Factors associated with insulin resistance in a longitudinal study of Ugandan youth with and without HIV.

Prospective investigations from sub-Saharan Africa on metabolic complications in youth with perinatally acquired HIV (PHIV) are lacking. We investigated the changes in insulin resistance in Ugandan PHIV on ART and uninfected controls and their relationship with inflammation, HIV, and cardiovascular disease (CVD) risk factors. Participants 10-18 years of age were included in a prospective study performed in Kampala, Uganda. We compared baseline and changes in insulin resistance (by HOMA-IR) and in markers of inflammation at baseline and 96 weeks. PHIVs were on ART with HIV-1 RNA level 400 copies/ml or less. Generalized Estimating Equation models were used to assess associations between HOMA-IR, and demographic as well as inflammatory markers. Of the 197 participants recruited at baseline (101 PHIV, 96 HIV-negative), 168 (89 PHIV, 79 HIV-negative) had measurements at 96 weeks. At baseline, median (Q1, Q3) age was 13 years (11,15), 53.5% were women, median CD4 + cell counts were 988 cells/µl (631, 1310). At baseline, HOMA-IR was significantly higher in PHIV than in controls ( P  = 0.03). HOMA-IR did not significantly change by week 96 in either group, and at 96 weeks, was similar between groups ( P  = 0.15). HOMA-IR was not associated with any inflammatory markers, or any specific ART. In longitudinal analysis, age and Tanner stage remained associated with higher HOMA-IR throughout the study period, after adjusting for HIV status. In this longitudinal cohort of virally suppressed PHIV in Uganda, PHIV have decreased insulin sensitivity compared to controls, however this difference does not persist through adolescence. ART and immune activation do not appear to affect glucose homeostasis in this population.

Depression, suicidality, substance-use and associated factors among people living with HIV the COVID-19 pandemic in Uganda.

BACKGROUND: Mental disorders are common in people living with HIV (PLHIV) but they are often unrecognized and untreated. Furthermore, the COVID-19 pandemic has disrupted the already limited mental health services in low resource countries such as Uganda, and yet the extent to which the COVID-19 mitigation measures have affected the mental health of PLHIV is not fully known. We aimed to determine the burden of depression, suicidality, substance use and associated factors among adult PLHIV who were seeking care at two HIV clinics in northern and southwestern Uganda. METHODS: We conducted a phenomenological qualitative and quantitative cross-sectional study among 431 PLHIV to determine the burden of depression, suicidality and substance-use disorders at two HIV clinics, at Lira Regional Referral Hospital and Mbarara Regional Referral Hospital in northern and southwestern Uganda respectively, during the COVID-19 lockdown. We used the Patient Health Questionnaire (PHQ-9) to assess for depression and suicidality, and the Michigan Assessment-Screening Test for Alcohol and drugs (MAST-AD) to assess for substance use disorder. We conducted descriptive statistics analysis to determine the burden of the disorders, and logistic regression to determine the associated factors. For the qualitative method we conducted in-depth interviews with 30 PLHIV and did thematic analysis. RESULTS: Of the 431 PLHIV surveyed, mean age was 40.31 ± 12.20 years; 53.1% (n = 229) had depression; 22.0% (n = 95) had suicidality; and 15.1% (n = 65) had substance-use disorder. Female gender (PR = 1.073, 95%CI 1.004-1.148, P = 0.038), lack of formal education (PR = 1.197, 95% CI 1.057-1.357, P = 0.005), substance-use disorder (PR = 0.924, 95%CI 0.859-0.994, P = 0.034) and suicidality (PR = 0.757, 95%CI 0.722-0.794, p = 0.000) were associated with depression after adjusting for confounders. Further analysis showed that being female (PR = 0.843, 95% CI 0.787-0.903, P = 0.000*) and having depression (PR = 0.927, 95% CI 0.876-0.981, P = 0.009) and owning a large business (PR = 0.886, 95% CI 0.834-0.941, p = 0.000*) were significantly associated with having a substance-use disorder. Only depression was independently associated with suicidality after adjusting for confounding factors (PR 0.108, 95%CI 0.054-0.218, p = 0.000*). For the qualitative results, there were three apriori themes: a) Burden of depression, b) substance-use, and c) suicidality among the PLHIV during the COVID-19 containment measures. CONCLUSION: There was high prevalence of depression, suicidality and substance-use disorder in adult PLHIV in Uganda during the COVID-19 pandemic and the associated lockdown measures. The three mental health problems seem to have bidirectional relationships and gender has a lot of contribution to the relationships. Interventions aimed at any of the disorders should consider these bidirectional relationships.

