Malnutrition, Growth Response and Metabolic Changes Within the First 24 Months After ART Initiation in HIV-infected Children Treated Before the Age of 2 Years in West Africa.

BACKGROUND: There is limited information about malnutrition, growth evolution and metabolic changes among children initiated early on lopinavir-based antiretroviral therapy (ART) in Africa. METHODS: HIV-1-infected children, age <2 years were initiated on ART, as part of the MONOD ANRS 12206 project, conducted in Burkina Faso and Côte d'Ivoire. Weight-for-age, height-for-age and weight-for-height Z scores defined malnutrition [Z score less than -2 standard deviations (SDs)] using World Health Organization growth references. Biologic data were collected every 6 months. Factors associated with baseline malnutrition were evaluated using multivariate logistic regression, and with growth evolution in the first 24 months on ART using linear mixed models. RESULTS: Between 2011 and 2013, 161 children were enrolled: 64% were from Abidjan, 54% were girls. At ART initiation, median age was 13.7 months (interquartile range 7.7; 18.4), 52% were underweight (weight-for-age), 52% were stunted (height-for-age) and 36% were wasted (weight-for-height). Overall, baseline malnutrition was more likely for children living in Burkina Faso, with low birth weight, never breastfed and older age (12-24 months). Growth improved on ART, mainly within the first 6 months for weight, and was greater for the most severely malnourished children at baseline, but 8%-32% remained malnourished after 24 months. Over the 24-month period of ART, there was a significant increase of hypercholesterolemia and decrease of anemia and hypoalbuminemia. CONCLUSIONS: Prevalence of malnutrition was high before ART initiation. Even though growth improved on ART, some children remained malnourished even after 2 years of ART, highlighting the need for more active nutritional support.

Efavirenz-based simplification after successful early lopinavir-boosted-ritonavir-based therapy in HIV-infected children in Burkina Faso and Côte d'Ivoire: the MONOD ANRS 12206 non-inferiority randomised trial.

BACKGROUND: The 2016 World Health Organization guidelines recommend all children <3 years start antiretroviral therapy (ART) on protease inhibitor-based regimens. But lopinavir/ritonavir (LPV/r) syrup has many challenges in low-income countries, including limited availability, requires refrigeration, interactions with anti-tuberculous drugs, twice-daily dosing, poor palatability in young children, and higher cost than non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs. Successfully initiating LPV/r-based ART in HIV-infected children aged <2 years raises operational challenges that could be simplified by switching to a protease inhibitor-sparing therapy based on efavirenz (EFV), although, to date, EFV is not recommended in children <3 years. METHODS: The MONOD ANRS 12026 study is a phase 3 non-inferiority open-label randomised clinical trial conducted in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso (ClinicalTrial.gov registry: NCT01127204). HIV-1-infected children who were tuberculosis-free and treated before the age of 2 years with 12-15 months of suppressive twice-daily LPV/r-based ART (HIV-1 RNA viral load (VL) <500 copies/mL, confirmed) were randomised to two arms: once-daily combination of abacavir (ABC) + lamivudine (3TC) + EFV (referred to as EFV) versus continuation of the twice-daily combination zidovudine (ZDV) or ABC + 3TC + LPV/r (referred to as LPV). The primary endpoint was the difference in the proportion of children with virological suppression by 12 months post-randomisation between arms (14% non-inferiority bound, Chi-squared test). RESULTS: Between May 2011 and January 2013, 156 children (median age 13.7 months) were initiated on ART. After 12-15 months on ART, 106 (68%) were randomised to one of the two treatment arms (54 LPV, 52 EFV); 97 (91%) were aged <3 years. At 12 months post-randomisation, 46 children (85.2%) from LPV versus 43 (82.7%) from EFV showed virological suppression (defined as a VL <500 copies/mL; difference, 2.5%; 95% confidence interval (CI), -11.5 to 16.5), whereas seven (13%) in LPV and seven (13.5%) in EFV were classed as having virological failure (secondary outcome, defined as a VL ≥1000 copies/mL; difference, 0.5%; 95% CI, -13.4 to 12.4). No significant differences in adverse events were observed, with two adverse events in LPV (3.7%) versus four (7.7%) in EFV (p = 0.43). On genotyping, 13 out of 14 children with virological failure (six out of seven EFV, seven out of seven LPV) had a drug-resistance mutation: nine (five out of six EFV, four out of seven LPV) had one or more major NNRTI-resistance mutations whereas none had an LPV/r-resistance mutation. CONCLUSIONS: At the VL threshold of 500 copies/mL, we could not conclusively demonstrate the non-inferiority of EFV on viral suppression compared to LPV because of low statistical power. However, non-inferiority was confirmed for a VL threshold of <1000 copies/mL. Resistance analyses highlighted a high frequency of NNRTI-resistance mutations. A switch to an EFV-based regimen as a simplification strategy around the age of 3 years needs to be closely monitored. TRIAL REGISTRATION: ClinicalTrial.gov registry n° NCT01127204 , 19 May 2010.

