Effects of switching to dolutegravir/lamivudine from tenofovir alafenamide fumarate/emtricitabine/dolutegravir or abacavir/lamivudine/dolutegravir on body weight and lipid profile in Japanese people living with HIV.

The two-drug regimen of dolutegravir/lamivudine (DTG/3TC) is currently an optional antiretroviral therapy (ART). Despite its reported advantages on body weight and lipid profile, the same effects have not yet been reported for Asian population. We conducted a single-center retrospective study involving Japanese people living with HIV (PLWH). They were divided into four groups: those who had received abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) and continued the same (ABC-ON group) or switched to DTG/3TC (ABC-OFF group), those who had received tenofovir alafenamide fumarate/emtricitabine/dolutegravir (TAF/FTC/DTG) and continued the same (TAF-ON group) or switched to DTG/3TC (TAF-OFF group). We compared changes in viral load, CD4⁺ cell count, CD4⁺/CD8⁺ ratio, body weight, BMI, lipid profiles, estimated glomerular filtration rate (eGFR), and fibrosis index based on four factors (FIB4-index) between the pre-switch and post-switch period. Of the 541 PLWH on DTG-based ART, 165, 94, 264 and 18 constituted the ABC-ON, ABC-OFF, TAF-ON, and TAF-OFF groups, respectively. Neither viral rebound nor CD4+decline was observed in the post-switch period in all groups. Multivariate analysis showed significant reduction in total cholesterol, LDL-C and HDL-C in the ABC-OFF group (-6.280, -6.957 and -2.268, p = 0.040, 0.012 and 0.022, respectively), but not in the TAF-OFF group (-3.000, 6.708 and 0.046, p = 0.607, 0.276 and 0.983, respectively). No significant changes were observed in body weight, eGFR, or FIB4-index at 72 weeks after the discontinuation of ABC or TAF. Switching from ABC/3TC/DTG to DTG/3TC lowered lipids significantly, but not with TAF/FTC/DTG. Neither switch affected body weight or other markers.

Ikegaya K ，Muramatsu T ，Sekiya R ，Sekine Y ，Harada Y ，Miyashita R ，Yamaguchi T ，Ichiki A ，Chikasawa Y ，Bingo M ，Yotsumoto M ，Hagiwara T ，Amano K ，Takeuchi H ，Kinai E ... -  《-》

Efficacy and safety of switch to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir/abacavir/lamivudine: Results from an open-label extension of a phase 3 randomized, double-blind, multicenter, active-controlled, non-inferiority study.

The 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. Participants 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. Among 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. Switching 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.

Brar I ，Ruane PJ ，Berhe M ，Brinson C ，Benson P ，Henry K ，Liu H ，Andreatta K ，Hindman JT ，Ramgopal M ... -  《-》

Safety and efficacy of lamivudine/dolutegravir vs. bictegravir/emtricitabine/tenofovir alafenamide in antiretroviral-naive adults with HIV-1 infection in Shanghai, China: a single-centre retrospective study.

Yang J ，Wang L ，Zhang X ，Liu L ，Shen Y ，Qi T ，Wang Z ，Song W ，Tang Y ，Xu S ，Sun J ，Chen Y ，Shen Y ，Chen J ，Zhang R ... -  《-》

Long-term metabolic changes with bictegravir/emtricitabine/tenofovir alafenamide or dolutegravir-containing regimens for HIV.

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% at Week 240. Median weight and body mass index (BMI) increased over time with B/F/TAF (n = 628), DTG/ABC/3TC (n = 315), and DTG + F/TAF (n = 325). There were no significant differences in change in weight or BMI between the B/F/TAF and DTG + F/TAF groups or between the B/F/TAF and DTG/ABC/3TC groups at Week 144 in either trial, nor were there differences in other metabolic parameters, including incidence of treatment-emergent diabetes mellitus and hypertension through Week 144. Among PWH receiving B/F/TAF (baseline through Week 240), weight increases were greatest soon after initiating antiretroviral therapy (i.e., Weeks 0-48), particularly in participants with baseline viral load > 100,000 copies/ml and/or CD4 count < 200 cells/µl. In multivariate modeling (B/F/TAF pooled data), lower baseline CD4 count and higher HIV-1 RNA were associated with lower baseline weight and greater weight gain, but not absolute weight, from Week 48 through Week 240. No significant difference in weight change from baseline to Week 144 was found between bictegravir and DTG, or between B/F/TAF and a non-TAF-containing regimen, in these two randomized trials. Furthermore, weight gain following treatment initiation was greatest in the first year of treatment and most pronounced in individuals with more advanced HIV at baseline, supporting the hypothesis that weight gain following initial treatment is linked to a "return to health" in people with advanced HIV.

Daar ES ，Orkin C ，Sax PE ，Hagins D ，Pozniak A ，Workowski K ，Brinson C ，Tiraboschi JM ，Liu H ，Deaton C ，Cohen C ，Madera S ，Hindman JT ，Ramgopal M ... -  《-》

Comparing the long-term effectiveness and safety of dolutegravir/lamivudine versus bictegravir/emtricitabine/tenofovir alafenamide fumarate as first-line regimens: a real life multicentre cohort.

We compared the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) in our cohort of treatment-naive people with HIV (PWH). In a multicentre cohort of treatment-naive PWH starting a first-line regimen with either dolutegravir plus lamivudine or BIC/FTC/TAF, Kaplan-Meier survival analysis was used to estimate time to virological failure (VF) and time to treatment discontinuation (TD), whereas Cox regression was used to evaluate predictors of VF and TD. Changes in CD4+ cell count were assessed via non-parametric tests, and linear regression analyses were performed to explore predictors of CD4+ cell count changes. One hundred and seventy individuals were included: 66 started dolutegravir plus lamivudine (DTG group) and 104 started BIC/FTC/TAF (BIC group). During follow-up, we observed two VFs in the DTG group [1.7 per 100 person-years of follow-up (PYFU)] and two in the BIC group (1.7 per 100 PYFU). Estimated probability of remaining free from VF at Week 144 was 95.9% in the DTG group and 95.2% in the BIC group (log-rank P = 0.955). Four TDs were observed in the DTG group (3.4 per 100 PYFU) and 21 in the BIC group (17.6 per 100 PYFU). Estimated probability of maintaining the study regimen at Week 144 was 90.3% in the DTG group and 70.0% in the BIC group; individuals in the BIC group had a higher probability of TD (log-rank P = 0.003). In both groups, the CD4+ count improved significantly during follow-up. Our study shows that both strategies are effective and safe, with few VFs and TDs due to tolerability issues.

Ciccullo A ，Baldin G ，Cervo A ，Moschese D ，Lagi F ，Cossu MV ，Grimaldi A ，Giacomelli A ，Rusconi S ，Sterrantino G ，Borghetti A ，Antinori S ，Mussini C ，Di Giambenedetto S ... -  《-》