Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

Abstract

BACKGROUND:

HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to t NVP or placebo to prevent postnatal infection: we report final 18-month outcomes.

METHODS:

Randomized, placebo-controlled trial in 4 African countries. Infant diagnostic HIV testing was performed regularly from birth through 18 months. Kaplan-Meier analysis was used to assess 18-month cumulative infant HIV infection, HIV infection/or death, and mortality rates.

RESULTS:

Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower among infants receiving daily NVP from 6 weeks to 6 months 1.1% [95% confidence interval (CI): 0.2% to 1.8%], compared with placebo 2.4% (95% CI: 1.3% to 2.6%), P = 0.049, but not significantly lower thereafter. Eighteen-month postnatal infection rates were low: 2.2% (95% CI: 1.1% to 3.3%) versus 3.1% (95% CI: 1.9% to 4.4%), respectively, P = 0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18-month postnatal infection rates (0.5%, 95% CI: 0.0% to 1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI: 1.9% to 5.5%), and infants of mothers with CD4 counts of ≥ 350 cells per cubic millimeter not receiving ART (4.8%, 95% CI: 2.7% to 6.8%; P = 0.46). There were no differences in adverse events between study arms.

CONCLUSIONS:

This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age 6 weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.

• Authors: Mary Glenn Fowler, Hoosen Coovadia, Casey M Herron, Yvonne Maldonado, Tsungai Chipato, Dhayendre Moodley, Philippa Musoke, Jim Aizire, Karim Manji, Lynda Stranix-Chibanda, Wafaie Fawzi, Vani Chetty, Lindiwe Msweli, Rodrick Kisenge, Elizabeth Brown, Anthony Mwatha, Susan H Eshleman, Paul Richardson, Melissa Allen, Kathleen George, Philip Andrew, Sheryl Zwerski, Lynne M Mofenson, J Brooks Jackson, HPTN 046 Protocol Team
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 65 Issue 3 Pg. 366-74 (Mar 01 2014) ISSN: 1944-7884 [Electronic] United States
• PMID: 24189151 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Placebos
• Nevirapine

Topics

• Adolescent
• Adult
• Africa
• Anti-HIV Agents (administration & dosage, adverse effects)
• Breast Feeding
• Chemoprevention (adverse effects, methods)
• Double-Blind Method
• Female
• HIV Infections (prevention & control, transmission, virology)
• HIV-1 (isolation & purification)
• Humans
• Infant
• Infant, Newborn
• Infectious Disease Transmission, Vertical (prevention & control)
• Male
• Nevirapine (administration & dosage, adverse effects)
• Placebos (administration & dosage)
• Treatment Outcome
• Young Adult