Virological response and resistances over 12 months among HIV-infected children less than two years receiving first-line lopinavir/ritonavir-based antiretroviral therapy in Cote d'Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort.

INTRODUCTION: Lopinavir/ritonavir-based antiretroviral therapy (ART) is recommended for all HIV-infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12-month response to lopinavir/ritonavir-based antiretroviral therapy in a cohort of West African children treated before the age of two years. METHODS: HIV-1-infected, ART-naive except for a prevention of mother-to-child transmission (PMTCT), tuberculosis-free, and less than two years of age children with parent's consent were enrolled in a 12-month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed. RESULTS: Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8-18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost-to-follow-up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed-up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09-6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03-7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05-6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation. CONCLUSION: Twelve-month VS rate on lopinavir/ritonavir-based ART was high, comparable to those in Africa or high-income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy-to-identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.

[A plea for introduction of hepatitis B vaccination at birth in Côte d'Ivoire]. / Plaidoyer pour l?introduction du vaccin contre l?hépatite virale B à la naissance en Côte d?Ivoire.

The Côte d'Ivoire National Immunization Technical Advisory Group 2015 work plan included elaboration of an opinion on inclusion of hepatitis B vaccination at birth in the Expanded Program on Immunization (EPI) in Côte d'Ivoire. A task force was set up to conduct this assessment according to a systematized method. The task force analysed scientific articles on the burden of hepatitis B in Côte d'Ivoire, the burden of mother-child transmission, the impact of hepatitis B vaccination at birth in countries which have adopted this strategy, the efficacy and safety of hepatitis B vaccine in newborns, the cost-effectiveness of hepatitis B vaccination at birth, and the best strategy to introduce hepatitis B vaccination at birth in the EPI. The National Immunization Technical Advisory Group of Côte d'Ivoire finally recommended introduction of a dose of hepatitis B vaccine at birth in the context of the Expanded Program on Immunization with maintenance of three doses of pentavalent vaccine (DPT-HepB-Hib) at 6, 10, and 14 weeks of age.

Costs of Care of HIV-Infected Children Initiating Lopinavir/Ritonavir-Based Antiretroviral Therapy before the Age of Two in Cote d'Ivoire.

OBJECTIVES: To access the costs of care for Ivoirian children before and after initiating LPV/r-based antiretroviral therapy (ART) before the age of two. METHODS: We assessed the direct costs of care for all HIV-infected children over the first 12 months on LPV/r-based ART initiated <2 years of age in Abidjan. We recorded all drug prescriptions, ART and cotrimoxazole prophylaxis delivery, medical analyses/examinations and hospital admissions. We compared these costs to those accrued in the month prior to ART initiation. Costs and 95% confidence intervals (95%CI) were estimated per child-month, according to severe morbidity. RESULTS: Of the 114 children screened, 99 initiated LPV/r-based ART at a median age of 13.5 months (IQR: 6.8-18.6); 45% had reached World Health Organization stage 3 or 4. During the first 12 months on ART, 5% died and 3% were lost to follow-up. In the month before ART initiation, the mean cost of care per child-month reached $123.39 (95%CI:$121.02-$125.74). After ART initiation, it was $42.53 (95%CI:$42.15-$42.91); 50% were ART costs. The remaining costs were non-antiretroviral drugs (18%) and medical analyses/examinations (14%). Mean costs were significantly higher within the first three months on ART ($48.76, 95%CI:$47.95-$49.56) and in children experiencing severe morbidity ($49.76, 95%CI:$48.61-50.90). CONCLUSION: ART reduces the overall monthly cost of care of HIV-infected children < 2 years. Because children were treated at an advanced HIV disease stage, the additional costs of treating severe morbidity on ART remain substantial. Strategies for treating HIV-infected children as early as possible must remain a priority in Côte d'Ivoire.

