[62] MULTICENTRE, RANDOMIZED CONTROLLED TRIAL, ASSESSING THE SAFETY AND EFFICACY OF NEVIRAPINE IN ADDITION TO ZIDOVUDINE FOR THE PREVENTION OF PERINATAL HIV IN THAILAND: PHPT-2 UPDATE

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] MULTICENTRE, RANDOMIZED CONTROLLED TRIAL, ASSESSING THE SAFETY AND EFFICACY OF NEVIRAPINE IN ADDITION TO ZIDOVUDINE FOR THE PREVENTION OF PERINATAL HIV IN THAILAND: PHPT-2 UPDATE

[AUTHOR(S):] M Lallemant^1,2, G Jourdain², S Le Coeur^2,3, JY Mary⁴, K McIntosh⁵, N Ngo-Giang Huong², E Guerrin-Tran⁶, S Koetsawang⁶ and V Thaineua⁷
¹UR54, Institut de Recherche pour le Developpement, Chiang Mai, Thailand; ²Harvard School of Public Health, Chiang Mai, Thailand; ³Institut National d'Etudes Demographiques, Paris, France; ⁴Paris 7 University/INSERM U444, Paris, France; ⁵Harvard School of Medicine, Boston, USA; ⁶Perinatal HIV Prevention Trial, Chiang Mai, Thailand; ⁷ Mahidol University, Bangkok, Thailand; and ⁸ Ministry of Public Health, Nonthaburi, Thailand

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No.62
Antiviral Therapy 2003; 8(Suppl. 1):S

[ABSTRACT:] Background: ZDV starting at 28 weeks' gestation decreases in utero transmission to 1-2%, yet 4-5% intrapartum transmission still occurs. Adding NVP to ZDV during labor and in neonates may further reduce intrapartum transmission.

Methods: Eligibility: ZDV prophylaxis as soon as possible after 28 wks' gestation (>2 wks), labor oral loading dose and 1 wk for infants (6 wks if mother <4 wks); formula feeding. 3-arms 1) NVP+ZDV mother/ NVP+ZDV infant; 2) NVP+ZDV mother/placebo+ZDV infant; 3) placebo+ZDV mother/placebo+ZDV infant (Reference). Dosing: NVP mother 200 mg po at onset of labor, NVP infant 6 mg po 48-72 hours after birth.

Endpoint: HIV-infected infants (2 PCR+ on 2 samples); vs uninfected (2 PCR after 1 month). After the first interim analysis based on 629 outcomes, the ZDV alone arm was discontinued as HIV transmission was higher than in the NVP+ZDV mother/NVP+ZDV infant arm (P≤0.00036).

Results: As of March 5, 2003, 1833 women (ARV naïve: 99%) have been enrolled and 1726 have delivered. Median baseline CD4+: 370/mm³ (18%<200); log viral load: 3.94; Delay between study treatment intake and delivery: 6.7 hours (13%<2 hrs; 26%<3 hrs); non-elective C-sections: 21%. Infants: Median delay from birth to study treatment intake: 48.5 hrs (98%<72 hrs). The second interim analysis in February 2003 did not raise safety concerns and confirmed the first analysis results. Enrolment was stopped on March 1, 2003 as the planned sample size for non-inferiority comparison of NVP+ZDV mother/placebo+ZDV infant with NVP+ZDV mother/NVP+ZDV infant (delta 2.5%, power 80%) had been reached.

Conclusions: While adding NVP during labour and in the neonate to oral ZDV prophylaxis significantly decreases HIV transmission, the need for the infant NVP dose still needs to be established. Sponsors: NIH R01 HD39615, USA; ANRS 1208 and IRD, France; Ministry of Public Health, Thailand; Boehringer-Ingelheim (study treatment), Glaxo-Smith-Kline (ZDV), Roche Diagnostics (DNAPCR).

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