Prevalence of undiagnosed HIV among children in South Africa, Côte d'Ivoire and Zimbabwe: a model-based analysis to inform paediatric HIV screening programmes.

INTRODUCTION: To improve the diagnosis and survival of children living with HIV (CLWH), the World Health Organization recommends testing approaches beyond traditional infant HIV testing programmes. Information about undiagnosed HIV prevalence among children of varying ages in the general population is needed to guide innovative national/subnational case-finding and testing approaches. METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to estimate the prevalence of undiagnosed HIV in 2-, 5- and 10-year-old children in South Africa, Côte d'Ivoire and Zimbabwe in 2018. We simulated cohorts of children born in 2008 (10-year-olds), 2013 (5-year-olds) and 2016 (2-year-olds). Country-/year-specific inputs for pregnant/breastfeeding women included: HIV prevalence (4.2-32.3%), HIV incidence (0.03-0.24%/month), knowledge of HIV status (27-89%) and antiretroviral drug coverage (36-95%). Paediatric inputs included early infant testing coverage (6-95%) and breastfeeding duration (0-20 months). We projected the proportion of surviving CLWH in whom HIV remained undiagnosed and the undiagnosed HIV prevalence among surviving children of each age in the general population. For children born in 2016, we projected survival and diagnosis of all CLWH through 2026. We conducted sensitivity analyses on model parameters. RESULTS: In 2018, the projected proportion of surviving CLWH whose HIV remained undiagnosed in South Africa/Côte d'Ivoire/Zimbabwe was 44.2%/55.8%/52.9% among 2-year-old CLWH; 29.0%/37.8%/33.2% among 5-year-old CLWH; and 18.3%/25.4%/23.1% among 10-year-old CLWH. Projected general population undiagnosed HIV prevalence in South Africa/Côte d'Ivoire/Zimbabwe was 0.44%/0.32%/0.68% among 2-year-olds; 0.25%/0.17%/0.41% among 5-year-olds; and 0.24%/0.14%/0.38% among 10-year-olds. Among all CLWH born in 2016, 50-54% were projected to die without HIV diagnosis (and subsequently without treatment) within 10 years after birth; 80-85% of these deaths occurred in the first 2 years. CONCLUSIONS: Projected population-level undiagnosed HIV prevalence is low and sharply decreases after age 2, with more CLWH dying than being diagnosed. Despite low undiagnosed prevalence in the general population of older children, we project that a large proportion of CLWH remain undiagnosed, suggesting that innovative strategies targeting untested children of all ages outside of health facility settings should be prioritized. Programmes could consider routine testing of the general population of children below 2 in all settings and children of all ages in high-prevalence settings.

Evaluating Point-of-Care Nucleic Acid Tests in Adult Human Immunodeficiency Virus Diagnostic Strategies: A Côte d'Ivoire Modeling Analysis.

BACKGROUND: The World Health Organization (WHO) human immunodeficiency virus (HIV) diagnostic strategy requires 6 rapid diagnostic tests (RDTs). Point-of-care nucleic acid tests (POC NATs) are costlier, less sensitive, but more specific than RDTs. METHODS: We simulated a 1-time screening process in Côte d'Ivoire (CI; undiagnosed prevalence: 1.8%), comparing WHO- and CI-recommended RDT-based strategies (RDT-WHO, RDT-CI) and an alternative: POC NAT to resolve RDT discordancy (NAT-Resolve). Costs included assays (RDT: $1.47; POC NAT: $27.92), antiretroviral therapy ($6-$22/month), and HIV care ($27-$38/month). We modeled 2 sensitivity/specificity scenarios: high-performing (RDT: 99.9%/99.1%; POC NAT: 95.0%/100.0%) and low-performing (RDT: 91.1%/82.9%; POC NAT: 93.3%/99.5%). Outcomes included true-positive (TP), false-positive (FP), true-negative (TN), or false-negative (FN) results; life expectancy; costs; and incremental cost-effectiveness ratios (ICERs: $/year of life saved [YLS]; threshold ≤$1720/YLS [per-capita gross domestic product]). RESULTS: Model-projected impacts of misdiagnoses were 4.4 years lost (FN vs TP; range, 3.0-13.0 years) and a $5800 lifetime cost increase (FP vs TN; range, $590-$14 680). In the high-performing scenario, misdiagnoses/10 000 000 tested were lowest for NAT-Resolve vs RDT-based strategies (FN: 409 vs 413-429; FP: 14 vs 21-28). Strategies had similar life expectancy (228 months) and lifetime costs ($220/person) among all tested; ICERs were $3450/YLS (RDT-CI vs RDT-WHO) and $120 910/YLS (NAT-Resolve vs RDT-CI). In the low-performing scenario, misdiagnoses were higher (FN: 22 845-30 357; FP: 83 724-112 702) and NAT-Resolve was cost-saving. CONCLUSIONS: We projected substantial clinical and economic impacts of misdiagnoses. Using POC NAT to resolve RDT discordancy generated the fewest misdiagnoses and was not cost-effective in high-performing scenarios, but may be an important adjunct to existing RDT-based strategies in low-performing scenarios.

