Cécile Cames

Lipodystrophy and metabolic disorders in HIV-1-infected adults on 4- to 9-year antiretroviral therapy in Senegal: a case-control study.

Objective:To assess adverse effects of long-term highly active antiretroviral therapy (HAART), that is, lipodystrophy and metabolic disorders, in a cohort of African patients. Methods:One hundred eighty HIV-1-infected patients treated with HAART for 4-9 years in Dakar and 180 age-matched and sex-matched controls were enrolled. Regional subcutaneous fat changes were assessed by physicians, and fasting blood samples were drawn. Centralization of body fat was estimated using skinfold ratio, waist circumference, and waist to hip ratio (WHR). Results:Mean duration of HAART was 5.4 years. Main drugs received were zidovudine, stavudine, and protease inhibitors. The prevalence of moderate-severe lipodystrophy was 31.1% (95% confidence interval: 24.3 to 37.9), with 13.3%, 14.5%, and 3.3% for lipoatrophy, lipohypertrophy, and mixed forms, respectively. Mild-severe lipodystrophy affected 65.0% (58.0; 72.0) of patients. Stavudine was the only independent risk factor (any vs. none: odds ratio = 2.8; 1.4 to 5.5). Patients had lower body mass index and skinfolds but greater centralization of body fat (WHR, P < 0.0001 and skinfold ratio, P < 0.001), fasting glucose (P < 0.0001), homeostasis model assessment insulin resistance, and triglyceride levels (P < 0.01 for both) than controls. Moderately-severely lipodystrophic patients had higher triglyceride and low-density lipoprotein cholesterol than other patients (P < 0.001 and P < 0.05, respectively). Conclusions:Moderate-severe lipodystrophy affected one third of West African patients on long-term HAART and was associated with a less favorable metabolic profile.

Randomized trial of piperaquine with sulfadoxine-pyrimethamine or dihydroartemisinin for malaria intermittent preventive treatment in children.

Background The long terminal half life of piperaquine makes it suitable for intermittent preventive treatment for malaria but no studies of its use for prevention have been done in Africa. We did a cluster randomized trial to determine whether piperaquine in combination with either dihydroartemisin (DHA) or sulfadoxine-pyrimethamine (SP) is as effective, and better tolerated, than SP plus amodiaquine (AQ), when used for intermittent preventive treatment in children delivered by community health workers in a rural area of Senegal. Methods Treatments were delivered to children 3–59 months of age in their homes once per month during the transmission season by community health workers. 33 health workers, each covering about 60 children, were randomized to deliver either SP+AQ, DHA+PQ or SP+PQ. Primary endpoints were the incidence of attacks of clinical malaria, and the incidence of adverse events. Results 1893 children were enrolled. Coverage of monthly rounds and compliance with daily doses was similar in all groups; 90% of children received at least 2 monthly doses. Piperaquine combinations were better tolerated than SP+AQ with a significantly lower risk of common, mild adverse events. 103 episodes of clinical malaria were recorded during the course of the trial. 68 children had malaria with parasitaemia >3000/µL, 29/671 (4.3%) in the SP+AQ group, compared with 22/604 (3.6%) in the DHA+PQ group (risk difference 0.47%, 95%CI −2.3%,+3.3%), and 17/618 (2.8%) in the SP+PQ group (risk difference 1.2%, 95%CI −1.3%,+3.6%). Prevalences of parasitaemia and the proportion of children carrying Pfdhfr and Pfdhps mutations associated with resistance to SP were very low in all groups at the end of the transmission season. Conclusions Seasonal IPT with SP+PQ in children is highly effective and well tolerated; the combination of two long-acting drugs is likely to impede the emergence of resistant parasites. Trial Registration ClinicalTrials.gov NCT00529620

Reduced Quantitative Ultrasound Bone Mineral Density in HIV-Infected Patients on Antiretroviral Therapy in Senegal

