Dataset Information

Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens.

ABSTRACT:

Background

Cardiometabolic outcomes were investigated 3 years after switching to the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) vs continuing 3-/4-drug tenofovir alafenamide (TAF)-based regimens in a multicenter phase 3 noninferiority study based on an open-label randomized design.

Method

Adults with virologically suppressed HIV-1 switched to once-daily DTG/3TC (n = 369) or continued TAF-based regimens (n = 372). Cardiometabolic health parameters were assessed through week 144 via mixed-model repeated measures or logistic regression analyses, adjusting for baseline variables.

Results

At week 144, 13% (42/316) of the DTG/3TC group and 12% (37/303) of the TAF-based regimen group had ≥10% weight gain from baseline (adjusted odds ratio, 1.11; 95% CI, .68-1.80). Adjusted change from baseline in serum leptin, a surrogate marker of adiposity, was similar between groups (treatment ratio, 1.00; 95% CI, .89-1.13). The lipid profile generally favored DTG/3TC in the baseline boosted subgroup. Adjusted odds revealed no clinically meaningful differences between groups: homeostatic model assessment of insulin resistance ≥2 (adjusted odds ratio, 0.79; 95% CI, .50-1.26), metabolic syndrome (International Diabetes Federation criteria, 0.99; .59-1.68), hepatic fibrosis (fibrosis-4 index score ≥1.45, 1.39; .63-3.06), and coronary artery disease risk (Framingham risk score ≥10%, 0.92; .56-1.49). Baseline variables and characteristics associated with odds of each cardiometabolic parameter outcome were consistent with known risk factors, including age, sex, race, and some disease characteristics.

Conclusions

Cardiometabolic health 3 years after switching to DTG/3TC was comparable to that for individuals continuing TAF-based regimens, further supporting DTG/3TC as a robust switch option with a stable metabolic profile.

Trial registration

ClinicalTrials.gov NCT03446573.

SUBMITTER: Batterham RL

PROVIDER: S-EPMC10375426 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens.

Batterham Rachel L RL Espinosa Nuria N Katlama Christine C McKellar Mehri M Scholten Stefan S Smith Don E DE Ait-Khaled Mounir M George Nisha N Wright Jonathan J Gordon Lori A LA Moodley Riya R Wynne Brian B van Wyk Jean J

Open forum infectious diseases 20230712 7

<h4>Background</h4>Cardiometabolic outcomes were investigated 3 years after switching to the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) vs continuing 3-/4-drug tenofovir alafenamide (TAF)-based regimens in a multicenter phase 3 noninferiority study based on an open-label randomized design.<h4>Method</h4>Adults with virologically suppressed HIV-1 switched to once-daily DTG/3TC (n = 369) or continued TAF-based regimens (n = 372). Cardiometabolic health parameters were assessed through week 1 ...[more]

PMID: 37520420

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Project description:BackgroundDespite evidence shown of dolutegravir (DTG)-related neurotoxicity, which may be more common when combined with abacavir (ABC), its reversibility has not been explored in a clinical trial.MethodsWe conducted a randomized, multicenter, open-label, pilot trial to evaluate the reversibility of patient-reported neuropsychiatric symptoms, developed or worsened on DTG/ABC/lamivudine (DTG/ABC/3TC), in virologically suppressed patients switched to cobicistat-boosted-elvitegravir/emtricitabine/tenofovir-alafenamide (EVG/COBI/FTC/TAF). Participants were randomized to immediate switch (baseline) or to defer switch (week 4), and then all completed 24 weeks of follow up on EVG/COBI/FTC/TAF. At each visit, participants completed Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression (HAD) scales and were interviewed about 11 neuropsychiatric symptoms potentially related with DTG through a questionnaire. At baseline and at the end of follow up, they also performed neurocognitive testing. Our primary objective was to compare changes in neuropsychiatric symptoms and PSQI and HAD scales between arms at week 4. Secondary objectives were to evaluate changes in neuropsychiatric symptoms and PSQI and HAD scales at weeks 4, 12, and 24 after switching to EVG/COBI/FTC/TAF and in neurocognitive performance and magnetic resonance imaging biomarkers at end of follow up.ResultsThirty-eight participants were included. Study arms were similar at baseline. At week 4, neuropsychiatric symptoms and PSQI and HAD scores remained unchanged in participants receiving DTG/ABC/3TC and improved significantly in participants receiving EVG/COBI/FTC/TAF. These significant improvements were also observed at weeks 4, 12, and 24 after all participants switched to EVG/COBI/FTC/TAF. In addition, global neurocognitive performance improved (NPZ-7) after switching to EVG/COBI/FTC/TAF.ConclusionsNeuropsychiatric symptoms in patients on DTG/ABC/3TC could resolve or improve after switching to EVG/COBI/FTC/TAF.

Project description:BackgroundDarunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking.MethodsAdult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL) ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin).ResultsBetween September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/μL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, -2.4%; 95% confidence interval [CI], -11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, -2%; 95% CI, -8.1 to 3.5). There were no differences in CD4 cell count or weight changes.ConclusionsWe could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.

Project description:BackgroundThe phase 3 randomized, active-controlled GS-US-380-1844 (NCT02603120) study evaluated switching to the single-tablet regimen bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) from dolutegravir (DTG), abacavir (ABC), and lamivudine (3TC) among people with HIV-1. Previously, results from the 48-week double-blind phase showed that switching to B/F/TAF was noninferior to remaining on DTG/ABC/3TC and that B/F/TAF was well tolerated. Here, we show the long-term safety and efficacy of switching to B/F/TAF from DTG/ABC/3TC among people with HIV-1.MethodsParticipants were virologically suppressed people with HIV-1 (HIV-1 RNA <50 copies/mL for ≥ 3 months prior to screening) receiving DTG/ABC/3TC at baseline. Participants were randomized 1:1 to switch to B/F/TAF or remain on DTG/ABC/3TC. Following 48 weeks of treatment with B/F/TAF or DTG/ABC/3TC in the double-blind phase, participants had the option to enter an open-label extension phase, during which they received B/F/TAF. Virologic, immunologic, and safety outcomes during treatment with B/F/TAF through the open-label extension up to 168 weeks, including preexisting and treatment-emergent resistance, were analyzed.ResultsAmong 547 participants in the all-B/F/TAF analysis set, virologic suppression (HIV-1 RNA < 50 copies/mL) was maintained in 99% to 100% of participants up to 168 weeks into B/F/TAF treatment, including in those with preexisting resistance; no treatment-emergent resistance was detected. CD4 cell counts remained stable during B/F/TAF treatment, with median (interquartile range) changes from baseline of -17 (-120, 65) cells/µL at week 48 and -9 (-100, 108) cells/µL at week 96. Safety and tolerability findings were consistent with previously reported findings up to week 48; most drug-related adverse events were grade 1 or 2 in severity; no new safety signals were identified.ConclusionSwitching to B/F/TAF from DTG/ABC/3TC was associated with continued high rates of virologic suppression up to week 168, with no treatment-emergent resistance. B/F/TAF was well tolerated throughout the study period.

Dataset Information

Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens.

Background

Method

Results

Conclusions

Trial registration

Publications

Cardiometabolic Parameters 3 Years After Switch to Dolutegravir/Lamivudine vs Maintenance of Tenofovir Alafenamide-Based Regimens.

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