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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>We studied the 36-month immunological response to HAART in HIV-1 infected women in Côte 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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Incidence and risk factors of severe adverse events with nevirapine-based antiretroviral therapy in HIV-infected women. MTCT-Plus program, Abidjan, Côte d'Ivoire

<p>Abstract</p> <p>Background</p> <p>In resource-limited settings where nevirapine-containing regimen is the preferred regimen in women, data on severe adverse events (SAEs) according to CD4 cell count are limited. We estimated the incidence of SAEs according to CD4 cell count and identify their risk factors in nevirapine-treated women.</p> <p>Methods</p> <p>All HIV-infected women who initiated nevirapine-containing regimen in the MTCT-Plus operational program in Abidjan, Côte d'Ivoire, were eligible for this study. Laboratory and clinical (rash) SAEs were classified as grade 3 and 4. Cox models were used to identify factors associated with the occurrence of SAEs.</p> <p>Results</p> <p>From August 2003 to October 2006, 290 women initiated a nevirapine-containing regimen at a median CD4 cell count of 186 cells/mm³(IQR 124-266). During a median follow-up on treatment of 25 months, the incidence of all SAEs was 19.5/100 patient-years. The 24-month probability of occurrence of hepatotoxicity or rash was not different between women with a CD4 cell count >250 cells/mm³and women with a CD4 cell count ≤250 cells/mm³(8.3% <it>vs</it>. 9.9%, Log-rank test: p = 0.75). In a multivariate proportional hazard model, neither CD4 cell count >250 cells/mm³at treatment initiation nor initiation NVP-based regimen initiated during pregnancy were associated with the occurrence of SAEs.</p> <p>Conclusion</p> <p>CD4 cell count >250 cells/mm³was not associated with a higher risk of severe hepatotoxicity and/or rash, as well as initiation of ART during pregnancy. Pharmacovogilance data as well as meta-analysis on women receiving NVP in these settings are needed for better information about NVP toxicity.</p

18-Month Effectiveness of Short-Course Antiretroviral Regimens Combined with Alternatives to Breastfeeding to Prevent HIV Mother-to-Child Transmission

OBJECTIVE: We assessed the 18-month effectiveness of short-course (sc) antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT) of HIV-1 in Abidjan, Côte d'Ivoire. METHODOLOGY: HIV-1 infected pregnant women received from >/=32-36 weeks of gestation scZidovudine (ZDV)+/-Lamivudine (3TC)+single-dose Nevirapine (sdNVP) at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001-2003). Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994-2000) exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged >/=18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR) and effectiveness (HIV-free survival) were compared by exposure group using a Cox model. FINDINGS: Among 926 live-born children enrolled, 107 (11.6%) were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16-30%) in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10-27%) in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6-14%) in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4-11%) in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2-10%) in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20-70%) for ZDV+sdNVP formula fed children to 63% (CI:40-80%) for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART), home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa, even in short-term breastfed children. The two sc antiretroviral combinations associated to any of the two infant feeding interventions, formula-feeding and shortened breastfeeding, reduce significantly MTCT with long-term benefit until age 18 months and without increasing mortality

Knowledge, attitudes, and beliefs of health care workers regarding alternatives to prolonged breast-feeding (ANRS 1201/1202, Ditrame Plus, Abidjan, Côte d'Ivoire).: Health providers attitude toward alternatives to prolonged breastfeeding

International audienceThe Ditrame Plus project conducted in Abidjan, C?d'Ivoire, is aimed at the prevention of mother-to-child transmission of HIV in combining perinatal antiretroviral interventions with a systematic proposal of alternatives to prolonged breast-feeding: formula feeding from birth, or exclusive breast-feeding for 3 months then early cessation of breast-feeding. We surveyed all health care workers involved in this project in November 2003 using a self-administered anonymous questionnaire to investigate their knowledge, attitudes, and beliefs regarding the infant feeding interventions proposed since March 2001. Their knowledge regarding infant practices proposed within the study was consistent and their attitude was in accordance with the study protocol. However, proposing alternatives to prolonged breast-feeding causes difficulties for health care workers that should be taken into account when tailoring such complex interventions

Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Côte d'Ivoire.

International audienceBACKGROUND: Pregnancy outcomes in women receiving highly active antiretroviral treatment (HAART) in Africa are not well described. METHODS: HIV-1-infected pregnant women in the ANRS Ditrame Plus and the MTCT-Plus projects were included. Between March 2001 and July 2003, when HAART was not yet available, women eligible for HAART received a short-course antiretroviral regimen, zidovudine (ZDV) or (ZDV + lamivudine) and single dose of nevirapine for preventing mother-to-child transmission (PMTCT group). Between August 2003 and August 2007, eligible women for HAART received it (HAART group). The frequencies of low birth weight (LBW) (<2500 g), stillbirth and infant mortality are reported. Risk factors associated with LBW were investigated using a logistic regression model. RESULTS: Of the 326 HIV-infected pregnant women, 175 women received short-course antiretroviral (median CD4 cell count 177 cells/microl) and 151 received HAART (median CD4 cell count 182 cells/microl). At 12 months, three paediatric infections (2.3%) occurred in the HAART group vs. 25 (16.1%) in the PMTCT group (P < 0.001). The rate of LBW was 22.3% in the HAART group and 12.4% in the PMTCT group (P = 0.02). In multivariable analysis (n = 309), after adjustment on maternal CD4 cell count, WHO stage, age and maternal BMI, HAART initiated before pregnancy [adjusted odds ratio (OR) 2.88, 95% confidence interval (CI) 1.10-7.51] and during pregnancy (adjusted OR 2.12, 95% CI 1.15-4.65) and maternal BMI at delivery (adjusted OR 2.43, 95% CI 1.20-4.91) were associated with LBW. CONCLUSION: HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with LBW

Variation of CD4 Count and Percentage during Pregnancy and after Delivery: Implications for HAART Initiation in Resource-Limited Settings.

International audienceWe studied whether the use of T-lymphocyte CD4 (CD4) absolute count instead of CD4 percentage could affect the decision process regarding HAART initiation in African HIV-infected pregnant women. A prospective cohort in Abidjan, C?d'Ivoire before HAART was available. Participating women received a perinatal antiretroviral prophylaxis (zidovudine + single-dose of nevirapine). CD4 count and percentage were measured by flow cytometry at baseline (32 weeks of amenorrhea) and at 1 month after delivery. A signed-rank test was used to compare the distributions of the CD4 absolute count and percentage values. A total of 325 HIV-1-infected pregnant women were included. At baseline, their median CD4 count was 355 cells/mm(3) and the median CD4 percentage was 24.8%; 17.8% of women had a CD4 count <200 cells/mm(3) and 14.8 % had a CD4 percentage <15%. One month after delivery, the median CD4 count was 489 cells/mm(3) (vs. baseline: p < 0.001), the median CD4 percentage was 25.6% (vs. baseline: p = 0.107), 9.5% of women had CD4 count <200 cells/mm(3) (vs. baseline: p < 0.001), and 15.1% of women had a CD4 percentage <15% (vs. baseline: p = 0.823). When combining the CD4 count and the WHO clinical stage, the proportion of women who met the WHO 2006 criteria for initiating HAART was 28.3% at baseline but 17.2% only at 1 month after delivery (p < 0.001). Between the prepregnancy and the postdelivery periods, the CD4 count experienced a significant increase, whereas the CD4 percentage remained unchanged. To accurately target the most appropriate time to start HAART, the CD4 percentage could be more reliable than the absolute count in sub-Saharan African pregnant women