Short-course Zidovudine and Lamivudine or single-dose Nevirapine-containing PMTCT Compromises 12-Month Response to HAART in African Women, Abidjan, Côte d’Ivoire (2003-2006)
P Coffie1, D Ekouevi2, M L Chaix3, B Tonwe-Gold4, S Toure4, I Viho4, C Amani-Bosse4, V Leroy1, C ROUZIOUX3, François Dabis*1, D Ekouevie1, and MTCT-Plus Initiative of ICAP
1INSERM 593, Univ Victor Segalen, Bordeaux, France; 2ANRS DITRAME PLUS Project, PACCI Collaboration, Abidjan, Côte d`Ivoire; 3Ctr Hosp Univ Necker, Univ Rene Descartes, Paris, France; and 4MTCT-Plus Prgm, ACONDA, Abidjan, Côte d`Ivoire
Background: We studied
the response to HAART of women exposed to single-dose nevirapine (sdNVP) or
short course zidovudine±lamivudine (ZDV±3TC) for prevention of mother-to-child
transmission (PMTCT) regimens.
prospective cohort of the Côte d’Ivoire MTCT-Plus program, all women eligible
were HIV-1 infected, had had ≥1 pregnancy, and had initiated HAART with
stavudine (d4T)/ZDV, 3TC, and NVP/efavirenz (EFV). Exposed women received short
course (ZDV±3TC)+sdNVP during previous pregnancy.
Genotypic resistance testing was performed at week-4 post partum. Immunological
failure was defined by a fall of >30% from peak CD4 count, virological
failure by a plasma HIV RNA>500 copies/mL 12 months after HAART initiation.
Multivariate logistic regression investigated factors associated to treatment
HAART-treated women, 109 (44%) were unexposed, 81 received sc(ZDV+3TC)+sdNVP, 5
short course (ZDV+3TC), 50 short course ZDV+sdNVP, and 2 sdNVP only. No ZDV
mutation was detected (n = 115); 11
of 73 (14.6%) 3TC-exposed women tested post partum had 3TC resistance
mutations. Of 73 short course (ZDV+3TC)+sdNVP exposed
women, 3/ (4.1%) had NVP-resistance mutations, and of 42 short course ZDV+sdNVP exposed women, 16
(38.1%) did so. HAART was initiated 19 months in median after exposure.
Baseline median CD4 count was 188 cells/mm3 (IQR 126 to 264). Of 219
women, virological failure was identified in 42 (19.2%). In multivariate
analysis, factors associated with virological failure were a poor self-reported
adherence (adjusted odds ratio [aOR] 12.7, 95% confidence interval [CI] 3.0 to
53.9), 3TC-resistance mutations post partum (aOR 6.9, CI 1.1 to 42.9), and a
baseline CD4+ count <200/mm3 (aOR 0.3, CI 0.2 to 0.8),
controlling for resistance mutations / exposure to NVP, maternal age, WHO
clinical stage, and hemoglobinemia. 3TC-exposed women who did not develop
resistance mutations post partum were not at increased risk of virological
failure (p = 0.11 in adjusted
analysis). Exposure to sdNVP was not statistically associated with virological
failure (aOR 1.8, CI 0.5 to 6.5 for NVP resistance; aOR 0.4, CI 0.1 to 1.4 for
NVP exposure without resistance). Immunological failure was identified in 26
women of 235 (11.1%); the only associated factor was poor adherence (aOR 12.3;
CI 3.2 to 47.8). Exposure to 3TC and NVP ± post-partum resistance mutations to
these drugs did not predict immunological failure (p = 0.57 and 0.12, respectively in multivariate analysis), like
baseline CD4+ count, WHO clinical stage, age and hemoglobinemia.
course (ZDV±3TC) and sdNVP may induce viral resistance to NVP or 3TC that can
impair the subsequent women’s response to HAART, an adverse phenomenon to be
taken into account in PMTCT guidelines.