Growth and health outcomes at school age in HIV-exposed, uninfected Zambian children: follow-up of two cohorts studied in infancy.

BACKGROUND: Early growth and health of HIV-exposed, uninfected (HEU) children is poorer than that of their HIV-unexposed, uninfected (HUU) counterparts but there is little information about longer term effects of early HIV exposure. We previously recruited two cohorts of HEU and HUU Zambian infants and documented the poorer infant growth and health of the HEU compared to the HUU children. We followed up HEU and HUU children from these cohorts when they were school-aged and compared their growth, health, biochemical markers of acute or chronic disease, and school grades. METHODS: We recruited 111 HEU and 279 HUU children aged 6-12 years. We measured anthropometry, determined health by questionnaire and clinical examination, viewed the child's most recent school report, and measured blood pressure, haemoglobin (Hb), HbA1c, glucose, cholesterol, and C-reactive protein (CRP). RESULTS: Anthropometric measures were lower among HEU than HUU children, significantly so for hip circumference (age- and sex-adjusted difference -1.74 cm; 95% confidence interval (CI) -3.24, -0.24; P = 0.023) and mid-upper-arm circumference (adjusted difference -0.63 cm, 95% CI -1.23, -0.04; P = 0.037) and with borderline effects for body mass index, thigh circumference and subscapular skinfolds. HEU children had significantly lower total, trunk, and limb fat percentages. All anthropometric and body composition differences became non-significant after adjustment for sociodemographic variables which differed between HEU and HUU children. More HEU than HUU children reported minor illnesses and were prescribed medication at the time of visit. There were no differences in biochemical markers between groups. HEU children had lower math grades than HUU children even after adjustment for socioeconomic variables. CONCLUSIONS: Although HEU children were smaller and had lower percent fat than HUU children, this appeared to be due mainly to their poorer socioeconomic status. Reasons for lower school grades require further research

Appetite testing in HIV-infected African adults recovering from malnutrition and given antiretroviral therapy.

OBJECTIVE: The Nutritional Support for Africans Starting Antiretroviral Therapy (NUSTART) trial was designed to determine whether nutritional support for malnourished HIV-infected adults starting antiretroviral therapy (ART) can improve early survival. Appetite is related to health outcomes in this population, but the optimal appetite metric for field use is uncertain. We evaluated two measures of appetite with the goal of improving understanding and treatment of malnutrition in HIV-infected adults. DESIGN: Longitudinal cohort study embedded in a clinical trial of vitamin and mineral-fortified, v. unfortified, lipid-based nutritional supplements. SETTING: HIV clinics in Mwanza, Tanzania and Lusaka, Zambia. SUBJECTS: Malnourished (BMI<18.5 kg/m2) HIV-infected adults starting ART. RESULTS: Appetite measurements, by short questionnaire and by weight of maize porridge consumed in a standardized test, were compared across time and correlated with changes in weight. Appetite questionnaire scores, from polychoric correlation, and porridge test results were normally distributed for Tanzanians (n 187) but clustered and unreliable for Zambians (n 297). Among Tanzanian patients, the appetite score increased rapidly from referral for ART, plateaued at the start of ART and then increased slowly during the 12-week follow-up. Change in appetite questionnaire score, but not porridge test, correlated with weight change in the corresponding two-week intervals (P=0.002) or over the whole study (P=0.05) but a point estimate of hunger did not predict weight change (P=0.4). CONCLUSIONS: In Tanzania change in appetite score correlated with weight change, but single point measurements did not. Appetite increases several weeks after the start of ART, which may be an appropriate time for nutritional interventions for malnourished HIV-infected adults

Micronutrient Adequacy and Dietary Diversity Exert Positive and Distinct Effects on Linear Growth in Urban Zambian Infants.

BACKGROUND: In the monitoring of infant and young child feeding, dietary diversity is used as an indicator of micronutrient adequacy; however, their relation may have weakened with the increasing use of fortified complementary foods. OBJECTIVE: The objectives were to assess the relation between dietary diversity and micronutrient adequacy in an urban infant population with a high consumption of fortified foods and to investigate whether dietary diversity and micronutrient adequacy were independently associated with subsequent growth. METHODS: We used longitudinal data on 811 infants in the Chilenje Infant Growth, Nutrition, and Infection Study conducted in Lusaka, Zambia. The relation between mean micronutrient adequacies and dietary diversity scores derived from 24-h diet recalls at 6 mo of age was investigated with the use of Spearman rank correlation. Multiple linear regression was used to assess the association between micronutrient adequacy, dietary diversity, and subsequent growth to 18 mo of age. RESULTS: Overall mean micronutrient density adequacy (MMDA) and MMDA of "problem micronutrients," defined as those micronutrients (calcium, iron, zinc) with mean density adequacies less than half of estimated needs, were correlated with dietary diversity scores (ρ = 0.36 and 0.30, respectively, both P < 0.0001). Consumption of "sentinel foods" (iron rich, fortified, animal source, dairy) showed better correlation with MMDA than with dietary diversity (ρ = 0.58-0.69, all P < 0.0001). In fully adjusted analyses, MMDA calcium, iron, zinc, and dietary diversity, but not overall MMDA, were associated with linear growth to 18 mo (both P ≤ 0.028). CONCLUSIONS: Micronutrient adequacy in infants consuming fortified foods may be more accurately assessed using locally specific sentinel food indicators rather than dietary diversity scores. Nonetheless, dietary diversity has a positive effect on subsequent linear growth apart from that of micronutrient adequacy, warranting its continued monitoring and further investigation into the mechanisms underlying this finding. This trial was registered at www.controlled-trials.com as ISRCTN37460449

