Shifting dynamics of HIV transmission timing among infants in the era of option B+ and implications for infant testing

Background: Universal antiretroviral treatment(ART) for HIV-positive pregnant women is anticipated to significantly reduce mother-to-child HIV transmission (MTCT). The World Health Organization recommends infant HIV testing at 4-6 weeks to capture in-utero/intrapartum/early breastfeeding transmission. In-utero infection is associated with high mortality of 20-30% by age 8-12 weeks. We conducted an implementation research study to determine the relative yield of HIV birth testing.
Methods: HIV-positive and negative pregnant women were enrolled in an observational cohort to evaluate effectiveness of universal maternal ART within 13 health facilities in Lesotho following introduction of Option B+. HIV birth testing (DNA PCR within two weeks of birth) was introduced at study sites in addition to routine six-week infant testing, per national guidelines. Dried blood spots were collected at birth for PCR testing (Roche CAP/CTM HIV v2) followed by routine six-week testing. Data were analyzed to identify HIV transmission rates at birth and six weeks.
Results: Among 602 women (median age, 29 years; median gestational age at first ANC visit, 24 weeks), 427/602 (70%) of their infants were tested at birth, 497/602 (83%) were tested at 6 weeks, and 363/422 (86%) of infants uninfected at birth were retested at 6 weeks. In utero HIV infection with positive birth PCR occurred in 5/427 (1.2%) infants. An additional 2 infants, one with a prior negative birth test and a second without a prior birth test tested positive at 6 weeks, for a cumulative MTCT incidence of 1.25% (95%CI: 0.5%-2.6%). The 6-week MTCT rate was 1/211 (0.5%) among women who initiated ART before pregnancy compared to 6/331 (1.8%) among women who started ART during pregnancy. Maternal HIV RNA levels were associated with transmission: median HIV RNA was 1.27 log10 copies/mL among non-transmitting women versus 5.03 log10 copies/mL among transmitting women.
Conclusions: Universal antenatal maternal ART resulted in very low 6-week MTCT (< 1.5%); MTCT rates were lowest with pre-pregnancy ART initiation. Among infants, in contrast to pre-ART era, where ~30% of infections occurred in utero, most infections (5/7, 71%) were identified at birth, suggesting that introduction of birth testing, if accompanied by rapid infant ART initiation, could significantly impact the health of infected infants.

A. Tiam1,2, S. Kassaye3, R. Machekano1, M. Gill1, V. Tukei4, M. Mokone4, S. Mohale4, M. Makhohlisa4, M. Letsie5, M. Tsietso5, I. Seipati5, A. Isavwa4, L. Guay1,6
1Elizabeth Glaser Pediatric AIDS Foundation, Research, Washington, United States, 2University of Bergen, Medicine and Dentistry, Centre for International Health, Bergen, Norway, 3Georgetown University, Washington, United States, 4Elizabeth Glaser Pediatric AIDS Foundation, Research, Maseru, Lesotho, 5Ministry of Health, Disease Control, Maseru, Lesotho, 6George Washington University, Milken Institute School of Public Health, Washington, United States