Two-drug dolutegravir-based regimen a valid alternative for pregnant women with HIV

For pregnant women with HIV who are receiving dolutegravir (DTG)-based therapies, the two-drug regimen works just as well as three-drug regimens at keeping the viral load to "undetectable" levels without exerting serious adverse effects on neonatal outcomes, according to a study presented at HIV Glasgow 2022 Congress.

The retrospective analysis included 11 pregnant women on DTG plus lamivudine (3TC) and 13 on DTG plus two nucleoside reverse transcriptase inhibitors (2NRTIs). These women were either naïve to treatment or already on combination antiretroviral therapy (ART) before pregnancy.

At delivery, three women in the three-drug group had a detectable viral load as compared to only one in the two-drug group. One woman on DTG/3TC experienced a viral blip during the third trimester probably due to intake of vitamin and iron supplements plus ART at the same time, although the viral load returned negative at the time of delivery. [HIV Glasgow 2022, abstract P005]

The median CD4 count was 570 cells/mcL in the first trimester and 588 cells/mcL at delivery in the three-drug group as compared with 554 cells/mcL in the first trimester and 555 cells/mcL at delivery in the two-drug group.

Birth outcomes among women who delivered <37 weeks were similar, regardless of the regimen used. All infants had received antiretroviral prophylaxis and tested negative on follow-up. There were no reports of neonatal malformations.

“Numerous data from clinical trials and real-life studies has shown that the two-drug regimen DTG/3TC was noninferior to three-drug regimens. [In pregnant women], guidelines recommend regimens including DTG plus a backbone of two NRTIs,” according to presenting study author Dr Layla Pagnucco of IRCCS Fondazione Policlinico San Matteo in Pavia, Italy. [AIDS 2022;36:39-48; Clin Infect Dis 2022;doi:10.1093/cid/ciac130; J Acquir Immune Defic Syndr 2020;83:e2-e5; Lancet HIV 2020;7:e332-e339; https://tinyurl.com/23bl2z5a]

“In this case series report, DTG/3TC regimen may represent a valid therapeutic option during pregnancy in patients in whom, for various reasons, DTG/2NRTI regimen is not indicated. Further data and studies are needed to support the evidence of efficacy and safety of DTG/3TC in pregnancy,” Pagnucco added.

Dolutegravir vs efavirenz

In another study that compared DTG against efavirenz (EFV), there has been no significant difference detected in the overall risk of neonatal deaths, stillbirths, or cases of mother-to-child HIV transmission.

The analysis included 1,074 pregnant women with HIV who received either DTG with EFV as first-line treatment across five trials (DolPHIN-1, DolPHIN-2, ADVANCE, NAMSAL, and IMPAACT-2010). The DolPHIN trials were conducted in South Africa and Uganda, ADVANCE in South Africa, NAMSAL in Cameroon, and IMPAACT-2010 internationally. DolPHIN-1, DolPHIN-2, and IMPAACT-2010 involved women already pregnant at screening.

Pooled data showed no significant difference between the DTG and EFV arms in the composite of vertical transmission and neonatal deaths (45 vs 24 events, respectively; odds ratio, 1.20; p=0.49). None of the infants in any of the trials developed neural tube defects. [HIV Glasgow 2022, abstract P040]

In ADVANCE, women who were on DTG/emtricitabine (FTC)/tenofovir alafenamide (TAF) for 4 years had a higher risk of developing clinical obesity compared with those on DTG/FTC/disoproxil fumarate (TDF) or EFV/FTC/TAF (42 percent vs 27 percent and 20 percent).

The present data may have important implications, as first-line treatment with DTG leads to rapid suppression of HIV RNA that, in turn, might lower the risk of vertical transmission, according to Dr Andrew Hill of University of Liverpool, Department of Pharmacology and Therapeutics, Liverpool, UK, who presented the results of the study. “This analysis includes outcomes after first-line treatment typically up to 6 months before birth.”

Hill, however, cautioned that outcomes for women becoming pregnant after long-term treatment could be different due to DTG being associated with elevated risk of clinical obesity, especially if combined with TAF/FTC.