SEATTLE – In HIV-positive pregnant women who had not previously been on antiretroviral therapy (ART), initiation of treatment with dolutegravir during the third trimester led to lower viral loads at delivery and reduced HIV transmission to offspring compared to treatment with efavirenz. The result comes from a study conducted in South Africa and Uganda. Both drugs were combined with two nucleoside reverse transcriptase inhibitors (NRTIs).
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ART-naive women who start ART during the third trimester often do not achieve sufficient reduction of viral load, and the researchers believed that integrase inhibitors like dolutegravir may lead to greater success because they can lead to viral clearance faster than other classes of drugs, which aren’t powerful enough to get viral loads to undetectable levels by the time of delivery. In fact, women who start therapy in the third trimester are at a 600% higher risk of transmitting the virus to offspring, and infant mortality is doubled in the first year of life, according to Saye Khoo, MD, professor of molecular and clinical pharmacology at the University of Liverpool (England).
“Clearly the viral load and undetectable viral load at the time of delivery is the best proxy for the lowest risk of mother to child transmission,” Dr. Khoo said at the Conference on Retroviruses & Opportunistic Infections. “This study clearly showed that there were big differences between dolutegravir and efavirenz. Viral load was undetectable in 74% in the dolutegravir group compared to 43% in efavirenz, which was highly significant.”
In the open-label DolPHIN-2 study, 268 women were randomized after week 28 of their pregnancy (median, 31 weeks) to receive dolutegravir or efavirenz plus two NRTIs. The dolutegravir group was more likely to achieve viral load less than 50 copies/mL at delivery (74% vs. 43%; adjusted risk ratio, 1.66; 95% confidence interval, 1.32-2.09). The trend occurred across subanalyses that included baseline viral load, baseline CD4 count, and gestation at initiation. 93% of the women in the dolutegravir group had a viral load less than 1,000 copies/mL, compared with 83% in the efavirenz group (RR, 1.11; 95% CI, 1.00-1.23).
There were no differences between the two groups with respect to frequency of severe adverse events, organ class of severe adverse events, gestational age at delivery, births earlier than 34 weeks, or births earlier than 37 weeks.
Four stillbirths occurred in the dolutegravir arm, and none in the efavirenz group. “Each of these was examined in great detail, as you might imagine. There were clear explanations for the cause of death, and it was related to maternal infection in two cases and obstetric complications in the other two,” said Dr. Khoo. There were no observations of neural tube defects – a concern that has been raised in the use of dolutegravir at the time of conception.
“I think we did see clear differences in virologic response in the arms, and so that would argue that dolutegravir certainly could be considered in these high-risk scenarios,” said Dr. Khoo.
The study was funded by the University of Liverpool. Dr. Khoo reported consulting for and receiving research funding from ViiV.
SOURCE: Khoo S et al. CROI 2019, Abstract 40 LB.