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Extended-dose Nevirapine to 6 Weeks of Age for Infants in Ethiopia, India, and Uganda: A Randomized Trial for Prevention of HIV Transmission through Breastfeeding
Jayagowri Sastry*1,2,3,4 and The Six Week Extended Dose Nevirapine (SWEN) Study Team
1BJ Med Coll, Pune, India; 2Johns Hopkins Univ, Baltimore, MD, US; 3Addis Ababa Univ Faculty of Med, Ethiopia; and 4Makerere Univ Sch of Med, Kampala, Uganda
Background: In Ethiopia, India, and Uganda, 3 separate, but coordinated, randomized, controlled clinical trials underwent a combined
analysis evaluating whether daily nevirapine (NVP) given to breastfed infants
through 6 weeks of age can decrease HIV transmission through breastfeeding
(BF).
Methods: HIV-infected women breastfeeding their infants
were eligible. Arm 1 (single-dose NVP) consisted of 200 mg NVP to women in
labor and 2 mg/kg NVP to newborns after birth. Arm 2 (SWEN) consisted of the
single-dose NVP regimen in Arm 1 plus infant dosing of 5 mg NVP daily from day
8 to 42. Risk of HIV infection and death at 6 weeks and 6 months of age in
infants HIV– at birth (determined by polymerase chain reaction
[PCR]), was estimated using inverse variance-weighted Kaplan-Meier and relative
risk (RR).
Results: Modified intent-to-treat analysis included 986
single-dose NVP infants and 901 SWEN infants (excluding those with missing
specimens and those with indeterminate or confirmed HIV infection at birth).
For the primary endpoint of HIV transmission as of 6 months of age, SWEN
infants had a 20% lower risk than single-dose NVP infants (6.9% vs 9.0%; RR
0.800, 95%CI 0.584 to 1.096; p = 0.164). This was not statistically
significant at an alpha of 0.05 level. At 6 weeks of age, SWEN infants had a
46% lower risk of HIV infection than single-dose NVP arm infants (2.5% vs 5.3%;
RR 0.536, 95%CI 0.336 to 0.855; p = 0.009). Mortality at 6 months of age
for SWEN arm vs single-dose NVP arm was 1.1% vs 3.6% (RR 0.471, 95%CI 0.256 to
0.867; p = 0.016). The risks of post-natal HIV transmission or death in
the SWEN arm vs the single-dose NVP arm were 3.7% vs 6.8% (RR 0.583, 95%CI
0.391 to 0.870; p = 0.008) at 6 weeks and 8.0% vs 11.6% (RR 0.729, 95%CI
0.549 to 0.967; p = 0.028) at 6 months, respectively. The numbers of
infants with serious adverse events were similar in each arm.
Conclusions: Daily NVP from day 8 to 42 of life in
breastfed infants of HIV-infected mothers is feasible, as safe, and more
effective than single-dose NVP alone in improving HIV-free survival at 6 months
of age.
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