SEATTLE – In HIV-positive pregnant women, an antiretroviral therapy (ART) regimen that included the integrase inhibitor raltegravir (RAL-ART) led to faster viral load (VL) reduction and a greater proportion of women with a VL of less than 200 copies/mL at delivery, compared with patients treated with an efavirenz-based ART (EFV-ART). There were no statistically significant differences between the two arms with respect to percentage of stillbirths, preterm delivery, or rates of HIV infection in the newborn.
“There are lots of advantages of these [integrase inhibitor] drugs, and we’d like to have pregnant women take advantage of them. The problem is, there’s no requirement of drug manufacturers to study the drugs in pregnancy. So these studies are put off until after the drug is licensed, and we’re playing catch-up,”, professor of pediatrics at Boston University, said in an interview. Dr. Mirochnick presented the results at the Conference on Retroviruses and Opportunistic Infections.
Another integrase inhibitor, dolutegravir, has a better resistance profile than that of raltegravir, but concerns over neural tube defects observedled both the Food and Drug Administration and the European Medicines Agency to issue safety warnings for that drug. The current study did not raise concern, since it began at 20 weeks’ gestation, well after the period when neural tube defects might occur. “I think it just demonstrates that [integrase inhibitors] are safe in mid- to late-pregnancy,” said Dr. Mirochnick.
It remains to be seen whether a potential link to neural tube defects, if it is a real effect, is due to a specific drug or the mechanism of action of integrase inhibitors more generally. “It’s a question we don’t have an answer to. So you have to balance the potential benefits and potential risks, and that’s probably a decision best made by an individual woman and her care provider. Some women do very well on a particular regimen and they don’t want to change, and you run the risk when you change that you’ll get a viral rebound. What do you tell women who are on dolutegravir and are thinking about becoming pregnant? That’s a controversial question. There are risks with both courses,” said Dr. Mirochnick.
The study comprised 408 patients recruited from centers in Brazil, Tanzania, South Africa, Thailand, Argentina, and the United States. The patients were between 20 and 37 weeks’ gestation and had not previously received ART. They were randomized to RAL-ART or EFV-ART. About 12% of patients were Asian, 36% were black, 52% were Hispanic, and 1% were white.
Overall, 94% of patients on RAL-ART had a VL less than 200 copies/mL at delivery, compared to 84% of EFV-ART patients (P = .001). The effect appeared to be driven by patients who enrolled later in pregnancy: There was no significant difference in those enrolled in weeks 20-28, but suppression occurred in 93% of the RAL-ART group versus 71% of the EFV-ART group among those enrolled in weeks 29-37 (P = .04).
Tolerability was slightly better in the RAL-ART group, with 99% versus 97% of patients staying on their assigned therapy (P = .05). In both groups, 30% of women experienced an adverse event of grade 3 or higher, as did 25% of live-born infants in both groups.
A total of 92% of women in the RAL-ART group had a sustained VL response through delivery, compared with 64% in the EFV-ART group (P less than .001). The median time to achieving a VL less than 200 copies/mL was 8 days in the RAL-ART group and 15 days in the EFV-ART group (generalized log-rank test P less than .001).
There was one stillbirth in the EFV-ART arm and three in the RAL-ART arm, with 11% in the EFV-ART group having preterm delivery compared with 12% in the RAL-ART group. In addition, the proportion of HIV-infected infants was lower in the RAL-ART arm (1% versus 3%). These differences were not significant.
The National Institutes of Health funded the study. Glaxo/ViiV, Merck, and Bristol-Myers Squibb supplied study drugs. Dr. Mirochnick has received research funding from those companies.
SOURCE: Mark Mirochnick et al. CROI 2019, .