Background Bone status in HIV-infected patients on antiretroviral treatment (ART) is poorly documented in resource-limited settings. We compared bone mineral density between HIV-infected patients and control subjects from Dakar, Senegal. Methods A total of 207 (134 women and 73 men) HIV-infected patients from an observational cohort in Dakar (ANRS 1215) and 207 age- and sex-matched controls from the general population were enrolled. Bone mineral density was assessed by quantitative ultrasound (QUS) at the calcaneus, an alternative to the reference method (i.e. dual X-absorptiometry), often not available in resource-limited countries. Results Mean age was 47.0 (±8.5) years. Patients had received ART for a median duration of 8.8 years; 45% received a protease inhibitor and 27% tenofovir; 84% had undetectable viral load. Patients had lower body mass index (BMI) than controls (23 versus 26 kg/m2, P<0.001). In unadjusted analysis, QUS bone mineral density was lower in HIV-infected patients than in controls (difference: −0.36 standard deviation, 95% confidence interval (CI): −0.59;−0.12, P = 0.003). Adjusting for BMI, physical activity, smoking and calcium intake attenuated the difference (−0.27, CI: −0.53;−0.002, P = 0.05). Differences in BMI between patients and controls explained a third of the difference in QUS bone mineral density. Among patients, BMI was independently associated with QUS bone mineral density (P<0.001). An association between undetectable viral load and QUS bone density was also suggested (β = 0.48, CI: 0.02;0.93; P = 0.04). No association between protease inhibitor or tenofovir use and QUS bone mineral density was found. Conclusion Senegalese HIV-infected patients had reduced QUS bone mineral density in comparison with control subjects, in part related to their lower BMI. Further investigation is needed to clarify the clinical significance of these observations.

A Summary Index of Feeding Practices Is Positively Associated with Height-for-Age, but Only Marginally with Linear Growth, in Rural Senegalese Infants and Toddlers

Several studies have shown an association between an infant and young child feeding index (ICFI) and height-for-age Z-score (HAZ) in Latin America and Africa. A previous study was unable to reproduce these findings in 500 rural Senegalese 12-42-mo-old children. The relationship of ICFI, dietary diversity index (DDI), food variety index (FVI), meal frequency index (MFI), and breastfeeding (BF) to HAZ and growth in height/length over 6 mo was studied in 1060 6-36-mo-old Senegalese children during 2 visits. List-based food frequencies were recalled for the past 24 h, and height/length and weight measurements were taken. Indicators were transformed into tertiles in age-specific subgroups. DDI, FVI, MFI, and ICFI were poorly concordant across visits at all ages (weighted κ: 0.02-0.25). In cross-sectional analyses that pooled children from the 2 visits, HAZ was positively associated with DDI and FVI at 6-12, 12-18, and 18-24 mo and with ICFI at 6-12 and 18-24 mo (P < 0.001 and P < 0.05, respectively) but was negatively associated with BF at 12-18, 18-24, and 24-30 mo. The length increment between visits was positively associated with MFI and ICFI, measured during the first visit in 18-24-mo-olds (P < 0.001 and P < 0.05, respectively) but not with DDI, FVI, or BF at any age. In conclusion, ICFI, DDI, and FVI were associated with HAZ, particularly during infancy, whereas no indicator was associated with linear growth in this age group. Therefore, the strong association between HAZ and ICFI during infancy may be partly due to maternal adaptation to infant clues, i.e., greater appetite for and interest in non-breast-milk foods among taller infants.

Growth and maturation of Sereer adolescent girls (Senegal) in relation to seasonal migration for labor

This study compares the growth and maturity status of Sereer girls (Senegal) temporarily migrating to an urban setting during the dry season to work as maids in the capital city, Dakar, with girls remaining in rural communities. A total of 343 girls, aged 12.5–14.5 were surveyed: 222 lived year‐round in several villages (sedentes) and 121 girls worked in Dakar for 8 months of the year (migrants). All girls were born and reared under the same conditions and in the same rural communities in Senegal. Growth and nutritional status were assessed with anthropometry, and the body mass index (BMI) was calculated. Sexual maturation was assessed by stage of breast development and occurrence of menarche. A questionnaire on housing conditions, food consumption patterns, nature of work, health status, and reasons for leaving the villages was administered to 57 urban girls. Overall, the girls were small relative to NCHS/WHO reference values: 30–40% were lower than −2 z‐scores of age‐specific medians. They also had less subcutaneous fat. Only nine girls had attained menarche and 30% were prepubertal in breast development. The migrants had a significantly higher body mass and BMI and thicker skinfolds than sedentes, but there was no difference in stature. The migrants were also more sexually mature than the sedentes. Comparison of anthropometric status 2 years before migration, in 1995, showed no differences between migrant and sedentes girls. Within migrant girls, those with two or more stays in Dakar were taller and heavier than newcomers. These results suggest that seasonal movement to the city results in improved nutritional status, as reflected in larger body mass and increased fatness. These factors appear to be associated with better living conditions in the city. Am. J. Hum. Biol. 11:539–550, 1999.

