15th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 3-6, 2008

Conf Retrovir Opportunistic Infect 2008 Feb 3-6;15: (abstract no. 42LB)

Taha Taha ¹, M Thigpen², N Kumwenda¹, D Hoover³, G Kafulafula⁴, Q Li¹, L Mipando⁵, K Nkanaunena⁵, M Fowler⁶, and L Mofenson^7
1Johns Hopkins Univ Bloomberg Sch of Publ Hlth, Baltimore, MD, US; ²CDC, Atlanta, GA, US; ³Rutgers Univ, Piscataway, NJ, US; ⁴Univ of Malawi Coll of Med, Blantyre; ⁵Johns Hopkins Univ Coll of Med, Blantyre, Malawi; ⁶Johns Hopkins Univ Sch of Med, Baltimore, MD, US; and ⁷Natl Inst of Child Hlth and Devt, NIH, Bethesda, MD, US

BACKGROUND: Postnatal HIV transmission is a major problem and accounts for ~ 45% of overall mother to child transmission of HIV-1 in resource-constrained settings. We evaluated if 14 weeks of extended daily infant antiretroviral prophylaxis with nevirapine (NVP) or NVP+zidovudine (ZDV) with early weaning would reduce postnatal transmission of HIV.

METHODS: Breastfeeding HIV-1-infected women who provided informed consent were enrolled in a randomized, open label, controlled phase III trial in Blantyre, Malawi. Infants were randomized immediately after birth to: a short, control regimen of single-dose NVP + 1 week ZDV alone; the control regimen plus extended daily NVP (ExtNVP) to age 14 weeks; the control regimen plus extended daily NVP+ZDV (ExtNVP/ZDV) to age 14 weeks. The primary endpoint was HIV infection at 9 months in infants who were uninfected at birth. The analysis was based on a discrete Kaplan-Meier method.

RESULTS: This analysis includes 3016 infants enrolled before August 7, 2007 who were uninfected at birth and had data on HIV infection status (1003 control, 1016 ExtNVP, and 997 ExtNVP/ZDV). Breastfeeding frequency was high from birth to 6 months, with a substantial reduction in all arms between 6 and 9 months (from 91% to 32% in control, 90% to 27% in ExtNVP, and 90% to 29% in ExtNVP/ZDV). By 14 weeks, large differences in HIV infection occurred: 10.0% in control, 3.1% in ExtNVP (p<0.00001 vs control), and 4.0% in ExtNVP/ZDV (p<0.00001 vs control). These differences were still evident at 9 months, as shown in the table. There was no significant difference in postnatal transmission (p=0.29), death (p=0.67), or HIV infection/death (p=0.63) between the ExtNVP and ExtNVP/ZDV arms. Most infant deaths were due to gastroenteritis and pneumonia. Grade 2 or higher serious adverse events did not differ in treatment arms.

CONCLUSIONS: Daily antiretroviral prophylaxis with NVP or NVP/ZDV for the first 14 weeks of life was safe and significantly reduced risk of postnatal HIV infection at age 9 months compared to single-dose NVP+1 week ZDV, and significantly increased 9 month HIV-free survival. Use of 2 drugs (NVP/ZDV) was not superior to NVP alone in terms of transmission, mortality or HIV-free survival.

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2008-02-03
42LB

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