Missed opportunities of inclusion in a cohort of HIV-infected children to initiate antiretroviral treatment before the age of two in West Africa, 2011 to 2013.

INTRODUCTION: The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso. METHODS: All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion. RESULTS: Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father's refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency. CONCLUSIONS: Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.

[Growth in steroid-responsive nephrotic syndrome in Cote d'Ivoire]. / La croissance staturale des enfants ayant un syndrome néphrotique cortico-sensible en Côte d'Ivoire.

We realized one of the first observational studies in sub-Saharan Africa whose aim was to analyze the growth in steroid-responsive nephrotic syndrome. This was a retrospective study, involving 30 children followed for nephrotic syndrome in pediatric nephrology unit of the University Hospital of Yopougon (Abidjan) from 28.02.2005 to 19.12.2010. Each child was followed for two years and we are interested in demographic characteristics and the evolution of size. At the end of our study, it appears that: the mean age was 89.33 ± 43.41 months (7.44 years) with a sex ratio of 3,28. At the end of the two years of follow-up, patients had received a median dose of steroids 6151 ± 3832 mg/m(2), 9111 ± 1376 mg/m(2) and 8664 ± 5379 mg/m(2), respectively, for a relapse or no, two and at least three relapses. Fourteen patients had received vitamin D therapy and calcium. At the end of follow-up, four children had growth retardation. An average gain in Z-score was noted at the end of follow-up in girls and boys respectively +0.06 and +0.36. The growth retardation observed in our study was not associated with different growth periods (P=0.116), gender (P=0.548) and the mean Z-scores observed at the end of follow-up was not significantly different between the sexes (P=0.26). Growth retardation observed was not related to the cumulative dose administered (P=0.15), number of relapse (P=1.000).

Universal HIV screening at postnatal points of care: which public health approach for early infant diagnosis in Côte d'Ivoire?

BACKGROUND: Universal HIV pediatric screening offered at postnatal points of care (PPOC) is an entry point for early infant diagnosis (EID). We assessed the parents' acceptability of this approach in Abidjan, Côte d'Ivoire. METHODS: In this cross-sectional study, trained counselors offered systematic HIV screening to all children aged 6-26 weeks attending PPOC in three community health centers with existing access to HAART during 2008, as well as their parents/caregivers. HIV-testing acceptability was measured for parents and children; rapid HIV tests were used for parents. Both parents' consent was required according to the Ivorian Ethical Committee to perform a HIV test on HIV-exposed children. Free HIV care was offered to those who were diagnosed HIV-infected. FINDINGS: We provided 3,013 HIV tests for infants and their 2,986 mothers. While 1,731 mothers (58%) accepted the principle of EID, only 447 infants had formal parental consent 15%; 95% confidence interval (CI): [14%-16%]. Overall, 1,817 mothers (61%) accepted to test for HIV, of whom 81 were HIV-infected (4.5%; 95% CI: [3.5%-5.4%]). Among the 81 HIV-exposed children, 42 (52%) had provided parental consent and were tested: five were HIV-infected (11.9%; 95% CI: [2.1%-21.7%]). Only 46 fathers (2%) came to diagnose their child. Parental acceptance of EID was strongly correlated with prenatal self-reported HIV status: HIV-infected mothers were six times more likely to provide EID parental acceptance than mothers reporting unknown or negative prenatal HIV status (aOR: 5.9; 95% CI: [3.3-10.6], p = 0.0001). CONCLUSIONS: Although the principle of EID was moderately accepted by mothers, fathers' acceptance rate remained very low. Routine HIV screening of all infants was inefficient for EID at a community level in Abidjan in 2008. Our results suggest the need of focusing on increasing the PMTCT coverage, involving fathers and tracing children issued from PMTCT programs in low HIV prevalence countries.