Special considerations concerning the use of antiretroviral drugs in children.

INTRODUCTION: Antiretroviral therapy is extremely effective in both children and adults infected with HIV. Treatment indications have rapidly expanded; ideally, with rare exceptions, all infected children should now be treated. Areas covered: The use of antiretroviral drugs in children is based largely on extrapolations from experience with adult patients. Pharmacokinetic studies are required in addition to formal studies, which are difficult to conduct in pediatric situations, extending from birth to adolescence. However, despite often inadequate galenic formulation, treatment of children is easier than generally thought. No major or irreversible toxicity has been observed with the latest generation of molecules. Several observations suggest that very early treatment, beginning shortly after birth, provides better long-term immunological control of infection. Expert commentary: All HIV-infected children should be treated with antiretroviral drugs. Manufacturers should propose appropriate dosage forms, including combined forms in particular, and should support pharmacological and tolerance studies in pediatric patients of various ages. Very early treatment maximizes the chances of long-term immunological control.

HIV-1 DNA concentrations and evolution among African HIV-1-infected children under antiretroviral treatment (ANRS 1244/1278).

OBJECTIVES: The objectives of this study were to describe the pretreatment HIV-1 DNA concentrations in children infected with HIV and to evaluate the impact of antiretroviral therapy (ART) on HIV-DNA concentrations. METHODS: This was a retrospective analysis of all children followed up in the 'Programme Enfant Yopougon' cohort, Abidjan, Côte d'Ivoire, from 2000 to 2004, who had cryopreserved peripheral blood mononuclear cells (PBMCs) and plasma samples. HIV-DNA was measured using a real-time PCR assay. Mixed-model analysis was used to analyse the factors associated with change in HIV-DNA concentration. RESULTS: The study included 121 children infected with HIV-1. The median age at inclusion was 6 years (IQR: 3.5-9) and children were at an advanced stage of HIV disease (46.6% and 20.3% presenting CDC stage B and CDC stage C, respectively). At baseline, the median HIV-DNA concentration was 3.4 log10 copies/10(6) PBMCs (IQR: 3.1-3.6). Fifty-four children were initiated on ART during follow-up. After 24 months of ART, HIV-DNA load decreased by 0.32 (IQR: 0.08-0.57) log10 copies/10(6) PBMCs. The only factor associated with the HIV-DNA decrease was a concomitant low HIV-RNA viral load result. Children with efficient ART had a 0.51 log10 copies (IQR: 0.40-0.86) HIV-DNA decrease per million PBMCs. CONCLUSIONS: HIV-DNA concentrations decreased following ART initiation in a large African paediatric cohort. This decline was exclusively associated with the decrease in ongoing replication level achieved. Our study points out that a strong adherence is needed for ART to be efficient on the viral reservoirs, and further reinforces that adherence support is also essential to diminish the reservoir.

Morbidity after antiretroviral therapy initiation in HIV-1-infected children in West Africa: temporal trends and relation to CD4 count.

BACKGROUND: Although 90% of HIV-1-infected children live in sub-Saharan Africa, morbidity data after highly active antiretroviral therapy (HAART) initiation in these settings are limited. The objective of this study was to document the incidence of AIDS-defining events and non-AIDS-defining diseases in African children receiving HAART. METHODS: Incidences rates (IRs) of AIDS-defining events and 10 other common diseases were estimated overall and by current CD4-strata (<15%, 15 - <25% and ≥25%) from 2 prospective cohorts of African children. RESULTS: One hundred eighty-eight children contributing to 355 children-years were included. The documented morbidity IRs per 100 children-years were upper respiratory infections, 100 (87-114); infectious diarrhea, 37 (31-44); World Health Organization (WHO) stage 2 events, 22.9 (18.2-28.1); and WHO stage 3/4 events, 12.3 (9.1-16.7). IRs of WHO stage 2 events, severe bacterial infections, infectious diarrhea and pneumonia decreased linearly across all CD4%-strata, whereas WHO stage 3/4 events and viral infections occurred mostly when CD4% <15%. Overall, IRs decreased during the first 2 years on HAART except for upper respiratory infection, mycosis and oral candidiasis. CONCLUSION: This incidence of AIDS- and non-AIDS-defining diseases declined substantially after HAART in 2 African cohorts, although estimates remained high compared with high-resource settings. Without renewed efforts to increase antiretroviral scale-up, children in developing countries will continue to have a high burden of infections.