Relationship between mortality and feeding modality among children born to HIV-infected mothers in a research setting: the Kesho Bora study.

Objective:To assess the relationship between infant feeding practices and mortality by 18 months of age among children born to HIV-infected mothers in the Kesho Bora trial (Burkina-Faso, Kenya and South Africa). Methods:Enrolled HIV-infected women were counseled to choose between breastfeeding up to 6 months or replacement feeding from delivery. Multivariable Cox models were used to compare the infant mortality risks according to feeding practices over time defined as never breastfed, weaned or still breastfed. The category ‘still breastfed’ was disaggregated as exclusively, predominantly or partially breastfed to compare modes of breastfeeding. The relationship between weaning and mortality was also assessed using marginal structural models to control for time-dependent confounders, such as maternal or infant morbidity (reverse causality). Results:Among 795 mothers, 618 (77.7%) initiated breastfeeding. Mortality rates by 18 months among uninfected and infected children were 6 and 38%, respectively. Never breastfed and weaned children were at greater risk of death compared with those still breastfed. Adjusted hazard ratios were 6.7 [95% confidence interval (CI)=2.5–17.9; P < 0.001] and 6.9 (CI = 2.8–17.2; P < 0.001) for never breastfed and weaned children, respectively. Estimation of the effect of weaning using marginal structural models led to similar results. No statistically significant differences were observed according to mode of breastfeeding (exclusive, predominant or partial). Conclusion:Within 6 months after birth, weaned or never breastfed children were at about seven-fold higher risk of dying compared with children who were still breastfed despite a context in which interventions were provided to reduce risks associated with replacement feeding.

Morbidity in relation to feeding mode in African HIV-exposed, uninfected infants during the first 6 mo of life: the Kesho Bora study

BACKGROUND Refraining from breastfeeding to prevent HIV transmission has been associated with increased morbidity and mortality in HIV-exposed African infants. OBJECTIVE The objective was to assess risks of common and serious infectious morbidity by feeding mode in HIV-exposed, uninfected infants ≤6 mo of age with special attention to the issue of reverse causality. DESIGN HIV-infected pregnant women from 5 sites in Burkina Faso, Kenya, and South Africa were enrolled in the prevention of mother-to-child transmission Kesho Bora trial and counseled to either breastfeed exclusively and cease by 6 mo postpartum or formula feed exclusively. Maternal-reported morbidity (fever, diarrhea, and vomiting) and serious infectious events (SIEs) (gastroenteritis and lower respiratory tract infections) were investigated for 751 infants for 2 age periods (0-2.9 and 3-6 mo) by using generalized linear mixed models with breastfeeding as a time-dependent variable and adjustment for study site, maternal education, economic level, and cotrimoxazole prophylaxis. RESULTS Reported morbidity was not significantly higher in nonbreastfed compared with breastfed infants [OR: 1.31 (95% CI: 0.97, 1.75) and 1.21 (0.90, 1.62) at 0-2.9 and 3-6 mo of age, respectively]. Between 0 and 2.9 mo of age, never-breastfed infants had increased risks of morbidity compared with those of infants who were exclusively breastfed (OR: 1.49; 95% CI: 1.01, 2.2; P = 0.042). The adjusted excess risk of SIEs in nonbreastfed infants was large between 0 and 2.9 mo (OR: 6.0; 95% CI: 2.2, 16.4; P = 0.001). Between 3 and 6 mo, the OR for SIEs was sensitive to the timing of breastfeeding status, i.e., 4.3 (95% CI: 1.2, 15.3; P = 0.02) when defined at end of monthly intervals and 2.0 (95% CI: 0.8, 5.0; P = 0.13) when defined at the beginning of intervals. Of 52 SIEs, 3 mothers reported changes in feeding mode during the SIE although none of the mothers ceased breastfeeding completely. CONCLUSIONS Not breastfeeding was associated with increased risk of serious infections especially between 0 and 2.9 mo of age. The randomized controlled trial component of the Kesho Bora study was registered at Current Controlled Trials (www.controlled-trials.com) as ISRCTN71468401.

