Expert Consensus Statement on an Updated Definition of Unintended Weight Loss Among Persons With Human Immunodeficiency Virus in the Modern Treatment Era.

The era of modern antiretroviral therapy (ART) has markedly improved health and survival among persons with human immunodeficiency virus (HIV) (PWH). In the pre-ART era, wasting was associated with HIV disease progression to acquired immunodeficiency syndrome and death. Effective ART has reduced the prevalence and incidence of this pre-ART form of HIV-associated wasting. However, a subgroup of ART-treated virally suppressed PWH continue to lose weight, often accompanied by aging-related comorbidities and/or functional deficits. For this subgroup of patients, the older definition of HIV-associated wasting (HIVAW) cannot and should not be applied. An expert panel comprising the authors of this white paper convened to review the existing definition of HIVAW and to create an updated definition that they termed HIV-associated weight loss, based on clinically defined parameters among contemporary PWH receiving ART. Here, clinical features and laboratory biomarkers associated with HIV-associated weight loss are reviewed and approaches to screening and treatment are considered. Available management approaches, including the use of current US Food and Drug Administration-approved medications for HIVAW and other available therapies are discussed. The expert panel also identified knowledge gaps and provided recommendations for clinicians, payers, and researchers.

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.

The effects of an ActRIIb receptor Fc fusion protein ligand trap in juvenile simian immunodeficiency virus-infected rhesus macaques.

There are no approved therapies for muscle wasting in children infected with human immunodeficiency virus (HIV), which portends poor disease outcomes. To determine whether a soluble ActRIIb receptor Fc fusion protein (ActRIIB.Fc), a ligand trap for TGF-ß/activin family members including myostatin, can prevent or restore loss of lean body mass and body weight in simian immunodeficiency virus (SIV)-infected juvenile rhesus macaques (Macaca mulatta). Fourteen pair-housed, juvenile male rhesus macaques were inoculated with SIVmac239 and, 4 wk postinoculation (WPI) treated with intramuscular injections of 10 mg ⋅ kg(-1) ⋅ wk(-1) ActRIIB.Fc or saline placebo. Body weight, lean body mass, SIV titers, and somatometric measurements were assessed monthly for 16 wk. Age-matched SIV-infected rhesus macaques were injected with saline. Intervention groups did not differ at baseline. Gains in lean mass were significantly greater in the ActRIIB.Fc group than in the placebo group (P < 0.001). Administration of ActRIIB.Fc was associated with greater gains in body weight (P = 0.01) and upper arm circumference than placebo. Serum CD4(+) T-lymphocyte counts and SIV copy numbers did not differ between groups. Administration of ActRIIB.Fc was associated with higher muscle expression of myostatin than placebo. ActRIIB.Fc effectively blocked and reversed loss of body weight, lean mass, and fat mass in juvenile SIV-infected rhesus macaques.

[Wasting syndrome in HIV-infected patients].

The review of literature analyzes scientific data on wasting syndrome in HIV-infected patients. It considers its etiology, diagnosis,and therapeutic approaches.

A Case of Hypercalcemia and Overexpression of CYP27B1 in Skeletal Muscle Lesions in a Patient with HIV Infection After Cosmetic Injections with Polymethylmethacrylate (PMMA) for Wasting.

Foreign body-induced granuloma is an uncommon yet clinically significant cause of hypercalcemia. The molecular mechanisms are uncertain, although extrarenal calcitriol production has been proposed. We describe severe hypercalcemia associated with increased levels of plasma calcitriol in a patient with HIV and local granulomatous reaction 5 years after injection of polymethylmethacrylate (PMMA) as dermal filler for cosmetic body sculpting. Extensive evaluation revealed no identifiable cause of increased calcitriol levels. Nuclear imaging was remarkable for diffuse uptake in the subcutaneous tissues of the buttocks. Subsequent muscle biopsy and immunohistochemical staining showed strong local expression of CYP27B1 within histiocytes surrounding globules of PMMA. This case highlights an unfortunate complication of dermal fillers and shows that inflammatory cells can express high levels of CYP27B1 even without frank granulomas. The growing trend of body contour enhancement using injectable fillers should raise suspicion for this cause of hypercalcemia in clinical practice. Patients with HIV who receive this treatment for lipodystrophy or other cosmetic purposes may have increased susceptibility to hypercalcemia in the setting of underlying chronic inflammation. This may be a concern when changing anti-retroviral therapy, since alterations in levels of HIV viremia may initiate or contribute to worsening hypercalcemia.

