The objective of this Competitive Continuation (Type 2) application is to request additional funding to complete an ongoing NIH-sponsored Phase III clinical trial in Pune, India entitled """"""""Prevention of Mother-to- Infant HIV Transmission in India"""""""", which was initiated 16August 2002. This study is a randomized, 2-arm, open-labeled trial among HIV-infected mothers and their breast-fed infants designed to compare the safety and efficacy of standard maternal/infant single dose nevirapine (NVP) (Arm 1) to the single dose NVP regimen plus low-dose daily infant NVP for 6 weeks post-partum (Arm 2). The primary outcome of this trial is the comparison of infant HIV infection rates at 6 months post-partum. This study also has secondary objectives, including the measurement of maternal NVP drug resistance at 9 months postpartum, as well as the measurement of mortality and morbidity rates among participating mothers and their infants. Between16 August 2002 and 31 July 2004, more than 20,800 consenting mothers have been HIV screened and 408 eligible mothers have been enrolled in the clinical trial. This Type 2 proposal was initially submitted for review 1 Sept. 2003, revised and re-submitted 30 Dec. 2003 and has now been revised a 3rd time toaddress the key concerns of the most recent review about accrual and retention. Since the last submission of this proposal, 2 key changes have occurred that will greatly facilitate the successful completion of this trial. First, our enrollment rate for the trial in India has more than doubled from an average of 3/week, between August 32 and December 03, to an average of 6/week, since January 2004. Secondly, in February 2004, the NIAID DSMB for this clinical trial recommended the merging of the primary endpoint data from this trial in India,with data from similar trial sites in Ethiopia and Uganda. This recommendation was facilitated by the consistency n trial designs, study interventions, eligibility criteria, data management procedures and study procedures for all three sites. The total sample size for this new merged analysis is 1964, which will include data from 730 nfants from our trial site in India. The revised analysis plan also greatly reduces the time (from 3 to 2 years) and the cost of this proposal (now 44.2% of the cost requested with our last grant submission). At our current accrual rate, we expect to reach our new target of 730 in India by the end of July 2005.
