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

Antiretroviral (ARV) Therapy in Resource Poor Countries: What do we Need in Real Life?

Significant progresses have been made in the last 5 years towards the ultimate goal to provide universal access to care for all HIV/AIDS patients needing antiretroviral treatment in resource-poor countries. However, many barriers are still to be overcome, including (●) cost of care for the individual, (●) stigma, (●) lack of qualified human resources and infrastructure, especially in the rural setting, (●) rescue drugs for failing patients and (●) pediatric formulations. Priority actions to be promoted if the fight against HIV/AIDS is to be successful include: (i) promoting access to care in the rural areas, (ii) strengthening of basic health infrastructures, (iii) waiving of users’ fee to get ARV, (iv) a larger variety of drugs, with particular regard to fixed dose combination third line drugs and pediatric formulations, (v) local quality training and (vi) high quality basic and translational research. While the universal access to HIV care is crucial in developing countries, a strong emphasis on prevention should be maintained along

Prophylactic treatment uptake and compliance with recommended follow up among HIV exposed infants: a retrospective study in Addis Ababa, Ethiopia

<p>Abstract</p> <p>Background</p> <p>Children are being infected by HIV/AIDS mainly through mother-to-child transmission. In Ethiopia currently more than 135,000 children are living with HIV/AIDS. The aim of this study was to describe the pattern of ARV uptake after birth, co-trimoxazole prophylaxis and follow up compliance, and to examine which factors are associated with the intervention outcome.</p> <p>Methods</p> <p>A retrospective quantitative study design was used for data collection through two hospitals. All infants who were delivered by HIV infected mothers between October 2008 and August 2009 were included and information regarding treatment adherence during their first 6 months of age was collected.</p> <p>Findings</p> <p>118 HIV exposed infant-mother pairs were included in the study. 107 (90.7%) infants received ARV prophylaxis at birth. Sixty six (56%) of the infants were found to be adherent to co-trimoxazole prophylactic treatment. The majority (<it>n </it>= 110(93.2%)) of infants were tested HIV negative with DNA/PCR HIV test at the age of sixth weeks. Infants who took ARV prophylaxis at birth were found to be more likely to adhere with co-trimoxazole treatment: [OR = 9.43(95% CI: 1.22, 72.9)]. Similarly, infants whose mothers had been enrolled for HIV/ART care in the same facility [OR = 14(95% CI: 2.6, 75.4)], and children whose fathers were tested and known to be HIV positive [OR = 3.0(95% CI: 1.0, 9.0)] were more likely to adhere than their counterparts. Infants feeding practice was also significantly associated with adherence <it>χ</it>²-test, <it>p </it>< 0.01.</p> <p>Conclusion</p> <p>The proportion of ARV uptake at birth among HIV exposed infants were found to be high compared to other similar settings. Mother-infant pair enrolment in the same facility and the infant's father being tested and knew their HIV result were major predictors of infants adhering to treatment and follow up. However, large numbers of infants were lost to follow up.</p

12-month mortality and loss-to-program in antiretroviral-treated children: The IeDEA pediatric West African Database to evaluate AIDS (pWADA), 2000-2008

<p>Abstract</p> <p>Background</p> <p>The IeDEA West Africa Pediatric Working Group (pWADA) was established in January 2007 to study the care and treatment of HIV-infected children in this region. We describe here the characteristics at antiretroviral treatment (ART) initiation and study the 12-month mortality and loss-to-program of HIV-infected children followed in ART programs in West Africa.</p> <p>Methods</p> <p>Standardized data from HIV-infected children followed-up in ART programs were included. Nine clinical centers from six countries contributed to the dataset (Benin, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal). Inclusion criteria were the followings: age 0-15 years and initiated triple antiretroviral drug regimens. Baseline time was the date of ART initiation. WHO criteria was used to define severe immunosuppression based on CD4 count by age or CD4 percent < 15%. We estimated the 12-month Kaplan-Meier probabilities of mortality and loss-to-program (death or loss to follow-up > 6 months) after ART initiation and factors associated with these two outcomes.</p> <p>Results</p> <p>Between June 2000 and December 2007, 2170 children were included. Characteristics at ART initiation were the following: median age of 5 years (Interquartile range (IQR: 2-9) and median CD4 percentage of 13% (IQR: 7-19). The most frequent drug regimen consisted of two nucleoside reverse transcriptase inhibitors and one non-nucleoside reverse transcriptase inhibitors (62%). During the first 12 months, 169 (7.8%) children died and 461(21.2%) were lost-to-program. Overall, in HIV-infected children on ART, the 12-month probability of death was 8.3% (95% Confidence Interval (CI): 7.2-9.6%), and of loss-to-program was 23.1% (95% CI: 21.3-25.0%). Both mortality and loss-to program were associated with advanced clinical stage, CD4 percentage < 15% at ART initiation and year (> 2005) of ART initiation.</p> <p>Conclusion</p> <p>Innovative and sustainable approaches are needed to better document causes of death and increase retention in HIV pediatric clinics in West Africa.</p