Human Immunodeficiency Virus Infection and Male Hypogonadism: A Review.

Hypogonadism is a common complication among HIV infected patients. The prevalence of hypogonadism is 30 to 50% in HIV infected men with wasting syndrome and 20 to 25% in those without wasting syndrome. HIV infection affects the entire hypothalamus-pituitary-gonadal axis via both direct and indirect effects, which are defined in four categories, 1) direct effect of HIV particles, 2) opportunistic infections, 3) HIV-related malignancy and its treatment, and 4) medications that are used for HIV infection or its opportunistic infection. The association between HIV infection, hypogonadism, and cardiovascular diseases has yet to be determined; however, there are data that HIV infection and its treatment, particularly protease inhibitors, worsened the metabolic profiles, which were surrogate markers of cardiovascular diseases. Considerably more attention should be paid to the diagnosis of hypogonadism in this group particularly because HIV infection increases both sex hormone-binding globulin and total testosterone level. Testosterone replacement shows benefits on mood, body composition, and seems to benefit the metabolic profile in HIV infected men with low body mass index.

The CD4:CD8 ratio is associated with markers of age-associated disease in virally suppressed HIV-infected patients with immunological recovery.

OBJECTIVES: Inversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response. METHODS: A cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/µL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height(2) (ALM) measured by dual-energy X-ray absorptiometry (DEXA)]. RESULTS: CD4:CD8 ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2-7.1], arterial stiffness (OR 4.8; 95% CI 1.0-23.5) and lower eGFR (OR 5.2; 95% CI 1.0-64.4), but not sarcopenia (OR 0.7; 95% CI 0.2-2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/µL and those with CD4 counts > 500 cells/µL. CONCLUSIONS: The CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions.

Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: prospective cohort study.

BACKGROUND: Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment. METHODS: In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months. RESULTS: Men with wasting at baseline regained LMI at a greater rate than FMI (4.55 kg/m2 (95% confidence interval (CI): 1.26, 7.83 versus 3.16 (95% CI: 0.80, 5.52)) per month, respectively during initial tuberculosis therapy. In contrast, women with wasting regained FMI at greater rate than LMI (3.55 kg/m2 (95% CI: 0.40, 6.70) versus 2.07 (95% CI: -0.74, 4.88)), respectively. Men with wasting regained BMI at a rate of 6.45 kg/m2 (95% CI: 3.02, 9.87) in the first three months whereas women, had a rate of 3.30 kg/m2 (95% CI: -0.11, 6.72). There were minimal changes in body composition after month 3 and during months 12 to 24. CONCLUSION: Wasted tuberculosis patients regain weight with treatment but the type of gain differs by gender and patients may remain underweight after the initial phase of treatment.

Maternal mortality among HIV-infected pregnant women in Tanzania.

OBJECTIVE: To investigate risk factors for maternal mortality among HIV-infected women in Tanzania. DESIGN: Prospective cohort study. SETTING: HIV care and treatment clinics in Dar es Salaam, Tanzania. POPULATION: HIV-infected pregnant women. METHODS: Data were collected for all patients enrolled in an HIV/AIDS care and treatment program. Between November 2004 and September 2011, there were 18 917 women pregnant at least once during the follow-up. Thirteen percent of these women had more than one pregnancy, with 21 645 pregnancies occurring. Logistic regression was used to explore the predictors of maternal death among these women. MAIN OUTCOME MEASURES: Maternal mortality. RESULTS: During the study period, 363 maternal deaths occurred, giving a maternal mortality ratio of 1729 [95% confidence interval (CI) 1553-1905] per 100 000 live births. Being wasted [odds ratio (OR) 3.38, 95% CI 2.58-4.45] or anemic (OR 2.26, 95% CI 1.70-3.00) was associated with a higher risk of maternal mortality. Women who were initiated on antiretroviral therapy before their pregnancy had a 55% decreased risk of maternal mortality (95% CI 0.29-0.70) compared with women who were not. The risk of maternal mortality decreased with the length of time on antiretroviral therapy during pregnancy, by 8% for each additional month (OR 0.92, 95% CI 0.88-0.96). CONCLUSIONS: Maternal mortality was high among HIV-infected women. Initiating women on antiretroviral therapy as early as possible and providing nutritional interventions during pregnancy should be considered as means to reduce the maternal mortality among these women.

