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Extended Infant Post-exposure Prophylaxis with Antiretroviral Drugs Significantly Reduces Postnatal HIV Transmission: The PEPI-Malawi Study
Taha Taha*1, M Thigpen2, N Kumwenda1, D Hoover3, G Kafulafula4, Q Li1, L Mipando5, K Nkanaunena5, M Fowler6, and L Mofenson7
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.
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At 9 months:
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Control
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ExtNVP
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ExtNVP/ZDV
|
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HIV infection
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13.0%
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7.2%
(p = 0.0004 vs control)
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8.7%
(p = 0.014 vs control)
|
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Death
|
8.9%
|
6.8%
(p = 0.12 vs control)
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6.3%
(p = 0.05 vs control)
|
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HIV infection or death
|
17%
|
11%
(p = 0.0009 vs control)
|
12%
(p = 0.0043 vs control)
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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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