Victor Musiime

Makerere University · Department of Paediatrics and Child Health

Suicide remains a global public health concern and is a leading cause of death among adolescents. Adolescents with perinatally-acquired HIV (PHIV) are particularly vulnerable to suicide and other challenges, including discrimination, stigma, educational difficulties, risk-taking behaviors, and medical complications. In Uganda, adolescents with PHIV...

Background Pneumonia remains the leading cause of mortality among children under 5 years. Poor nutritional status increases pneumonia mortality. Nutritional status assessed by anthropometry alone does not provide information on which body composition element predicts survival. Body composition proxy measures including arm-fat-area (AFA), arm-muscle...

Background. Refeeding syndrome is a complication developed by children being managed for severe acute malnutrition (SAM). It is caused by changes in electrolyte balance once high-caloric feeding is reinitiated. Phosphorus, potassium, and magnesium are the main electrolytes affected when it occurs. However, hypophosphatemia is the hallmark of the di...

This study examined the changes in the lipidome and associations with immune activation and cardiovascular disease markers in youth living with perinatally acquired HIV (YPHIV). The serum lipidome was measured in ART-treated YPHIV (n=100) and HIV- Ugandan children (n=98) Plasma markers of systemic inflammation, monocyte activation, gut integrity, T...

Background Darunavir is a potent HIV protease inhibitor with a high barrier to resistance. We conducted a nested pharmacokinetic sub-study within CHAPAS-4 to evaluate darunavir exposure in African children with HIV, taking once-daily darunavir/ritonavir for second-line treatment. Methods We used data from the CHAPAS-4 pharmacokinetic sub-study tre...

One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children...

We examined relationships between neurocognition and immune activation in Ugandan adolescents with perinatally acquired HIV (PHIV). Eighty-nine adolescents in Kampala, Uganda (32 virally suppressed [<400 copies/mL] PHIV and 57 socio-demographically matched HIV- controls) completed a tablet-based neurocognitive test battery. Control derived z-scores...

Background Despite global efforts to eliminate mother-to-child-transmission of HIV (MTCT), many children continue to become infected. We determined the prevalence of HIV among children with severe acute malnutrition (SAM) and that of their mothers, at admission to Mwanamugimu Nutrition Unit, Mulago Hospital, Uganda. We also assessed child factors a...

Background Children living with HIV requiring second-line antiretroviral therapy (ART) have limited options, an unmet need considering children require life-long ART. Methods Children from Uganda, Zambia, Zimbabwe were randomised to one of four second-line anchor drugs: dolutegravir(DTG), ritonavir-boosted darunavir(DRV/r), atazanavir(ATV/r), or l...

Background Children living with HIV have few second-line antiretroviral therapy(ART) options, especially fixed-dose-combinations(FDC). Methods Children from Uganda, Zambia, Zimbabwe were randomised to second-line tenofovir alafenamide(TAF)/emtricitabine(FTC) or standard-of-care(SOC) backbone (abacavir(ABC) or zidovudine(ZDV) with lamivudine(3TC)) i...

Background Tetanus is a potentially life-threatening neurologic disorder caused by the toxin-producing bacterium Clostridium tetani. Primary prevention is achieved through vaccination, typically administered during infancy, however, breakthrough cases of tetanus in fully immunized individuals, especially in pediatric populations have been noted pos...

Young adults with perinatally acquired HIV (PAH) face numerous challenges, including antiretroviral therapy (ART) adherence, managing onward HIV transmission risks and maintaining wellbeing. Sharing one’s HIV status with others (onward HIV disclosure) may assist with these challenges but this is difficult. We developed and tested the feasibility of...

Objectives To examine the voluntariness of consent in paediatric HIV clinical trials and the associated factors. Design Mixed-methods, cross-sectional study combining a quantitative survey conducted concurrently with indepth interviews. Setting and participants From January 2021 to April 2021, we interviewed parents of children on first-line or s...

Antiretroviral therapy for children living with HIV (CLHIV) under 3 years of age commonly includes lopinavir/ritonavir (LPV/r). However, the original liquid LPV/r formulation has taste and cold storage difficulties. To address these challenges, LPV/r oral pellets have been developed. These pellets can be mixed with milk or food for administration a...

Objective Neuropsychological (NP) tests are increasingly computerized, which automates testing, scoring, and administration. These innovations are well-suited for use in resource-limited settings, such as low- to middle- income countries (LMICs), which often lack specialized testing resources (e.g., trained staff, forms, norms, equipment). Despite...