Evaluation of dried blood spot diagnosis using HIV1-DNA and HIV1-RNA Biocentric assays in infants in Abidjan, Côte d'Ivoire. The Pedi-Test DBS ANRS 12183 Study.

This study evaluates HIV infant diagnosis on DBS using Biocentric HIV1-DNA and HIV1-RNA assays, in field conditions in Côte d'Ivoire. Paediatric screening was offered to children≤3 years in clinical sites in Côte d'Ivoire in 2008. For each HIV-infected child, two non-infected children were included and blood samples were collected. HIV-DNA results obtained on EDTA blood samples with Biocentric assay were the reference for HIV infant diagnosis. Plasma and DBS viral loads were measured using HIV-RNA Biocentric assay. DBS samples were also tested for HIV-DNA detection using both Biocentric and Amplicor Roche assays. Sensitivity, specificity and concordance between tests were calculated. Overall samples from 138 HIV-exposed children, 46 infected, 92 non-infected were included. All tests were 100% sensitive and specific including 100% concordance with the two HIV-DNA assays. The median level of HIV-DNA on EDTA samples was 3.15 log10 copies/10(6) PBMCs; the median level of HIV RNA in plasma and DBS were respectively 5.82 and 5.17 log10 copies/ml (Pearson's correlation R2=0.92, p<0.0001). The threshold for detectable HIV-RNA on DBS was 3.3 log10. Although there are differences between viral load measured on DBS and plasma, the two Biocentric assays present very good performances for HIV infant diagnosis on DBS while cheap and feasible.

Notification of HIV status disclosure and its related factors in HIV-infected adolescents in 2009 in the Aconda program (CePReF, CHU Yopougon) in Abidjan, Côte d'Ivoire, The PRADO-CI Study.

INTRODUCTION: We studied the frequency of documentation of disclosure of HIV status in medical charts and its correlates among HIV-infected adolescents in 2009, in Abidjan, Côte d'Ivoire. METHODS: The PRADO-CI is a cross-sectional study aimed at studying HIV-infected adolescents' social, psychological, and behavioural difficulties and their determinants in Abidjan, Côte d'Ivoire. In this study, we present specific analyses on disclosure. All HIV-infected adolescents aged 13-21 years and followed at least once in 2009 in two urban HIV-care centres in Abidjan (Cepref and Yopougon Teaching Hospital) were enrolled in the study. Standardized data were extracted from medical records to document if there was notification of disclosure of HIV status in the medical record. Frequency of notification of HIV disclosure was estimated with its 95% confidence interval (CI) and correlates were analyzed using logistic regression. RESULTS: In 2009, 229 adolescents were included: 126 (55%) males; 93% on antiretroviral therapy (ART), 61% on cotrimoxazole prophylaxis. Their median age was 15 years at the time of the study. Among the 193 patients for whom information on HIV status disclosure was documented (84%), only 63 (32.6%; 95% CI=26.0-39.3%) were informed of their status. The proportion of adolescents informed increased significantly with age: 19% for 13-15 years, 33% for 16-18 years and 86% for 19-21 years (p <0.0001). Adolescents on ART tended to be more likely to be informed of their HIV status (34.5%) than those not treated (13.3%) (p=0.11). Those on cotrimoxazole were significantly more likely to be informed (39.6%) than those not (21.9%) (p=0.01). Disclosure was significantly higher in adolescents with a history of ART regimen change (p=0.003) and in those followed in the Cepref (48.4%) compared to the Yopougon Teaching Hospital (24.8%), (p=0.001). In multivariate analyses, disclosed HIV status was significantly higher in those followed-up in the Cepref compared to the other centre: adjusted odds ratio (aOR)=3.5 (95% CI: 1.1-10.9), and among older adolescents compared to those aged 13-15 years: [16-18 years] aOR=4.2 (95% CI: 1.5-11.5) and [>18 years]: aOR=22.1 (95% CI: 5.2-93.5). CONCLUSIONS: HIV disclosure rate was low among Ivoirian HIV adolescents and was site- and age-dependent. There is a need for practical interventions to support HIV disclosure to adolescents which provides age-appropriate information about the disease.