Persistent immune activation and altered gut integrity over time in a longitudinal study of Ugandan youth with perinatally acquired HIV.

Introduction: Perinatally acquired HIV infection (PHIV) occurs during a critical window of immune development. We investigated changes in systemic inflammation and immune activation in adolescents with PHIV and those without HIV (HIV-) in Uganda. Methods: A prospective observational cohort study was performed in 2017-2021 in Uganda. All participants were between 10-18 years of age and without active co-infections. PHIVs were on ART with HIV-1 RNA level ≤400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4+ and CD8+), oxidized LDL, markers of gut integrity and fungal translocation. Groups were compared using Wilcoxon rank sum tests. Changes from baseline were examined with 97.5% confidence intervals on relative fold change. P values were adjusted for false discovery rate. Results: We enrolled 101 PHIV and 96 HIV-; among these, 89 PHIV and 79 HIV- also had measurements at 96 weeks. At baseline, median (Q1, Q3) age was 13 yrs (11,15), and 52% were females. In PHIV, median CD4+ cell counts were 988 cells/µL (638, 1308), ART duration was 10 yrs (8, 11), and 85% had viral load <50 copies/mL throughout the study, 53% of participants had a regimen switch between visits, 85% of whom switched to 3TC, TDF and DTG. Over 96 weeks, while hsCRP decreased by 40% in PHIV (p=0.12), I-FABP and BDG both increased by 19 and 38% respectively (p=0.08 and ≤0.01) and did not change in HIV- (p≥0.33). At baseline, PHIVs had higher monocyte activation (sCD14) (p=0.01) and elevated frequencies of non-classical monocytes (p<0.01) compared to HIV- which remained stable over time in PHIV but increased by 34% and 80% respectively in HIV-. At both time points, PHIVs had higher T cell activation (p ≤ 0.03: CD4+/CD8+ T cells expressing HLA-DR and CD38). Only in PHIV, at both timepoints, oxidized LDL was inversely associated with activated T cells(p<0.01). Switching to dolutegravir at week 96 was significantly associated an elevated level of sCD163 (ß=0.4, 95% CI=0.14,0.57, p<0.01), without changes in other markers. Conclusion: Ugandan PHIV with viral suppression have some improvement in markers of inflammation over time, however T-cell activation remains elevated. Gut integrity and translocation worsened only in PHIV over time. A deeper understanding of the mechanisms causing immune activation in ART treated African PHIV is crucial.

Behavioral and psycho-social impairments among people living with dementia and their management by caregivers in South-Western Uganda: a qualitative study.

OBJECTIVES: This study aimed to explore the behavioral and social impairments among people living with dementia (PLWD) in rural southwestern Uganda. It also explored the burden of caregivers for people living with dementia. METHODS: This was a qualitative study among people living with dementia and their caregivers. We consecutively enrolled 30 people living with dementia with their caregivers from their homes. We conducted in-depth interviews using a semi-structured interview guide. We did a thematic content analysis. RESULTS: The themes under-reported behavioral impairment were; difficulty in personal care, physical inactivity, and impaired judgment. Under the social and cognitive impairment theme, there was the failure to be in social gatherings like church, community groups, and markets. Under the caregivers' role, their burden included managing behavioral, social, and cognitive impairments of PLWD. Although caregivers were committed to caring for PLWDs, this required sacrificing time at the expense of income-generating activities. CONCLUSIONS: Dementia hinders the behavioral and social aspects of the affected people. Caregivers are highly burdened to care for PLWD. Strategies to minimize caregivers' burden while caring for people living with dementia are recommended.

Longitudinal Changes in Subclinical Vascular Disease in Ugandan Youth With Human Immunodeficiency Virus.