Evolution of lipid levels in HIV-infected children treated or not with HAART in Abidjan, Cote d'Ivoire.

OBJECTIVE: To describe lipid levels in antiretroviral (ARV)-naïve HIV-infected Ivorian children and assess their evolution after ARV-treatment initiation. METHODS: Lipid concentrations were assessed at baseline and at least 6 months later in 93 children. Fifty-six children initiated ARV treatment at baseline, and 37 remained untreated. RESULTS: At baseline, 65, 92 and 84% of the children had low levels of total cholesterol, HDL and APOA1, respectively, whereas 75 and 70% had triglycerides and APOB levels in the normal range. At baseline, low level of HDL cholesterol and high level of triglycerides were associated with high viral load and low levels of CD4 cell count. Levels of total, HDL cholesterol and APOA1 increased over time, and treatment was associated with a higher increase whereas levels of triglycerides and APOB decreased in treated children and remained stable in untreated group. CONCLUSIONS: The initiation of antiretroviral treatment was associated with a normalization of the infection-related lipid profile.

Relationship of CD4+ T-cell counts and plasma HIV-1 RNA levels with serological HBeAg/anti-HBe patterns obtained in West-African HBV-HIV-1-co-infected children.

HBeAg/anti-HBe and hepatitis B virus (HBV) DNA from 34 HIV-1-infected children from Ivory Coast with chronic hepatitis B (CHB) were longitudinally analyzed according to CD4 and HIV-1 RNA. The mean CD4% value was significantly (p = 0.03) lower in 59 (52.7%) samples showing a usual CHB (HBeAg-positive/anti-HBe-negative and HBV DNA-positive), as compared with 30 (26.8%) HBeAg-positive/anti-HBe-positive and HBV DNA-positive and 23 (20.5%) HBeAg-negative/anti-HBe-positive and HBV DNA-negative (15.1% vs. 18.5% and 20.0%). The mean HIV-1 RNA concentrations were significantly (p = 0.01) higher in specimens HBV DNA-positive (4.47 and 4.30 log(10)/ml, respectively) vs. HBV DNA-negative (3.43 log(10)/ml). HIV-1 has a significant impact on CHB acquired in childhood.

CD4 cell response before and after HAART initiation according to viral load and growth indicators in HIV-1-infected children in Abidjan, Côte d'Ivoire.

OBJECTIVE: To analyze the determinants of CD4 change in children during 3 periods: before highly active antiretroviral therapy (HAART), during the first year after HAART initiation, and past 1 year after HAART initiation. METHODS: One hundred seventy-seven children enrolled in a prospective cohort in Abidjan received HAART during a mean follow-up of 30 months. A linear mixed-effects model was used for the first period, a mixed-effects piecewise model for the second period, and an asymptotic mixed-effects model for long-term CD4 dynamics. RESULTS: Before HAART initiation, CD4 percentage decreased along time [beta = -0.59 (-0.92 to -0.26)] was positively associated with body mass index for age [beta = 0.47 (0.22 to 0.72)] and negatively associated with viral load [beta = -1.01 (-1.90 to -0.13)]. During the first year of treatment, the CD4 decrease reverted to a steep increase that was negatively associated with age at HAART initiation [beta = -0.24 (-0.4 to -0.07)] and with the mean viral load under HAART [beta = -1.51 (-2.21 to -0.81)]. The long-term CD4 percentage was also negatively associated with the mean viral load under HAART [beta = -4.97 (-6.22 to -3.72)] and age at HAART initiation [beta = -0.82 (-1.12 to -0.51)]. CONCLUSIONS: Before HAART initiation, the CD4 cell percentage was associated with growth indicators whereas, after HAART, an early increase and a long-term plateau were negatively associated with the viral load and age at HAART initiation.