Vitamin D status and incidence of pulmonary tuberculosis, opportunistic infections, and wasting among HIV-infected Tanzanian adults initiating antiretroviral therapy.

BACKGROUND: Maintaining vitamin D sufficiency may decrease the incidence of pulmonary tuberculosis and other infectious diseases. We present the first prospective study of vitamin D among human immunodeficiency virus (HIV)-infected adults receiving antiretrovirals in sub-Saharan Africa. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) level was assessed at antiretroviral therapy (ART) initiation for 1103 HIV-infected adults enrolled in a trial of multivitamins (not including vitamin D) in Tanzania. Participants were prospectively followed at monthly visits at which trained physicians performed a clinical examination and nurses took anthropometric measurements and assessed self-reported symptoms. Cox proportional hazards models estimated hazard ratios (HRs) of morbidity outcomes. RESULTS: After multivariate adjustment, vitamin D deficiency (defined as a concentration of <20 ng/mL) had a significantly greater association with incident pulmonary tuberculosis, compared with vitamin D sufficiency (HR, 2.89; 95% confidence interval [CI], 1.31-7.41; P = .027), but no association was found for vitamin D insufficiency (defined as a concentration of 20-30 ng/mL; P = .687). Deficiency was also significantly associated with incident oral thrush (HR, 1.96; 95% CI, 1.01-3.81; P = .046), wasting (HR, 3.10; 95% CI, 1.33-7.24; P = .009), and >10% weight loss (HR, 2.10; 95% CI, 1.13-3.91; P = .019). Wasting results were robust to exclusion of individuals experiencing pulmonary tuberculosis. Vitamin D status was not associated with incident malaria, pneumonia, or anemia. CONCLUSIONS: Vitamin D supplementation trials for adults receiving ART appear to be warranted.

HIV enteropathy and 'Slim disease': Historical and current perspectives.

OBJECTIVES: Chronic diarrhoea and severe wasting associated with HIV infection were first described in East African patients as slim disease (SD) in 1985. The main histological features are flattening of the villi (villous atrophy) and crypt hyperplasia (elongated crypts), i.e., HIV enteropathy (HIVE). Selective loss of mucosal clusters of differentiation 4 (CD4)+ T helper (Th)17+ lymphocytes is the immunological hallmark of HIVE. This review explores (i) the historical background of HIVE and SD, (ii) the relationship between gut mucosal CD4+ Th17+ and intestinal-resident intra-epithelial gamma delta (IRIE) T lymphocytes in pathogenesis of HIVE, (iii) the role of cytokines in regulation of intestinal epithelial proliferation, and (iv) the role of antiretroviral therapy in HIVE. METHODS: Recent studies have highlighted the role of IRIE T lymphocytes, mostly CD8+, in regulating gut epithelial regeneration. CD4+Th17+ and IRIE T cells are necessary to maintain intestinal barrier integrity and mucosal antimicrobial immune defence. However, the immunological cross-talk between such lymphocyte sub-sets culminating in HIVE is uncertain. We undertook a narrative literature review under the headings 'HIVE', 'SD', and 'Highly active antiretroviral therapy (HAART). Relevant studies were located using the electronic search engines Google Scholar and PubMed from 1984 to 2022. RESULTS: Depletion of Th17+ cells in the lamina propria, attributed to low-level viraemia, is accompanied by concomitant increase in the density of gut mucosal IRIE T lymphocytes in AIDS. The latter express a broad range of cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-17) and chemokines e.g., keratinocyte growth factor, post exposure to HIV-infected cells. Keratinocyte growth factor induces epithelial proliferation mainly in the crypts, leading to functional immaturity of enterocytes, reduced gut absorptive surface area and malabsorption in animal experiments. Of note, the absence of IRIE T cells is associated with a reduction in epithelial cell turnover. Patients with HIVE receiving early HAART show enhanced expression of mucosal repair genes and improvement of gut symptoms. CONCLUSION: Multiple lines of enquiry suggest HIVE is directly related to HIV infection and is a consequence of perturbations in mucosal CD4+Th17+ and IRIE T lymphocytes. The pathological result is enterocyte immaturity and dysfunction. SD whose main features are malabsorption, diarrhoea and weight loss, is a severe clinical expression of HIVE. A better understanding of immuno-pathogenesis of HIVE opens a window of opportunity for the potential use of immunotherapy in HIV disease and other T cell-mediated enteropathies.

