HIV, TB, inflammation and other correlates of serum phosphate: A cross-sectional study.

BACKGROUND: There is little information about serum phosphate levels among patients with pulmonary tuberculosis (TB) and HIV infection. OBJECTIVE: We aimed to assess the role of TB, HIV, inflammation and other correlates on serum phosphate levels. METHODS: A cross-sectional study was conducted among TB patients and age- and sex-matched non-TB controls. Pulmonary TB patients were categorized as sputum -negative and -positive, based on culture. Age- and sex-matched non-TB controls were randomly selected among neighbours to sputum-positive TB patients. Data on age, sex, alcohol and smoking habits were obtained. HIV status, serum phosphate, and the acute phase reactants C-reactive protein (serum CRP) and α1-acid glycoprotein (serum AGP) were determined. Linear regression analysis was used to identify correlates of serum phosphate. RESULTS: Of 1605 participants, 355 (22.1%) were controls and 1250 (77.9%) TB patients, of which 9.9% and 50.4% were HIV-infected. Serum phosphate was determined before start of TB treatment in 44%, and 1-14 days after start of treatment in 56%. Serum phosphate was up to 0.10 mmol/L higher 1-3 days after start of TB treatment, and lowest 4 days after treatment, after which it increased. In multivariable analysis, TB patients had 0.09 (95% CI: 0.05; 0.13) mmol/L higher serum phosphate than controls, and those with HIV had 0.05 (95% CI: 0.01; 0.08) mmol/L higher levels than those without. Smoking was also a positive correlate of serum phosphate, whereas male sex and age were negative correlates. CONCLUSION: While HIV and TB are associated with higher serum phosphate, our data suggest that TB treatment is followed by transient reductions in serum phosphate, which may reflect hypophosphataemia in some patients.

Nutritional status is the major factor affecting grip strength of African HIV patients before and during antiretroviral treatment.

OBJECTIVES: Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. METHODS: The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index <18.5 kg/m2 ) and requiring ART. The relationship of grip strength to nutritional, infectious and demographic factors was assessed by multivariable linear regression at referral for ART (n = 1742) and after 12 weeks (n = 778) and 2-3 years of ART (n = 273). RESULTS: In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength. CONCLUSIONS: In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition.

A longitudinal study of systemic inflammation and recovery of lean body mass among malnourished HIV-infected adults starting antiretroviral therapy in Tanzania and Zambia.

BACKGROUND/OBJECTIVES: The effects of inflammation on nutritional rehabilitation after starting antiretroviral therapy (ART) are not well understood. We assessed the relationship between inflammation and body composition among patients enrolled in the Nutritional Support for African Adults Starting Antiretroviral therapy (NUSTART) trial in Tanzania and Zambia from 2011 to 2013. SUBJECTS/METHODS: HIV-infected, ART-eligible adults with body mass index (BMI) of <18.5 kg/m(2) enrolled in the NUSTART trial were eligible for this study. Anthropometric and body composition data were collected at recruitment and 6 and 12 weeks post ART and C-reactive protein (CRP) was measured at recruitment and 6 weeks. The relationships between CRP and body composition were assessed using multiple regression. RESULTS: Of the 1815 trial participants, 838 (46%) had baseline and 6-week CRP measurements. Median age was 36 years, 55% were females and median CD4 count was 135 cells/µl. A one-log reduction in CRP at 6 weeks was associated with increased mid-upper arm circumference (0.45 cm; 95% CI: 0.30, 0.61), calf circumference (0.38 cm; 0.23, 0.54), waist circumference (0.98 cm; 0.59, 1.37), BMI (0.37 kg/m(2); 0.24, 0.50) and fat-free mass (0.58 kg; 0.26, 0.91), but not with fat mass (0.09 kg; -0.17, 0.34). Fat-free mass gains persisted at 12 weeks and were more closely associated with 6-week CRP values than with baseline values. CONCLUSIONS: Reduction in CRP shortly after ART initiation was associated with higher fat-free mass gains. Further studies are warranted to determine whether interventions to reduce systemic inflammation will enhance gains in fat-free mass.