Virologic and immunologic response to antiretroviral therapy and predictors of HIV type 1 drug resistance in children receiving treatment in Abidjan, Côte d'Ivoire.

We describe changes in HIV-1 viral load, CD4+ T cell percentage, and incidence of drug resistance and factors associated with drug resistance for 134 children receiving antiretroviral therapy (ART) for approximately 1 year in Abidjan. Between August 1998 and September 2003, ART was initiated for 395 HIV-infected children ages 0-15 years in the Côte d'Ivoire national drug access initiative. All 1-year samples with detectable HIV RNA >1000 copies/ml were tested for HIV-1 drug resistance and changes in viral load and CD4+ T cell counts were also determined. At treatment initiation, 80% of children had CD4+ T cell percentages <15% and a median viral RNA load of 5.6 log copies/ml. The median age at treatment initiation was 7 years with only 25% of patients less than 4 years of age. Of the 134 children receiving therapy, 72 (54%) had undetectable viral load. The estimated 1-year viral load decline was 1.9 log10 copies/ml and the CD4+ T cell percentage increase was 10.9%. The estimated 1-year cumulative probability for developing any class of drug resistance was 0.44 (95% CI, 0.35, 0.53). In a multivariate analysis, the magnitude of virologic response to therapy was inversely associated with development of drug resistance. Children with less CD4+ T cell rise from baseline values and the use of dual therapy were also associated with the development of drug resistance. Guidelines are needed for the treatment of pediatric HIV infection in Africa in order to minimize the occurrence of drug resistance and enhance better virologic, immunologic, and clinical outcomes.

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.

Frequent occurrence of chronic hepatitis B virus infection among West African HIV type-1-infected children.

BACKGROUND: The aim of this study, conducted in Ivory Coast, was to evaluate the prevalence and evolution of viral hepatitis in children coinfected with human immunodeficiency virus type 1 (HIV-1). METHODS: Hepatitis B virus (HBV) and hepatitis C virus (HCV) markers were retrospectively and longitudinally assessed among 280 HIV-1-infected children enrolled in the Agence Nationale de Recherches sur le SIDA et les Hépatites Virales B et C 1244/1278 cohort. Among these, 173 (61.8%) received highly active antiretroviral therapy (HAART), including lamivudine (3TC) for 122 children. Detection of the hepatitis B s antigen (HBsAg) was performed on specimens collected at inclusion and 6 months later. If results of both tests were positive, hepatitis B e antigen (HBeAg)/hepatitis B e antibody (HBeAb) and HBV DNA levels were measured at inclusion and during follow-up. A fourth-generation HCV enzyme immunoassay was used for HCV screening at inclusion. RESULTS: In our pediatric cohort, no patients were infected with HCV, but the prevalence of HBsAg at inclusion was 12.1% (34 of 280; 95% confidence interval [CI], 8.6-16.6). Among the HBV-HIV-1-coinfected children, a high rate of positive HBeAg chronic hepatitis B (CHB) was noted at inclusion (82.4% [ 28 of 34]; 95% CI, 65.5%-93.2%) and after a median follow-up of 18 months (78.3%; 95% CI, 45.5%-92.7%), with no significant difference between children treated with HAART (with or without 3TC) and untreated ones. These children showed high HBV DNA levels (usually >8.0 log(10) copies/mL) and viral population consisting of nearly exclusively wild-type HBeAg-positive HBV strains, strongly suggesting that most of them were in the initial immunotolerant phase of chronic hepatitis B. CONCLUSION: In sub-Saharan Africa, children with chronic hepatitis B and who are treated with 3TC-based HAART are at risk of developing 3TC resistance. Further studies are required to guide the management of HBV-HIV-1-coinfected children.

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.

Long-term survival and immuno-virological response of African HIV-1-infected children to highly active antiretroviral therapy regimens.