Attitudes and practices of health care workers toward routine HIV testing of infants in Côte d'Ivoire: the PEDI-TEST ANRS 12165 Project.

OBJECTIVE: We assessed attitudes and practices of health care workers (HCWs) toward HIV counselling and testing (CT) routinely offered to infants in health facilities in Abidjan, Côte d'Ivoire. METHODS: We performed a cross-sectional survey inquiring on systematic HIV CT offered to children aged 6-26 weeks attending postnatal care for either immunization or pediatric care and to their parents in 4 community health centres rolling-out access to antiretroviral therapy. Data were collected using standardized anonymous self-questionnaires directed to all HCWs involved. RESULTS: One-hundred five HCWs were interviewed in 2008: 30% were social workers, 27% physicians, 24% nurses and 19% laboratory technicians. Among immunization staff (n = 45), none trained in child CT versus 26% in pediatric services (n = 60, P < 0001). Almost all staff believed that it is important to offer HIV screening services to children and the best place could be during pediatric consultations. In their daily work, 22% of immunization staff and 48% of pediatric care staff had already been dealing with early HIV CT (P = 0.01). Facing a child suspected to be HIV infected, only 54% of providers in pediatrics and 71% in immunization would offer CT to all family members (P = 0.01). CONCLUSIONS: In Abidjan, although HCWs were generally in favour of pediatric HIV screening, very few had received specific training to do so. Deleguation of CT to the primary care level could improve coverage of CT services. It is urgent to train HCWs to promote early infant HIV diagnosis to improve earlier access to antiretroviral therapy in West African HIV-infected children.

18-month occurrence of severe events among early diagnosed HIV-infected children before antiretroviral therapy in Abidjan, Côte d'Ivoire: a cohort study.

OBJECTIVE: To assess the 18-month field effectiveness on severe events of a pediatric package combining early HIV-diagnosis and targeted cotrimoxazole prophylaxis in HIV-infected children from age six-week before the antiretroviral era, in Abidjan, Côte d'Ivoire. METHODS: Data from two consecutive prevention of HIV mother-to-child transmission programs were compared: the ANRS 1201/1202 Ditrame-Plus cohort (2001-2005) and the pooled data of the ANRS 049a Ditrame randomized trial and its following open-labeled cohort (1995-2000), used as a reference group. HIV-infected pregnant women > or = 32-36 weeks of gestation were offered a short-course peri-partum antiretroviral prophylaxis (ZDV in Ditrame, and ZDV +/- 3TC+single-dose (sd) NVP in Ditrame-Plus). Neonatal prophylaxis was provided in Ditrame-Plus only: 7-day ZDV and sdNVP 48-72 h after birth. A 6-week pediatric HIV-RNA diagnosis was provided on-line in the Ditrame-Plus while it was only oriented on clinical symptoms in Ditrame. Six-week HIV-infected children received a daily cotrimoxazole prophylaxis in Ditrame-Plus while no prophylaxis was provided in Ditrame. The determinants of severe events (death or hospitalization > 1 day) were assessed in a Cox regression model. RESULTS: Between 1995 and 2003, 98 out of the 1121 live-births were diagnosed as HIV-infected in peri-partum: 45 from Ditrame-Plus and 53 from Ditrame. The 18-month Kaplan-Meier cumulative probability of presenting a severe event was 66% in Ditrame-Plus (95% confidence interval [95%CI]: 50%-81%) and 77% in Ditrame (95%CI: 65%-89%), Log Rank test: p = 0.47. After adjustment on maternal WHO clinical stage, maternal death, 6-week pediatric viral load, birth-weight, and breastfeeding exposure, the 18-month risk of severe event was lower in Ditrame-Plus than in Ditrame (adjusted Hazard Ratio (aHR): 0.55, 95%CI: 0.3-1.1), although the difference was not statistically significant; p = 0.07). Maternal death was the only variable determinant of the occurrence of severe events in children (aHR: 3.73; CI: 2.2-11.2; p = 0.01). CONCLUSION: Early cotrimoxazole from 6 weeks of age in HIV-infected infants seemed to reduce probability of severe events but the study lacked statistical power to prove this. Even with systematic cotrimoxazole prophylaxis, infant morbidity and mortality remained high pointing towards a need for early pediatric HIV-diagnosis and antiretroviral treatment in Africa.