Effects on anthropometry and appetite of vitamins and minerals given in lipid nutritional supplements for malnourished HIV-infected adults referred for antiretroviral therapy: results from the NUSTART randomized controlled trial.

BACKGROUND: The evidence base for effects of nutritional interventions for malnourished HIV-infected patients starting antiretroviral therapy (ART) is limited and inconclusive. OBJECTIVE: We hypothesized that both vitamin and mineral deficiencies and poor appetite limit weight gain in malnourished patients starting ART and that vitamin and mineral supplementation would improve appetite and permit nutritional recovery. DESIGN: The randomized controlled Nutritional Support for Africans Starting Antiretroviral Therapy trial was conducted in Mwanza, Tanzania, and Lusaka, Zambia. ART-naive adults referred for ART and with body mass index <18.5 kg/m received lipid-based nutritional supplements either without (LNS) or with added vitamins and minerals (LNS-VM), beginning before ART initiation. Participants were given 30 g/d LNS from recruitment until 2 weeks after starting ART and 250 g/d from weeks 2 to 6 of ART. RESULTS: Of 1815 patients recruited, 365 (20%) died during the study and 813 (45%) provided data at 12 weeks. Controlling for baseline values, anthropometric measures were consistently higher at 12-week ART in the LNS-VM than in the LNS group but statistically significant only for calf and mid-upper arm circumferences and triceps skinfold. Appetite did not differ between groups. Using piecewise mixed-effects quadratic models including all patients and time points, the main effects of LNS-VM were seen after starting ART and were significant for weight, body mass index, and mid-upper arm circumference. CONCLUSIONS: Provision of high levels of vitamins and minerals to patients referred for ART, delivered with substantial macronutrients, increased nutritional recovery but did not seem to act through treatment group differences in appetite

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality

Effects on body composition and handgrip strength of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Lipid-based nutrient supplements (LNS) may be beneficial for malnourished HIV-infected patients starting antiretroviral therapy (ART). We assessed the effect of adding vitamins and minerals to LNS on body composition and handgrip strength during ART initiation. ART-eligible HIV-infected patients with BMI <18·5 kg/m2 were randomised to LNS or LNS with added high-dose vitamins and minerals (LNS-VM) from referral for ART to 6 weeks post-ART and followed up until 12 weeks. Body composition by bioelectrical impedance analysis (BIA), deuterium (2H) diluted water (D2O) and air displacement plethysmography (ADP), and handgrip strength were determined at baseline and at 6 and 12 weeks post-ART, and effects of LNS-VM v. LNS at 6 and 12 weeks investigated. BIA data were available for 1461, D2O data for 479, ADP data for 498 and handgrip strength data for 1752 patients. Fat mass tended to be lower, and fat-free mass correspondingly higher, by BIA than by ADP or D2O. At 6 weeks post-ART, LNS-VM led to a higher regain of BIA-assessed fat mass (0·4 (95 % CI 0·05, 0·8) kg), but not fat-free mass, and a borderline significant increase in handgrip strength (0·72 (95 % CI -0·03, 1·5) kg). These effects were not sustained at 12 weeks. Similar effects as for BIA were seen using ADP or D2O but no differences reached statistical significance. In conclusion, LNS-VM led to a higher regain of fat mass at 6 weeks and to a borderline significant beneficial effect on handgrip strength. Further research is needed to determine appropriate timing and supplement composition to optimise nutritional interventions in malnourished HIV patients

Micronutrient fortification to improve growth and health of maternally HIV-unexposed and exposed Zambian infants: a randomised controlled trial

Background: The period of complementary feeding, starting around 6 months of age, is a time of high risk for growth faltering and morbidity. Low micronutrient density of locally available foods is a common problem in low income countries. Children of HIV-infected women are especially vulnerable. Although antiretroviral prophylaxis can reduce breast milk HIV transmission in early infancy, there are no clear feeding guidelines for after 6 months. There is a need for acceptable, feasible, affordable, sustainable and safe (AFASS by WHO terminology) foods for both HIV-exposed and unexposed children after 6 months of age. Methods and Findings: We conducted in Lusaka, Zambia, a randomised double-blind trial of two locally made infant foods: porridges made of flour composed of maize, beans, bambaranuts and groundnuts. One flour contained a basal and the other a rich level of micronutrient fortification. Infants (n = 743) aged 6 months were randomised to receive either regime for 12 months. The primary outcome was stunting (length-for-age Z < -2) at age 18 months. No significant differences were seen between trial arms overall in proportion stunted at 18 months (adjusted odds ratio 0.87; 95% CI 0.50, 1.53; P = 0.63), mean length-for-age Z score, or rate of hospital referral or death. Among children of HIV-infected mothers who breastfed <6 months (53% of HIV-infected mothers), the richly-fortified porridge increased length-for-age and reduced stunting (adjusted odds ratio 0.17; 95% CI 0.04, 0.84; P = 0.03). Rich fortification improved iron status at 18 months as measured by hemoglobin, ferritin and serum transferrin receptors. Conclusions: In the whole study population, the rich micronutrient fortification did not reduce stunting or hospital referral but did improve iron status and reduce anemia. Importantly, in the infants of HIV-infected mothers who stopped breastfeeding before 6 months, the rich fortification improved linear growth. Provision of such fortified foods may benefit health of these high risk infants