BACKGROUND: In Africa, facing the scaling-up of HAART, there is an urgent need to monitor accurately the long-term benefits of these lifelong treatments. METHODS: Survival and immuno-virological response were assessed for 78 children in the ANRS 1244/1278 Children's cohort (Abidjan, Côte d'Ivoire) who were enrolled from October 2000 for treatment with HAART and followed to September 2004. Initial HAART consisted of two nucleoside reverse transcriptase inhibitors with either nelfinavir (NFV) or efavirenz (EFV). For the comparison of immunological and virological responses, CD4 cell counts and HIV-1 RNA viral load were assessed by performing time-point specific and longitudinal data analysis. RESULTS: At baseline, the median CD4 cell percentage was 7.5% and the median HIV-1 RNA viral load was 5.37 log10 copies/ml. The survival probability was high (0.86 at month 42; 95% confidence interval, 0.77-0.92) with no difference according to whether the HAART regimen contained NFV or EFV. At 36 and 42 months of follow-up, an immune recovery was observed with median CD4 cell percentages reaching 23.1% and 24.8%, respectively, with no difference according to the HAART regimen (longitudinal data analysis). At the same time points, a sustained viral suppression was also obtained, with undetectable viral load achieving in 46.5% and 45.0%, respectively, regardless of whether the HAART regimen. CONCLUSION: This study demonstrates the durability of both clinical and biological response to HAART in African children.

Serum lactate levels in infants exposed peripartum to antiretroviral agents to prevent mother-to-child transmission of HIV: Agence Nationale de Recherches Sur le SIDA et les Hépatites Virales 1209 study, Abidjan, Ivory Coast.

BACKGROUND: Mitochondrial toxicity was described in infants exposed to long-term antiretroviral regimens containing nucleoside analogues for the prevention of mother-to-child transmission of HIV. We measured the serum lactate levels in children born to HIV-1 infected African women receiving short-term antiretroviral prevention of mother-to-child transmission of HIV regimens. METHODS: A prospective study was conducted in women-child pairs from the third trimester of pregnancy to 3 months of life. The exposed group was formed by children exposed in utero to nucleoside analog antiretroviral regimens, zidovudine or zidovudine + lamivudine from 32 to 36 weeks of amenorrhea until delivery. All of these women received nevirapine single dose at the beginning of labor. The children received zidovudine during the first 7 days of life and a nevirapine single dose at day 3. The control group was formed by infants born to HIV-1-infected women who had received nevirapine single dose only and who were not exposed to nucleoside analog antiretroviral regimens. Serum lactate levels were measured at 4, 6, and 12 weeks of life by Cobas Integra 400. RESULTS: A total of 836 blood samples from 338 infants was collected (262 exposed and 76 controls). Median lactacidemia was 1.8 mmol/L (interquartile range: 1.2-2.7 mmol/L). Overall serum lactate levels > or = 2.5 mmol/L, defining hyperlactatemia, were observed in 39 of the 292 infants who had > or = 2 serum lactate measurements. The 3-month period prevalence of hyperlactatemia did not differ between the exposed group and the control group. All of the serum lactate levels returned to normal values in all of the subsequent samples. No case of symptomatic hyperlactatemia was detected during the study period. CONCLUSIONS: Increased lactate levels were identified equally in infants whose mother received short-term nucleoside analogs or nevirapine single dose for prevention of mother-to-child transmission of HIV. Although not rare, hyperlactatemia was not related to short-term exposure to nucleoside analog antiretroviral regimens.

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.

Genotypic human immunodeficiency virus type 1 drug resistance in highly active antiretroviral therapy-treated children in Abidjan, Côte d'Ivoire.

OBJECTIVE: To estimate the frequency of human immunodeficiency virus type 1 (HIV-1) displaying genotypic drug resistance in highly active antiretroviral therapy (HAART)-treated children in Abidjan. METHODS: Among the 269 HIV-1-infected children enrolled in the ANRS 1278 prospective observational cohort between October 2000 and September 2003, 115 [median age, 6.35 years (range, 1.2-15)] required treatment and received HAART for at least 6 months. Treatment consisted of 2 nucleoside analogue reverse transcriptase inhibitors associated with nelfinavir (70.5%) or efavirenz (29.5%). Plasma HIV-1 RNA and CD4+ T cell counts were determined at baseline and every 6 months thereafter. Genotypic resistance tests were performed in cases of virologic failure (viral load >or=3 log10 copies/mL) after at least 6 months of HAART. RESULTS: After a median of 10.2 months of HAART, 66% (76 of 115) of children were in virologic success. Most of these children were infected with CRF02 strains. Twenty-seven viruses displayed resistance to at least 1 antiretroviral drug (27 of 38, 71%). Thirteen, 9 and 5 children had viruses with resistance to 1, 2 or 3 of the drugs included in their regimen, respectively. Resistance to lamivudine and/or to non-nucleoside analogue reverse transcriptase inhibitors was frequent among the 38 children in virologic failure. The 90M, 46L, 88S or 54V mutations were found in 11 (38%) of the 29 children taking nelfinavir. The overall frequency of viruses showing genotypic resistance to at least 1 antiretroviral drug was 23% (27 of 115) among the treated children. CONCLUSION: These results are similar to what is generally observed in industrialized countries. Despite these encouraging results, efforts are needed to maximize the long-term efficiency of treatment and to minimize the risk of emergence of drug resistance in treated children.

