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.

Even though antiretroviral therapy (ART) access for human immunodeficiency virus (HIV)-infected children increased dramatically, anaemia has continued as a challenge regardless of a cluster of differentiation (CD4) count and viral load. Hence, the present study aimed to assess the determinants of iron deficiency anaemia among children living with HIV after the initiation of ART. An institution-based unmatched case–control study was conducted among consecutively selected 712 children on HIV care from 1 September to 30 October 2022 in the Metekel zone. A pre-tested and structured data extraction checklist was used to collect the data. Data were analysed using STATA version 16 software. Binary logistic regression was used to find the association between independent variables and anaemia. The level of statistical significance was declared at a value of P < 0⋅05. A total of 712 HIV-positive children (178 cases and 534 controls) were included in this study, with a completeness rate of 98⋅8 %. In multivariable analysis, variables that have a statistically significant association with anaemia were as follows: CD4 count <350 (Adjusted Odds Ratio [AOR] 2⋅76; 95 % CI 1⋅76, 4⋅34), World Health Organization (WHO) clinical stage III (AOR 7⋅9; 95 % CI 3⋅5, 17⋅91) and stage IV (AOR 7⋅8; 95 % CI 3⋅37, 18⋅1), cotrimoxazole prophylaxis therapy (AOR 0⋅5; 95 % CI 0⋅31, 0⋅8) and mid-upper arm circumference (MUAC) ≤11⋅5 mm (AOR 2⋅1; 95 % CI 1⋅34, 3⋅28). The present study found that CD4 count, WHO clinical stage, cotrimoxazole prophylaxis therapy and MUAC were significantly associated with anaemia in children on ART. Therefore, continuous screening of anaemia and nutritional treatment is essential in these patients.

The US government invests substantial sums to control the HIV/AIDS epidemic. To monitor progress toward epidemic control, PEPFAR, or the President’s Emergency Plan for AIDS Relief, oversees a data reporting system that includes standard indicators, reporting formats, information systems, and data warehouses. These data, reported quarterly, inform understanding of the global epidemic, resource allocation, and identification of trouble spots. PEPFAR has developed tools to assess the quality of data reported. These tools made important contributions but are limited in the methods used to identify anomalous data points. The most advanced consider univariate probability distributions, whereas correlations between indicators suggest a multivariate approach is better suited. For temporal analysis, the same tool compares values to the averages of preceding periods, though does not consider underlying trends and seasonal factors. To that end, we apply two methods to identify anomalous data points among routinely collected facility-level HIV/AIDS data. One approach is Recommender Systems, an unsupervised machine learning method that captures relationships between users and items. We apply the approach in a novel way by predicting reported values, comparing predicted to reported values, and identifying the greatest deviations. For a temporal perspective, we apply time series models that are flexible to include trend and seasonality. Results of these methods were validated against manual review (95% agreement on non-anomalies, 56% agreement on anomalies for recommender systems; 96% agreement on non-anomalies, 91% agreement on anomalies for time series). This tool will apply greater methodological sophistication to monitoring data quality in an accelerated and standardized manner.

Early life exposures and growth patterns may affect long-term risk of chronic non-communicable diseases (NCD). We followed up in adolescence two Zambian cohorts (n 322) recruited in infancy to investigate how two early exposures – maternal HIV exposure without HIV infection (HEU) and early growth profile – were associated with later anthropometry, body composition, blood lipids, Hb and HbA1c, blood pressure and grip strength. Although in analyses controlled for age and sex, HEU children were thinner, but not shorter, than HIV-unexposed, uninfected (HUU) children, with further control for socio-demographic factors, these differences were not significant. HEU children had higher HDL-cholesterol than HUU children and marginally lower HbA1c but no other biochemical or clinical differences. We identified three early growth profiles – adequate growth, declining and malnourished – which tracked into adolescence when differences in anthropometry and body fat were still seen. In adolescence, the early malnourished group, compared with the adequate group, had lower blood TAG and higher HDL, lower grip strength (difference: −1·87 kg, 95 % CI −3·47, −0·27; P = 0·02) and higher HbA1c (difference: 0·5 %, 95 % CI 0·2, 0·9; P = 0·005). Lower grip strength and higher HbA1c suggest the early malnourished children could be at increased risk of NCD in later life. Including early growth profile in analyses of HIV exposure reduced the associations between HIV and outcomes. The results suggest that perinatal HIV exposure may have no long-term effects unless accompanied by poor early growth. Reducing the risk of young child malnutrition may lessen children’s risk of later NCD.

