Long-term effectiveness, safety, and tolerability of doravirine in antiretroviral-experienced people with HIV in real life.

Real-life data on doravirine (DOR) in different drug combinations are limited. We evaluated the effectiveness of DOR plus two nucleos(t)ide reverse transcriptase inhibitors (NRTI), mainly abacavir/lamivudine, and dual therapies in people with HIV (PWH), mostly virologically suppressed. Ambispective observational study that enrolled adults PWH who initiated a DOR-based regimen from September 2020 to February 2022 at a referral center in Spain. Participants were grouped as follows: A, received DOR plus two NRTI; B, dual therapy (DT) with DOR plus dolutegravir (DTG) or darunavir/cobicistat (DRVc); C, DOR plus ≥two antiretroviral drugs. The primary endpoints were treatment effectiveness at week 48 by intention-to-treat (ITT) and per-protocol analysis (OT). A cohort of 187 participants, 91% virologically suppressed, were analyzed after a median follow-up of 112 weeks (80-136). Group A received DOR plus abacavir/lamivudine (ABV/3TC) (n = 109) or tenofovir/emtricitabine (TFV/3TC) (n = 45). At week 48, the effectiveness of DOR plus ABV/3TC by ITT was 90.8% (CI95, 88.0-93.6), better than with TFV/FTC [73.3% (66.7-79.9); P = 0.003]. Only one virologic failure was observed. Mild adverse effects were the cause of treatment discontinuation in 7.8%, followed by switching to a single-tablet regimen. In group B, the effectiveness by ITT was 92.9% (CI95, 88.0-97.8) at week 48. No adverse effects or virologic failure were registered in this group. DOR plus two NRTI or DT have long-term effectiveness and safety as a switching option for PWH, mostly virologically suppressed. The DOR plus ABV/3TC combination has shown even better effectiveness than TFV/FTC.IMPORTANCEDOR-based regimens have shown long-term effectiveness and safety in PWH, mostly virologically suppressed. The combination of DOR plus ABV/3TC has shown even better safety and effectiveness than TFV/FTC. DOR plus two NRTI offers cost benefits compared to other regimens.

Zidovudine/Lamivudine vs. Abacavir/Lamivudine vs. Tenofovir/Emtricitabine in fixed-dose combinations as initial treatment for HIV patients: a systematic review and network meta-analysis / Zidovudina/Lamivudina vs Abacavir/Lamivudina vs Tenofovir/Emtricitabina en combinaciones de dosis fija como tratamiento inicial en pacientes con VIH: revisión sistemática y metanálisis en red

Abstract Introduction: Initial treatment of the HIV is based on the use of three drugs, two of which are nucleoside analog reverse-transcriptase inhibitors. There are three combinations of these drugs which have been approved by different guidelines, each with divergent results in terms of efficacy and safety. Objective: To compare the efficacy and safety of these three combinations. Methods: Systematic review and network meta-analysis of randomized clinical trials comparing fixed doses of Tenofovir Disoproxil Fumarate / Emtricitabine (TDF/FTC), Abacavir / Lamivudine (ABC/3TC) and Zidovudine / Lamivudine (ZDV/3TC). Results: Seven clinical trials met the eligibility criteria. The results suggested higher efficacy with TDF/FTC vs. ABC/3TC at 96 weeks and vs. ZDV/3TC at 48 weeks. However, there is clinical and statistical heterogeneity. Subgroup analysis were performed by third drug and by level of viral load prior to treatment, and found no differences in virological control. Network meta-analysis could only be carried out with TDF/FTC vs. ZDV/3TC, and the proportion of patients with virological response, with no differences at 48 weeks nor at 96 weeks. Direct comparisons showed an increased risk of bone marrow suppression of ZDV/3TC vs. TDF/FTC and of ABC/3TC hypersensitivity reactions vs. ZDV/3TC Conclusions: The results did not show differences in effectiveness among the interventions. However, due to the heterogeneity of the third drug and the follow-up time between the included studies, this result is not definitive. The results raise the need for further studies to help improve treatment recommendations in patients infected with HIV.

Resumen Introducción: El tratamiento inicial de la infección por VIH se basa en el uso de tres medicamentos, dos de ellos inhibidores de transcriptasa reversa análogos de nucleósido. Existen tres combinaciones de estos medicamentos aprobadas por diferentes guías, con resultados divergentes en cuanto a eficacia y seguridad. Objetivo: Comparar la eficacia y seguridad de las 3 combinaciones Métodos: Revisión sistemática y metanálisis en red de ensayos clínicos con asignación aleatoria comparando dosis fijas de Tenofovir Disoproxil Fumarato/Emtricitabina (TDF/FTC), Abacavir/Lamivudina (ABC/3TC) y Zidovudina/Lamivudina (ZDV/3TC). Resultados: Siete ensayos clínicos cumplieron los criterios de elegibilidad. Los resultados sugirieron mayor eficacia con TDF/FTC vs ABC/3TC a 96 semanas y vs. ZDV/3TC a 48 semanas. Sin embargo, existe heterogeneidad clínica y estadística. Se realizó análisis de subgrupos por tercer medicamento y por nivel de carga viral previa al tratamiento, sin encontrar diferencias en control virológico. Se pudo realizar metanálisis en red con TDF/FTC vs ZDV/3TC y proporción de pacientes con respuesta virológica, sin diferencias a las 48 semanas ni 96 semanas. Las comparaciones directas evidenciaron mayor riesgo de supresión de médula ósea de ZDV/3TC vs TDF/FTC y de reacciones de hipersensibilidad de ABC/3TC vs ZDV/3TC. Conclusión: Los resultados no demostraron diferencias en efectividad entre las intervenciones; sin embargo, debido a heterogeneidad en cuanto al tercer medicamento y el tiempo de seguimiento entre los estudios incluidos, dicho resultado no es definitivo. Los resultados plantean la necesidad de realizar nuevos estudios que ayuden a mejorar las recomendaciones de tratamiento en los pacientes infectados por el VIH.