Diagnosed tuberculosis during the follow-up of a cohort of human immunodeficiency virus-infected children in Abidjan, Côte d'Ivoire: ANRS 1278 study.

INTRODUCTION: Most data on tuberculosis in human immunodeficiency virus (HIV)-infected children in Africa come from hospital-based and cross-sectional studies. OBJECTIVES: To estimate the incidence of tuberculosis in HIV-infected children participating in an observational cohort. METHODS: HIV-infected children in Abidjan, Côte d'Ivoire, are followed in a prospective cohort. At enrollment, all children had a physical examination, CD4 lymphocyte counts, chest radiograph and a tuberculin test. Quarterly follow-up visits are organized. All patients with suspected tuberculosis undergo specific investigations including gastric aspiration and culture. All isolates are tested for susceptibility. RESULTS: From October 2000 to December 2003, 129 girls and 153 boys were recruited. Of children without a current or previous diagnosis of tuberculosis, 6.5% (13 of 199) had a tuberculin test result of >5 mm, compared with 17.5% of children (10 of 57) with current or previous tuberculosis (P < 0.02). Forty-eight children (17%) had a history of treated tuberculosis, and 27 children were being treated for tuberculosis at enrollment or during the first month of follow-up. Eleven children were diagnosed with tuberculosis after the first month of follow-up, and the diagnosis of mycobacterial infection was confirmed in 7 cases. Of 5 tested isolates of Mycobacterium tuberculosis, 3 were resistant to at least 1 antitubercular drug. Cumulative incidence of tuberculosis was 2060/100,000 at 12 months, 3390/100,000 at 2 years and 5930/100,000 at 3 years. The 3-year risk was 12,400/100,000 in immunocompromised children (CD4 <15%) and 3300/100,000 in other children (P < 0.0001). CONCLUSION: The risk of tuberculosis among HIV-infected children in Côte d'Ivoire is strongly associated with the degree of immunodeficiency in HIV infection.

Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission.

OBJECTIVES: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy of two more PMTCT drug combinations. DESIGN: An open-label intervention cohort in Abidjan. METHODS: In 2001-2002, consenting women started oral ZDV 300 mg twice daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =32 weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a cohort receiving a short regimen of ZDV > or = 36-38 weeks in 1995-2000 in the same population. RESULTS: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV + NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIV-infected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9-9.1%) with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC + NVPsd (P = 0.34 compared with ZDV + NVPsd). CONCLUSIONS: A short-course of ZDV + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could be added to international guidelines.

Highly active antiretroviral therapies among HIV-1-infected children in Abidjan, Côte d'Ivoire.

OBJECTIVE: To describe the effect of highly active antiretroviral therapy (HAART) in HIV-1-infected African children. STUDY DESIGN: Observational ANRS 1244 cohort of 159 children with HIV between October 2000 and September 2002; 78 children (49%) receiving HAART were followed for a mean duration of 21 months. METHODS: Weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ), CD4 lymphocyte count and HIV-1 RNA viral load were measured before initiating HAART and every 6 months during treatment. Probability of survival and incidences of pneumonia and acute diarrhoea were calculated. RESULTS: Values before and after 620 days of HAART, respectively, were -2.02 and -1.39 for mean WAZ, (P < 0.01); -2.03 and -1.83 for mean HAZ (P = 0.51); 0.07 and 0.025/child-month (P = 0.002) for incidence of pneumonia; and 0.12 and 0.048/child-month for incidence of acute diarrhoea (P < 0.001) (incidence changes statistically significant only in children < 6.5 years). Overall, the probability of survival under HAART was 72.8% at 24 months for children with < 5% CD4 cells versus 97.8% in children with >/= 5% (P < 0.01). At HAART initiation, median viral load and CD4 cell percentage were 5.41 log10 copies/ml and 7.7%, respectively. After 756 days of HAART, on average, 50% of patients had undetectable viral load and 10% had 2.4-3.0 log10 copies/ml. The median CD4 percentage was 22.5%. CONCLUSION: In resource-limited setting, it is possible to use HAART to treat African children. This treatment appears as effective as in developed countries.