Efficacy of six-week extended-dose nevirapine varies by infant birth weight with greatest relative efficacy in low birth weight infants

Low birth weight (LBW), defined by the World Health Organization (WHO) as birth weight less than 2500 g, is a significant public health issue in resource-limited settings, particularly in Sub Saharan Africa and South Asia where the estimated annual incidence is 14% and 28–31%, respectively, and the HIV burden among women of reproductive age is high [1,2]. Maternal HIV infection is an independent risk factor for LBW [3,4], and LBW infants of HIV-infected women are at increased risk for mother-to-child transmission (MTCT) of HIV and death [5,6,7]. Amidst a rapidly evolving landscape, optimizing maternal and infant drug regimens for prevention of MTCT (PMTCT) of HIV infection remains a research priority. LBW infants, however, have been understudied.

 

Most recent WHO HIV PMTCT guidelines recommend lifelong combination antiretroviral treatment (ART) for pregnant and breastfeeding HIV-infected women (national PMTCT programme Option B or B+) and six weeks of daily weight-based nevirapine for all breastfed, HIV-exposed infants [8,9]. To date, several trials support extended nevirapine prophylaxis in infancy to prevent breast-milk MTCT of HIV infection [6,10–15]. However, safety and efficacy data in LBW infants are limited as most studies have either excluded or enrolled LBW infants in small numbers [6,11,15–20]. Notably, based on their relative physiologic immaturity, LBW infants may metabolize and respond differently to nevirapine than normal birth weight infants. Specific cytochrome P-450 enzymes isoforms with varying activity levels are differentially expressed throughout development, which leads to differences in nevirapine elimination in fetuses, neonates, and throughout infancy [21,22]. Thus, the impact of extended nevirapine prophylaxis may vary by infant birth weight and optimal dosing may not be known.

 

The present study aims to assess whether the impact of six-week extended-dose nevirapine (SWEN) prophylaxis varies with infant birth weight. The India SWEN study, a randomized clinical trial of SWEN versus single-dose nevirapine (SD) for PMTCT of HIV-1 infection via breast milk, presents a unique opportunity as LBW infants comprise approximately 40% of the study population, infants were randomized to treatment arm at birth, and HIV-1 transmission was assessed through age 12 months [10,12]. We report our secondary safety and efficacy analyses of the India SWEN study stratified by infant birth weight.