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.

Trial registration: ClinicalTrials.gov NCT01061151.

Keywords: HIV and breastfeeding; HIV/AIDS; antiretroviral therapy (ART); postpartum maternal health.

Figure 1:

Description of the PROMISE 1077 BF/FF women included in the analysis. This analysis includes all women on three-drug ART during pregnancy who were randomized postpartum to continue or discontinue, as well as all women randomized to continue ART at cessation of breastfeeding (black boxes).

Figure 2:

CONSORT flow diagram for women included in the analysis^*

Figure 3:

CD4 T-cell counts over time (median, 10^th and 90^th percentile, and proportion <350 cells/mm³). The median CD4 T-cell counts in the continue (blue) and discontinue (red) arms are shown at each follow-up visit. The proportion with CD4 T-cells below 350 cells/mm³ are shown across the top of the figure at each time point.

Figure 4:

Survival curves for key study findings (A) Primary Composite Endpoint; (B) WHO 2 and 3 events; (C) Safety Endpoint