Policy decisions and the practice of public health nutrition need to be based on solid evidence, developed through rigorous research studies where objective measures are used and results that run counter to dogma are not dismissed but investigated. In recent years, enhancements in study designs, and methodologies for systematic reviews and meta-analysis, have improved the evidence-base for nutrition policy and practice. However, these still rely on a full appreciation of the strengths and limitations of the measures on which conclusions are drawn and on the thorough investigation of outcomes that do not fit expectations or prevailing convictions. The importance of ‘hard facts’ and ‘misfits’ in research designed to advance knowledge and improve public health nutrition is illustrated in this paper through a selection of studies from different stages in my research career, focused on the nutritional requirements of resource-poor populations in Africa and Asia.

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.

Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.

Retention in care is a key feature of the cascade of continuum of care, playing an important role in achieving therapeutic success and being crucial for reduction of HIV transmission. The aim of this study was to evaluate the rate of retention in care in a large referral centre in the North of Italy and to identify predictors associated with failed retention. All new HIV-infected subjects were consecutive enrolled from 1 January 2008 to 31 December 2014. Demographics, immune-virological status, hepatitis co-infection and timing of initiation of combined antiretroviral therapy (cART) data were collected at baseline and at the time of last observation. Failed retention in care was defined as lack of laboratory data, clinical visits and drug dispensation for more than 6 months from the last visit. Cox regression analysis was used. Multivariate analysis of variables with P<0.05 in univariate analysis was performed. We enrolled 269 patients (mean age 46.1 years). Males were 197 (73%), Italian 219 (81%) with mean length of disease of 5.1 years. cART was prescribed for 257 patients (95%). The rate of retention in care was 78.4% and the rate of virological suppression was 75%. Predictors of being loss to follow-up were foreign origin (P = 0.048), CD4+ count <200/mmc (P = 0.001) and not being treated for HIV infection (P = 0.0004). Predictors of cART efficacy were shorter duration of HIV infection and baseline HIV-RNA <100 000 copies/ml. These findings underline the necessity to improve retention in care by identifying groups at increased risk of being loss to follow-up. Retention in care of vulnerable population is crucial to reach 90-90-90 UNAIDS endpoint.

Bioelectrical impedance analysis (BIA) is an inexpensive, quick and non-invasive method to determine body composition. Equations used in BIA are typically derived in healthy individuals of European descent. BIA is specific to health status and ethnicity and may therefore provide inaccurate results in populations of different ethnic origin and health status. The aim of the present study was to test the validity of BIA in Ethiopian antiretroviral-naive HIV patients.

BIA was validated against the 2H dilution technique by comparing fat-free mass (FFM) measured by the two methods using paired t tests and Bland–Altman plots. BIA was based on single frequency (50 kHz) whole-body measurements. Data were obtained at three health facilities in Jimma Zone, Oromia Region, South-West Ethiopia. Data from 281 HIV-infected participants were available. Two-thirds were female and the mean age was 32·7 (sd 8·6) years. Also, 46 % were underweight with a BMI below 18·5 kg/m2. There were no differences in FFM between the methods. Overall, BIA slightly underestimated FFM by 0·1 kg (−0·1, 95 % CI −0·3, 0·2 kg). The Bland–Altman plot indicated acceptable agreement with an upper limit of agreement of 4·5 kg and a lower limit of agreement of −4·6 kg, but with a small correlation between the mean difference and the average FFM. BIA slightly overestimated FFM at low values compared with the 2H dilution technique, while it slightly underestimated FFM at high values. In conclusion, BIA proved to be valid in this population and may therefore be useful for measuring body composition in routine practice in HIV-infected African individuals.

Scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has reduced the incidence of pulmonary tuberculosis (PTB) in South Africa. Despite the strong association of HIV infection with extrapulmonary tuberculosis (EPTB), the effect of ART on the epidemiology of EPTB remains undocumented. We conducted a retrospective record review of patients initiated on treatment for EPTB in 2009 (ART coverage <5%) and 2013 (ART coverage 41%) at four public hospitals in rural Mopani District, South Africa. Data were obtained from TB registers and patients’ clinical records. There was a 13% decrease in overall number of TB cases, which was similar for cases registered as EPTB (n = 399 in 2009 vs. 336 in 2013; P < 0·01) and for PTB (1031 vs. 896; P < 0·01). Among EPTB cases, the proportion of miliary TB and disseminated TB decreased significantly (both P < 0·01), TB meningitis and TB of bones increased significantly (P < 0·01 and P = 0·02, respectively) and TB pleural effusion and lymphadenopathy remained the same. This study shows a reduction of EPTB cases that is similar to that of PTB in the context of the ART scale-up. The changing profile of EPTB warrants attention of healthcare workers.

Malnourished HIV-infected patients starting antiretroviral therapy (ART) are at high risk of early mortality, some of which may be attributed to altered electrolyte metabolism. We used data from a randomised controlled trial of electrolyte-enriched lipid-based nutritional supplements to assess the association of baseline and time-varying serum phosphate and K concentrations with mortality within the first 12 weeks after starting ART. Baseline phosphate results were available from 1764 patients and there were 9096 subsequent serum phosphate measurements, a median of 6 per patient. For serum K there were 1701 baseline and 8773 subsequent measures, a median of 6 per patient. Abnormally high or low serum phosphate was more common than high or low serum K. Controlling for other factors found to affect mortality in this cohort, low phosphate which had not changed from the previous time interval was associated with increased mortality; the same was not true for high phosphate or for high or low K. Both increases and decreases in serum electrolytes from the previous time interval were generally associated with increased mortality, particularly in the electrolyte-supplemented group. The results suggest that changes in serum electrolytes, largely irrespective of the starting point and the direction of change, were more strongly associated with mortality than were absolute electrolyte levels. Although K and phosphate are required for tissue deposition during recovery from malnutrition, further studies are needed to determine whether specific supplements exacerbate physiologically adverse shifts in electrolyte levels during nutritional rehabilitation of ill malnourished HIV patients.

Anaemia, redistribution of Fe, malnutrition and heightened systemic inflammation during HIV infection confer an increased risk of morbidity and mortality in HIV patients. We analysed information on Fe status and inflammation from a randomised, double blind, controlled phase-III clinical trial in Lusaka, Zambia and Mwanza, Tanzania. Malnourished patients (n 1815) were recruited at referral to antiretroviral therapy (ART) into a two-stage nutritional rehabilitation programme, randomised to receive a lipid-based nutrient supplement with or without added micronutrients. Fe was included in the intervention arm during the second stage, given from 2 to 6 weeks post-ART. Hb, serum C-reactive protein (CRP), serum ferritin and soluble transferrin receptor (sTfR) were measured at recruitment and 6 weeks post-ART. Multivariable linear regression models were used to assess the impact of the intervention, and the effect of reducing inflammation from recruitment to week 6 on Hb and Fe status. There was no effect of the intervention on Hb, serum ferritin, sTfR or serum CRP. A one-log decrease of serum CRP from recruitment to week 6 was associated with a 1·81 g/l increase in Hb (95 % CI 0·85, 2·76; P< 0·001), and a 0·11 log decrease in serum ferritin (95 % CI − 0·22, 0·03; P= 0·012) from recruitment to week 6. There was no association between the change in serum CRP and the change in sTfR over the same time period (P= 0·78). In malnourished, HIV-infected adults receiving dietary Fe, a reduction in inflammation in the early ART treatment period appears to be a precondition for recovery from anaemia.