BACKGROUND: Prospective investigations on the risk of cardiovascular disease among youth with perinatally acquired human immunodeficiency virus (PHIV) in sub-Saharan Africa are lacking. METHODS: A prospective observational cohort study was performed in 101 youth (aged 10-18 years) with PHIV and 97 who were human immunodeficiency virus (HIV) uninfected (HIV-), from 2017 to 2021 at the Joint Clinical Research Center in Uganda. Participants with PHIV were receiving antiretroviral therapy (ART) and had HIV-1 RNA levels ≤400 copies/mL. The common carotid artery intima-media thickness (IMT) and pulse wave velocity (PWV) were evaluated at baseline and at 96 weeks. Groups were compared using unpaired t-test, and potential predictors of IMT and PWV were assessed using quantile regression. RESULTS: Of the 198 participants recruited at baseline, 168 (89 with PHIV, 79 HIV-) had measurements at 96 weeks. The median age (interquartile range) age was 13 (11-15) years; 52% were female, and 85% had viral loads <50 copies/mL that remained undetectable at week 96. The baseline mean common carotid artery IMT was slightly higher in participants with PHIV compared with controls (P < .01), and PWV did not differ between groups (P = .08). At week 96, IMT decreased and PWV increased in the PHIV group (P ≤ .03); IMT increased in the HIV- group (P = .03), with no change in PWV (P = .92). In longitudinal analyses in those with PHIV, longer ART duration was associated with lower PWV (ß = .008 [95% confidence interval, -.008 to .003]), and abacavir use with greater IMT (ß = .043 [.012-.074]). CONCLUSIONS: In healthy Ugandan youth with PHIV, virally suppressed by ART, the common carotid artery IMT did not progress over 2 years. Prolonged and early ART may prevent progression of subclinical vascular disease, while prolonged use of abacavir may increase it.

Impact of COVID-19 on Well-Being and Physical Activity in Ugandan Children With and Without HIV.

BACKGROUND: The present study aims to understand the socioeconomic and physical activity impact of the COVID-19 pandemic on children living with perinatally acquired HIV (PHIV) and without HIV (HIV-) in Kampala (Uganda). METHODS: The authors included children aged 10-18 years who filled out questionnaires at baseline (2017-2018, prepandemic) and 2 years later (March 2020-January 2021, pandemic) in an observational cohort study at Joint Clinical Research Centre (Kampala). Physical activity energy expenditure was calculated using a youth compendium from the National Collaborative on Childhood Obesity Research. Descriptive and standard test statistics including Kruskal-Wallis were used. RESULTS: One hundred and ninety-eight children from Kampala Uganda were included prepandemic (101 PHIV and 97 HIV-); 131 (71 PHIV and 60 HIV-) had information collected during the pandemic. At baseline, median and interquartile range age was 13 years (11; 15), and 52% were females. During the pandemic, overall weekly physical activity increased by a median of 854 minutes (interquartile range: 270-1890), and energy expenditures increased by 16% in both PHIV and in HIV- (P < .001 for groups overall prepandemic vs pandemic). CONCLUSIONS: The authors found in this Ugandan cohort of children that children engaged in more physical activity. Further research is warranted to understand the long-term effects of the pandemic on children's well-being.

Perceptions of Undergraduates and Mentors on the Appropriateness, Acceptability, and Feasibility of the HEPI-TUITAH Micro-Research Approach to HIV Training in Uganda.

Purpose: To evaluate the perceptions of undergraduates and mentors on the appropriateness, acceptability, and feasibility of a mentored seed-grant (micro-research) by Health Professions Education Partnership Initiative - Transforming Ugandan Institutions Training Against HIV/AIDS (HEPI-TUITAH) program on HIV training in Uganda. Methods: We conducted a cross-sectional descriptive qualitative study with focus groups, on HIV micro-research training, with undergraduate health professions students and faculty mentors across three partner institutions in rural Uganda. Results: A total of 24 students and 13 mentors (5-8 per group) took part in the focus group discussions. Most participants stated that the HEPI-TUITAH micro-research program was acceptable, appropriate and feasible for health professions undergraduate students. The interprofessional education approach of bringing together students from different programs and years of study was valuable especially for peer mentorship. There was a need to provide for institution-based training in addition to the centrally organized training for the benefit of all the team members. Participants also noted a need for the program to find a way of providing the students with data collection experience even with the COVID-19 pandemic situation. Conclusion: The HEPI-TUITAH micro-research program was perceived as acceptable, appropriate, and feasible for health professions undergraduate students. It also promoted teamwork and academic collaboration. Provision for institution-based micro-research training activities and data collection experiences for the undergraduate students even during the COVID-19 pandemic would make the program more valuable. The lessons learnt will be applied to future training cohorts to optimize program impact and may be useful for similar programs in other settings.

