Among the principal reasons for recommending initiating antiretroviral treatment (ART) among pregnant patients who are HIV positive is to prevent transmission of the virus to their unborn children. This number was estimated at 1.3 million pregnant women, as of 2018.
Among the principal reasons for recommending initiating antiretroviral treatment (ART) among pregnant patients who are HIV positive is to prevent transmission of the virus to their unborn children. This number was estimated at 1.3 million pregnant pregnant women, as of 2018. However, optimal treatment regimens remain unclear.
An international team of investigators published their study results earlier this month in Lancet HIV showing the superiority of ART containing raltegravir, an integrase inhibitor, compared with efavirenz, a nonnucleoside reverse transcriptase inhibitor. Both drugs are well established in their safety and efficacy for reducing the HIV viral load among nonpregnant patients, but the results of initiating them during pregnancy remain unclear. Is one superior?
Between September 5, 2013, and December 11, 2018, 408 women pregnant women at 20 to 28 weeks gestation (n = 205) and 28 to 36 weeks gestation (n = 203) were enrolled in the open-label, randomized trial from 19 hospitals and clinics in Argentina (n = 20), Brazil (n = 190), South Africa (n = 60), Tanzania (n = 84), Thailand (n = 47), and the United States (n = 7). To qualify for study inclusion, they had to be ART-naïve or have received a maximum of 8 weeks of zidovudine, have confirmed HIV-positive status from 2 tests, and be between 20 and 36 weeks gestation.
All patients were randomized to 150-mg lamivudine and 300-mg zidovudine (or an approved alternative) plus either 400-mg raltegravir (n = 206) twice daily or 600-mg efavirenz (n = 202) nightly. The median ages in the raltegravir and efavirenz groups were 27 (range, 23-32) and 25 (range, 22-31) years, respectively. The study participants were evaluated at initial screening for study inclusion; study entry; weeks 1, 2, and 4, then every 2 weeks until delivery; and at 2, 6, 16, and 24 weeks post partum. The children born were evaluated at birth and ages 2, 16, and 24 weeks. Most women (390 live births, 4 stillbirths) had their babies during the course of the study (200, raltegravir; 194, efavirenz), and 307 (153 and 154, respectively) were included in the efficacy analysis.
The primary outcome was confirmed viral load below 200 copies/mL at delivery, with secondary outcomes being the safety and tolerability of both ART regimens.
Overall, 94% (144) of the raltegravir group and 84% (129) of the efavirenz group achieved the primary viral load outcome (absolute difference, 10%; 95% CI, 3%-18%; P = .0015). The raltegravir group also had a lower rate of children born with HIV than the efavirenz group: 0.5% (95% CI, <0.1%-2.9%) versus 3.3% (95% CI, 1.2%-7.0%), respectively.
In addition, the raltegravir group reached viral suppression in a shorter time frame than did the efavirenz group (hazard ratio, 1.84; 95% CI, 1.48-2.30; P <.0001), despite both groups being on their regimens for similar time frames before giving birth: median, 11.3 weeks (interquartile range, 6.9-15.6).
Also, significant differences in treatment efficacy were evident according to gestational age at study entry (P = .040): At 28 to 36 weeks gestation, 93% (76 of 82) of the raltegravir group compared with 71% (55 of 78) of the efavirenz group achieved the viral load goal.
Adverse events considered severe or life-threatening occurred at almost equal rates in the mothers (30%; 61, raltegravir and 59, efavirenz) and their infants (25%; 50 and 48, respectively).
“In a composite analysis of efficacy and tolerability, the difference in outcomes between raltegravir and efavirenz was even more pronounced and was driven by the faster viral load reduction with raltegravir,” the authors concluded. “Raltegravir was shown to be a potent and well tolerated antiretroviral. These results support the use of raltegravir in pregnant women who present late for care, particularly those initiating treatment after 28 weeks of gestation.”
João EC, Morrison RL, Shapiro DE, et al. Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial. Lancet HIV. 2020;7:e322-e331. doi:10.1016/S2352-3018(20)-30038-2