Kirsten Bork

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.

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.

Early infant feeding patterns and HIV-free survival: findings from the Kesho-Bora Trial (Burkina Faso, Kenya, South Africa)

Objective: To investigate the association between feeding patterns and HIV-free survival in children born to HIV-infected mothers and to clarify whether antiretroviral (ARV) prophylaxis modifies the association. Methods: From June 2005 to August 2008, HIV-infected pregnant women were counseled regarding infant feeding options, and randomly assigned to triple-ARV prophylaxis (triple ARV) until breastfeeding cessation (BFC) before age 6 months or antenatal zidovudine with single-dose nevirapine (short-course ARV). Eighteen-month HIV-free survival of infants HIV-negative at 2 weeks of age was assessed by feeding patterns (replacement feeding from birth, BFC <3 months, BFC ≥3 months). Results: Of the 753 infants alive and HIV-negative at 2 weeks, 28 acquired infection and 47 died by 18 months. Overall HIV-free survival at 18 months was 0.91 [95% confidence interval (CI): 0.88–0.93]. In the short-course ARV arm, HIV-free survival (0.88; CI: 0.84–0.91) did not differ by feeding patterns. In the triple ARV arm, overall HIV-free survival was 0.93 (CI: 0.90–0.95) and BFC <3 months was associated with lower HIV-free survival than BFC ≥3 months (adjusted hazard ratio: 0.36; CI: 0.15–0.83) and replacement feeding (adjusted hazard ratio: 0.20; CI: 0.04–0.94). In the triple ARV arm, 4 of 9 transmissions occurred after reported BFC (and 5 of 19 in the short-course arm), indicating that some women continued breastfeeding after interruption of ARV prophylaxis. Conclusions: In resource-constrained settings, early weaning has previously been associated with higher infant mortality. We show that, even with maternal triple-ARV prophylaxis during breastfeeding, early weaning remains associated with lower HIV-free survival, driven in particular by increased mortality.

Postpartum weight change among HIV-infected mothers by antiretroviral prophylaxis and infant feeding modality in a research setting.

Objective:To assess the relationship between infant feeding, triple-antiretroviral prophylaxis and weight from 2 weeks (baseline) to 6 months postpartum among HIV-infected mothers in a mother-to-child transmission (MTCT) of HIV-prevention trial in five sub-Saharan African sites. Methods:HIV-infected pregnant women with CD4+ cell counts of 200–500 cells/&mgr;l were counselled to choose breastfeeding to 6 months or replacement feeding from delivery. They were randomized to receive perinatal zidovudine and single-dose nevirapine or triple-antiretroviral MTCT prophylaxis until breastfeeding cessation. Mixed-effect linear models were used to compare maternal weight trajectories over time by infant feeding mode. Antiretroviral prophylaxis and BMI at baseline were examined as potential effect modifiers. Results:Among 797 mothers, 620 (78%) initiated breastfeeding. Wasting (BMI <18.5) was rare at baseline (2%), whereas overweight/obesity (BMI ≥ 25) was common (40%). In the model including all women, breastfeeding was not associated with weight loss up to 6 months, irrespective of baseline BMI and antiretroviral prophylaxis. Triple-antiretroviral prophylaxis was associated with weight gain among replacement-feeding mothers with baseline BMI at least 25 (+0.54 kg/month; P < 0.0001). In the model including breastfeeding mothers only, triple-antiretroviral prophylaxis was associated with weight gain among mothers with baseline BMI at least 25 who ceased breastfeeding before 3 months postpartum (+0.33 kg/month; P = 0.03). Conclusion:The results suggest that breastfeeding up to 6 months postpartum is not detrimental for postpartum weight among well nourished HIV-infected mothers at intermediate-disease stage. In the absence of breastfeeding or after weaning, triple-antiretroviral prophylaxis is associated with weight gain among women with high BMI, even after cessation of prophylaxis.

Formula-Feeding of HIV-Exposed Uninfected African Children Is Associated with Faster Growth in Length during the First 6 Months of Life in the Kesho Bora Study

Background: Early feeding patterns may affect the growth of HIV-exposed children and thus their subsequent health and cognition.Objective: We assessed the association of infant feeding (IF) mode with length-for-age z score (LAZ) and stunting from age 2 d to 18 mo in HIV-exposed African children within a controlled randomized trial, which evaluated triple antiretrovirals initiated during pregnancy and continued for 6 mo postpartum to prevent HIV transmission.Methods: HIV-infected pregnant women with CD4+ counts of 200-500 cells/mm3 from Burkina Faso, Kenya, and South Africa were advised to exclusively breastfeed for up to 6 mo or to formula-feed from birth. Factors associated with LAZ were investigated in all uninfected children by using mixed-effects linear models; those associated with stunting (LAZ <-2) at 6 or 12 mo were assessed in multiple logistic regression after exclusion of children stunted at age 2 d. Independent variables were IF mode: formula feeding (FF), exclusive breastfeeding (EBF) <3 mo, or EBF ≥3 mo (reference); sex; trial arm; maternal characteristics; and site.Results: Among 728 children, FF was associated with a greater increase in LAZ from 2 d to 6 mo (+0.07 z score/mo, P < 0.001). Between 6 and 18 mo, FF and EBF <3 mo were both associated with greater mean LAZ than was EBF ≥3 mo (+0.52 z scores and +0.43 z scores, respectively, P < 0.001). Among children not stunted at 2 d, FF was independently associated with a reduced risk of stunting at 6 mo (OR: 0.24; 95% CI: 0.07, 0.81; P = 0.021), whereas EBF <3 mo was not (OR: 0.49; 95% CI: 0.22, 1.10; P = 0.09).Conclusions: In this observational study of HIV-exposed uninfected infants, growth in length in the first 6 mo of life was faster in formula-fed infants than in exclusively breastfed infants. The plausibility of residual confounding and reverse causality is discussed. This trial was registered at www.controlled-trials.com as ISRCTN71468401.