Lipid-based nutrient supplements containing vitamins and minerals attenuate renal electrolyte loss in HIV/AIDS patients starting antiretroviral therapy: A randomized controlled trial in Zambia.

BACKGROUND & AIMS: Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. METHODS: 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. RESULTS: Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups. CONCLUSIONS: The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings. TRIAL REGISTRATION: www.pactr.org ID number: PACTR201106000300631.

Effect of vitamin D supplementation of low birth weight term Indian infants from birth on cytokine production at 6 months.

BACKGROUND/OBJECTIVES: Vitamin D deficiency has been associated with impaired resistance to infection, which may be mediated by alterations in cytokine responses. We investigated the effect of vitamin D supplementation to infants on whole blood in-vitro cytokine production and on the inflammatory marker, plasma C-reactive protein (CRP). SUBJECTS/METHODS: Blood samples were taken at 6 months of age from infants participating in the DIVIDS (Delhi Infant Vitamin D Supplementation) randomized controlled trial of weekly vitamin D supplements (1400 IU = recommended intake) from birth to 6 months with the aim of decreasing mortality and severe morbidity. We measured plasma CRP and whole blood in-vitro production of tumour necrosis factor-α (TNFα), interferon-γ (INFγ), interleukin (IL)-10 and IL-13 following no stimulation or stimulation with lipopolysaccharide or phytohemagglutinin. RESULTS: Although the intervention improved vitamin D status in a severely deficient population, there were no differences between treatment groups in plasma CRP or in the production of any of the cytokines in either unstimulated or stimulated cultures. Recent illness had limited association with immunological markers. Plasma 25-hydroxyvitamin D levels were not associated with CRP or production of any cytokines. CONCLUSIONS: Vitamin D supplementation did not affect plasma CRP or whole blood cytokine production of vitamin D-deficient low birth weight infants. This is consistent with the lack of effect of vitamin D on mortality and severe morbidity among infants in the DIVIDS trial.

Human cytomegalovirus infant infection adversely affects growth and development in maternally HIV-exposed and unexposed infants in Zambia.

BACKGROUND: Human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) coinfections have been shown to increase infant morbidity, mortality, and AIDS progression. In HIV-endemic regions, maternal HIV-exposed but HIV-uninfected infants, which is the majority of children affected by HIV, also show poor growth and increased morbidity. Although nutrition has been examined, the effects of HCMV infection have not been evaluated. We studied the effects of HCMV infection on the growth, development, and health of maternally HIV-exposed and unexposed infants in Zambia. METHODS: Infants were examined in a cohort recruited to a trial of micronutrient-fortified complementary foods. HIV-infected mothers and infants had received perinatal antiretroviral therapy to prevent mother-to-child HIV transmission. Growth, development, and morbidity were analyzed by linear regression analyses in relation to maternal HIV exposure and HCMV infection, as screened by sera DNA for viremia at 6 months of age and by antibody for infection at 18 months. RESULTS: All HCMV-seropositive infants had decreased length-for-age by 18 months compared with seronegative infants (standard deviation [z]-score difference: -0.44 [95% confidence interval {CI}, -.72 to -.17]; P = .002). In HIV-exposed infants, those who were HCMV positive compared with those who were negative, also had reduced head size (mean z-score difference: -0.72 [95% CI, -1.23 to -.22]; P = .01) and lower psychomotor development (Bayley test score difference: -4.1 [95% CI, -7.8 to -.5]; P = .03). HIV-exposed, HCMV-viremic infants were more commonly referred for hospital treatment than HCMV-negative infants. The effects of HCMV were unaffected by micronutrient fortification. CONCLUSION: HCMV affects child growth, development, and morbidity of African infants, particularly in those maternally exposed to HIV. HCMV is therefore a risk factor for child health in this region.

