Dolutegravir/Lamivudine in Treatment-Naïve Pregnant Women
ConditionHIV-1-infection
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexFemale
Age15+
SponsorFundación Huésped
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Confirmed HIV-1 infection: All tests must use blood, serum, or plasma samples. Documentation may be obtained from medical records. HIV-1 positive is defined as having HIV-1 RNA in plasma ≥ 1000 copies/mL, plus one antibody test or two positive HIV antibody tests (two different rapid tests or one rapid test and one positive ELISA/EIE test). If any of these diagnostic test results are not available, they will be performed at the SCR visit. In all cases, an HIV viral load test will be performed.
Not exposed to prior antiretroviral therapy (ART): No prior antiretroviral therapy, including exposure to PrEP and/or PEP in the last 6 months.
Ability to sign the informed consent form.
Plasma HIV-1 RNA ≥1000 copies/mL. Viral load from the last 30 days may be valid. . Age ≥ 16 years or older in Argentina, ≥ 15 years or older in Brazil. The participant must be of the age required in their country of residence to give legal informed consent. Otherwise, informed consent must be signed by a parent or legal guardian, according to country guidelines, in addition to the participant.
Disqualifiers
Documented resistance to 3TC (presence of the M184V/I mutation) or DTG (defined as the presence of G118R, Q148 H/K/R, or R263K).
Active hepatitis C infection. 3. Active hepatitis B (HBsAg positive or detectable HBV viral load in cases with isolated positive HBV anti-core).
Hemoglobin <8 g/dL.
Fetal abnormalities detected on ultrasound
Trial design
Design model
Parallel
Treatments tested in this trial
Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Drug1 pill QD
TDF/XTC or TAF/FTC plus Dolutegravir (XTC stand for lamivudine OR emtricitabine)
Drug1 pill of each QD
Treatment groups
210 Participants
are divided into 2 treatment groupsGroup A: ExperimentalExperimental treatment 1 intervention
Group B: Active ComparatorActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
To evaluate the virological response to Dolutegravir/Lamivudine in pregnant women with HIV who are starting antiretroviral therapy and vertical transmission in exposed neonates
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.
Time frame
From enrollment to the end of treatment at 6 months after deliverySecondary outcomes
1
- To evaluate the incidence of adverse maternal events.
Frequency of grade 2 or higher maternal adverse events, by type and severity, from baseline to 6 months postpartum
Time frame
From enrollment to the end of treatment at 6 months after delivery2
- To evaluate perinatal outcomes at delivery
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.
Time frame
From enrollment to the end of treatment at 6 months after delivery3
- To evaluate maximum virological suppression at delivery
Proportion of pregnant women with plasma viral load below 50 copies/mL at delivery.
Time frame
From enrollment to the end of treatment at 6 months after delivery4
- To evaluate the incidence of changes in body weight exceeding what is expected for gestation
Average total weight gain and BMI during pregnancy, compared with recommendations based on pre-pregnancy BMI.
Time frame
From enrollment to the end of treatment at 6 months after deliveryOther outcomes
1
- To explore the non-inferiority of DTG+3TC therapy compared to DTG+TDF/XTC or DTG+TAF/FTC treatment.
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.
Time frame
From enrollment to the end of treatment at 6 months after delivery2
- To evaluate the frequency of antiretroviral therapy withdrawal or modification before delivery.
Proportion of participants requiring a change in antiretroviral regimen (due to lack of efficacy, adverse events, medical decision, or other reasons) before delivery
Time frame
From enrollment to the end of treatment at 6 months after deliverySponsors and contacts
Click on the lead sponsor to view all of their trials.
Fundación Huésped
Lead sponsor
ViiV Healthcare
Collaborator
Source ClinicalTrials.gov