TY - JOUR
T1 - Efficacy of six-week extended-dose nevirapine varies by infant birth weight with greatest relative efficacy in low birth weight infants
AU - Gupte, Nikhil
AU - Kinikar, Aarti
AU - McIntire, Katherine N.
AU - Bhosale, Ramesh
AU - Patil, Sandesh
AU - Suryavanshi, Nishi
AU - Mave, Vidya
AU - Kulkarni, Vandana
AU - Bollinger, Robert C.
AU - Gupta, Amita
N1 - Publisher Copyright:
© 2016 Gupte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/9
Y1 - 2016/9
N2 - Latest World Health Organization guidelines recommend weight-based nevirapine prophylaxis for all HIV-exposed infants in resource-limited settings, yet low birth weight (LBW) infants (< 2500 g) have been understudied. Using data from the NIH-funded India six-week extended-dose nevirapine (SWEN) study, a randomized clinical trial of SWEN versus single-dose nevirapine (SD) for prevention of breast-milk HIV-1 transmission, we examined the relative impact of SWEN among 737 mother-infant pairs stratified by infant birth weight. Birth weight groups were defined as very LBW (VLBW) ô 2000 g, moderate LBW (MLBW) >2000 g and ô 2500 g, and normal birth weight (NBW) > 2500 g. Outcomes were HIV-1 infection, HIV-1 infection or death by 12 months, and severe adverse events (SAEs). The Kaplan-Meier method was used to estimate probability of efficacy outcomes in birth weight groups, and differential effects of SWEN by birth weight group were examined using Cox proportional hazards models adjusting for independent risk factors for HIV maternal-to-child transmission and significant covariates. Among 50 VLBW, 249 MLBW, and 433 NBW infants, 50% were randomized to SWEN; median gestational age was 36, 38 and 38 weeks, respectively; and there was no difference in breastfeeding duration (p = 0.99). Compared to SD: SWEN-treated VLBW had lower estimates of HIV-1 infection (13% vs. 38%, p = 0.004) and HIV-1 infection or death (13% vs. 41%, p = 0.002); SWENtreated MLBW had lower estimated HIV-1 infection (13% vs. 17%, p = 0.042); and efficacy endpoints were similar by treatment arm in NBW. In multivariate analysis, SWEN was associated with reduced risk of HIV-1 infection or death by 83% (p = 0.03) in VLBW versus 45% (p = 0.05) in MLBW. SAE frequency was similar by treatment arm in VLBW (68% vs. 76%, p = 0.53) and MLBW (37% vs. 36%, p = 0.93). SWEN may safely increase HIV-free survival among HIV-exposed LBW infants with greatest protective advantage among infants ô 2000 g.
AB - Latest World Health Organization guidelines recommend weight-based nevirapine prophylaxis for all HIV-exposed infants in resource-limited settings, yet low birth weight (LBW) infants (< 2500 g) have been understudied. Using data from the NIH-funded India six-week extended-dose nevirapine (SWEN) study, a randomized clinical trial of SWEN versus single-dose nevirapine (SD) for prevention of breast-milk HIV-1 transmission, we examined the relative impact of SWEN among 737 mother-infant pairs stratified by infant birth weight. Birth weight groups were defined as very LBW (VLBW) ô 2000 g, moderate LBW (MLBW) >2000 g and ô 2500 g, and normal birth weight (NBW) > 2500 g. Outcomes were HIV-1 infection, HIV-1 infection or death by 12 months, and severe adverse events (SAEs). The Kaplan-Meier method was used to estimate probability of efficacy outcomes in birth weight groups, and differential effects of SWEN by birth weight group were examined using Cox proportional hazards models adjusting for independent risk factors for HIV maternal-to-child transmission and significant covariates. Among 50 VLBW, 249 MLBW, and 433 NBW infants, 50% were randomized to SWEN; median gestational age was 36, 38 and 38 weeks, respectively; and there was no difference in breastfeeding duration (p = 0.99). Compared to SD: SWEN-treated VLBW had lower estimates of HIV-1 infection (13% vs. 38%, p = 0.004) and HIV-1 infection or death (13% vs. 41%, p = 0.002); SWENtreated MLBW had lower estimated HIV-1 infection (13% vs. 17%, p = 0.042); and efficacy endpoints were similar by treatment arm in NBW. In multivariate analysis, SWEN was associated with reduced risk of HIV-1 infection or death by 83% (p = 0.03) in VLBW versus 45% (p = 0.05) in MLBW. SAE frequency was similar by treatment arm in VLBW (68% vs. 76%, p = 0.53) and MLBW (37% vs. 36%, p = 0.93). SWEN may safely increase HIV-free survival among HIV-exposed LBW infants with greatest protective advantage among infants ô 2000 g.
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U2 - 10.1371/journal.pone.0162979
DO - 10.1371/journal.pone.0162979
M3 - Article
C2 - 27689883
AN - SCOPUS:84991781154
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 9
M1 - e0162979
ER -