Effect of multiple micronutrient-fortified food on mild morbidity and clinical symptoms in Zambian infants: results from a randomised controlled trial.

BACKGROUND/OBJECTIVES: We aimed to assess the effects on mild morbidity of a richly micronutrient-fortified complementary/replacement food given to Zambian infants aged 6-18 months. Previous results (The Chilenje Infant Growth, Nutrition and Infection Study Team, 2010) showed an increase in the rate of hospital referral for pneumonia in the same cohort. SUBJECT/METHODS: A total of 743 six-month-old healthy Zambian infants were randomised to receive either a richly or a basal micronutrient-fortified porridge for 12 months. Mild morbidity was defined as an illness that did not cause death or require hospitalisation and was diagnosed on clinical examination at scheduled visits. RESULTS: There was no evidence of an effect of trial arm on overall mild morbidity during the study (odds ratio (OR)=1.04, 95% confidence interval (CI)=0.90, 1.20, P=0.62). Infants in the richly fortified arm had significantly more visits in which they were diagnosed with lower respiratory tract infections/pneumonia (OR=1.65, 95% CI=1.06, 2.59, P=0.03) and fewer visits in which a diagnosis of urinary tract infection was made (OR=0.43, 95% CI=0.21, 0.87, P=0.02). Maternally reported symptoms were similar between trial arms. CONCLUSION: Compared with the basal diet, the richly micronutrient-fortified food was associated with more episodes of lower respiratory infections/pneumonia diagnosed at scheduled visits, which reinforces our previously reported findings of a higher incidence in hospital referral for pneumonia.

Early growth of infants of HIV-infected and uninfected Zambian women.

OBJECTIVE: Parental HIV infection may affect even those exposed children who remain uninfected. We investigated early growth, an indicator of overall health, of infants born to Zambian mothers recruited for a study of breastfeeding and postpartum health. METHODS: HIV-infected and uninfected women in Lusaka were followed regularly from late pregnancy to 16 weeks postpartum. Infant weight and length were measured at birth, 6 and 16 weeks. Infant HIV status could not be specifically determined in this cohort so comparisons were between all infants of HIV-uninfected mothers (n = 184) and those infants of HIV-infected mothers who were known to be alive and showed no clinical evidence of HIV infection at age 2-4 years (n = 85). RESULTS: Most infants were exclusively or predominantly breastfed until 16 weeks. At all time points infants of HIV-infected mothers tended to have lower weight and length standard deviation (Z) scores (significant for weight at 6 weeks; P = 0.04), even after adjustment for their lower gestational age at birth, compared with infants of uninfected mothers. In multivariate analyses the major factors affecting weight or length at 6 or 16 weeks of age were birth weight or length, and maternal subclinical mastitis, primiparity and weight during pregnancy. CONCLUSIONS: Early growth of infants of HIV-infected mothers is less than that of uninfected mothers, in part associated with subclinical mastitis, and this effect cannot be overcome with intensive support of mothers to follow international recommendations regarding exclusive breastfeeding.

Factors associated with postpartum physical and mental morbidity among women with known HIV status in Lusaka, Zambia.

The objective of our study was to investigate factors associated with postpartum physical and mental morbidity among women in Lusaka, Zambia with particular reference to known HIV status. Our study was part of the Breastfeeding and Postpartum Health (BFPH) longitudinal cohort study conducted between June 2001 and July 2003. Women were recruited at 34 weeks gestation and followed up to 16 weeks postpartum. Data on maternal health were collected at 3, 7, 10, and 14 days and at 3, 4, 5, 6, 9, 12, and 16 weeks postpartum. Maternal mental health data were collected from April 2002 onwards at recruitment and at seven days and six weeks postpartum. Data on physical morbidity were collected for 429 women (218 HIV-negative, 211 HIV-positive) and data on mental morbidity were collected for 272 women (134 HIV-negative, 138 HIV-positive). Multivariate logistic regression was used to examine factors associated with postpartum physical or mental morbidity. Postpartum physical morbidity was associated with HIV status, parity > or =5 and age < 20 years. Neither antenatal nor postpartum mental morbidity, as indicated by a self-reporting questionnaire 20-item (SRQ-20) score > or =7, were associated with HIV status or with postpartum physical morbidity in this population. Larger comparative studies are required to corroborate or contest these findings.

Maternal micronutrient status and decreased growth of Zambian infants born during and after the maize price increases resulting from the southern African drought of 2001-2002.

OBJECTIVE: To investigate the effects on maternal micronutrient status and infant growth of the increased maize prices that resulted from the southern African drought of 2001-2002. DESIGN: Longitudinal cohort study. SETTING: A maternal and child health clinic in Lusaka, Zambia. SUBJECTS: Maternal and infant health and nutrition data and maternal plasma were being collected for a study of breast-feeding and postpartum health. Samples and data were analysed according to whether they were collected before (June to December 2001), during (January 2002 to April 2003) or after (May 2003 to January 2004) the period of increased maize price. Season and maternal HIV status were controlled for in analyses. RESULTS: Maize price increases were associated with decreased maternal plasma vitamin A during pregnancy (P = 0.028) and vitamin E postpartum (P = 0.042), with the lowest values among samples collected after May 2003 (vitamin A: 0.96 micromol l(-1), 95% confidence interval (CI) 0.84-1.09, n = 38; vitamin E: 30.8 micromol mmol(-1) triglycerides, 95% CI 27.2-34.8, n = 64) compared with before January 2002 (vitamin A: 1.03 micromol l(-1), 95% CI 0.93-1.12, n = 104; vitamin E: 38.9 micromol mmol(-1) triglycerides, 95% CI 34.5-43.8, n = 47). There were no significant effects of sampling date on maternal weight, haemoglobin or acute-phase proteins and only marginal effects on infant weight. Infant length at 6 and 16 weeks of age decreased progressively throughout the study (P-values for time of data collection were 0.51 at birth, 0.051 at 6 weeks and 0.026 at 16 weeks). CONCLUSIONS: The results show modest effects of the maize price increases on maternal micronutrient status. The most serious consequence of the price increases is likely to be the increased stunting among infants whose mothers experienced high maize prices while pregnant. During periods of food shortages it might be advisable to provide micronutrient supplements even to those who are less food-insecure.

Low-cost intervention to decrease mastitis among lactating women.

UNLABELLED: Mastitis is a common maternal health problem which can lead to serious infant health problems such as poor growth and HIV infection. Anti-secretory factor (AF), which can be induced in milk by maternal consumption of a low-cost cereal product, has been associated with decreased mastitis. CONCLUSION: Consumption of cereals which induce AF should be investigated as a potential intervention in less-developed countries where the consequences of mastitis for infants are most severe.

Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y.

OBJECTIVES: To determine whether subclinical vitamin D deficiency in Indian children under 5 y of age is a risk factor for severe acute lower respiratory infection (ALRI). DESIGN: A hospital-based case-control study. SETTING: Sanjeevani Paediatrics Hospital, a private hospital in Indapur, India. PARTICIPANTS: A total of 150 children including 80 cases and 70 controls, aged 2-60 months, were enrolled. Case definition of severe ALRI as given by the World Health Organization was used for cases. Controls were healthy children attending outpatients' service for immunization. MAIN OUTCOME MEASURE: Association of serum 25-hydroxyvitamin D3 (25OHD3) with severe ALRI, controlling for demographic and other potential risk factors. RESULTS: Serum 25OHD3 increased with age. Factors significantly associated with decreased risk of severe ALRI in univariate analysis were: exclusive breastfeeding in the first 4 months (cases 35/78 (45%), controls 41/64 (64%); P=0.02); introduction of other dietary liquids than milk only after 6 months (cases 46/70 (66%), controls 31/66 (47%); P=0.03); use of liquid petroleum cooking fuel (cases 32/80 (40%), controls 40/70 (57%); P=0.04); infant not covered in swaddling cloths when exposed to sunlight before crawling (cases 11/52 (21%), controls 25/54 (46%); P=0.006); and serum 25OHD3>22.5 nmol/l (cases 16/80 (20%), controls 48/70 (69%); P<0.001). In multivariate analysis, factors associated with significantly lower odds ratio for having severe ALRI were: serum 25OHD3>22.5 nmol/l (OR: 0.09; 95% CI 0.03-0.24; P<0.001) and exclusive breastfeeding in the first 4 months of life (OR 0.42; 95% CI 0.18-0.99; P=0.046) with age and height/age as significant covariates. CONCLUSION: Subclinical vitamin D deficiency and nonexclusive breastfeeding in the first 4 months of life were significant risk factors for severe ALRI in Indian children.