Incident HIV-Associated Wasting/Low Weight Is Associated with Nearly Doubled Mortality Risk in the Modern ART Era.

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016-2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death.

[Prevalence of Encephalitozoon intestinalis and Enterocytozoon bieneusi in HIV positive patients to Maracaibo, Venezuela]. / Prevalencia de Encephalitozoon intestinalis y Enterocytozoon bieneusi en pacientes VIH positivos de Maracaibo, Venezuela.

Microsporidioses are considered emerging and opportunistic infections in immunocompromised individuals worldwide. The purpose of this study was to identify the species of intestinal microsporidia in patients with HIV-AIDS from the Servicio Autónomo Hospital Universitario de Maracaibo, Venezuela (SAHUM). Fecal samples were collected from 50 patients with confirmed diagnosis of HIV, during the years 2007 and 2008; the CD4 values were obtained from 42 patients. The samples were analyzed by separate PCRs to identify Encephalitozoon intestinalis and Enterocytozoon bieneusi. Microsporidia species showed a 36% prevalence: ten patients had Encephalitozoon intestinalis, four Enterocytozoon bieneusi and four both species. An inverse and statistically significant relationship between the CD4 count and the presence of microsporidia in the fecal sample was also found. It is remarkable the high prevalence of microsporidia species observed in the HIV patients studied, with a predominance of E. intestinalis.

Prognostic value of indeterminate IFN-γ release assay results in HIV-1 infection.

In this prospective, longitudinal study on 948 HIV-1-infected patients, subjects with an indeterminate IFN-γ (gamma interferon) release assay (IGRA) result at baseline were at significantly higher risk of developing AIDS-defining manifestations other than tuberculosis (TB) irrespective of CD4(+) T cell count. Thus, in HIV-1-infected patients with advanced quantitative CD4(+) T cell depletion, an indeterminate IGRA might indicate an additional loss of global T cell function, warranting detailed clinical evaluation and careful follow-up.

Does HIV infection affect growth and puberty of Cameroonian children?

OBJECTIVES: This study aimed to describe growth and pubertal development of adolescents with HIV infection under highly active antiretroviral therapy (HAART) in Cameroon. DESIGN: Through an observational study, we included 74 adolescents aged 9-17 years who were taking HAART and had attended two care units in Cameroon for at least 6 months. Weight and height were measured and transferred to 2007 WHO curves for 5- to 19-year-olds. Stunting was defined by a height for age z-score less than -2 standard deviations. Wasting was defined by a BMI z-score for age less than -2 standard deviations. Pubertal development was assessed using Tanner stages. We looked into the association between HIV infection characteristics, HAART regimen, and growth/puberty abnormalities with multivariate analysis. The Mann-Whitney U-test was used to compare median values with a p-value ≤0.05. RESULTS: The median age was 13 (11.2-14.7) years. Stunting affected 44% of the children. Wasting affected 9.7% of the adolescents. The age at onset of puberty was in the normal range in both boys and girls. Adolescents aged 12-14 years (OR 3.4 [95% CI, 1.3-8.8], p=0.012) with a past history of opportunistic infection and taking HAART with protease inhibitors were more likely to have stunting. CONCLUSION: In the Cameroonian setting, growth was mainly affected by stunting, but pubertal development was normal in all patients. This may reflect the benefits of HAART in children with HIV infection.

Under-nutrition and associated factors among children on ART in Southern Ethiopia: a facility-based cross-sectional study.

