SEATTLE – Women presenting late in pregnancy with HIV infection were successfully treated with integrase inhibitors in randomized trials, reducing circulating virus faster than efavirenz-based therapy, researchers reported here.
In one trial, treatment with the integrase inhibitor raltegravir (Isentress) reduced circulating virus to undetectable levels in a median of 8 days compared to a median of 15 days treatment with efavirenz, reported Mark Mirochnick, MD, of Boston University School of Medicine/Boston Medical Center.
And in a second trial, treatment with another integrase inhibitor, dolutegravir (Tivicay), about 74% of women on the drug had undetectable viral loads at delivery compared with 43% of women treated with efavirenz combination therapy, reported Saye Khoo, MBBS, MD, of the University of Liverpool, England.
In a press conference at the annual Conference on Retroviruses and Opportunistic Infections, moderator Elaine Abrams, MD, of Columbia University in New York City, told MedPage Today, “Treatment with integrase inhibitors is now used throughout pregnancy in women with HIV infection. What these studies show is that is can be initiated in women who are in later stages of pregnancy.”
Raltegravir vs efavirenz
In his study, Mirochnick suggested, “These data from the first large randomized trial comparing an integrase inhibitor with efavirenz-based antiretroviral therapy initiated during pregnancy support the use of raltegravir-based antiretroviral therapy during pregnancy, especially for women starting antiretroviral late in gestation.”
He and colleagues enrolled 408 women in the study. All the patients, in addition to either raltegravir or efavirenz, were treated with two nucleoside transcriptase inhibitors as part of the antiretroviral regimen.
Among 183 women in the raltegravir arm of the trial evaluable for response, 173 of them (95%) achieved an undetectable viral load (defined as <200 copies/mL) at delivery, versus 151 of 179 (84%) in the efavirenz arm (P<0.001).
In a subgroup enrolled at 20 to <28 weeks gestation, 97% in both arms achieved viral suppression to undetectable levels at delivery. Among women who initiated treatment 28 weeks or later, 94% of the raltegravir-treated women and 72% of the efavirenz group achieved undetectable viral loads.
About 93% of the women on raltegravir were able to achieve rapid, sustained virologic response and remained on the study drug through delivery compared with 67% of the patients on efavirenz (P<0.001).
“Both regimens were well tolerated in women initiating antiretroviral therapy during pregnancy,” Mirochnick said. “Viral load reduction with raltegravir antiretroviral therapy was faster leading to more women with delivery viral load of less than 200 copies/mL.”
He said there were no significant differences in occurrence of adverse events of Grade 3 or worse among women or infants, stillbirths, or preterm births. One child whose mother was on raltegravir was born with HIV infection compared with 4 infants whose mothers were taking efavirenz (P>0.05), he reported.
Dolutegravir vs efavirenz
In his DolPHIN trial, Khoo and colleagues observed that the 268 mothers treated with the integrase inhibitor had viral loads reduced more quickly than among the 115 assigned to receive efavirenz. At delivery, 74% of the women on dolutegravir had achieved viral suppression to less than 50 copies/mL versus 43% of patients assigned to efavirenz (adjusted risk ratio 1.66, 95% CI 1.32-2.09), Khoo said at the press conference.
Achievement of viral loads less than 1,000 copies/mL at delivery was observed in 93% of dolutegravir-treated women compared with 83% of the women on efavirenz combination antiretroviral therapy (adjusted RR 1.11, 95% CI 1.00-1.23).
Khoo reported that dolutegravir was well-tolerated in pregnancy with no differences with efavirenz in frequency or organ class of severe adverse events. There were no significant differences between the groups in median gestational age at delivery or in the numbers of births at less than 34 weeks. Four stillbirths occurred in the dolutegravir arm. Of the 279 live births in the trial, eight born to mothers on dolutegravir and nine to mothers on efavirenz had congenital abnormalities. There were seven infant deaths – four in the dolutegravir arm and three in the efavirenz arm. The three cases of mother-to-child transmission of HIV all occurred in the dolutegravir arm, but were considered to have been in utero transmissions.
“Late presentation in pregnancy is associated with poor outcomes despite antiretroviral therapy and regardless of trial arm,” Khoo concluded.
Mirochnick disclosed relevant relationships with Gilead Sciences, Merck & Co., and ViiV Healthcare. Khoo disclosed relevant relationships with ViiV HealthCare. Abrams disclosed relevant relationships with ViiV Healthcare.