- Category: Pregnancy & HIV MTCT
- Published on Tuesday, 18 March 2014 00:00
- Written by Carole Leach-Lemens
Pregnant women taking efavirenz-based antiretroviral therapy (ART) had significantly better virological outcomes at the time of delivery compared to those taking lopinavir/ ritonavir in a randomized study in rural Uganda, according to a report at the 21st Conference on Retroviruses and Opportunistic Infections (CROI 2014) in Boston this month.
However both regimens, overall, had very high virological suppression rates and were extremely effective in preventing mother-to-child HIV transmission during pregnancy and breast-feeding noted Deborah Cohan from the University of California at San Francisco, reporting on behalf of the PROMOTE study team.
The findings from this secondary analysis of a randomized open-label study evaluating efavirenz (Sustiva or Stocrin) compared to lopinavir boosted with ritonavir (Kaletra) for the prevention of placental malaria, support the 2013 World Health Organization (WHO) guidelines recommending efavirenz-based combination ART for all pregnant women regardless of CD4 count -- known as Option B+ -- as a first-line option, with ART containing lopinavir/ritonavir as an alternative.
These new guidelines, however, were recommended within the context of significant research gaps that included maternal and infant outcomes, antiretroviral toxicity, and alternative ART regimens.
PROMOTE enrolled pregnant women living with HIV who had not previously taken HIV treatment at between 12 and 28 weeks of gestation. The women were randomized to receive either lopinavir/ritonavir or efavirenz with zidovudine (AZT, Retrovir) and lamivudine (3TC, Epivir), starting at enrollment until 1 year of breast-feeding and followed for 6 weeks after cessation of breast-feeding.
The dose of lopinavir/ritonavir increased from 400 mg/100 mg twice-daily to 600 mg/150 mg twice-daily at thirty weeks. All women received cotrimoxazole prophylaxis and insecticide-treated bed nets, and infants received zidovudine or nevirapine (Viramune) prophylaxis in accordance with Ugandan guidelines. Women received nutritional counseling to breast-feed for 1 year after delivery.
This substudy compared virological, immunological, and safety outcomes between the 2 arms of the study.
Of the 593 women screened, 389 were eligible and enrolled, of whom 348 completed the study, and data were available for 377 women at delivery.
At baseline, there were no significant differences in the 2 arms of the study. The mean age was 29 years and the median duration of gestation at enrollment was 21 weeks. This was a first pregnancy for fewer than 10%, with over two-thirds having 3 or more children at home. The median CD4 T-cell count in both arms was over 350 cells/mm3, yet over 90% were at WHO stage 1. Malnutrition was a significant issue, with a mean body mass index (BMI) at enrollment of 21.8. At baseline, the median HIV RNA was 4.3 and 4.1 log for the efavirenz and lopinavir/ritonavir arms, respectively.
Women taking efavirenz were significantly more likely to achieve viral suppression (<400 copies/mL) at delivery compared to women on lopinavir/ritonavir, 98% (166 out of 170) vs 86% (153 out of 178), respectively. However, no differences were seen at 8 weeks after starting ART while pregnant, with close to 90% of women achieving viral suppression in both arms, and with similar findings at weeks 24 and 48 after delivery.
Looking at all viral loads measured (1335 measurements from 374 women), a 50% lower odds of viral suppression among women on lopinavir/ritonavir was seen. Cohan noted, however, this is within a context of overall very high levels of virological suppression for both regimens.
Women taking lopinavir/ritonavir had significantly greater CD4 cell count recovery compared to women taking efavirenz at delivery, (+57 and -7 cells/mm3, respectively) and at 24 weeks postpartum (+178 and +109 cells/mm3, respectively).
WHO grade 4 adverse events were rare and did not differ by arm. Kaposi’s sarcoma was diagnosed in 1 woman in the efavirenz arm and pulmonary TB in 1 woman in the lopinavir/ritonavir arm. However, diarrhea and nausea and vomiting (grades 1 and 2) were significantly more likely among women taking lopinavir/ritonavir, both before and after delivery. Grade 3 and 4 adverse events, mostly anemia and neutropenia, were similar between the arms. There were no differences in preterm births, miscarriages, stillbirths, or neonatal death between the 2 arms.
The HIV transmission rate was 0.5% (2 out of 374 live births). Both were in the lopinavir/ritonavir arm, 1 in utero and 1 during breast-feeding. HIV-free survival was high and did not differ between the efavirenz and lopinavir/ritonavir arms, 97% and 93%, respectively.
Differences at delivery may potentially be explained by efavirenz being more potent than lopinavir/ritonavir, as well as by adherence and drug exposure during pregnancy, Cohan noted. Self-reported adherence rates were high in both arms, but self-reporting is vulnerable to social desirability bias, she added.
While pharmacokinetic studies suggest lopinavir/ritonavir exposure may be inadequate before delivery, it is unclear whether this explains the differential virologic suppression, Cohan said.
Cohan concluded, "these data provide reassurance that high levels of viral suppression are achievable, demonstrate that infants have a low risk of HIV acquisition with these regimens, and show that women can successfully initiate ART when they present to the antenatal clinic and maintain therapy thereafter."
She added, "the ultimate goal of lifelong suppressive therapy is to keep these women healthy."
D Cohan, P Natureeba, A Plenty, et al. Efficacy and Safety of LPV/r Versus EFV in HIV+ Pregnant and Breast-Feeding Ugandan Women.21st Conference on Retroviruses and Opportunistic Infections (CROI 2014). Boston, March 3-6. Abstract 69.