PERFIL DE PACIENTES EM USO DE TERAPIA DUPLA COM DOLUTEGRAVIR E LAMIVUDINA, COORTE RETROSPECTIVA DE VIDA REAL

Introdução: O uso a longo prazo dos antirretrovirais (ARVs) e suas toxicidades são um desafio no atual manejo de pessoas vivendo com HIV/aids (PVHA). Com ARVs mais potentes e com maior barreira genética, a terapia dupla (TD) está atualmente recomendada em várias situações. Métodos: Análise retrospectiva realizada até agosto/2022 em PVHA atendidas no CRT DST/AIDS, São Paulo, utilizando TD baseada em Dolutegravir (DTG) 50 mg + Lamivudina (3TC) 300 mg ≥ 365 dias. Dados foram capturados dos prontuários e inseridos na plataforma REDCAP juntamente a verificação de dispensas de ARVs pelo Sistema de Controle Logístico de Medicamentos (SICLOM). Resultados: Em um total 8849 pacientes ativos na instituição, identificamos 383 elegíveis à inclusão e análise. Características da população: homem cisgênero 294 (76,1%), brancos 284 (74,1%), ensino superior completo 171 (44,6%), mediana de idade 56,9 anos, mediana de idade no diagnóstico 38 anos, tempo médio de infecção pelo HIV 16,9 anos, contagem linfócitos TCD4 >500 células 315 (82,2%). Identificamos 9 óbitos (2 doença cardiovascular, 2 COVID-19 e 5 sem dados), 371 vivos em seguimento e 3 sem dados. Em relação aos ARVs: tempo médio de exposição 13,5 anos, número médio de esquemas prévios 3,1 (1 naive, 249 um a três esquemas e 133 quatro ou mais), exposição prévia aos Inibidores de Integrase 218 (56,9%). Principais esquemas prévios a TD: Tenofovir (TDF) + 3TC + DTG 166 (43%), Abacavir (ABC) + 3TC + DTG 44 (11,4%), Zidovudina (AZT) + 3TC + DTG 32 (8,3%), TDF + 3TC + Efavirenz (EFZ) 30 (7,8%), ABC + 3TC + EFZ 29 (7,5%) e 82 outros esquemas. Principais razões para TD: comorbidade óssea 110, comorbidade renal 95, conveniência posológica 82, comorbidade cardiovascular 44, outros eventos adversos 40 (lipodistrofia, elevação de transaminases e dislipidemia) e 54 (14%) sem dados. Identificamos pacientes com mais de uma razão. Em relação a manutenção da TD: 371 (96,9%) mantiveram uso, 8 trocas de esquema (2 falhas virológicas, 1 otimização de TARV após blip sem confirmação de falha, 1 presença de M184V em genotipagem prévia e 4 motivos clínicos) e 4 sem dados. Tempo médio de uso de TD no momento da análise 2,4 anos. Não foi possível avaliar ausência de falha virológica prévia em toda população. Conclusão: Uso de TD com Dolutegravir e Lamivudina, pode ser uma opção segura em PVHA em supressão viral, em uso de terapia antirretroviral há vários anos, sem falha virológica prévia

Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2) : results of a randomised, double-blind, placebo-controlled, phase 3 trial

Background Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose. Methods ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing. Findings Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36 center dot 0 (15 center dot 0-62 center dot 0) days. Vaccine efficacy was 75 center dot 2% (adjusted 95% CI 54 center dot 6-87 center dot 3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55 center dot 6%] of 3015 vs 896 [57 center dot 5%] of 1559, respectively; systemic adverse events, 1764 [58 center dot 5%] of 3015 vs 821 [52 center dot 7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity. Interpretation A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed. Funding Janssen Research & Development. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd