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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 ≥5 and age [ABSTRACT FROM AUTHOR]

Background: Adolescents with HIV (AWH) frequently exhibit impaired growth, which manifests as stunting and wasting. We studied trajectories in leg-length (appendicular), sitting (axial), and standing height among AWH on antiretroviral therapy (ART), determining peak height velocity (PHV) and age at PHV (aPHV)., Methods: Analyses used VITALITY trial data from Zimbabwe and Zambia (PACTR20200989766029), which recruited AWH (11-19 years) established on ART to determine whether vitamin D 3 /calcium supplementation improves bone health. The study enrolled participants between January and December 2021. Weight-for-age and height-for-age z-scores (WAZ/HAZ) were calculated from 12-weekly anthropometry over 96 weeks. Height trajectory analyses used SuperImposition by Translation And Rotation (SITAR) methods adjusting for height, tempo (aPHV) and velocity. Linear associations between vitamin D/calcium supplementation, HIV-specific factors, WAZ, HAZ, and SITAR parameters were determined., Results: Overall, 842 participants (53·2% female; median age 15·5 [IQR:13·2-17·9] years), were taking ART for median 9·8(IQR:6·3-12·3) years. Mean(SD) HAZ was 1·21(1·05) in females, -1·68(1·05) in males. Overall, 251(29·8%) AWH were stunted (HAZ < -2) and 253(30%) wasted (WAZ < -2). Standing, appendicular and axial aPHVs were: Female 13·4, 13·3, 13·9 years; Males 15·3, 15·0, 15·8 years. Unsuppressed viral-load(VL) and delayed ART initiation (age > 4-years) were associated with later aPHV and shorter axial height in females. In all, unsuppressed VL had a more negative effect on aPHV for axial (Females: β = 0·39 years [95%CI:0·12,0·65]; Males: β = 0·45 [95%CI:0·10,0·80]) than appendicular growth (Females: β = 0.31 [95%CI 0·08,0·53]; Males: β = 0·2 [95%CI:-0·17,0·56]). Conversely, delayed ART initiation was more negatively related to aPHV for appendicular (Females: β = 0·25 [95% CI:0·08,0·43]; Males: β = 0·63 [95%CI:0·32, 0·93] than axial growth (Females: β = 0·13 [95%CI:-0·08,0·34]; Males: β = 0·56 [95%CI:0·28,0·86]. Lower HAZ and WAZ were associated with lower height, later aPHV and lower PHV. At 48-week vitamin-D 3 /calcium supplementation had no effect on the growth pattern., Conclusion: Unsuppressed viral load and delayed ART-initiation predicted later aPHV. Stunting and wasting were associated with attenuated growth velocity and later aPHV. Adolescents with HIV experience persistent linear growth impairments, potentially persisting into adulthood., Trial Registration: (PACTR20200989766029|| http://www.pactr.org/ ); First registered on 03/09/2020., Competing Interests: Declarations. Ethics approval and consent to participate: All methods were carried out in line with the Declaration of Helsinki and written informed consent was obtained from guardians with written assent from participants aged <18 years. Participants aged 18 years or older and emancipated minors (those aged below 18 years who are married or have children) provided independent informed consent [32]. The study was approved by the Biomedical Research and Training Institute Institutional Review Board (reference AP158/2020), the Harare Central Hospital Ethics committee (reference HCHEC 030320/12), the Medical Research Council of Zimbabwe (reference A/2626), the University of Zambia Biomedical Research Ethics Committee (reference 1116-2020), and the London School of Hygiene and Tropical Medicine Ethics Committee (reference 22030). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis, and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in Southern Africa. A pre-planned secondary analysis was performed of baseline data from the vitamin D for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology trial (PACTR20200989766029) which enrolled ALWH (11-19 yr) taking antiretroviral therapy for ≥6 mo, and recorded socio-demographic, clinical and dietary data. After over-night fasting, vitamin D metabolites (25(OH)D, 1,25(OH)2D, and 24,25(OH)2D), intact parathyroid hormone (PTH), and bone turnover markers (BTMs) (C-terminal telopeptide of type I collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)) were measured. Tandem Mass Spectrometry measured vitamin D metabolites, while intact PTH and BTMs were analyzed by electrochemiluminescence immunoassay. Stratified by 25(OH)D (<75 vs ≥75 nmol/L), associations between standardized concentrations (β = standard deviations) of vitamin D metabolites, intact PTH and BTMs were assessed using structural equations modelling (SEM) adjusted for age, sex, and country (Zimbabwe/Zambia). Among the 842 ALWH enrolled, the median dietary calcium intake was 100 mg (IQR: 55-145). The SEM showed PTH was positively associated (β: 0.21; 95% CI, 0.1, 0.32) with 1,25(OH)2D, only when 25(OH)D was <75 vs ≥75 nmol/L (β: 0.23; 95%CI, -0.13, 0.59), with evidence of an interaction (β: -0.11; 95%CI, -0.20, -0.02). A positive relationship between 25(OH)D and 24,25(OH)2D was seen irrespective of 25(OH)D concentration. 24,25(OH)2D was inversely related to BTMs, particularly when 25(OH)D was <75 nmol/L (CTX: β: -0.15; 95% CI, -0.24, -0.06 and P1NP: β: -0.14; 95%CI, -0.22, -0.06). There was interaction between dietary calcium and 25(OH)D on PTH (β: -0.15; 95% CI, -0.22, -0.07) suggesting an interaction between low 25(OH)D and low dietary calcium which increases PTH. In conclusion, associations between 25(OH)D, PTH, 1,25(OH)2D, and BTMs in ALWH appear dependent upon 25(OH)D concentrations <75 nmol/L and calcium intake. A novel, potentially causal pathway between 25(OH)D, 24,25(OH)2D, and BTMs was seen. Findings enhance understanding of vitamin D metabolism in people living with HIV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The prevalence of poor linear growth among African children with perinatally acquired HIV remains high. There is concern that poor linear growth may to lead to later total and central fat deposition and associated non-communicable disease risks. We investigated associations between height-for-age Z score (HAZ) and total and regional fat and lean mass measured by dual-energy X-ray absorptiometry, expressed as internal population Z scores, among 839 Zimbabwean and Zambian perinatally HIV-infected male and female adolescents aged 11-19 years. Stunting (HAZ < -2) was present in 37 % of males and 23 % of females. HAZ was strongly positively associated with total, trunk, arm and leg fat mass and lean mass Z scores, in analyses controlling for pubertal stage, socio-economic status and HIV viral load. Associations of linear growth with lean mass were stronger than those with fat outcomes; associations with total and regional fat were similar, indicating no preferential central fat deposition. There was no evidence that age of starting antiretroviral therapy was associated with HAZ or body composition. Non-suppressed HIV viral load was associated with lower lean but not fat mass. The results do not support the hypothesis that poor linear growth or stunting are risk factors for later total or central fat deposition. Rather, increased linear growth primarily benefits lean mass but also promotes fat mass, both consistent with larger body size. Nutritional and/or HIV infection control programmes need to address the high prevalence of stunting among perinatally HIV-infected children in order to mitigate constraints on the accretion of lean and fat mass.

