SEATTLE – At the 2018 Conference on Retroviruses and Opportunistic Infections, investigators reported that the rate of adverse pregnancy outcomes was 23% among HIV-positive women who took isoniazid to prevent tuberculosis during pregnancy, but just 17% among women who waited until after delivery.
Dr. Nicole Salazar-Austin
It was an international, randomized trial that included 156 women, and outcomes included in utero demise and low birth weight. The investigators concluded that the World Health Organization needed to reconsider its recommendation for isoniazid preventative treatment (IPT) during HIV pregnancy in areas where tuberculosis (TB) is common.
The news was in the exact opposite direction at this year’s conference: An observational study of 151 pregnant HIV-positive women in Soweto, South Africa, found no evidence of poor maternal or infant outcomes with isoniazid prophylaxis, according to investigators led by Nicole Salazar-Austin, MD, a pediatric instructor at Johns Hopkins University, Baltimore.
The team was alarmed by the 2018 findings, so it decided to take a closer look with their own data. They compared outcomes in 69 HIV-positive women (46%) who reported initiating IPT during pregnancy with 82 who did not from January 2011 through January 2014. There was higher use of combination antiretroviral therapy in the IPT group, and viral loads below 400 copies/mL were more common.
The proportion of neonates born prematurely was lower in the IPT group than in the group not using it, but this did not reach significance (10% vs. 22%; P = 0.06). There was no difference in fetal demise (1% in both groups); low birth weight (9% vs. 12%; P = 0.51); or congenital anomalies (1% vs. 2%, P = 1.0).
A composite of the four outcomes actually showed fewer events among infants exposed to IPT (16% vs. 28%; P = 0.08). The outcomes held when stratified by viral load suppression and when other causes of poor infant outcomes – advanced HIV disease, advanced maternal age, and low weight gain during pregnancy – were taken into account.
As an observational study based on self-report, the new work was much less rigorous than the 2018 randomized trial, Dr. Salazar-Austin noted. Also, the work was part of a larger project that was not designed specifically to study pregnancy outcomes. IPT was initiated by public antenatal and HIV clinics, not by the study team.
Still, “we hope that these results provide some reassurance that IPT can be used in the second or third trimester among pregnant women with HIV,” Dr. Salazar-Austin said.
So, how to mesh the two studies? Like everything in medicine, it comes down to a risk/benefit analysis.
“For pregnant women living in a household with an active TB case, maybe the benefit outweighs the risk, especially if they are living with HIV. Whether all women living with HIV in a high [TB] burden [area] should receive isoniazid is still somewhat in question. I think we need to weigh” IPT during HIV pregnancy on an “individual basis moving forward,” she said.
Women in the observational trial were a median of about 30 years old. The median CD4 T-cell count at enrollment was about 370 cells/mm3.
The work was funded by the National Institutes of Health. Dr. Salazar-Austin didn’t have any disclosures.
SOURCE: Salazar-Austin NM et al. CROI 2019, Abstract 77.