Dolutegravir 50mg / Abacavir 600mg / Lamivudine 300mg tablets

ObjectiveThis study evaluated rates of treatment-emergent resistance-associated mutations (TE-RAMs) and discontinuation due to adverse events (DC-AEs) across integrase strand transfer inhibitor (INSTI)-based single-tablet regimens and injectable cabotegravir + rilpivirine (CAB + RPV) in virologically suppressed people with HIV.MethodsA systematic literature review was conducted for phase 2-4 randomized controlled trials with ≥48 weeks of follow-up involving virologically suppressed people with HIV aged ≥12 years and published January 2003-March 2024. A random-effects network meta-analysis estimated comparative rates of TE-RAMs and DC-AEs among regimens at 48 weeks. Risk of bias and strength of evidence were assessed using Cochrane RoB and CINeMA, respectively.ResultsFourteen (7509 participants) and nine (4656 participants) studies were included in the TE-RAMs and DC-AEs analyses, respectively. No significant differences in rates of TE-RAMs were observed; risk ratios (RRs) for TE-RAMs for bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and CAB + RPV every 4 weeks (Q4W) versus CAB + RPV every 8 weeks (Q8W) were 0.22 (95% CI, 0.02-2.04), 0.22 (95% CI, 0.00-19.85) and 0.40 (95% CI, 0.14-1.09). Compared with CAB + RPV Q4W and Q8W, DC-AEs were significantly lower with B/F/TAF (RR, 0.15 [95% CI, 0.03-0.75] and RR, 0.16 [95% CI, 0.04-0.67], respectively) and DTG/ABC/3TC (RR, 0.05 [95% CI, 0.01-0.48] and RR, 0.05 [95% CI, 0.01-0.46], respectively).ConclusionsIn virologically suppressed people with HIV, switching to CAB + RPV Q8W yielded a non-significant increased risk of TE-RAMs compared with INSTI-based 2- and 3-drug regimens and CAB + RPV Q4W. Both CAB + RPV Q4W and Q8W had significantly higher risks of DC-AEs than B/F/TAF and DTG/ABC/3TC. Findings highlight the importance of considering both resistance and tolerability when switching regimens.

Abstract licence: CC BY-NC

Late presentation of HIV-1 infection is linked to gut dysbiosis, impaired immune reconstitution, excess inflammation, immune activation, and increased morbidity and mortality. It is unclear if antiretroviral therapy initiation can reverse HIV-associated gut dysbiosis at all, or if specific antiretroviral regimens are more effective in restoring the gut microbiota than others. This has important implications for the long-term health of individuals with HIV. In this multicenter, open-label, randomized clinical trial (NCT02337322), 88 antiretroviral-naïve individuals with advanced HIV-1 infection (median CD4+ T cells of 34 cells/mm3) were randomized (1:1) to initiate lamivudine/abacavir plus either dolutegravir or ritonavir-boosted darunavir, and were followed for 2 years. Both groups had similar HIV-1 suppression rates and recovery of CD4+ T cells. However, treatment with dolutegravir led to increased gut microbial richness and diversity and enrichment of specific microbial taxa and metabolic pathways. These changes were associated with reduced inflammation and lower immune activation, outcomes that did not occur with darunavir/ritonavir. After two years, participants on dolutegravir-based therapy had gut microbiota profiles more closely resembling those of people without HIV, compared to individuals taking darunavir/ritonavir. In summary, dolutegravir-based therapy restores the gut microbiota more effectively than darunavir/ritonavir in patients who present late with HIV.

Abstract licence: CC BY-NC-ND