Effectiveness of AZT and Nevirapine in Preventing HIV Transmission From Ugandan Mothers to Their Newborns

Summary

The purpose of this study is to see if nevirapine (NVP) or zidovudine (AZT), given to mothers during labor and delivery and to their babies during the first week of life, can reduce the rate of mothers passing HIV to their babies. About 25 percent of HIV-infected mothers pass HIV infection to their babies during labor and delivery. There is an urgent need to find a simpler way to prevent mother-to-infant transmission during labor and delivery. The proposed NVP schedule is simpler and possibly could be used in Uganda.

Timeline

Start

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Primary completion

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Completion

2004-11

Outcome

Met primary endpoint

paper the zidovudine and nevirapine groups were: 10.4% and 8.2% at birth (p=0.354); 21.3% and 11.9% by age 6-8 weeks (p=0.0027); PMID 10485720 ↗

paper INTERPRETATION: Nevirapine lowered the risk of HIV-1 transmission during the first 14-16 weeks of life by nearly 50% in a breastfeeding population. PMID 10485720 ↗

Publications

• Background Eshleman SH, Mracna M, Guay L, Deseyve M, Cunningham S, Musoke P, Mmiro F, Jackson JB. Selection of nevirapine resistance (NVPR) mutations in Ugandan women and infants receiving NVP prophylaxis to prevent HIV-1 vertical transmission (HIVNET-012). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 516)
• Results Guay LA, Musoke P, Fleming T, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Ducar C, Deseyve M, Emel L, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Dransfield K, Bray D, Mmiro F, Jackson JB. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial. Lancet. 1999 Sep 4;354(9181):795-802. doi: 10.1016/S0140-6736(99)80008-7.
• Results Jackson JB, Musoke P, Fleming T, Guay LA, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Owor M, Ducar C, Deseyve M, Mwatha A, Emel L, Duefield C, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Gigliotti M, Bray D, Mmiro F. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003 Sep 13;362(9387):859-68. doi: 10.1016/S0140-6736(03)14341-3.
• Results Eshleman SH, Guay LA, Mwatha A, Brown ER, Cunningham SP, Musoke P, Mmiro F, Jackson JB. Characterization of nevirapine resistance mutations in women with subtype A vs. D HIV-1 6-8 weeks after single-dose nevirapine (HIVNET 012). J Acquir Immune Defic Syndr. 2004 Feb 1;35(2):126-30. doi: 10.1097/00126334-200402010-00004.
• Results Eshleman SH, Guay LA, Fleming T, Mwatha A, Mracna M, Becker-Pergola G, Musoke P, Mmiro F, Jackson JB. Survival of Ugandan infants with subtype A and D HIV-1 infection (HIVNET 012). J Acquir Immune Defic Syndr. 2002 Nov 1;31(3):327-30. doi: 10.1097/00126334-200211010-00009.
• Results Eshleman SH, Becker-Pergola G, Deseyve M, Guay LA, Mracna M, Fleming T, Cunningham S, Musoke P, Mmiro F, Jackson JB. Impact of human immunodeficiency virus type 1 (hiv-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv network for prevention trials 012 study). J Infect Dis. 2001 Oct 1;184(7):914-7. doi: 10.1086/323153. Epub 2001 Aug 13.
• Results Eshleman SH, Mracna M, Guay LA, Deseyve M, Cunningham S, Mirochnick M, Musoke P, Fleming T, Glenn Fowler M, Mofenson LM, Mmiro F, Jackson JB. Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). AIDS. 2001 Oct 19;15(15):1951-7. doi: 10.1097/00002030-200110190-00006.
• Results Eshleman SH, Guay LA, Mwatha A, Cunningham SP, Brown ER, Musoke P, Mmiro F, Jackson JB. Comparison of nevirapine (NVP) resistance in Ugandan women 7 days vs. 6-8 weeks after single-dose nvp prophylaxis: HIVNET 012. AIDS Res Hum Retroviruses. 2004 Jun;20(6):595-9. doi: 10.1089/0889222041217518.
• Results Eshleman SH, Guay LA, Wang J, Mwatha A, Brown ER, Musoke P, Mmiro F, Jackson JB. Distinct patterns of emergence and fading of K103N and Y181C in women with subtype A vs. D after single-dose nevirapine: HIVNET 012. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):24-9. doi: 10.1097/01.qai.0000174656.71276.d6.
• Results Jackson JB, Parsons T, Musoke P, Nakabiito C, Donnell D, Fleming T, Mirochnick M, Mofenson L, Fowler MG, Mmiro F, Guay L. Association of cord blood nevirapine concentration with reported timing of dose and HIV-1 transmission. AIDS. 2006 Jan 9;20(2):217-22. doi: 10.1097/01.aids.0000198089.93196.84.
• Results Eshleman SH, Hoover DR, Chen S, Hudelson SE, Guay LA, Mwatha A, Fiscus SA, Mmiro F, Musoke P, Jackson JB, Kumwenda N, Taha T. Resistance after single-dose nevirapine prophylaxis emerges in a high proportion of Malawian newborns. AIDS. 2005 Dec 2;19(18):2167-9. doi: 10.1097/01.aids.0000194800.43799.94.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Nevirapine	Small molecule	2 mg/kg	Oral
Subject	Nevirapine	Small molecule	200 mg	Oral
Subject	Zidovudine	Small molecule	4 mg/kg	Oral
Subject	Zidovudine	Small molecule	300 mg	Oral

Indications