OBJECTIVE: To determine whether maternal use of tenofovir disoproxil fumarate for treatment of HIV in pregnancy predicts fetal and infant growth. METHODS: The study population included HIV-uninfected live-born singleton infants of mothers enrolled in the International Maternal Pediatric Adolescent AIDS Clinical Trials Group protocol P1025 (born 2002-2011) in the United States and exposed in utero to a combined (triple or more) antiretroviral regimen. Infant weight at birth and 6 months was compared between infants exposed and unexposed to tenofovir in utero using 2-sample t test, chi test, and multivariable linear and logistic regression models, including demographic and maternal characteristics. RESULTS: Among 2025 infants with measured birth weight, there was no difference between those exposed (N = 630, 31%) versus unexposed to tenofovir in mean birth weight (2.75 vs. 2.77 kg, P = 0.64) or mean gestational age- and sex-adjusted birth weight z-score (WASZ) (0.14 vs. 0.14, P = 0.90). Among 1496 infants followed for 6 months, there was no difference in mean weight at 6 months between tenofovir-exposed (N = 457, 31%) and tenofovir-unexposed infants (7.64 vs. 7.59 kg, P = 0.52) or in mean WASZ (0.29 vs. 0.26, P = 0.61). Tenofovir exposure during the second/third trimester, relative to no exposure, significantly predicted underweight (WASZ < 5%) at age 6 months [odds ratio (95% confidence interval): 2.06 (1.01 to 3.95), P = 0.04]. Duration of tenofovir exposure did not predict neonatal or infant growth. CONCLUSIONS: By most measures, in utero exposure to tenofovir did not significantly predict infant birth weight or growth through 6 months of age.

HIV-infected individuals have poor responses to inactivated influenza vaccines. To evaluate the potential role of regulatory T (Treg) and B cells (Breg), we analyzed their correlation with humoral and cell-mediated immune (CMI) responses to pandemic influenza (pH1N1) monovalent vaccine in HIV-infected children and youth. Seventy-four HIV-infected, 4- to 25-y old participants in a 2-dose pH1N1 vaccine study had circulating and pH1N1-stimulated Treg and Breg measured by flow cytometry at baseline, post-dose 1 and post-dose 2. Concomitantly, CMI was measured by ELISPOT and flow cytometry; and antibodies by hemagglutination inhibition (HAI). At baseline, most of the participants had pH1N1-specific IFNgamma ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNgamma ELISPOT responses did not change post-dose 1 and significantly decreased post-dose 2. In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination. The decrease in IFNgamma ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFbeta+% Breg and Treg, respectively. In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNgamma ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%. In conclusion, in HIV-infected children and youth, influenza-specific Treg and Breg may contribute to poor responses to vaccination. However, robust humoral and CMI responses to vaccination may result in increased circulating Treg and/or Breg, establishing a feed-back mechanism.