

Prior studies demonstrate that non-White patients are less likely to achieve human immunodeficiency virus (HIV) suppression compared to White patients due to lack of health insurance. This study aims to determine whether racial disparities in the HIV care cascade persist among a cohort of privately and publicly insured patients. This retrospective analysis evaluated HIV care outcomes during the first year of care. Eligible patients were aged 18–65 years, treatment-naïve, and seen between 2016 and 2019. Demographic and clinical variables were extracted from the medical record. Differences in the proportion of patients achieving each HIV care cascade stage by race were evaluated using unadjusted chi-square testing. Risk factors for viral non-suppression at 52 weeks were analyzed using multivariate logistic regression. We included 285 patients; ninety-nine were White, 101 were Black, and 85 identified as Hispanic/LatinX ethnicity. Significant differences in retention in care for Hispanic/LatinX patients (odds ratio (OR): 0.214, 95% confidence interval (CI): 0.067–0.676) and viral suppression for both Black (OR: 0.348, 95% CI: 0.178, 0.682) and Hispanic/LatinX patients (OR: 0.392, 95% CI: 0.195, 0.791) compared to White patients were observed. In multivariate analyses, Black patients were less likely to achieve viral suppression compared to White patients (OR: 0.464, 95% CI: 0.236, 0.902). This study showed that non-White patients were less likely to achieve viral suppression after 1 year despite insurance and suggests that other unmeasured factors may disproportionately affect viral suppression in these patients. Interventions to identify and address these factors are needed to improve HIV care outcomes for non-White populations.

Abstract Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Clinical trials of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) demonstrated potent efficacy and favorable safety in older PLWH; however, real-world data would be useful to validate these results. Retrospective cohort study. We evaluated records from PLWH aged ≥50 years at the Orlando Immunology Center who were switched to B/F/TAF between February 2018 and August 2019. Eligible patients had baseline HIV-1 RNA <50 copies/mL and 48 weeks of follow-up data. The primary endpoint was maintenance of HIV-1 RNA <50 copies/mL at Week 48. The impact of switching to B/F/TAF on drug–drug interactions (DDIs) and safety parameters were also assessed. Three-hundred and fifty patients met inclusion criteria, median age was 57 years, 20% were women, and 43% were non-White. Fifty-five percent of patients switched from integrase inhibitor-based regimens; the most common reason for switch was simplification. At Week 48, 330 (94%) patients maintained an HIV-1 RNA <50 copies/mL and 20 (6%) had an HIV-1 RNA between 50 and 400 copies/mL. One-hundred and forty potential DDIs were identified in 121 (35%) patients taking a boosting agent or rilpivirine at baseline that were resolved after switching to B/F/TAF. Treatment-related adverse events occurred in 51 (15%) patients (all Grade 1–2) and led to 8 discontinuations. In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH.

Abstract Background Cohort studies suggest higher rates of discontinuations (DCs) and adverse events (AEs) with integrase inhibitors (INSTIs) than is reported in clinical trials. Here, we assess DC of different INSTIs in combination with one of two tenofovir prodrugs in the first year following initiation defined as “early DC” in a real-world cohort of treatment-naïve patients. Methods This analysis evaluated treatment-naïve patients at a single center initiating raltegravir (RAL), elvitegravir/cobicistat (EVG/c), dolutegravir (DTG) or bictegravir (BIC) in combination with emtricitabine/tenofovir alafenamide (F/TAF) or emtricitabine/tenofovir disoproxil fumarate (F/TDF) between 10/2007-1/2020. Eligible patients had a minimum follow-up of 1 year. The primary endpoint was incidence of early INSTI DC. Secondary endpoints included AEs and risk factors for early INSTI DC and treatment-related AEs. Results 331 patients were included. Median age was 32 years, 89% were male, 43% were non-White, 8% started RAL-based therapy, 46% started EVG/c-based therapy, 22% started DTG-based therapy and 24% started BIC/F/TAF. 36 discontinued INSTI-based therapy early yielding an incidence rate of 0.17 DCs per person-years (PPY) among RAL patients, 0.14 DCs PPY among EVG/c patients, 0.22 DCs PPY among DTG patients, and 0 DCs PPY among BIC patients, p=0.006. Treatment-related AEs occurred in 27% of RAL patients, 42% of EVG/c patients, 50% of DTG patients, and 43% of BIC patients p=0.607; and were responsible for early DC rates of 0.022 in 3 EVG/c patients and 0.075 in 5 DTG patients. No treatment-related early DCs occurred among RAL or BIC patients. No evaluated factor was significantly associated with early INSTI DC, however DTG use was significantly associated with treatment-related AEs (aOR 3.46, 95% confidence interval: [1.20; 10.82]). Table 1. Risk factors for early integrase inhibitor discontinuation and treatment-related adverse events Conclusion In this cohort, early DCs occurred in 11% initiating INSTI-based therapy, however of these only 2% were treatment-related. These data support use of INSTI-based regimens as preferred options for treatment-naïve patients living with HIV due to their favorable safety and tolerability profiles. 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) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Advisor or Review Panel member, Speaker’s Bureau)Theratechonologies (Advisor or Review Panel member)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Scientific Research Study Investigator, Advisor or Review Panel member)