Segurança de esquemas contendo dolutegravir no tratamento da infecção pelo HIV no Brasil.

Abstract

Since 2017, dolutegravir (DTG) has been part of first-line treatment regimens for initiation of antiretroviral therapy (ART) in Brazil, in addition to being used in the third line of treatment, in cases of resistance to other antiretrovirals. Observational studies evaluating the safety of DTG in Brazil are scarce and necessary to know the safety profile of the drug in real life. The objective of this study was to assess the safety of regimens containing DTG for the treatment of people living with HIV (PLHIV) in Brazil. Three studies were developed within the scope of this thesis. In study 1, We conducted a quantitative descriptive study to describe the adverse drug reactions (ADRs) reported among the 249,066 individuals using DTG who participated in the DTG Active Pharmacovigilance Project in Brazil from April 2017 to August 2019 and assess incompleteness of notification data. In study 2, We conducted a prospective cohort study to assess the incidence of ADR on ART within a 12-month period after initiation of DTG-based and EFV-based regimens in 433 PLHIV in Belo Horizonte and the factors associated with this outcome. In study 3, We conducted a prospective cohort study to assess the incidence of neuropsychiatric ADRs in the first 12 months after initiation of DTG-based and EFV-based regimens in 433 PLHIV in Belo Horizonte and the factors associated with this outcome. In study 1, 3,472 (1.4%) subjects reported ADRs at least once. The most severe and clinically relevant reactions were neuropsychiatric (suicidal depression, suicide attempt and self-mutilation ideation) and neural tube malformation in pregnant women. The DTG Active Pharmacovigilance Project showed consistent results and good completeness of data. In study 2, 217 (50.1%) subjects had ADRs at 12 months of follow-up. ADRs were recorded in 60.8% of the individuals using EFV and in 28.2% of the individuals using DTG. The most frequent ADRs were gastrointestinal, psychiatric and nervous system disorders being more frequent. The mean time to develop the first ADR was 210.6 days (95%CI 195.5-225.8). Factors associated with ADRs were concomitant use of other medications (HR: 2.00; 95%CI 1.38-2.89), alcohol use (HR: 0.64; 95%CI 0.49-0.85) and use of DTG-based regimen (HR: 0.40; 95%CI 0.28-0.58). In study 3, 152 (35.1%) had neuropsychiatric ADRs at 12 months of follow-up, with neuropsychiatric ADRs recorded in 44.3% of individuals using EFV and in 16.2% of individuals using DTG. The incidence density was 35.3/100 person-years. The subjects mainly presented sleep disorders and disturbances (21.3%) and neurological disorders (13.9%). A lower chance of neuropsychiatric ADRs was associated with the use of DTG-based regimen (OR: 0.24; 95%CI 0.14-0.40) and the presence of signs and symptoms of anxiety or depression at the beginning of treatment (OR: 0.57; 95%CI 0.37-0.89). The results of the studies suggest good tolerability and safety of DTG-based regimens in clinical practice, especially when compared to the EFV-based regimen.