RT Journal
A1 Mandelbrot L, Landreau-Mascaro A, Rekacewicz C, et al
T1 LAmivudine-zidovudine combination for prevention of maternal-infant transmission of hiv-1
JF JAMA
JO JAMA
YR 2001
FD April 25
VO 285
IS 16
SP 2083
OP 2093
DO 10.1001/jama.285.16.2083
UL http://dx.doi.org/10.1001/jama.285.16.2083
AB Context 
                  Zidovudine reduces maternal-infant transmission of human immunodeficiency
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 nonbreastfeeding population.Design and Setting 
                  The Agence Nationale de Recherches sur le SIDA (ANRS) 075 Study, an
open-label, nonrandomized intervention trial conducted in the context 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 899 pregnant women who had received zidovudine monotherapy in May 1994
to February 1997 as standard care.Intervention 
                  The study cohort received lamivudine in addition to the standard Pediatric
AIDS Clinical Trial Group 076 Study zidovudine prophylaxis regimen. Lamivudine
was initiated in women at 32 weeks' gestation through delivery 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 children through
age 18 months; maternal plasma HIV-1 RNA levels through 6 weeks after delivery.Results 
                  The transmission rate in the study group was 1.6% (7/437; 95% confidence
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, maternal
plasma HIV-1 RNA level was less than 500 copies/mL at delivery in 74%; the
median decrease was 1.24 (range, −1.63 to 3.40) log10 copies/mL.
The M184V lamivudine resistance mutation was detected at 6 weeks after delivery
in specimens from 52 of 132 women. The most frequent serious adverse events
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 mitochondrial
dysfunction.Conclusions 
                  Lamivudine-zidovudine may be effective in preventing maternal-infant
HIV transmission. However, severe adverse effects and emergence of resistance
to lamivudine occurred. Thus, the role of this combination therapy in this
setting is as yet unclear, and further research involving a variety of strategies
is needed to definitively ascertain its utility for preventing maternal-infant
HIV transmission.