Comparison of armspan, arm length and tibia length as predictors of actual height of disabled and nondisabled children in Dharavi, Mumbai, India.

OBJECTIVES: To investigate appropriate measurements to predict height in children with physical impairments to facilitate the accurate assessment of nutritional status in field studies. DESIGN: Case-control cross-sectional study. SETTING: Dharavi, a large slum in Mumbai, India. SUBJECTS: In total, 141 children with mixed disabilities and 162 nondisabled control children, aged 2-6 y. METHODS: Height/length, armspan, arm length and tibia length were measured to the nearest 0.1 cm using standard procedures. The relations between armspan, arm length and tibia length with height in controls were investigated using linear regression. RESULTS: Armspan (R(2)=0.93, P<0.001, n=158), arm length (R(2)=0.81, P<0.001, n=162) and tibia length (R(2)=0.72, P<0.001, n=161) were found to be strong predictors of height based on data from nondisabled control children. These measurements could be used to determine a more accurate height for children with physical impairments where the nature of the impairment may interfere with height measurements. CONCLUSIONS: Armspan, arm length and tibia length can be used to determine accurate height for children with physical impairments, for example, children with a nonambulatory status or those with kyphosis or scoliosis of the spine.

Serum leptin in disabled and non-disabled children in an Indian slum population.

OBJECTIVE: To assess the concentration of serum leptin in a population of malnourished children and to compare the leptin levels of disabled and non-disabled children in this population. DESIGN: Case-control study. SUBJECTS: Eighty-one children, comprising 41 children with mixed disabilities and 40 non-disabled controls, were selected from 425 children involved in a case-control study assessing the nutritional status of children with disabilities in an Indian slum population. METHODS: Leptin was measured in the serum samples and was compared with anthropometry (weight-for-age Z-scores (WAZ), height-for-age Z-scores (HAZ), weight-for-height Z-scores (WHZ), body mass index (BMI), mid-upper-arm circumference (MUAC), sub-scapular skinfold thickness and triceps skinfold thickness) and serum acute phase proteins. RESULTS: The children were very malnourished with WAZ=-2.07 (s.d. 1.15), HAZ=-2.15 (s.d. 1.85) and WHZ=-1.07 (s.d. 0.83). Leptin was extremely low in both the disabled (1.44 ng/ml; 95% confidence interval, CI, 1.23-1.69) and the non-disabled (1.19 ng/ml; 95% CI 1.04-1.35) children. There were no differences between the disabled and non-disabled groups as a whole but 15 children with neurological disabilities had significantly higher (P<0.05) serum leptin (1.65 ng/ml; 95% CI 1.29-2.06) than the non-disabled children. Girls (1.55 ng/ml; 95% CI 1.29-1.87) had significantly higher concentrations of leptin than boys (1.11 ng/ml; 95% CI 1.02-1.22; P=0.002). Leptin did not correlate with any biochemical or anthropometric measures. CONCLUSIONS: In this population, where malnutrition was common, serum leptin levels were very low and did not correlate with anthropometry. SPONSORSHIP: UK Department for International Development; Virgin Airways through the Great Ormond Street Hospital Trustees.

Variation in breastmilk HIV-1 viral load in left and right breasts during the first 3 months of lactation.

The mechanism and risk factors associated with mother-to-child transmission of HIV-1 through breastfeeding remain unclear; breastmilk viral load may be an important determinant of transmission. Analysis of breastmilk cell-free viral load in samples taken from each breast at 1, 6 and 14 weeks postpartum showed that HIV-1 is shed intermittently and load may differ considerably between breasts of an individual woman at any given time. Breastmilk HIV-1 load was undetectable in approximately one-third of samples.

Feeding mode, intestinal permeability, and neopterin excretion: a longitudinal study in infants of HIV-infected South African women.

Exclusive breast feeding has been associated with a lower rate of mother-to-child HIV transmission than breast feeding plus other foods. To obtain further information on biologic outcomes of different feeding modes, we examined 272 infants of HIV-infected South African women at ages 1, 6, and 14 weeks. At each visit information about infant diet and morbidity was collected and infants underwent a lactulose/mannitol dual sugar intestinal permeability test. In a subset of infants, urinary neopterin excretion was measured as an indicator of immune system activation. Infants who had themselves become HIV-infected by 14 weeks had higher ( p <.01) intestinal permeability at 6 and 14 weeks and slightly (.05 < p <.1) higher neopterin excretion at all times than uninfected infants. At 1 week infants given no breast milk had higher ( p <.05) intestinal permeability than infants given breast milk exclusively or with other foods. Intestinal permeability in infants fed breast milk plus other foods was never increased relative to that of exclusively breastfed infants. Feeding mode had no effect on neopterin excretion. Thus, infant HIV infection induces changes in gut permeability and possibly immune system activation before clinical symptoms become apparent. The effects of feeding mode on infant intestinal permeability or urinary neopterin excretion do not explain a possible protective effect of exclusive breast feeding on mother-to-child transmission of HIV.

The effect of antenatal vitamin A and beta-carotene supplementation on gut integrity of infants of HIV-infected South African women.

BACKGROUND: Vitamin A is important for protection against diarrhea, and supplements may benefit gut function of infants of HIV-infected mothers. METHODS: We studied 238 infants of HIV-infected South African women participating in a randomized, double-blind, placebo-controlled trial of vitamin A during pregnancy (1.5 mg retinyl palmitate and 30 mg beta-carotene daily) plus 60 mg retinyl palmitate at delivery. The placebo group received identical placebo capsules at the same times. When infants were 1, 6, and 14 weeks of age, lactulose/mannitol dual sugar intestinal permeability tests were performed. RESULTS: Maternal vitamin A supplementation did not significantly affect infant gut permeability in the group as a whole at any time. By multiple regression analysis, HIV infection of the infant by 14 weeks was significantly associated with increased gut permeability at both 6 and 14 weeks. After controlling for birth weight, gestational age, current weight, feeding mode and recent morbidity, there was a trend toward an interaction between vitamin A supplementation and HIV infection (P = 0.086) at 14 weeks. Vitamin A made no difference to gut permeability of uninfected infants (lactulose/mannitol ratio for vitamin A group: 0.11, 95% confidence interval [CI] 0.08, 0.15, n = 73 and for placebo group: 0.09, 95% CI 0.06, 0.12, n = 76), but largely prevented the increase in the ratio of HIV-infected infants (vitamin A group: 0.17, 95% CI 0.13, 0.23, n = 23; placebo group: 0.50, 95% CI 0.37, 0.68, n = 20). The effects on the lactulose/mannitol ratio were related to changes in lactulose, not mannitol, excretion. Vitamin A supplementation was associated with significantly lower lactulose excretion at 1 and 14 weeks, suggesting the major effect of vitamin A was on maintaining the integrity of gut tight junctions. CONCLUSIONS: Vitamin A supplementation of HIV-infected pregnant women may prevent the deterioration in gut integrity in the subgroup of their infants who themselves become infected. Improving vitamin A status of HIV-infected infants may decrease their gastrointestinal morbidity.