BACKGROUND: Malnutrition is very common in HIV-infected individuals. Even though data from different settings are necessary to tackle it, pieces of evidence are limited especially in the case of the nutritional status of HIV-infected children. Hence, this study aims to assess the nutritional status and associated factors among children on antiretroviral therapy. METHODS: An institutional-based cross-sectional study was conducted among 383 HIV-positive children in Southern Ethiopia. Data were collected using an interviewer-administered questionnaire and anthropometry measurement. Data were coded and entered into Epi-Data Version 3.1 and analyzed using SPSS Version 25. Bi-variable and multi-variable binary logistic regression models were used to identify factors associated with nutritional status and variables with p-values <0.05 in multi-variable logistic regression were considered as statistically significant. RESULTS: The prevalence of wasting among HIV-positive children in Southern Ethiopiaselected Hospitals was 36.3% (95% CI, 31.6-41.0) while stunting on the same study population was 5.5% (95% CI, 3.4-7.8). Rural residence, lack of maternal education, low CD4 counts (< 500), using an unprotected water source, having a non-biological mother and recurrent oral lesion were significantly associated with wasting. Furthermore, history of hospital admission, recurrent oral lesion, low CD4 counts (< 500), advanced WHO clinical stage were statically associated with stunting with p-value < 0.05. CONCLUSION: This study found that the prevalence of under-nutrition among HIV-positive children in Ethiopia was significantly high. Therefore, timely identification and monitoring of nutritional problems should be necessary to enhance the effectiveness of ART treatment and to prevent further related complications.

Therapeutic effects of nandrolone and testosterone in adult male HIV patients with AIDS wasting syndrome (AWS): a randomized, double-blind, placebo-controlled trial.

PURPOSE: We aimed to compare therapeutic effects of intramuscular (IM) nandrolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome (AWS) with placebo control. METHODS: In this randomized, double-blind, placebo-controlled, 12-week trial, 104 patients with AWS who satisfied our inclusion criteria were randomly allotted in a 2:2:1 ratio to the 3 intervention groups: nandrolone, testosterone, and placebo. We administered 150 mg nandrolone and 250 mg testosterone (both IM, biweekly). The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the nandrolone decanoate, testosterone, and placebo groups. RESULTS: Intent-to-treat analysis was done. The nandrolone group recorded maximum mean increase in weight (3.20 kg; post hoc P < .01 compared to placebo). Body mass index (BMI) of subjects in the nandrolone group had a significantly greater increase (mean = 1.28) compared to both testosterone (post hoc P < .05) and placebo (post hoc P < .01). Waist circumference and triceps skinfold thickness of patients on nandrolone showed similar results. Nandrolone also ensured a better quality of life. Patients with low testosterone level (<3 ng/mL) benefited immensely from nandrolone therapy, which increased their weight and BMI significantly compared to placebo (P < .05). CONCLUSION: Our trial demonstrates the superior therapeutic effects of nandrolone in male AWS patients, including the androgen deficient.

The benefit of supplementary feeding for wasted Malawian adults initiating ART.

Food insecurity is considered to be an important contributor to HIV associated wasting in sub-Saharan Africa. Low body mass index (BMI) is a strong risk factor for early mortality during antiretroviral therapy (ART). Nutritional supplementation has become standard of care in wasted patients starting ART in many countries in the region, but there is no unequivocal evidence base for this intervention. Against this background, we performed a retrospective study to compare food supplementation versus no nutritional intervention in wasted adults starting ART in Blantyre, Malawi. All patients received free nevirapine, lamivudine, and stavudine. Participants in an effectiveness trial of two food supplements received either corn-soy blend (CSB) or ready-to-use food spread (RUFS) during the first 14 weeks of ART. Results were compared with a historical control group receiving no food supplement that was part of an observational cohort study of outcomes of the same ART regimen. Characteristics on initiation of ART were similar in the three groups, except the use of cotrimoxazole prophylaxis which was more frequent in the food-supplemented groups. Linear regression analysis showed that increase in BMI was greatest in the RUFS group and better in the CSB group than in those receiving no food supplementation at 14 weeks. These differences were no longer significant at 26 weeks. Lower BMI, CD4 count and hemoglobin, WHO clinical stage IV, male gender, and not receiving cotrimoxazole prophylaxis were independent risk factors for mortality at 14 and 26 weeks in the logistic regression analysis. Supplementary food use was not directly associated with improved survival.

