Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1

Context Zidovudine reduces maternal-infant transmission of human immunodefi ciency virus 1 (HIV-1) infection by two thirds. Combination antiretroviral therapies are potentially more effective prevention, Objectives To assess the safety of perinatal lamivudine-zidovudine therapy, especially in children, and its effects on viral load, acquisition of drug resistance, and maternal-infant transmission of HIV-1 in a nonbreastfeedin g population. Design and Setting The Agence Nationale de Recherches sur le SIDA (ANRS) 07 5 Study, an open-label, nonrandomized intervention trial conducted in the c ontext of an ongoing observational cohort study in 48 sites in France. Patients A total of 445 HIV-1-infected pregnant women were enrolled as the study cohort from February 1997 to September 1998; controls consisted of 89 9 pregnant women who had received zidovudine monotherapy in May 1994 to Feb ruary 1997 as standard care. Intervention The study cohort received lamivudine in addition to the standa rd Pediatric AIDS Clinical Trial Group 076 Study zidovudine prophylaxis reg imen. Lamivudine was initiated in women at 32 weeks' gestation through deli very at 150 mg twice per day orally; children received lamivudine, 2 mg/kg twice per day for 6 weeks. Main Outcome Measures HIV-1 infection status and tolerance of therapy in ch ildren through age 18 months; maternal plasma HIV-1 RNA levels through 6 we eks after delivery. Results The transmission rate in the study group was 1.6% (7/437; 95% confi dence interval [CI], 0.7%-3.3%). In a multivariable analysis, transmission in the study group was 5-fold lower than in controls. In the study group, m aternal plasma HIV-1 RNA level was less than 500 copies/mL at delivery in 7 4%; the median decrease was 1.24 (range, -1.63 to 3.40) log(10) copies/mL. The M184V lamivudine resistance mutation was detected at 6 weeks after deli very in specimens from 52 of 132 women. The most frequent serious adverse e vents in children were neutropenia and anemia, requiring blood transfusion in 9 children and premature treatment discontinuation in 19. Two uninfected children died at age 1 year from neurologic complications related to mitoc hondrial dysfunction. Conclusions Lamivudine-zidovudine may be effective in preventing maternal-i nfant HIV transmission. However, severe adverse effects and emergence of re sistance to lamivudine occurred, Thus, the role of this combination therapy in this setting is as yet unclear, and further research involving a variet y of strategies is needed to definitively ascertain its utility for prevent ing maternal-infant HIV transmission.