Dolutegravir/Lamivudine in Treatment-Naïve Pregnant Women

Overview

Protocol Number: FH-94 Study Objetives: Primary: * To evaluate the virological response to Dolutegravir/Lamivudine in naive pregnant women with HIV who are starting antiretroviral therapy and vertical transmission in exposed neonates. Secondary: * To evaluate the incidence of maternal adverse events. * To evaluate perinatal outcomes at delivery. * To evaluate maximum virological suppression at delivery. * To evaluate the incidence of changes in body weight exceeding what is expected for gestation. * To evaluate the immune response based on changes in CD4, CD8, and CD4/CD8 ratio values during pregnancy. * Assess baseline resistance and the development of resistance to virological failure to integrase inhibitors and INTRs during treatment with DTG+3TC or DTG+TDF/XTC or DTG+TAF/FTC. * To evaluate the incidence of HIV infection in children that breastfeed. * To evaluate safety outcomes and virological response of DTG+3TC compared to DTG+TDF/XTC or DTG+TAF/FTC. Exploratory: * To explore the non-inferiority of DTG+3TC therapy compared to DTG+TDF/XTC or DTG+TAF/FTC treatment. * To evaluate the frequency of antiretroviral therapy withdrawal or modification before delivery.

Primary endpoints: * Proportion of pregnant women who achieve an HIV-1 plasma viral load \<200 copies/mL at delivery after starting DTG+3TC (Intention-to-Treat Exposed analysis). * Proportion of children born without HIV infection at 6 weeks \& 6 months of age, defined by the negative result of negative virological tests (PCR) performed at birth (delivery visit and up to 72 hours after delivery), at 6 weeks, and at 6 months Secondary endpoints: * Frequency of grade 2 or higher maternal adverse events, by type and severity, from baseline to 6 months postpartum. * Frequency of spontaneous abortion, preterm delivery, congenital malformations at birth or identified and reported during the first 6 month of life, or intrauterine fetal death. * Proportion of pregnant women with plasma viral load below 50 copies/mL at delivery. * Average total weight gain and BMI during pregnancy, compared with recommendations based on pre-pregnancy BMI. * Changes in CD4 lymphocyte count and CD4/CD8 ratio between baseline and delivery visit values. * Frequency and type of mutations according to the International AIDS Society (IAS-USA drug resistance mutations, 2025) mutation guidelines panel at the baseline visit and in case of virological failure at any time during the study. * Proportion of HIV infection among breastfed children. * Frequency of grade 2 or higher maternal adverse events, by type and severity, between the two arms. Frequency of pregnant women with plasma viral load \<200 copies/mL in the two arms at delivery visit. Exploratory endpoints: * Difference in the proportion of pregnant women who achieve an HIV-1 plasma viral load of less than 50 copies/mL at delivery between the DTG+3TC and DTG+TDF/XTC or DTG+TAF/FTC groups, to explore the non-inferiority of the dual regimen. * Proportion of participants requiring a change in antiretroviral regimen (due to lack of efficacy, adverse events, medical decision, or other reasons) before delivery. Patient Population: HIV-1-infected Pregnant Women aged \>16 years (\>15 years for Brazil's sites) who are naïve to antiretroviral therapy Study design: Phase IV. Randomized, non-comparative, open-label, multicenter study. Regimens: Dolutegravir 50 mg /lamivudine 300 mg QD FDC. Dolutegravir 50 mg QD plus tenofovir 300 mg/emtricitabine 200mg or plus tenofovir 300 mg/ lamivudine 300 mg or tenofovir alafenamide 25 mg/emtricitabine 200 mg. Duration: 14 months approximately months (depending on gestational age at entry). Sample size: 210 subjects