Lay Health Workers in Community-Based Care and Management of Dementia: A Qualitative 'Pre' and 'Post' Intervention Study in Southwestern Uganda.

Background: The global need for efficient and cost-effective use of healthcare resources in low-income countries has led to the introduction of lay health workers (LHWs) as a link of the community to healthcare services. As such, the LHWs perform a variety of tasks such as education, support for care delivery, and social support across all disease types. However, little is known about their ability to support dementia care and management in the community. Purpose: The goal of the pilot intervention was to evaluate the 5-day training intervention for LHWs in rural southwestern Uganda in community-based care and management of people with dementia, and implementation of the knowledge and skills gained. Methods: This was a "pre" and "post" pilot intervention study which involved a qualitative assessment of LHWs' knowledge on community-based management and care for people with dementia. We focused on four core competency domains in the WHO dementia toolkit. The intervention included a five-day training of the LHWs on dementia care, eight weeks of implementation, and an evaluation of the experiences. Analysis focused on the needs assessment, early detection and management, community engagement, support for people with dementia; and evaluation of the eight weeks implementation. Results: Before the training, the LHWs did not know much about what dementia-related support to provide in the community. Activities were limited to general support, including nutrition, and health education. After the training, LHWs had a basic understanding of dementia and began sensitizing the communities. They felt more comfortable working with people with dementia and reported a notable change in the attitude of family members. However, they reported challenges in differentiating the signs of early dementia from superstitious beliefs. Conclusion: With enhanced capacity, LHWs may be able to support community-based management for people with dementia. A larger study is needed to explore potential roles for LHWs and further assess effectiveness of the LHWs' skills.

Mbarara University Research Training Initiative: Experiences and Accomplishments of the MEPI Junior D43 TW010128 Award in Uganda.

OBJECTIVE: In 2015, Mbarara University of Science and Technology was awarded the Mbarara University Research Training Initiative (MURTI) under grant number D43 TW010128 to build capacity of junior faculty to become the next generation of researchers in Africa. In this paper, we document the experiences and achievements of the research capacity building efforts at MUST. METHODS: We conducted a descriptive evaluation study which involved document review and in-depth interviews. We used "Reach" and 'Effectiveness' from the RE-AIM framework to guide the document review, and the organizational theory of implementation effectiveness to guide the in-depth interviews. RESULTS: In the MURTI program, we conducted 17 short courses between August 2015 and July 2021, a total of 6597 attendances were recorded. The most attended courses were responsible conduct of research (n = 826), qualitative research methods (n = 744), and data management (n = 613). Thirty-three fellows were recruited and funded to conduct mentored research leading to 48 publications and 14 extramural grant applications were yielded. From the in-depth interviews, the participants appreciated the research training program, the enhanced research skills attained, and the institutional capacity built. They attributed the success of the program to the training approach of using short courses, readiness of the junior faculty to change, and the supportive environment by the mentors and trainers in the program. CONCLUSION: The D43 TW010128 research training grant-built capacity for the junior faculty at MUST, enhanced their research skills, promoted research capacity institutionally and provided career development for the junior faculty. This was possible due to the positive attitude of the junior faculty (organizational readiness) to change and the supportive environment (mentors and trainers) during implementation of the grant. These two factors provided a favorable institutional climate that guaranteed success of the funding goals.

Increased monocyte and T-cell activation in treated HIV+ Ugandan children: associations with gut alteration and HIV factors.

INTRODUCTION: The pathophysiology of immune activation and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied. METHODS: We enrolled 101 children living with PHIV and 96 HIV-negative controls (HIV-). All participants were between 10 and 18 years of age with no known active infections. PHIVs were on ART with HIV-1 RNA level 400 copies/ml or less. We measured plasma and cellular markers of monocyte activation, T-cell activation (expression of CD38 and HLA-DR on CD4 and CD8), oxidized lipids, markers of gut integrity and fungal translocation. Spearman correlations and linear regression models were used. RESULTS: Overall median (Q1; Q3) age was 13 years (11; 15) and 52% were girls. Groups were similar by age, sex and BMI. Median ART duration was 10 years (8; 11). PHIVs had higher monocyte and T-cell activation; higher sCD14 (P = 0.01) and elevated frequencies of nonclassical monocytes (P < 0.001 for both). Markers of systemic inflammation (hsCRP), fungal translocation (BDG), intestinal permeability (zonulin) and oxidized lipids (ox LDL) correlated with monocyte and T-cell activation in PHIV (≤0.05). After adjusting for age, sex, ART duration, protease inhibitor and nonnucleoside reverse transcriptase inhibitor use, a modest association between BDG and activated CD4 T cells was observed (ß=0.65, P < 0.01). Oxidized LDL was inversely associated with activated T cells, inflammatory and nonclassical monocytes (P < 0.01). CONCLUSION: Ugandan children with perinatally acquired HIV with viral suppression have evidence of ongoing immune activation. Intestinal barrier dysfunction and fungal translocation may be involved in chronic immune dysfunction.

Micronutrients, Metabolic Complications, and Inflammation in Ugandan Children With HIV.

BACKGROUND: Selenium, zinc, and chromium are essential micronutrients. Their alterations have been associated with HIV disease progression, metabolic complications, and mortality. METHODS: This is a cross-sectional study in children with perinatally acquired HIV (PHIV, n = 57), HIV-exposed uninfected (HEU, n = 59), and HIV-unexposed uninfected (HIV-, n = 56) children aged 2 to 10 years old, age- and sex-matched, enrolled in Uganda. PHIV were on stable antiretroviral therapy (ART) with undetectable viral load. We measured plasma concentrations of selenium, zinc, and chromium as well as markers of systemic inflammation, monocyte activation, and gut integrity. RESULTS: Among PHIV children, 93% had viral load ≤20 copies/mL, median CD4 was 37%, and 77% were receiving a nonnucleotide reserve transcriptase regimen. Median age of all participants was 8 years and 55% were girls. Median selenium concentrations were higher in PHIV compared with the HEU and HIV groups (P < 0.001), 46% of children overall had low zinc status (P = 0.18 between groups). Higher selenium, but not chromium or zinc, was associated with lower IL6, sTNFRI and II, and higher beta d glucan, a marker of fungal translocation, zonulin, a marker of gut permeability, oxidized LDL and insulin resistance (P ≤ 0.01). CONCLUSION: In this cohort of PHIV on ART in Uganda, there is a high prevalence of low zinc status overall. Higher plasma selenium concentrations were associated with lower systemic inflammation and higher gut integrity markers. Although our findings do not support the use of micronutrient supplementation broadly for PHIV in Uganda, further studies are warranted to assess the role of selenium supplements in attenuating heightened inflammation.

Altered Intestinal Permeability and Fungal Translocation in Ugandan Children With Human Immunodeficiency Virus.

BACKGROUND: Children with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lifelong cumulative exposure to HIV and antiretroviral therapy (ART). The relationship between gut integrity, microbial translocation, and inflammation in PHIV is poorly understood. METHODS: This is a cross-sectional study in 57 PHIVs, 59 HIV-exposed but uninfected children, and 56 HIV-unexposed and -uninfected children aged 2-10 years old in Uganda. PHIVs were on stable ART with HIV-1 RNA <400 copies/mL. We measured markers of systemic inflammation, monocyte activation, and gut integrity. Kruskal-Wallis tests were used to compare markers by group and the Spearman correlation was used to assess correlations between biomarkers. RESULTS: The mean age of all participants was 7 years and 55% were girls. Among PHIVs, the mean CD4 % was 34%, 93% had a viral load ≤20 copies/mL, and 79% were on a nonnucleoside reverse transcriptase inhibitor regimen. Soluble cluster of differentiation 14 (sCD14), beta-D-glucan (BDG), and zonulin were higher in the PHIV group (P ≤ .01). Intestinal fatty acid binding protein (I-FABP) and lipopolysaccharide binding protein (LBP) did not differ between groups (P > .05). Among PHIVs who were breastfed, levels of sCD163 and interleukin 6 (IL6) were higher than levels in PHIV who were not breastfed (P < .05). Additionally, in PHIVs with a history of breastfeeding, sCD14, BDG, LBP, zonulin, and I-FABP correlated with several markers of systemic inflammation, including high-sensitivity C-reactive protein, IL6, d-dimer, and systemic tumor necrosis factor receptors I and II (P ≤ .05). CONCLUSIONS: Despite viral suppression, PHIVs have evidence of altered gut permeability and fungal translocation. Intestinal damage and the resultant bacterial and fungal translocations in PHIVs may play a role in the persistent inflammation that leads to many end-organ diseases in adults.Despite viral suppression, children with perinatally acquired human immunodeficiency virus (HIV) in Uganda have evidence of alterations in intestinal permeability and fungal translocation, compared to HIV-exposed but uninfected and HIV-unexposed children, which may play a role in HIV-associated chronic inflammation.

