PP18 Effectiveness And Safety Of Long-Acting Agents-Based Dual Therapy In HIV-1/AIDS Patients: A Network Meta-Analysis Of Observational Studies

Introduction Most treatment regimens for people living with HIV (PLHIV) require the intake of multiple daily pills, which can pose challenges to adherence. As an alternative, long-acting (LA) dual regimens have gained attention for their potential to simplify treatment. Given the importance of evaluating the long-term effects of LA regimens, this study aimed to synthesize evidence on their effectiveness and safety. Methods A systematic review was performed following the Cochrane Collaboration recommendations and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines, with searches in PubMed, Scopus, and Web of Science (July 2024) (PROSPERO-CRD42024570754). Longitudinal studies evaluating any dual-therapy antiretroviral regimen with LA agents (islatravir, cabotegravir, lenacapavir, rilpivirine, albuvirtide) for PLHIV were included. For each outcome of interest, data were pooled using bivariate meta-analysis (discontinuations due to adverse events) and network meta-analysis (NMA) (virologic failure [VF]), with results presented as risk ratios (RR) with 95 percent credibility intervals (CrIs); heterogeneity was assessed using the I-squared statistic . The surface under the cumulative rating curve analysis (SUCRA) was also conducted for the NMA. Results Thirty-two studies (2016 to 2024) evaluating 11 treatments were included. Four cohorts (n=2,570) were assessed in the NMA of VF, where the rilpivirine/dolutegravir (RPV/DTG) regimen was superior to non-LA regimens dolutegravir/lamivudine (RR −1.60, 95% CrI: −4.08, 0.91) and dolutegravir/doravirine (RR −0.42, 95% CrI: −1.68, 0.68), with SUCRA probabilities of 9.6 percent, 31 percent, and 59.5 percent, respectively. The triplet regimens dolutegravir plus tenofovir/emtricitabine and dolutegravir plus abacavir/lamivudine had the highest probabilities of leading to CD4+ count increases at six to 24 months (65.6 to 85.7% and 65.8 to 84.4%, respectively), followed by RPV/DTG (59 to 60%) and dolutegravir/lamivudine (46 to 53%). However, RPV/DTG regimens were considered safer than dolutegravir/lamivudine (RR 0.53, 95% CrI: 0.32, 0.89) regarding discontinuation due to adverse events. Conclusions This updated synthetized evidence suggested that the RPV/DTG regimen is a promising alternative for simplifying the treatment of PLHIV, demonstrating comparable effectiveness to the dolutegravir/lamivudine and dolutegravir/doravirine regimens, while offering better tolerability. However, considerations of drug accessibility and cost must be carefully weighed in the decision-making process in different settings.