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Benefits and Risks of the antiretroviral drugs for the Prevention of Mother-To-Child Transmission of
HIV-1 in Africa. The ANRS 1201/1202 Ditrame Plus project in Abidjan, Côte d’Ivoire
SUMMARY
The aim of the ANRS Ditrame Plus project in Abidjan, Côte d’Ivoire was to evaluate a package of peripartum
and postpartum interventions targeted at African HIV-infected women and children for PMTCT and to enhance
child survival in the HIV context. This package of interventions proposed since May 2000 includes HIV test
counseling services among pregnant women with rapid HIV testing, a PMTCT intervention with ARVs as well
as a nutritional component (artificial feeding from birth or early cessation of breastfeeding from three months of
age).
The effectiveness or field efficacy as well as the tolerance of the ARVs was studied. It included the identification
of nevirapine (NVP) resistance of HIV in mothers and HIV-infected infants that had been exposed to NVP single
dose (NVPsd) and the study of mitochondrial toxicity induced by zidovudine (ZDV) with lactate measurements
performed during the first 3 months of life among infants exposed to this drug in their PMTCT regimen.
The acceptance of prenatal counseling with rapid HIV test was 90% and the HIV-1 prevalence was 11% in 2002.
However, only 25% of the HIV-infected pregnant women identified started the PMTCT programme. Two factors
were associated with a poor uptake of the PMTCT package: a low level of school education and living with her
partner (Ekouévi, AIDS 2004). The overall uptake of the package of interventions was independent of the
immune status appreciated by the measurement of CD4+ count at prenatal counselling (Ekouévi, JAIDS 2004).
In the ANRS Ditrame Plus study, from March 2001 to July 2003, 793 HIV-infected pregnant women were
included: 420 received a short course of ZDV starting at 36 weeks of gestation + NVPsd for PMTCT and 373
received a short-course of ZDV+ lamivudine (3TC) starting at 32 weeks + NVPsd. The MTCT rate at six week
of life was 6.5% (95% confidence interval [CI] 3.9-9.1%) with ZDV+NVPsd and 4.7% (95% CI [2.4-7.0%])
with ZDV+3TC+NVPsd. No significant difference was found between these two ARV regimens. Using as a
reference group an historical cohort (ANRS 049) where women received a short-course ZDV regimen starting at
36-38 weeks in 1995-2000 in the same population, the MTCT reduction was 72% (95% CI [52-88%], p=0.002),
when comparing ZDV+NVPsd to ZDV alone after having adjusted on maternal CD4+ count, clinical stage and
breastfeeding (Dabis, AIDS 2005 in Press).
In the ANRS 1263 Ditrame Plus study (virological component of the ANRS Ditrame Plus project), among 63
HIV-infected women, the NVP mutation resistance was detectable in 21 women (33%) at four week postpartum
and in 6/26 (23%) of HIV-infected infants at four weeks. Maternal plasma HIV-1 RNA viral load at baseline (32
weeks of amenorrhea) and a high level of NVP concentration were associated with NVP resistance mutation
(Chaix, CROI 2004, San Francisco, USA).
In the ARNS 1209 study (toxicity component of the ANRS Ditrame Plus project), we hypothesized that the
screening of hyperlactatemia in neonates exposed to ARVs could help to identify early a possible mitochondrial
toxicity. There was no statistical difference between the 0-3 month prevalence of hyperlactatemia in infants
exposed to three different ARV regimens (p=0.17): the prevalence of hyperlactatemia was 11% with the
ZDV+NVPsd regimen, 17% with ZDV+3TC+NVPsd and 18% in the control group exposed to NVPsd only
(enrolment in this latter group is still ongoing). Thus, our preliminary findings do not confirm our study