AEGiS-13IAC: Preliminary efficacy, safety, tolerability, and pharmacokinetics of short course regimens of nucleoside analogues for the prevention of mother-to-child transmission (MTCT) of HIV.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Preliminary efficacy, safety, tolerability, and pharmacokinetics of short course regimens of nucleoside analogues for the prevention of mother-to-child transmission (MTCT) of HIV.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. TuOrB355)

Gray G, McIntyre J, Jivkov B, Schorn M, Lala S, Reynolds L, Ledeine J-M, Van Beek A, Schnittman S
G. Gray, Perinatal HIV Research Unit, Maternity Sector, Chris Hani Baragwanath Hosp., Old Potch Road, Soweto 2013, South Africa, Tel.: +27-11-938-3984, Fax: +27-11-938-3973, E-mail: gray@pixie.co.za

BACKGROUND: The rapid implementation of the ACTG 076 regimen in resource-rich countries has led to dramatic decreases in MTCT and pediatric HIV. However, these results have not been extended to the developing world where the majority of MTCT occurs because of the high cost of intervention and the logistics of a complex regimen. Several recent studies have shown the feasibility of reducing MTCT with short-course regimens that would be more applicable in the developing world.

METHODS: AI455-094 is a pilot study with the aim of evaluating the preliminary efficacy, safety, tolerability, and PK of orally administered d4T vs. ddI vs. d4T in combination with ddI vs. ZDV in HIV-1 infected mothers for the prevention of MTCT to their formula-fed newborns. 360 pregnant HIV-1 infected antiretroviral naive women from South Africa who were in weeks 34-36 gestation were randomized to oral prepartum and intrapartum drug of either d4T, ddI, d4T/ddI, or ZDV, followed by 6 weeks of oral postpartum therapy of the same drug to the newborns.

RESULTS: As of the time of submission of this abstract, 240 HIV-1-infected pregnant women have been randomized. The mean HIV RNA at enrollment for the first 104 mothers was 4.2 log₁₀ c/mL with a mean CD4 of 426 cells/mm³. By the time of delivery, the mean HIV RNA had decreased by 1.2 log₁₀ c/mL (mean treatment duration 4.2 weeks). All of the therapeutic arms have been well-tolerated to date; only one mother discontinued prematurely due to loss to follow-up. Seven infants discontinued, all due to death; the causes of death were mainly asphyxia and septicemia. To date, of the 108 newborns with at least week-6 DNA PCR results, 7 infants have been infected for an overall HIV-1 transmission rate of 6.5%.

CONCLUSION: This rate of HIV-1 MTCT compares very favorably with prior reports of short-course antiretroviral therapy. Complete safety and efficacy data by treatment arm on all subjects and their newborns will be presented.

Keywords: AEGIS, HIV, HIV Infections, Stavudine, Didanosine, Zidovudine, HIV-1, Anti-HIV Agents, Mothers, HIV Seropositivity, Safety, HIV Protease Inhibitors, South Africa, Child, Human, Female, Infant, Infant, Newborn, Pregnancy, transmission, pharmacokinetics, prevention & control
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TuOrB355