Subclinical Vascular Disease in Children With Human Immunodeficiency Virus in Uganda Is Associated With Intestinal Barrier Dysfunction.

BACKGROUND: The risk of cardiovascular disease (CVD) and its mechanisms in children living with perinatally acquired HIV (PHIV) in sub-Saharan Africa has been understudied. METHODS: Mean common carotid artery intima-media thickness (IMT) and pulse-wave velocity (PWV) were evaluated in 101 PHIV and 96 HIV-negative (HIV-) children. PHIV were on ART, with HIV-1 RNA levels ≤400 copies/mL. We measured plasma and cellular markers of monocyte activation, T-cell activation, oxidized lipids, and gut integrity. RESULTS: Overall median (interquartile range, Q1-Q3) age was 13 (11-15) years and 52% were females. Groups were similar by age, sex, and BMI. Median ART duration was 10 (8-11) years. PHIV had higher waist-hip ratio, triglycerides, and insulin resistance (P ≤ .03). Median IMT was slightly thicker in PHIVs than HIV- children (1.05 vs 1.02 mm for mean IMT and 1.25 vs 1.21 mm for max IMT; P < .05), while PWV did not differ between groups (P = .06). In univariate analyses, lower BMI and oxidized LDL, and higher waist-hip ratio, hsCRP, and zonulin correlated with thicker IMT in PHIV (P ≤ .05). After adjustment for age, BMI, sex, CD4 cell count, triglycerides, and separately adding sCD163, sCD14, and hsCRP, higher levels of intestinal permeability as measured by zonulin remained associated with IMT (ß = 0.03 and 0.02, respectively; P ≤ .03). CONCLUSIONS: Our study shows that African PHIV have evidence of CVD risk and structural vascular changes despite viral suppression. Intestinal intestinal barrier dysfunction may be involved in the pathogenesis of subclinical vascular disease in this population.

Hospitalization for severe malnutrition among HIV-infected children starting antiretroviral therapy.

OBJECTIVE: To describe early hospitalization for severe malnutrition in HIV-infected children initiating antiretroviral therapy (ART). DESIGN: Randomized trial of induction-maintenance and monitoring strategies in HIV-infected children. SETTING: Three tertiary hospitals in Uganda and one in Zimbabwe. PARTICIPANTS: 1207 HIV-infected children, median age 6 years (range, 3 months to 17 years). INTERVENTION: Abacavir, lamivudine and nevirapine or efavirenz were given; children in induction-maintenance arms also received zidovudine to week 36. Pre-ART inpatient/outpatient nutritional rehabilitation for children with baseline severe malnutrition. MAIN OUTCOME MEASURES: : Hospitalization for severe malnutrition and change in CD4 cell percentage by week 12 after ART. Mortality and change in weight-for-age Z-score (WAZ) by week 24 after ART. RESULTS: Thirty-nine of 1207 (3.2%) children were hospitalized for severe malnutrition (20 with oedema), median 28 days [interquartile range (IQR) 14, 36] after ART for marasmus and 26 days (IQR 14, 56) after ART for kwashiorkor. Hospitalized children had lower baseline and greater 24-week rise in WAZ than nonhospitalized children (P < 0.001). Twenty-nine of 39 (74%) children admitted for severe malnutrition had underlying infections. Of 220 children with advanced disease (baseline WAZ and CD4 cell Z-scores both <-3), 7.3% [95% confidence interval (CI) 3.8, 10.7] developed kwashiorkor and 3.6% (95% CI 1.2, 6.1) developed marasmus by week 12. CD4 cell percentage rise was similar among groups (P = 0.37). Twenty-four-week mortality was 32, 20 and 1.7% among children hospitalized with marasmus, kwashiorkor and not hospitalized, respectively, (P < 0.001). CONCLUSION: One in nine children with advanced HIV required early hospitalization for severe malnutrition after ART, with a 15-fold increase in 6-month mortality compared with nonhospitalized children. Integration of HIV/malnutrition services and further research to determine optimal ART timing, role of supplementary feeding and antimicrobial prophylaxis are urgently required.