Magnitude of underweight, wasting and stunting among HIV positive children in East Africa: A systematic review and meta-analysis.

BACKGROUND: Malnutrition on the background of HIV (Human Immunodeficiency Virus) infection is a complex medical condition that carries significant morbidity and mortality for affected children, with greater mortality from SAM (Severe Acute Malnutrition) among HIV-positive children than their HIV-negative peers. HIV-induced immune impairment heightened risk of opportunistic infection and can worsen nutritional status of children. HIV infection often leads to nutritional deficiencies through decreased food intake, mal-absorption and increased utilization and excretion of nutrients, which in turn can hasten death. OBJECTIVE: The aim of this systematic review and meta-analysis was to assess the magnitude of underweight, wasting and stunting among HIV positive children in East Africa. METHODS: The authors systematically reviewed and meta-analyzed studies that assessed the prevalence of underweight, wasting and stunting among HIV positive children in East Africa from PubMed, Cochrane Library, Google Scholar, and Gray Literatures using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline. The last search date was December 30/2019. The data was extracted in excel sheet considering country, study design, year of publication, prevalence reported. Then the authors transformed the data to STATA 14 for analysis. Heterogeneity across the studies was assessed by the Q and the I2 test. A weighted inverse variance random-effects model was used to estimate the magnitude of underweight, wasting and stunting. The subgroup analysis was done by country, year of publication, and study design. To examine publication bias, a funnel plot and Egger's regression test were used. RESULTS: For the analysis a total of 22 studies with 22074 patients were used. The pooled prevalence of under-weight, wasting, and stunting among HIV positive children in East Africa was found to be 41.63% (95%CI; 35.69-47.57; I2 = 98.7%; p<0.001), 24.65% (95%CI; 18.34-30.95; I2 = 99.2%; p<0.001), and 49.68% (95%CI; 42.59-56.77; I2 = 99.0%; p<0.001) respectively. The prevalence of under-weight among HIV positive children was found to be 49.67% in Ethiopia followed by 42.00 in Rwanda. It was high among cohort studies (44.87%). Based on the year of publication, the prevalence of under-weight among HIV positive children was found to be 40.88% from studies conducted from January 2008-December 2014, while it was 43.68% from studies conducted from 2015-2019. The prevalence of wasting among HIV positive children was found to be 29.7% in Tanzania followed by 24.94% in Ethiopia. Based on the study design, the prevalence of wasting among HIV positive children was found to be high in cohort studies (31.15%). The prevalence of stunting among HIV positive children was found to be 51.63% in Ethiopia, followed by 48.21% in Uganda. CONCLUSIONS: The results presented above provide evidence of a higher prevalence of under nutrition among HIV positive children in East Africa. Despite the country level variations of child under nutrition in East Africa, still it is high in all aspects compared to the studies from other parts of Africa. It is recommended that further systematic review and meta-analysis need to be conducted on magnitude of malnutrition among HIV positive children in Sub-Saharan Africa as a whole.

Macronutrient supplementation for malnourished HIV-infected adults: a review of the evidence in resource-adequate and resource-constrained settings.

Access to antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection has expanded rapidly throughout sub-Saharan Africa, but malnutrition and food insecurity have emerged as major barriers to the success of ART programs. Protein-calorie malnutrition (a common form of malnutrition in the region) hastens HIV disease progression, and food insecurity is a barrier to medication adherence. Analyses of patient outcomes have identified a low body mass index after the start of ART as an independent predictor of early mortality, but the causes of a low body mass index are multifactorial (eg, normal anthropometric variation, chronic inadequate food intake, and/or wasting associated with HIV infection and other infectious diseases). Although there is much information on population-level humanitarian food assistance, few data exist to measure the effectiveness of macronutrient supplementation or to identify individuals most likely to benefit. In this report, we review the current evidence supporting macronutrient supplementation for HIV-infected adults, we report on clinical trials in resource-adequate and resource-constrained settings, and we highlight priority areas for future research.