Adherence to Combination Prophylaxis for Prevention of Mother-to-Child-Transmission of HIV in Tanzania

BACKGROUND: Since 2008, Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend combination regimen for mother and infant starting in gestational week 28. Combination prophylaxis is assumed to be more effective and less prone to resistance formation compared to single-drug interventions, but the required continuous collection and intake of drugs might pose a challenge on adherence especially in peripheral resource-limited settings. This study aimed at analyzing adherence to combination prophylaxis under field conditions in a rural health facility in Kyela, Tanzania. METHODS AND FINDINGS: A cohort of 122 pregnant women willing to start combination prophylaxis in Kyela District Hospital was enrolled in an observational study. Risk factors for decline of prophylaxis were determined, and adherence levels before, during and after delivery were calculated. In multivariate analysis, identified risk factors for declining pre-delivery prophylaxis included maternal age below 24 years, no income-generating activity, and enrolment before 24.5 gestational weeks, with odds ratios of 5.8 (P = 0.002), 4.4 (P = 0.015) and 7.8 (P = 0.001), respectively. Women who stated to have disclosed their HIV status were significantly more adherent in the pre-delivery period than women who did not (P = 0.004). In the intra- and postpartum period, rather low drug adherence rates during hospitalization indicated unsatisfactory staff performance. Only ten mother-child pairs were at least 80% adherent during all intervention phases; one single mother-child pair met a 95% adherence threshold. CONCLUSIONS: Achieving adherence to combination prophylaxis has shown to be challenging in this rural study setting. Our findings underline the need for additional supervision for PMTCT staff as well as for clients, especially by encouraging them to seek social support through status disclosure. Prophylaxis uptake might be improved by preponing drug intake to an earlier gestational age. Limited structural conditions of a healthcare setting should be taken into serious account when implementing PMTCT combination prophylaxis

Reproductive Intentions and Outcomes among Women on Antiretroviral Therapy in Rural Uganda: A Prospective Cohort Study

Background: Antiretroviral therapy (ART) may influence the biological, social and behavioral determinants of pregnancy in HIV-infected women. However, there are limited longitudinal data on the reproductive intentions and outcomes among women on ART in Africa. Methodology /Principal Findings: Using a prospective cohort design, we analyzed trends in desire for children and predictors of pregnancy among a cohort of 733 HIV-infected women in rural Uganda who initiated ART between May 2003 and May 2004 and were followed up in their homes until June 2006. Women answered in-depth social and behavioral questionnaires administered every quarter in year 1 after initiating ART, and every 6 to 12 months thereafter. Use of family planning methods was assessed at 18 and 24 months after starting ART. We tested for non-constant pregnancy incidence by using a shape parameter test from the Weibull distribution. We modeled repeated measurements of all variables related to the women’s desire for children over time using a generalized estimating equation (GEE) extension to the logistic regression model. Risk factors for pregnancy were examined using Cox proportional hazards model. 711 women eligible for the study were followed-up for a median time of 2.4 years after starting ART. During this time, less than 7 % of women reported wanting more children at any time point yet 120 (16.9%) women experienced 140 pregnancies and pregnancy incidence increased from 3.46 per 100 women-years (WY) in the first quarter to 9.5 per 100 WY at 24 months (p,0.0001). This wa