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.

Early mixed feeding and breastfeeding beyond 6 months increase the risk of postnatal HIV transmission: ANRS 1201/1202 Ditrame Plus, Abidjan, Côte d'Ivoire.

OBJECTIVE: To evaluate the risk of postnatal HIV transmission among women in Abidjan, Côte d'Ivoire offered alternatives to prolonged breastfeeding, and to assess the impact of the breastfeeding pattern and duration on this risk. METHODS: In 2001-2003, HIV-infected pregnant women received peri-partum antiretroviral prophylaxis and were counselled antenatally regarding infant feeding options: formula feeding or exclusive breastfeeding with early cessation from 4 months of age. The primary outcome was HIV postnatal transmission by 18 months of age, defined by a positive HIV test after a negative test > or =30 days. The effect of the pattern (mixed feeding, defined as breastmilk plus food-based fluid, solid food or non-human milk) and duration (less vs. more than 6 months) of breastfeeding on postnatal transmission was assessed. RESULTS: Of 622 live-born infants who were HIV uninfected at or after 30 days, 15 were infected postnatally, 13/324 among breastfed, and 2/298 among formula-fed infants. The 18-month probability of remaining free from HIV infection was 0.95 [95% CI, 0.92-0.97] and 0.99 [95% CI, 0.97-1.00] in the breastfeeding and formula-feeding groups respectively (p<0.001). In adjusted analysis, breastfeeding for more than 6 months and mixed feeding during the first month of life were independently associated with a 7.5 (AOR 95% CI, 2.0-28.2, p=0.003)- and a 6.3 (95% CI, 1.1-36.4, p=0.04)-fold increase of postnatal transmission among breastfed children. CONCLUSIONS: Mixed feeding during the first month of life and breastfeeding beyond 6 months are strong determinants of HIV transmission and should be avoided when replacement feeding after breastfeeding cessation can be safely and sustainably provided.

Two-year morbidity-mortality and alternatives to prolonged breast-feeding among children born to HIV-infected mothers in Côte d'Ivoire.

BACKGROUND: Little is known about the long-term safety of infant feeding interventions aimed at reducing breast milk HIV transmission in Africa. METHODS AND FINDINGS: In 2001-2005, HIV-infected pregnant women having received in Abidjan, Côte d'Ivoire, a peripartum antiretroviral prophylaxis were presented antenatally with infant feeding interventions: either artificial feeding, or exclusive breast-feeding and then early cessation from 4 mo of age. Nutritional counseling and clinical management were provided for 2 y. Breast-milk substitutes were provided for free. The primary outcome was the occurrence of adverse health outcomes in children, defined as validated morbid events (diarrhea, acute respiratory infections, or malnutrition) or severe events (hospitalization or death). Hazards ratios to compare formula-fed versus short-term breast-fed (reference) children were adjusted for confounders (baseline covariates and pediatric HIV status as a time-dependant covariate). The 18-mo mortality rates were also compared to those observed in the Ditrame historical trial, which was conducted at the same sites in 1995-1998, and in which long-term breast-feeding was practiced in the absence of any specific infant feeding intervention. Of the 557 live-born children, 262 (47%) were breast-fed for a median of 4 mo, whereas 295 were formula-fed. Over the 2-y follow-up period, 37% of the formula-fed and 34% of the short-term breast-fed children remained free from any adverse health outcome (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI], 0.87-1.38; p = 0.43). The 2-y probability of presenting with a severe event was the same among formula-fed (14%) and short-term breast-fed children (15%) (adjusted HR, 1.19; 95% CI, 0.75-1.91; p = 0.44). An overall 18-mo probability of survival of 96% was observed among both HIV-uninfected short-term and formula-fed children, which was similar to the 95% probability observed in the long-term breast-fed ones of the Ditrame trial. CONCLUSIONS: The 2-y rates of adverse health outcomes were similar among short-term breast-fed and formula-fed children. Mortality rates did not differ significantly between these two groups and, after adjustment for pediatric HIV status, were similar to those observed among long-term breast-fed children. Given appropriate nutritional counseling and care, access to clean water, and a supply of breast-milk substitutes, these alternatives to prolonged breast-feeding can be safe interventions to prevent mother-to-child transmission of HIV in urban African settings.

