Carolyne Onyango-Makumbi1, Arthur H Owora1,2, Ramadhani S Mwiru3, Anthony Mwatha4, Alicia M Young4, Dhayendre Moodley5, Hoosen M Coovadia6, Lynda Stranix-Chibanda7, Karim Manji8, Yvonne Maldonado9, Paul Richardson10, Philip Andrew11, Kathleen George11, Wafaie Fawzi12, Mary Glenn Fowler13. 1. Makerere University-Johns Hopkins University Research Collaboration/MU-JHU CARE LTD, Kampala, Uganda. 2. Department of Biostatistics and Epidemiology, School of Public Health, Indiana University, Bloomington, IN. 3. Division of Global HIV/AIDS, Center for Global Health, U.S. Centers for Disease Control and Prevention, Dar es Salaam, Tanzania. 4. Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA. 5. Department of Obstetrics and Gynaecology, Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson R Mandela School of Medicine, University of KwaZulu Natal, Durban, South Africa. 6. Maternal Adolescent and Child Health (MatCH), University of the Witwatersrand, South Africa. 7. College of Health Sciences, University of Zimbabwe, Harare, Zimbabwe. 8. Department of Paediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania. 9. Division of Infectious Diseases, Department of Pediatrics, Stanford University, School of Medicine, Stanford, CA. 10. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore,MD. 11. Family Health International, Durham, NC. 12. Departments of Global Health and Population, Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 13. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD.
Abstract
BACKGROUND: Effects of prolonged nevirapine prophylaxis exposure on growth among HIV-exposed uninfected (HEU) infants are unknown. This study examines the impact of extended nevirapine prophylaxis from 6 weeks to 6 months on the growth of HEU infants followed for 18 months and also identifies correlates of incident wasting, stunting, underweight, and low head circumference in the HPTN 046 trial. METHODS: Intention-to-treat analysis examined the effect of extended nevirapine exposure on: weight-for-age Z-score, length-for-age Z-score, weight-for-length Z-score, and head circumference-for-age Z-score. Multivariable linear mixed-effects and Cox proportional hazard models were used to compare growth outcomes between the study arms and identify correlates of incident adverse growth outcomes, respectively. RESULTS: Compared to placebo, extended prophylactic nevirapine given daily from 6 weeks to 6 months did not affect growth in HEU breastfeeding (BF) infants over time (treatment × time: P > 0.05). However, overall growth declined over time (time effect: P < 0.01) when compared with WHO general population norms. Male sex was associated with higher risk of all adverse growth outcomes (P < 0.05), whereas short BF duration was associated with wasting (P = 0.03). Maternal antiretroviral therapy exposure was protective against underweight (P = 0.02). Zimbabwe tended to have worse growth outcomes especially stunting, compared to South Africa, Uganda and Tanzania (P < 0.05). CONCLUSIONS: It is reassuring that prolonged exposure to nevirapine for prevention-of-mother-to-child HIV transmission does not restrict growth. However, targeted interventions are needed to improve growth outcomes among at-risk HEU infants (i.e., male sex, short BF duration, lack of maternal antiretroviral therapy exposure, and resident in Zimbabwe).
RCT Entities:
BACKGROUND: Effects of prolonged nevirapine prophylaxis exposure on growth among HIV-exposed uninfected (HEU) infants are unknown. This study examines the impact of extended nevirapine prophylaxis from 6 weeks to 6 months on the growth of HEUinfants followed for 18 months and also identifies correlates of incident wasting, stunting, underweight, and low head circumference in the HPTN 046 trial. METHODS: Intention-to-treat analysis examined the effect of extended nevirapine exposure on: weight-for-age Z-score, length-for-age Z-score, weight-for-length Z-score, and head circumference-for-age Z-score. Multivariable linear mixed-effects and Cox proportional hazard models were used to compare growth outcomes between the study arms and identify correlates of incident adverse growth outcomes, respectively. RESULTS: Compared to placebo, extended prophylactic nevirapine given daily from 6 weeks to 6 months did not affect growth in HEU breastfeeding (BF) infants over time (treatment × time: P > 0.05). However, overall growth declined over time (time effect: P < 0.01) when compared with WHO general population norms. Male sex was associated with higher risk of all adverse growth outcomes (P < 0.05), whereas short BF duration was associated with wasting (P = 0.03). Maternal antiretroviral therapy exposure was protective against underweight (P = 0.02). Zimbabwe tended to have worse growth outcomes especially stunting, compared to South Africa, Uganda and Tanzania (P < 0.05). CONCLUSIONS: It is reassuring that prolonged exposure to nevirapine for prevention-of-mother-to-childHIV transmission does not restrict growth. However, targeted interventions are needed to improve growth outcomes among at-risk HEUinfants (i.e., male sex, short BF duration, lack of maternal antiretroviral therapy exposure, and resident in Zimbabwe).
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