Reduced Poliovirus vaccine neutralising-antibody titres in infants with maternal HIV-exposure.

BACKGROUND: Maternally HIV-exposed (mHIV-EU) infants have poor health even without HIV-1 infection. The responses to vaccination are less well defined. Immunity to oral Poliovirus vaccine (OPV) was studied in Zambian infants participating in a randomised controlled trial of micronutrient fortification to improve child health. METHOD: Maternally HIV-unexposed and mHIV-EU infants were recruited at 6 months age and randomised to basal or enriched micronutrient-fortified diets for 12 months. HIV-exposed mother-infant pairs had received perinatal nevirapine to prevent mother-to-child-transmission. In the cohort of 597 infants, neutralising-antibody titres to OPV were analysed at 18 months with respect to micronutrient fortification, maternal or infant HIV-1 infection, and human cytomegalovirus (HCMV) infection detected by antibodies and viraemia (serum DNA). Vaccine protection was defined as log2 titre>3. RESULTS: Compared to uninfected children, HIV-1-infected children had reduced neutralising antibody titres to OPV, irrespective of diet: log2 titre difference (95% confidence interval) -3.44 (-2.41; -4.46), P<0.01. OPV antibody titres were lower in HIV-infected children with HCMV viraemia compared to those without viraemia at 18 months, but did not reach significance: difference -2.55 (-6.10; 1.01), P=0.14. Breast-feeding duration was independently associated with increasing OPV titre (P-value<0.01). In mHIV-EU children there were reduced neutralising antibody titres to Poliovirus compared with maternally HIV-unexposed, irrespective of diet, maternal education and socioeconomic status: log2 titre difference (95% confidence interval) -0.56 (-0.98; -0.15), P<0.01. This difference was noticeably decreased after adjusting for breast-feeding duration, suggesting that in our study population less breast-feeding by HIV-positive mothers could explain the reduced OPV titres in mHIV-EU infants. CONCLUSION: The mHIV-EU infants had reduced polio vaccine antibody titres which were associated with reduced breast-feeding duration. This has important implications for polio eradication and control of vaccine-preventable diseases, in countries where childhood HIV-1 infection and maternal exposure are public health threats

Determinants of infant feeding choices by Zambian mothers: a mixed quantitative and qualitative study.

Choosing an infant feeding mode is complex for human immunodeficiency virus (HIV)-infected African women. We documented infant feeding choices by 811 mothers of infants aged less than 18 months enrolled in the Chilenje Infant Growth, Nutrition and Infection Study of fortified complementary or replacement foods. We also conducted 20 interviews and 4 focus group discussions among women and nurses to explore the issues in depth. Practices of most HIV-infected women did not closely follow national or international guidelines: 26% never initiated breastfeeding, and 55% were not breastfeeding by 6 months post partum. Women of lower socio-economic status and those not meeting criteria for safe replacement feeding were more likely to initiate breastfeeding, to continue longer and to stop at 6 months when provided with free food within the trial. Most HIV-negative women and women of unknown HIV status continued breastfeeding into the infant's second year, indicating limited 'spillover' of infant feeding messages designed for HIV-infected women into the uninfected population. Qualitative work indicated that the main factors affecting HIV-infected women's infant feeding decisions were the cost of formula, the advice of health workers, influence of relatives, stigma and difficulties with using an exclusive feeding mode. Rapidly changing international recommendations confused both mothers and nurses. Many HIV-infected women chose replacement feeding without meeting criteria to do this safely. Women were influenced by health workers but, for several reasons, found it difficult to follow their advice. The recently revised international HIV and infant feeding recommendations may make the counselling process simpler for health workers and makes following their advice easier for HIV-infected women

Survival among HIV-infected adults initiating antiretroviral therapy according to proliferating and naïve CD4 cell counts.

<p>(Left) Kaplan-Meier plot of survival over time among HIV-infected adults with high (dashed line) or low (solid line) absolute number of CD4⁺ cells expressing the proliferation of marker Ki67 (<i>p</i> = 0.0003 using log rank test). (Right) Kaplan-Meier plot of survival over time among HIV-infected adults with low (dashed line) or high (solid line) absolute number of CD4⁺ cells expressing the naïve markers CD45RA and CCR7 (<i>p</i><0.001 using the log rank test).</p