Acceptability of formula-feeding to prevent HIV postnatal transmission, Abidjan, Côte d'Ivoire: ANRS 1201/1202 Ditrame Plus Study.

OBJECTIVE: To describe the maternal acceptability of formula-feeding proposed to reduce postnatal HIV transmission in Abidjan, Côte d'Ivoire. METHODS: Each consenting HIV-infected pregnant women, age > or =18 years, who received a perinatal antiretroviral prophylaxis was eligible. Two hierarchical infant-feeding options were proposed antenatally: exclusive formula-feeding or short-term exclusive breast-feeding. Formula-feeding was provided free up to age 9 months. Determinants of acceptability were analyzed using a logistic regression. Formula-feeding failure was defined as having breast-fed one's child at least once. RESULTS: Between March 2001 and March 2003, 580 women delivered: 97% expressed their infant-feeding choice before delivery; 53% chose formula-feeding. Significant prenatal determinants for refusing formula-feeding were: living with her partner, being Muslim, having a low educational level, being followed in one of the study sites, having not disclosed her HIV status, and having been included within the first 6 months of the project. Among the 295 mothers who formula-fed, the Kaplan-Meier probability of success of the formula-feeding option was 93.6% at Day 2 (95% confidence interval [CI]: 90.7% to 96.3%) and 84.2% at 12 months (95% CI: 79.9% to 88.5%): 46 of 295 (15.6%) women breast-fed at least once, of whom 41% temporarily practiced mixed-feeding at Day 2 because of social stigma or newborn poor health. CONCLUSIONS: In settings with general access to clean water, structured antenatal counseling, and sustained provision of free formula, slightly over half of HIV-infected women chose to artificially feed their newborn infant. Low mixed-feeding rates were observed. This social acceptability must be balanced with mother-child long-term health outcomes to guide safe recommendations on infant-feeding among HIV-infected women in African urban settings.

Complementary feeding adequacy in relation to nutritional status among early weaned breastfed children who are born to HIV-infected mothers: ANRS 1201/1202 Ditrame Plus, Abidjan, Cote d'Ivoire.

