Efficacy of Six-Week Extended-Dose Nevirapine Varies by Infant Birth Weight with Greatest Relative Efficacy in Low Birth Weight Infants.
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) ≤ 2000 g, moderate LBW (MLBW) >2000 g and ≤ 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); SWEN-treated 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 ≤ 2000 g.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.
Nikhil
N
Gupte
Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.|Byramji Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, Maharashtra, India.
Aarti
A
Kinikar
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Katherine N
KN
McIntire
Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.|Byramji Jeejeebhoy Government Medical College and Sassoon General Hospitals, Pune, Maharashtra, India.
Ramesh
R
Bhosale
Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.
Sandesh
S
Patil
Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.
Nishi
N
Suryavanshi
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.
Vidya
V
Mave
Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.
Vandana
V
Kulkarni
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.|Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Robert C
RC
Bollinger
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.|Byramji Jeejeebhoy Government Medical College-Johns Hopkins University HIV Clinical Trials Unit, Biramji Jeejeebhoy Government Medical College, Pune, Maharashtra, India.|Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
Amita
A
Gupta
J Acquir Immune Defic Syndr. 2011 Aug 1;57(4):319-25
21423025
Lancet. 2012 Jan 21;379(9812):221-8
22196945
J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Nov 1;13(3):227-34
8898667
Clin Infect Dis. 2013 Jan;56(1):131-9
22997212
N Engl J Med. 2000 Oct 5;343(14):982-91
11018164
N Engl J Med. 2010 Jun 17;362(24):2271-81
20554982
Int J Gynaecol Obstet. 2011 Oct;115(1):20-5
21767835
AIDS. 2011 Mar 27;25(6):767-76
21330912
Lancet. 2008 Jul 26;372(9635):300-13
18657709
PLoS One. 2009;4(1):e4096
19119321
Lancet. 2012 Jun 30;379(9835):2449-58
22541418
Lancet. 1999 Mar 6;353(9155):786-92
10459959
BMC Infect Dis. 2015 Mar 18;15:130
25887574
AIDS. 2016 Mar 27;30(6):953-62
26691682
N Engl J Med. 2008 Jul 10;359(2):119-29
18525035
J Acquir Immune Defic Syndr. 2009 Nov 1;52(3):406-16
19730269
AIDS Res Hum Retroviruses. 2011 Aug;27(8):823-9
21241214
Int J Gynaecol Obstet. 2009 Jul;106(1):8-13
19345943
Lancet. 1999 Sep 4;354(9181):795-802
10485720
S Afr Med J. 2011 Sep 05;101(9):655-8
21920159
Ann Med Health Sci Res. 2014 Jul;4(4):615-8
25221715
N Engl J Med. 2003 Sep 18;349(12):1157-67
13679531
AIDS. 2005 Feb 18;19(3):309-18
15718842