Infant Feeding Modes And Determinants Among Hiv-1-infected African Women In The Kesho Bora Study

Objective:To assess breastfeeding modes and determinants in a prevention of mother-to-child transmission study. Design:HIV-1–infected pregnant women from 5 sites in Burkina Faso, Kenya, and South Africa were enrolled in the study that comprised 2 prospective cohorts and 1 randomized controlled trial. Women were counseled to either breastfeed exclusively up to 6 months or formula feed from birth. Methods:Determinants of breastfeeding initiation and continuation by 3 months postpartum were investigated using multiple logistic regression analysis. Neonatal morbidity was defined as mother-reported fever, diarrhea, or vomiting during the first month of life. Results:Among 1028, 781 women (76%) initiated breastfeeding and 565 of 995 (56%) were still breastfeeding at 3 months postpartum (30% exclusively, 18% predominantly, and 8% partially). Study site (Durban, Mombasa, and Nairobi compared with Bobo-Dioulasso), CD4 cell count (<200 cells/mm3), secondary schooling (compared with none), and emergency cesarean delivery (compared with vaginal delivery) were independently associated with a lower probability of ever breastfeeding. The odds of still breastfeeding by 3 months postpartum (among those breastfeeding by 1 month) were lower in Mombasa, Nairobi, and Somkhele (compared with Bobo-Dioulasso) and among infants with neonatal morbidity [0.60 (0.37–0.976)]. The odds of exclusive breastfeeding (EBF) by 3 months (if EBF by 1 month) were lower in Mombasa and Nairobi, in ill neonates [0.54 (0.31–0.93)] and boys [0.51 (0.34–0.77)]. Conclusions:EBF was of short duration, particularly for boys. The importance of neonatal morbidity for breastfeeding cessation requires further investigation. Infant feeding counseling might need adaptation to better support mothers of boys and ill neonates.

A sustainable food support for non-breastfed infants: implementation and acceptability within a WHO mother-to-child HIV transmission prevention trial in Burkina Faso.

OBJECTIVE To provide HIV-positive mothers who opted for exclusive breastfeeding or formula feeding from birth to 6 months postpartum as a means of prevention of mother-to-child transmission (PMTCT) of HIV with a sustainable infant food support programme (FSP) from 6 to 12 months postpartum. We describe the implementation and assessment of this pilot initiative. DESIGN The FSP included a 6-month provision of locally produced infant fortified mix (IFM; 418 kJ/100 g of gruel) for non-breastfed infants coupled with infant-feeding and psychosocial counselling and support. Acceptability and feasibility were assessed in a subsample of sixty-eight mother-infant pairs. SETTING The FSP was developed in collaboration with local partners to support participants in a PMTCT prevention study. Formula was provided for free from 0 to 6 months postpartum. Cessation by 6 months was recommended for breastfeeding mothers. RESULTS The FSP was positively received and greatly encouraged breastfeeding mothers to cease by 6 months. As recommended, most infants were given milk as an additional replacement food, mainly formula subsidised by safety networks. Among daily IFM consumers, feeding practices were satisfactory overall; however, the IFM was shared within the family by more than one-third of the mothers. Cessation of IFM consumption was observed among twenty-two infants, seventeen of whom were fed milk and five neither of these. CONCLUSIONS Without any food support most mothers would have been unable to provide appropriate replacement feeding. The food security of non-breastfed infants urgently needs to be addressed in HIV PMTCT programmes. Our findings on a simple cost-effective pioneer intervention provide an important foundation for this process.

Effects of Malnutrition on Children's Immunity to Bacterial Antigens in Northern Senegal

To evaluate immunity to vaccine-preventable diseases according to nutritional status, a longitudinal study was conducted in Senegalese children ages 1-9 years old. A linear regression analysis predicted that weight for age was positively associated with immunoglobulin G (IgG) response to tetanus toxoid in children born during the rainy season or at the beginning of the dry season. A relationship between village, time of visits, and levels of antibodies to tetanus showed that environmental factors played a role in modulating humoral immunity to tetanus vaccine over time. Moreover, a whole-blood stimulation assay highlighted that the production of interferon-γ (IFN-γ) in response to tetanus toxoid was compromised in stunted children. However, the absence of cytokine modulation in response to Mycobacterium tuberculosis-purified protein derivatives and phytohemagglutinin suggests that the overall ability to produce IFN-γ was preserved in stunted children. Therefore, these results show that nutritional status can specifically alter the efficacy of long-lasting immunity to tetanus.