Long-term ART Safe, Effective, Maintainable in Mothers With HIV

Long-term use of antiretroviral therapy (ART) can be maintained and is shown to be safe and effective among mothers in Africa living with HIV, according to new research findings.

Researcher also found that long-term maternal ART use can improve overall long-term health and survival of mothers with HIV and their children who have been exposed to HIV.

These findings were part of the PROMOTE study, which was published in Lancet HIV.

The longitudinal multicountry study enrolled 1987 mothers and 2522 children in Malawi, South Africa, Uganda, and Zimbabwe. Mothers were selected from an earlier perinatal clinical trial, PROMISE, which took place between 2011 and 2016 and in which they initiated ART.

After baseline enrollment into PROMOTE, the women and their children received follow-ups every 6 months for physical exams and laboratory tests and to collect data on their health, medical history, and ART use and adherence. Median (IQR) follow-up was 41.8 (35.8-42.0) months for mothers and 35.7 (23.8-42.0) months for children.

By the end of the study’s follow-up period, the retention rate was 96.5% among the mothers. Of this group, 1115 (89.1%) had an undetectable viral load at month 42, and this percentage varied by site between 81.7% and 93.8%.

“Adherence to ART use was excellent, as shown by the high rates of undetectable viral load, high CD4 count, and reported recent history of ART use,” the authors wrote. “High adherence reflects the participants’ confidence in these medications and the effect of regular and consistent counselling by the study team.”

General maternal health also improved over time. Between baseline and month 42, the proportion of women with “excellent” to “very good” health increased from 67.5% to 87.5%, unwell participants visiting a health center decreased from 14.7% to 2.8%, and participants admitted to a hospital decreased from 1.5% to 1.0%.

The overall pregnancy rate was 17.6 (95% CI, 16.5-18.7) per 100 women-years, and the mortality rate was 2.4 (1.4-3.9) per 1000 person-years for mothers and 3.4 (2.2-5.1) per 1000 person-years for children younger than 9 years.

Although a notable amount of participants experienced adverse events (AEs) throughout the study—34.4% of mothers and 16.5% of children—life-threating AEs specifically related to ART were rare, with only 28 events. Additionally, 15 mothers died during the study, and the authors said some of the deaths may have been related to efavirenz-induced liver toxicity.

Because of the rarity of serious, life-threatening AEs, the authors said the monitoring of long-term safety outcomes of ART did not reveal any major concerns and further research is necessary.

“An observation that deserves additional monitoring and proper investigation is the relatively high frequency of abortions and miscarriage at some sites (eg, in Uganda and Soweto) and the low live birth proportion in Uganda despite the high pregnancy rate,” they said. “We do not know if these observations relate to ART, prevailing biological or behavioural factors, or a reporting bias.”

The authors also said because of the positive effects on reducing viral load, ART could improve the mothers’ ability to have children and that many mothers of reproductive age in the study expressed the desire to have more children.

“Reproductive services should be strengthened and integrated to meet the improving health and changing expectations of these women,” the authors concluded.

Reference

Taha TE, Yende-Zuma N, Brummel SS, et al. Effects of long-term antiretroviral therapy in reproductive-age women in sub-Saharan Africa (the PEPFAR PROMOTE study): a multi-country observational cohort study. Lancet HIV. Published online April 27, 2022. doi:10.1016/S2352-3018(22)00037-6