Background COVID-19, first reported in Wuhan, China in December 2019, was declared a pandemic in March 2020, causing restrictions of movement of people and goods worldwide. This affected every aspect of life, including the conduct of clinical trials. We highlight the challenges faced by the PediCAP consortium and how we navigated them. Methods The...

Background Children with advanced HIV disease (AHD) are at an increased risk of morbidity and mortality. We describe mortality rates among infants with AHD hospitalized with severe pneumonia. Methods EMPIRICAL is an ongoing Phase II-III, open-label randomized factorial (2×2) trial supported by EDCTP (GA RIA2017MC_2013/#NCT03915366) to assess the i...

Background Infants living with HIV are at high risk of tuberculosis and death. Optimal antituberculosis therapy is essential for favourable clinical outcomes particularly in severely ill children. Using WHO-recommended weight-band dosing, younger children weighing <8kg are at risk of suboptimal exposures. We aimed to evaluate plasma concentration o...

Background Despite reduction of HIV-associated mortality in children with the implementation of antiretroviral treatment (ART), HIV-associated neurocognitive deficits are still of great concern. These are thought to result mainly from intra-cranial HIV-associated pathology. The contribution of extra-cranial infections like pneumonia is not well des...

Background Paediatric second line antiretroviral therapy (ART) formulations are limited. CHAPAS-4 (ISRCTN22964075), a 2X4 factorial randomised trial investigated efficacy and safety of 4 anchor drugs. Methods Children from Uganda, Zambia and Zimbabwe on non-nucleoside reverse transcriptase inhibitor-based regimens, requiring second line ART, were...

Background The World Health Organization (WHO) recommended Dolutegravir (DTG) as the preferred anchor drug for first and second line Anti-Retroviral Treatment (ART) regimen. Case reports and studies have demonstrated new onset hyperglycemia among adults initiated or transitioned to DTG. There is paucity of data on DTG-related hyperglycemia among ch...

Global health (GH) as an academic field is fraught with both historical and present systemic injustice, including unilateral partnerships, power asymmetry in grant funding and research agenda setting, lack of acknowledgment of low- and middle-income countries' contributions, and bias toward high-income countries' institutions. Reflecting on colonia...

Human immunodeficiency virus (HIV) is associated with persistent immune activation and dysfunction in people with HIV despite treatment with antiretroviral therapy (ART). Modulation of the immune system may be driven by: low-level HIV replication, co-pathogens, gut dysbiosis /translocation, altered lipid profiles, and ART toxicities. In addition, p...

Introduction We evaluated dolutegravir pharmacokinetics in infants with HIV receiving dolutegravir twice-daily with rifampicin-based TB-treatment compared to once-daily without rifampicin. Methods This pharmacokinetic substudy was nested in the EMPIRICAL trial for infants with HIV admitted with severe pneumonia. Infants aged 1-12 months, weighing...

Optimal antituberculosis therapy is essential for favourable clinical outcomes. Peak plasma concentrations of first-line antituberculosis drugs in infants with living HIV receiving WHO-recommended dosing were low compared to reference values for adults, supporting studies on increased doses of first-line TB drugs in infants.

Background The pharmacokinetics of abacavir (ABC) in African children living with HIV (CLHIV) weighing < 14 kg and receiving paediatric fixed-dose combinations (FDC) according to WHO weight bands dosing are limited. An ABC population pharmacokinetic model was developed to evaluate ABC exposure across different WHO weight bands. Methods Children en...

HIV remains a significant public health issue among young adults living in Uganda. There is a need for reliable and valid measures of key psychological and behavioural constructs that are related to important outcomes for this population. We translated, adapted and tested the psychometric properties of questionnaires measuring HIV stigma, HIV discl...

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 year...

Introduction Dolutegravir‐based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre‐conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we...

Background Severe Pneumonia is still the leading cause of morbidity and mortality among children worldwide. Many children with severe pneumonia are reported to die in hospital as well as following discharge due to malnutrition. Severe pneumonia is a catabolic illness, which predisposes to severe malnutrition. WHO and United Nations Children’s Fund...

Global health (GH) as an academic field is fraught with both historical and present systemic injustice, including unilateral partnerships; power asymmetry in grant funding and research agenda setting; lack of acknowledgment of contributions from low- and middle-income country collaborators; and disadvantageous bias toward low- and middle-income cou...

Background: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral...

Background Children living with perinatally acquired HIV (CLWH) survive into adulthood on antiretroviral therapy (ART). HIV, ART, and malnutrition can all lead to low bone mineral density (BMD). Few studies have described bone health among CLWH in Sub-Saharan Africa. We determined the prevalence and factors associated with low BMD among CLWH switch...

