Maternal health outcomes among HIV-infected breastfeeding women with high CD4 counts: results of a treatment strategy trial

Abstract

Background: IMPAACT PROMISE 1077BF/FF was a randomized study of antiretroviral therapy (ART) strategies for pregnant and postpartum women with high CD4 T-cell counts. We describe postpartum outcomes for women in the study who were randomized to continue or discontinue ART after delivery. Methods: Women with pre-ART CD4 cell counts ≥350 cells/mm3 who started ART during pregnancy were randomized postpartum to continue or discontinue treatment. Women were enrolled from India, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. The primary outcome was a composite of progression to AIDS-defining illness or death. Log-rank tests and Cox regression models assessed treatment effects. Incidence rates were calculated per 100 person-years. A post-hoc analysis evaluated WHO Stage 2/3 events. All analyses were intent-to-treat. Findings: 1611 women were enrolled (June 2011-October 2014) and 95% were breastfeeding. Median age at entry was 27 years, CD4 count 728 cells/mm3 and the majority of women were Black African (97%). After a median follow-up of 1.6 years, progression to AIDS-defining illness or death was rare and there was no significant difference between arms (HR: 0·55; 95%CI 0·14, 2·08, p=0·37). WHO Stage 2/3 events were reduced with continued ART (HR: 0·60; 95%CI 0·39, 0·90, p=0·01). The arms did not differ with respect to the rate of grade 2, 3 or 4 safety events (p=0·61). Interpretation: Serious clinical events were rare among predominately breastfeeding women with high CD4 cell counts over 18 months after delivery. ART had significant benefit in reducing WHO 2/3 events in this population.

The impact of short term Antiretroviral Therapy (ART) interruptions on longer term maternal health outcomes—A randomized clinical trial

“…The AIDS/death endpoint rate was low across all PROMISE comparison groups during the 4 year follow up period. These specific cohort analyses were similar to the prior PROMISE Maternal Health findings [11] as well as the 1077HS results [8].…”

“…This finding provides some evidence of the clinical benefit of ART on moderate HIV disease progression [2]. Overall, these subgroup 1077BF/1077FF Maternal Health findings assessing the impact of short term ART during pregnancy or post-delivery during breastfeeding followed by randomized treatment interruption, are similar to the findings in the PROMISE 1077HS study conducted in non-breastfeeding settings where women received ART during pregnancy; as well as the findings in the PROMISE 1077BF/1077FF Maternal Health analyses looking at disease progression to AIDS or death following birth among women on maternal ART during pregnancy [11]. However the findings are in contrast to the SMART trial results among a large population of older adults whose episodic ART interruption significantly increased the risk of opportunistic disease or death [12].…”

Enrollment and transition challenges in the International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) network’s PROMISE trial for resource-limited regions

“…PROMISE successfully enrolled 96% of the target population intending to breastfeed and the antepartum, postpartum, and maternal health components were successful in producing statistically and clinically important efficacy and safety results. 1–3,6,7…”

“…Additional details on the PROMISE study and its design are provided elsewhere. [1][2][3] During study design, the PROMISE team queried IMPAACT site investigators regarding the numbers of potentially eligible breastfeeding and formula-feeding women who delivered at their sites per year and the estimated numbers were included in the study protocol to justify accrual projections. The study team worked with the sites to develop detailed accrual plans with monthly projections and then distributed a report each month showing projected and actual accrual for each site.…”

“…The ''Promoting Infant and Maternal Survival Everywhere'' (PROMISE) study was a multinational randomized controlled strategy trial in resource-limited settings, with three randomization components designed to answer key research questions about the relative efficacy and safety of interventions to prevent perinatal transmission of HIV during pregnancy and breastfeeding and preserve maternal health after cessation of perinatal transmission risk. [1][2][3] The PROMISE study enrolled a total of 3747 HIV-infected women in Africa and India who were pregnant or had recently given birth, had relatively high CD4 cell counts (ø350 cells/mm 3 ), and had not met country-specific criteria for initiating antiretroviral therapy for their own care, along with their infants.…”