Adherence to extended postpartum antiretrovirals is associated with decreased breast milk HIV-1 transmission

Abstract

Objective Estimate association between postpartum antiretroviral adherence and breastmilk HIV-1 transmission Design Prospective cohort study Methods Mother-infant pairs were randomized after delivery to immediately begin receiving 28 weeks of either triple maternal antiretrovirals (zidovudine, lamivudine, and either nevirapine, nelfinavir, or lopinavir-ritonavir) or daily infant nevirapine as part of the Breastfeeding, Antiretrovirals, and Nutrition study. Associations between postpartum antiretroviral adherence and rate of breastmilk HIV-1 transmission were estimated using Cox models. We measured adherence over four postpartum time intervals using pill count, suspension bottle weight, and maternal self-report. Adherence was categorized and lagged by one interval. Missing adherence measures were multiply imputed. Infant HIV-1 infection was determined by DNA PCR every 2-6 weeks. The primary endpoint was infant HIV-1 infection by 38 weeks of age among infants alive and uninfected at 5 weeks. Results Analyses included 1479 mother-infant pairs and 45 transmission events. Using pill count and bottle weight information, 22-40% of mother-infant pairs at any given interval were <90% adherent. Having ≥90% adherence was associated with a 52% (95% CI 3-76%) relative reduction in the rate of breastmilk HIV-1 transmission, compared with having <90% adherence when controlling for study arm, breastfeeding status, and maternal characteristics. Complete case analysis rendered similar results (n=501; relative reduction 59%, 95% CI 6-82%). Conclusion Non-adherence to extended postpartum ART regimens in ‘real world’ settings is likely to be higher than that seen in BAN. Identifying mothers with difficulty adhering to antiretrovirals, and developing effective adherence interventions, will help maximize benefits of ARV provision throughout breastfeeding.

Maternal and Breastmilk Viral Load: Impacts of Adherence on Peripartum HIV Infections Averted—The Breastfeeding, Antiretrovirals, and Nutrition Study

“…17 However, we now more conclusively show that maintaining antiretroviral adherence alone is unlikely to prevent all breastmilk transmission in the first 28 weeks postpartum if triple ARVs are initiated after delivery. The sufficient set of mechanisms that cause breastmilk HIV transmission remain incompletely determined.…”

“…Nonetheless, we previously found consistent associations between adherence and breastmilk HIV transmission in BAN using pill count and self-reported adherence. 17 …”

“…Specifically, adherence was calculated by dividing the difference in the number of pills distributed and returned by the number of pills expected to be consumed under perfect compliance. 17 The observed distribution of maternal pill count adherence was skewed, with most women randomized to maternal ARVs having adherence values greater than 90%. The observed adherence distribution was anticipated due to mothers' high motivation to adhere to study drug in order to prevent HIV transmission to their infant.…”

Effect of Postnatal HIV Treatment on Clinical Mastitis and Breast Inflammation in HIV‐Infected Breast‐feeding Women

“…For all treatment analyses, the standard of care group was the referent and we assumed adherence to assigned intervention arms. 20 To account for competing risks (i.e. breast-feeding cessation, infant or maternal death), the proportional sub-distribution hazards model was employed to estimate hazard ratios of mastitis or breast inflammation while breast-feeding.…”

“…Participants were randomized to one of six arms in the original study and we assumed exchangeability between groups for this nested study. For all treatment analyses, the standard of care group was the referent and we assumed adherence to assigned intervention arms …”