OBJECTIVE: In high HIV prevalence resource-constrained settings, exclusive breastfeeding with early cessation is one of the conceivable interventions aimed at the prevention of HIV through breast milk. Nevertheless, this intervention has potential adverse effects, such as the inappropriateness of complementary feeding to take over breast milk. The purpose of our study first was to describe the nature and the ages of introduction of complementary feeding among early weaned breastfed infants up to their first birthday and second was to assess the nutritional adequacy of these complementary foods by creating a child feeding index and to investigate its association with child nutritional status. METHODS: A prospective cohort study in Abidjan, Côte d'Ivoire, was conducted in HIV-infected pregnant women who were willing to breastfeed and had received a perinatal antiretroviral prophylaxis. They were requested to practice exclusive breastfeeding and initiate early cessation of breastfeeding from the fourth month to reduce breast milk HIV transmission. Nature and ages of introductory complementary feeding were described in infants up to their first birthday by longitudinal compilation of 24-hour and 7-day recall histories. These recalls were done weekly until 6 weeks of age, monthly until 9 months of age, and then quarterly. We created an index to synthesize the nutritional adequacy of infant feeding practices (in terms of quality of the source of milk, dietary diversity, food, and meal frequencies) ranging from 0 to 12. The association of this feeding index with growth outcomes in children was investigated. RESULTS: Among the 262 breastfed children included, complete cessation of breastfeeding occurred in 77% by their first birthday, with a median duration of 4 months. Most of the complementary foods were introduced within the seventh month of life, except for infant food and infant formula that were introduced at age 4 months. The feeding index was relatively low (5 of 12) at age 6 months, mainly as a result of insufficient dietary diversity, but was improved in the next 6 months (8.5 of 12 at 12 months of age). Inadequate complementary feeding at age 6 months was associated with impaired growth during the next 12 months, with a 37% increased probability of stunting. CONCLUSION: Adequate feeding practices around the weaning period are crucial to achieving optimal child growth. HIV-infected women should turn to early cessation of breastfeeding only when they are counseled properly to provide adequate complementary feeding to take over breast milk. Our child feeding index could contribute to the assessment of the nutritional adequacy of complementary feeding around the weaning period and therefore help to detect children who are at risk for malnutrition.

Acceptability of exclusive breast-feeding with early cessation to prevent HIV transmission through breast milk, ANRS 1201/1202 Ditrame Plus, Abidjan, Côte d'Ivoire.

OBJECTIVE: We assessed the uptake of a nutritional intervention promoting exclusive breast-feeding with early cessation between 3 and 4 months of age to reduce postnatal transmission of HIV in Abidjan, Côte d'Ivoire. DESIGN: Between March 2001 and March 2003, HIV-infected pregnant women who had received perinatal antiretroviral prophylaxis were systematically offered prenatally 2 infant feeding interventions: artificial feeding or exclusive breast-feeding during 3 months and then early cessation of breast-feeding. Mother-infant pairs were closely followed for a period of 2 years, with continuous nutritional counseling and detailed collection of feeding practices. RESULTS: Among the 557 mothers enrolled, 262 (47%) initiated breast-feeding. Of these women, the probability of practicing exclusive breast-feeding from birth was 18% and 10% at 1 and 3 months of age, respectively. Complete cessation of breast-feeding was obtained in 45% and 63% by 4 and 6 months of age, respectively. Environmental factors such as living with a partner's family were associated with failure to initiate early cessation of breast-feeding. CONCLUSIONS: Acceptability of exclusive breast-feeding was low in this urban population. Shortening the duration of breast-feeding seemed to be feasible, however. Further investigations are ongoing to evaluate the safety and effectiveness of this intervention in reducing breast milk HIV transmission.

Is it possible to collect medicalized data in Africa? An experience in the pediatrics service in the University Hospital in Yopougon, Abidjan, Ivory Coast.

The aim of this study is to demonstrate that it can be relevant to implement medicalized data in the African hospitals in order to establish morbidity statistics and economical evaluation. A retrospective survey has been carried out on 300 children hospitalized in the paediatrics service in the Yopougon University Hospital from January 1st to December 31st 1999. Data have been collected on forms similar to the ones used in France for discharge summaries. The file batching used for these 300 files is the French DRG named GHM: it shows that, once the files have been divided up in main categories(CMD), CMD 18 (infectious and parasitic diseases) amounts to nearly half of the stays (43.7%). Likewise, in the Case Mix, GHM 611 (others infectious or parasitic diseases) represents, with 38%, more than one third of the stays. The most frequent diagnosis is the B50.9, plasmodium falciparum malaria without precision, with 24.3% of the stays. The patients' stays are shorter than in France. But according to the quality of the collected data, the inadequacy of the tools used and the category of the patients taken into consideration, these results have to be interpreted with restriction. However, this survey shows that it is possible to collect medicalized data in the African hospitals. Other services should feel concerned and more appropriate classifications that would reckon with epidemiological specificities should be applied.