There is limited information as to whether people who experience severe acute malnutrition (SAM) as young children are at increased risk of overweight, high body fat and associated chronic diseases in later life. We followed up, when aged 7-12 years, 100 Zambian children who were hospitalised for SAM before age 2 years and eighty-five neighbourhood controls who had never experienced SAM. We conducted detailed anthropometry, body composition assessment by bioelectrical impedance and deuterium dilution (D2O) and measured blood lipids, Hb and HbA1c. Groups were compared by linear regression following multiple imputation for missing variables. Children with prior SAM were slightly smaller than controls, but differences, controlling for age, sex, socio-economic status and HIV exposure or infection, were significant only for hip circumference, suprailiac skinfold and fat-free mass index by D2O. Blood lipids and HbA1c did not differ between groups, but Hb was lower by 7·8 (95 % CI 0·8, 14·7) g/l and systolic blood pressure was 3·4 (95 % CI 0·4, 6·4) mmHg higher among the prior SAM group. Both anaemia and high HbA1c were common among both groups, indicating a population at risk for the double burden of over- and undernutrition and associated infectious and chronic diseases. The prior SAM children may have been at slightly greater risk than the controls; this was of little clinical significance at this young age, but the children should be followed when older and chronic diseases manifest.

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/m 2 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 ( 2 H) diluted water (D 2 O) 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, D 2 O 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 D 2 O. 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 D 2 O 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.

Objective: To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets., Methods: This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test., Results: Among 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group., Conclusions: Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention.

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.

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.

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.

The present randomised trial investigated the effects of feeding Zambian infants from 6 to 18 months old either a richly or basal micronutrient-fortified complementary/replacement food on gut integrity and systemic inflammation. Blood samples were obtained from all infants (n 743) at 6 and 18 months for the assessment of serum C-reactive protein (CRP) and α1-acid glycoprotein (AGP). A subsample of 502 infants, selected from the main cohort to include a larger proportion of infants with HIV-positive mothers, was assigned to lactulose/mannitol gut permeability tests. Lactulose:mannitol (L:M) ratio analyses were adjusted for baseline urinary L:M ratio, socio-economic status, mother's education, season of birth and baseline stunting, and stratified by maternal antenatal HIV status, child's sex, concurrent breast-feeding status and anaemia at baseline. There was no significant difference in geometric mean L:M ratio between the richly fortified and basal-fortified porridge arms at 12 months (0·47 (95 % CI 0·41, 0·55) v. 0·41 (95 % CI 0·34, 0·49); P = 0·16 adjusted). At 18 months, the richly fortified porridge group had a significantly higher geometric mean L:M ratio than the basal-fortified group (0·23 (95 % CI 0·19, 0·28) v. 0·15 (95 % CI 0·12, 0·19); P = 0·02 adjusted). This effect was evident for all stratifications, significantly among boys (P = 0·04), among the infants of HIV-negative mothers (P = 0·01), among the infants of HIV-negative mothers not concurrently breast-fed (P = 0·01) and among those who were not anaemic at baseline (P = 0·03). CRP, but not AGP, was positively associated with L:M ratio, but there were no significant effects of the diet on either CRP or AGP. In conclusion, a richly fortified complementary/replacement food did not benefit and may have worsened intestinal permeability.

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., (© 2010 Blackwell Publishing Ltd.)

Background: HIV-exposed, uninfected (HIV-EU) children represent a large proportion of children in southern Africa. The reasons for their poorer growth and higher morbidity and mortality than their HIV-unexposed peers are unclear., Objective: We compared anthropometry of 125 HIV-EU with 382 HIV-unexposed young Zambian children participating in a trial of micronutrient-fortified complementary/replacement food., Design: The randomized controlled trial provided children from age 6 to 18 months with a porridge flour containing either a basal or a rich level of micronutrients. Weight and length were measured 3 monthly and head and arm circumferences and triceps and subscapular skinfolds 6 monthly., Results: There were no significant anthropometric differences between the 2 treatment groups. In unadjusted analyses, most anthropometric Z scores of HIV-EU children were lower than those of HIV-unexposed children; after adjustment for treatment arm, socioeconomic factors, breastfeeding and sex, head and arm circumference Z scores remained lower. Subscapular skinfold Z scores were lower among HIV-EU than HIV-unexposed children at 6 months but not 18 months., Conclusions: Socioeconomic factors accounted for some but not all of the impaired growth of HIV-EU children. Micronutrient malnutrition may not be the socioeconomic factor responsible for the growth faltering. Factors acting earlier in life had irreversible effects.

Subclinical mastitis, defined as raised milk sodium/potassium (Na/K) ratio, is associated with poor infant growth and, among HIV-infected women, with increased milk HIV viral load. We conducted a longitudinal cohort study in Lusaka, Zambia, in order to investigate the relative importance of several potential causes of subclinical mastitis: maternal infection, micronutrient deficiencies and poor lactation practice. Women (198 HIV-infected, 189 HIV-uninfected) were recruited at 34 weeks' gestation and followed up to 16 weeks postpartum for collection of information on their health, their infant's health, infant growth and infant feeding practices. Milk samples were collected from each breast at 11 postpartum visits and blood at recruitment and 6 weeks postpartum. The geometric mean milk Na/K ratio and the proportion of women with Na/K ratio > 1.0 in one or both breasts were significantly higher among HIV-infected than among uninfected women. Other factors associated with the higher mean Na/K ratio in univariable analyses were primiparity, high maternal alpha(1)-acid glycoprotein (AGP) at 6 weeks, maternal overall morbidity and specific breast symptoms, preterm delivery, low infant weight or length, infant thrush and non-exclusive breast feeding. In multivariable analyses, primiparity, preterm delivery, breast symptoms, HIV status and raised AGP were associated with the raised Na/K ratio. Thus the main factors associated with subclinical mastitis that are amenable to intervention are poor maternal overall health and breast health. The impact of improved postpartum health care, especially management of maternal infections and especially in primiparous women, on the prevalence of subclinical mastitis and its consequences requires investigation.

Exclusive breastfeeding (EBF) is optimal for infant health and is associated with decreased risk of mother-to-child HIV transmission compared with mixed feeding of breast milk and other foods. To investigate why many women stop EBF before the recommended 6 months, maternal and infant health and infant-feeding data were collected from 177 HIV-infected and 177-uninfected Zambian women regularly from 34 weeks gestation to 16 weeks postpartum. Despite strong support for good breastfeeding practice, only 37% of women were still EBF at week 16. Factors significantly associated with shorter duration of EBF were primiparity, maternal systemic illness, and infant length at 6 weeks. The results suggest that the association of EBF with lower rates of mother-to-child HIV transmission may not be causal but may be secondary to the reduced duration of EBF associated with poor maternal or infant health. Programs supporting EBF should include support for maternal health.