Dolutegravir

Results of a phase 3 trial support recommendations for the use of dolutegravir-based antiretroviral therapy (ART) during pregnancy and postpartum. These findings were published in The Lancet HIV.

In 2018, the World Health Organization (WHO) released guidelines recommending dolutegravir for use in first-line ART regimens.

The VESTED (ClinicalTrials.gov identifier: NCT03048422) trial was an open-label, randomized-controlled, phase 3 trial designed to evaluate the effects of guideline-directed ART in the setting of pregnancy. Women (N=643) at 14 to 28 weeks’ gestation with HIV infection were enrolled at 22 sites across 9 countries between 2018 and 2019. Study patients were randomly assigned 1:1:1 to receive either dolutegravir, emtricitabine, and tenofovir alafenamide (DTG/FTC/TAF; n=217); dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (DTG/FTC/TDF; n=215); or efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF; n=211). The primary safety outcomes were pairwise comparisons between ART regimens of the percentage of maternal and infant adverse events (AEs) of grade 3 and higher adverse event rates up to 50 weeks postpartum. Secondary efficacy outcomes were the percentage of women in the DTG-based ART groups vs EFV-based ART group with HIV viral loads of less than 200 copies/mL at 50 weeks post partum

Among patients included in the analysis, the median age was 26.6 (range, 18.1-44.5) years, 91% were Black, the median gestational age at baseline was 21.9 (range, 18.3-25.3) weeks, the median HIV viral load was 903 (range, 152-5183) copies/mL, the median CD4+ count was 466 (range, 308-624) cells/µL. In addition, 83% of patients used ART during pregnancy.

Overall, 28% of women experienced AEs of grade 3 and higher. The highest AE rate was observed among patients using DTG/FTC/TDF (31%), whereas those using DTG/FTC/TAF (25%) had the lowest rate. In general, clinical events were more common than laboratory events (20% vs 11%, respectively).

A total of 42 women experienced virologic failure during the study, the majority of whom were in the EFV/FTC/TDF group (n=22), followed by the DTG/FTC/TDF (n=11) and DTG/FTC/TAF (n=11) groups.

Characteristics of the 617 liveborn infants were similar between groups, with the exception of birthweight, preterm birth, and small for gestational age rates. Two major congenital anomalies were observed in both the DTG/FTC/TAF and DTG/FTC/TDF groups.

Among infants overall, 28% of infants had AEs of grade 3 or higher. The highest AE rate was observed among infants with mothers in the EFV/FTC/TDF group (31%), and the lowest rate was observed among infants with mothers in the DTG/FTC/TAF group (25%). In addition, HIV was diagnosed in 1 infant whose mother was in the DTG/FTC/TDF group, 1 infant whose mother was in the EFV/FTC/TDF group, and 2 infants whose mothers were in the DTG/FTC/TDF group.

Mortality occurred among significantly more infants whose mothers received EFV/FTC/TDF (n=14) compared with those whose mothers received either DTG/FTC/TAF (n=2; P =.0010) or DTG/FTC/TDF (n=4; P =.008) groups. Mortality was most commonly attributed to hypoxic-ischemic encephalopathy, sepsis, and pneumonia.

Study limitations include the inability to assess the effects of drug exposure at conception or during organogenesis on the occurrence of congenital anomalies or spontaneous abortion as patients were at 14 weeks’ gestations at baseline.

"These findings support the WHO recommendation to use dolutegravir in all populations, including in pregnant and post-partum women," the researchers concluded.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Chinula L, Ziemba L, Brummel S, et al; on behalf of the IMPAACT 2010/VESTED Study Team and Investigators. Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet HIV. Published online May 8, 2023. doi:10.1016/S2352-3018(23)00061-9