Immunological response to highly active antiretroviral therapy following treatment for prevention of mother to child transmission of HIV-1: a study in Côte d'Ivoire

Journal of the International AIDS Society Immunological response to highly active antiretroviral therapy following treatment for prevention of mother to child transmission of HIV-1: a study in Cte d'Ivoire Didier K Ekouevi 0 1 2 Patrick A Coffie 0 1 2 Marie-Laure Chaix 5 Besigin Tonwe-Gold 0 2 4 Clarisse Amani-Bosse 1 4 Valriane Leroy 0 2 Elaine J Abrams 3 Franois Dabis 0 2 0 Centre de recherche, Inserm U 897 , Bordeaux France 1 ANRS DITRAME PLUS Project, Programme PAC-CI , Abidjan , Cote d'Ivoire 2 Institut de Sante Publique, Epidemiologie et Developpement, Universite Victor Segalen Bordeaux 2, Bordeaux , France 3 MTCT-Plus Initiative, International Center for AIDS Care and Treatment Programs, Mailman School of Public Health, Columbia University , New York, NY , USA 4 MTCT-Plus initiative, ACONDA , Abidjan , Cote d'Ivoire 5 Universite Rene Descartes, EA 3620, Assistance Publique - Hopitaux de Paris, Laboratoire de Virologie, Hopital Necker Enfants Malades , Paris , France Background: Information is currently limited on the long-term follow up of HIV-1 infected women who are on highly active antiretroviral therapy (HAART) that contains nevirapine and lamivudine and who were previously exposed to antiretroviral drugs for the prevention of mother to child transmission (PMTCT) of HIV. Methods: We studied the 36-month immunological response to HAART in HIV-1 infected women in Cte d'Ivoire. The women were previously exposed to antiretroviral drug regimens for PMTCT, including single-dose nevirapine and/or short-course zidovudine with or without lamivudine. All HAART regimens included a non-nucleoside reverse transcriptase inhibitor. Results: At 36 months: the median absolute increase in CD4+ T cell count was +359 cells/mm3 (IQR: 210-466) in 200 women who had undergone 36-month follow-up visits; +359 cells/mm3 (IQR: 222-491) in 88 women not exposed to PMTCT antiretrovirals; and +363 cells/mm3 (IQR: 200-464) in 112 women exposed to at least one antiretroviral PMTCT regimen. Overall, 49 (19.8%) of the 247 women who initiated HAART met the immunological failure criteria at least once during follow up. The overall probability of immunological failure was 0.08 (95% CI: 0.12-0.15) at 12 months, and 0.21 (95% CI: 0.16-0.27) at 36 months. No difference was observed according to the presence or absence of resistance mutations to nevirapine or lamivudine in women tested at four weeks postpartum. In addition, at 36 months, 23% of women were lost to follow up, dead or had stopped their treatment. Conclusions: A non-nucleoside reverse transcriptase inhibitor-based antiretroviral regimen, initiated a year or more after PMTCT exposure and that includes nevirapine, remains a good option for at least the first 36 months of treatment. - Background Information is currently limited on the long-term follow-up of HIV-1 infected women who are on highly active antiretroviral therapy (HAART) containing nevirapine (NVP) and lamivudine (3TC) and who were previously exposed to antiretroviral (ARV) drugs for the prevention of mother to child transmission (PMTCT) of HIV [1-4]. A 12-month study showed a good immunological response in women previously exposed to ARV drugs for PMTCT [2]. However, in this study we found a higher risk of virological failure in women who had 3TC-acquired resistance mutation four weeks postpartum [2]. We now report the immunological response to HAART at 36 months in women previously exposed to short-course ARV prophylaxis and study factors associated with immunological failure or with immunological failure and death according to the history of PMTCT exposure. Methods A prospective cohort study was conducted in Abidjan, Cte dIvoire, between August 2003 and June 2009 among all HIV-infected women who initiated HAART in the MTCT-Plus initiative. The study population and study design have previously been described [2]. Very briefly, our population consisted of: (1) women never exposed to any treatment for PMTCT; (2) women exposed to single-dose NVP (sdNVP) and zidovudine (ZDV) for PMTCT; and (3) women exposed to shortcourse zidovudine (scZDV) and 3TC for PMTCT. The primary variable of interest was the presence of viral resistance mutation to NVP or 3TC measured at Week 4 postpartum. Two outcomes were considered after 36 months on HAART: (1) immunological failure, defined as a 50% fall from absolute CD4+ T cell count peak level [5]; and (2) a combined criteria, defined as either immunological failure or the occurrence of death during the first 36 months of follow up. The virological analyses were done retrospectively, and results were not available for clinical use. Decisions to switch antiretroviral regimens were thus made by local clinicians based on routinely collected immunological and clinical data. Other study variables measured at time of HAART initiation were included in the analysis: age, WHO clinical stage, body mass index, hemoglobinemia at HAART initiation, and self-reported adherence (seven-day selfreport at six, 12, 18, 24, 30 and 36 months) [5]. Cox regression was used to identify factors associated in univariable analysis (p < 0.20) with immunological failure or the combined criteria. We censored the follow up of each patient at the date of last visit, or death, or date of switch to a protease inhibitor (PI) to evaluate the response to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based treatment. Results From August 2003 to September 2005, 247 women initiated 3TC-containing HAART with either NVP or efavirenz (EFV). At HAART initiation, their median age was 28 years (interquartile range: 25-32) and their median CD4+ count was 188 cells/mm3 (IQR: 126-264). Overall, 28 women (11.3%) were classified at WHO clinical Stage 1; 110 (44.5%) at Stage 2; 96 (38.9%) at Stage 3; and 13 (5.3%) at Stage 4. A total of 109 women (44.1%) had never been exposed to a PMTCT ARV regimen during a previous pregnancy, and 138 (55.9%) had previously received a PMTCT regimen: 50 had received scZDV + sdNVP and two sdNVP only; 81 had received scZDV+sc3TC+sdNVP and five scZDV+3TC only. Among 73 of the 86 3TC-exposed women tested for resistance mutations at Week 4 postpartum, 11 (15.1%) had detectable 3TC resistance mutations. Among 111 of the 133 sdNVP-exposed women tested at Week 4 postpartum, 19 (17.1%) had detectable NVP resistance mutations. The first-line HAART regimen was ZDV+3TC+NVP in 234 (95.1%) women, and stavudine (d4T)+3TC+NVP in seven (2.9%) women; five women started HAART with ZDV+3TC+EFV and one began with d4T+3TC +EFV. The median time between exposure to sdNVP and initiation of HAART was 21 months (IQR: 13-26). During the 36 months of follow up, 30 women (12.1%) were lost to follow up, 10 (4.0%) stopped treatment at their own request, and 17 (6.9%) died. Furthermore, 19 out of 247 (7.7%) HIV-infected women switched to PIbased HAART. The reasons for switching were immunological failure in four patients and side effects related to NVP or EFV in 15 cases. The (...truncated)