Patricia M Flynn1, Taha E Taha2, Mae Cababasay3, Kevin Butler3, Mary G Fowler4, Lynne M Mofenson5, Maxensia Owor6, Susan Fiscus7, Lynda Stranix-Chibanda8,9, Anna Coutsoudis10, Devasena Gnanashanmugam11, Nahida Chakhtoura12, Katie McCarthy13, Lisa Frenkel14,15, Ingrid Beck15, Cornelius Mukuzunga16, Bonus Makanani17, Dhayendre Moodley18, Teacler Nematadzira9, Bangani Kusakara9, Sandesh Patil19, Tichaona Vhembo9, Raziya Bobat20, Blandina T Mmbaga21, Maysseb Masenya22, Mandisa Nyati23, Gerhard Theron24, Helen Mulenga25, David E Shapiro3. 1. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN. 2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 3. Center for Biostatistics in AIDS Research, Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA. 4. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. 5. Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC. 6. Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda. 7. Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC. 8. Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, University of Zimbabwe, Harare, Zimbabwe. 9. University of Zimbabwe Clinical Trials Research Centre, Harare, Zimbabwe. 10. Department of Pediatrics and Child Health, University of KwaZulu-Natal, Durban, South Africa. 11. Division of AIDS, National Institute of Allergy and Immunology, National Institutes of Health, Bethesda, MD. 12. Maternal and Pediatric Infectious Disease Branch, Division of Extramural Research, Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institutes of Health, Rockville, MD. 13. FHI 360, Durham, NC. 14. Department of Pediatrics and Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA. 15. Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA. 16. University of North Carolina Project-Malawi, Kamuzu Central Hospital, Lilongwe, Malawi. 17. Department of Obstetrics and Gynecology, College of Medicine, University of Malawi, Blantyre, Malawi. 18. Department of Obstetrics and Gynaecology, Centre for the AIDS Programme of Research in South Africa and School of Clinical Medicine, College of Health Sciences, University of KwaZulu Natal, Durban, South Africa. 19. Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical College and Johns Hopkins Clinical Trials Unit, Pune, India. 20. Department of Pediatrics and Child Health, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. 21. Department of Pediatrics, Kilimanjaro Christian Medical Centre and Kilimanjaro Christian Medical University College, Moshi, Tanzania. 22. Wits Reproductive Health and HIV Institute, Johannesburg, South Africa. 23. Perinatal HIV Research Unit, Chris Baragwanath Hospital, Johannesburg, South Africa. 24. Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; and. 25. Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
Abstract
BACKGROUND: Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the Promoting Maternal-Infant Survival Everywhere trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (<1%) in the 2 arms. We assessed whether maternal viral load (MVL) and CD4 cell counts were associated with breastfeeding HIV transmission. METHODS: MVL was collected at entry (7-14 days postpartum) and at weeks 6, 14, 26, and 50 postpartum. CD4 cell counts were collected at entry and weeks 14, 26, 38, and 50 postpartum. Infant HIV-1 nucleic acid test was performed at weeks 1 and 6, every 4 weeks until week 26, and then every 12 weeks. The associations of baseline and time-varying MVL and CD4 cell counts with transmission risk were assessed using time-to-event analyses by randomized treatment arm. RESULTS: Two thousand four hundred thirty-one mother-infant pairs were enrolled in the study. Baseline MVL (P = 0.11) and CD4 cell counts (P = 0.51) were not significantly associated with infant HIV-1 infection. Time-varying MVL was significantly associated with infant HIV-1 infection {hazard ratio [95% confidence interval (CI)]: 13.96 (3.12 to 62.45)} in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 1.04 (0.20 to 5.39)]. Time-varying CD4 cell counts were also significantly associated with infant HIV-1 infection [hazard ratio (95% CI): 0.18 (0.03 to 0.93)] in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 0.38 (0.08 to 1.77)]. CONCLUSIONS: In women receiving mART, increased MVL and decreased CD4 cell counts during breastfeeding were associated with increased risk of infant HIV-1 infection.
BACKGROUND: Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the Promoting Maternal-Infant Survival Everywhere trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (<1%) in the 2 arms. We assessed whether maternal viral load (MVL) and CD4 cell counts were associated with breastfeeding HIV transmission. METHODS: MVL was collected at entry (7-14 days postpartum) and at weeks 6, 14, 26, and 50 postpartum. CD4 cell counts were collected at entry and weeks 14, 26, 38, and 50 postpartum. Infant HIV-1 nucleic acid test was performed at weeks 1 and 6, every 4 weeks until week 26, and then every 12 weeks. The associations of baseline and time-varying MVL and CD4 cell counts with transmission risk were assessed using time-to-event analyses by randomized treatment arm. RESULTS: Two thousand four hundred thirty-one mother-infant pairs were enrolled in the study. Baseline MVL (P = 0.11) and CD4 cell counts (P = 0.51) were not significantly associated with infant HIV-1 infection. Time-varying MVL was significantly associated with infant HIV-1 infection {hazard ratio [95% confidence interval (CI)]: 13.96 (3.12 to 62.45)} in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 1.04 (0.20 to 5.39)]. Time-varying CD4 cell counts were also significantly associated with infant HIV-1 infection [hazard ratio (95% CI): 0.18 (0.03 to 0.93)] in the mART arm but not in the iNVP arm [hazard ratio (95% CI): 0.38 (0.08 to 1.77)]. CONCLUSIONS: In women receiving mART, increased MVL and decreased CD4 cell counts during breastfeeding were associated with increased risk of infant HIV-1 infection.
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