Background: Dolutegravir (DTG), combined with a backbone of two NRTIs, is currently the preferred first-line treatment for HIV in childhood. CHAPAS4 is an ongoing randomized controlled trial (#ISRCTN22964075) investigating second-line treatment options for children with HIV. We did a nested PK substudy within CHAPAS4 to evaluate the DTG exposure i...

Background: Integrase inhibitor (INSTI) with boosted darunavir (DRV/r), a regimen with a high-resistance barrier, avoiding NRTI toxicities, might be a switching option in children living with HIV (CLWHIV). Methods: SMILE is a randomised non-inferiority trial evaluating safety and antiviral efficacy of once-daily INSTI + DRV/r vs. continuing on c...

Background We evaluated the pharmacokinetics of tenofovir alafenamide fumarate (TAF) and tenofovir in a subset of African children enrolled in the CHAPAS-4 trial. Methods Children aged 3–15 years with human immunodeficiency virus infection failing first-line antiretroviral therapy were randomized to emtricitabine/TAF versus standard-of-care nucleo...

Introduction: Acute Kidney Injury (AKI) is associated with a high mortality yet survivors are at risk for Hypertension, chronic kidney disease, long term neurocognitive and behavioural problems. Early recognition of patients with possible AKI is crucial for better treatment outcome, hence a need for evidence to guide targeted screening of patients...

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...

Introduction: Many children and adolescents living with HIV still present with severe immunosuppression with morbidity and mortality remaining high in those starting antiretroviral therapy (ART) when hospitalized. Discussion: The major causes of morbidity and mortality in children living with HIV are pneumonia, tuberculosis, bloodstream infectio...

Background Worldwide, 1.7 million children younger than 15 years were living with HIV in 2021. Only 52% of them had access to antiretrovirals (ARVs). Lack of age-appropriate ARV formulations (i.e. easy to swallow for young infants, acceptable taste) remains the main obstacle to the access to ARVs. Therefore, a strawberry-flavoured Abacavir/Lamivudi...

Purpose: Hypothyroidism has been reported at a prevalence of 6% in children and adolescents with Sickle cell anemia. In this study, we determined the prevalence and factors associated with hypothyroidism among children with Sickle cell anemia attending the Sickle Cell Clinic, in Mulago hospital, Uganda. Methods: A cross-sectional study was condu...

Background SMILE, a multicentre randomized trial, compared the efficacy and safety of switching virologically suppressed children and adolescents with HIV to a once-daily dual regimen of dolutegravir plus ritonavir-boosted darunavir versus continuing standard ART. Within a nested pharmacokinetic (PK) substudy, we performed a population PK analysis...

Introduction Renal disease is asymptomatic in its early stages but on progression into advanced stage is expensive to manage requiring renal replacement therapy. Monitoring of children’s renal functionality is not routinely done but only on a doctor’s request. However, there is currently no published study on renal disease prevalence among children...

Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. The complete burden and outcomes in Uganda are unknown. The study was a multicenter retrospective chart review of children aged between 0 to 15 years diagnosed with NB from 2010 to 2020. Demographic, clinical and tumor-related characteristics were extracted for analysis. K...

Awareness of HIV serostatus helps individuals calibrate behaviour or link to care. Globally, young people (15-24years) contribute over 30% of new HIV infections. Despite progress in enhancing access to HIV services, HIV testing among young people in Uganda is below target. We determined the prevalence and factors influencing HIV testing among young...

Abstract Background Hunger and malnutrition are rampant among refugees and displaced populations, many of whom are infants and children. We sought to determine the prevalence and factors associated with thinness among children aged 5–17 years living in Nakivale refugee settlement, Isingiro district, southwestern Uganda. Methods This was a cross sec...

The chapter provides practical information on feeding malnourished children with protocols in the stabilization and rehabilitation phases with malnourished children, in the inpatient setting and on discharge or as an outpatient. Included are alternatives to commercially available F-75 and F-100 as well as good foods to feed malnourished children as...

Background Young children living with HIV have few treatment options. We aimed to assess the efficacy and safety of dolutegravir-based antiretroviral therapy (ART) in children weighing between 3 kg and less than 14 kg. Methods ODYSSEY is an open-label, randomised, non-inferiority trial (10% margin) comparing dolutegravir-based ART with standard of...

Introduction The risk of cardiovascular disease (CVD) and prospective investigations in youth living with perinatally acquired HIV (PHIV) in sub-Saharan Africa are lacking. Methods A prospective observational cohort study was performed in 101 PHIV and 97 HIV-, 10-18 years of age, from 2017-2021 at the JCRC in Uganda. PHIVs were on ART with HIV-1 R...

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...

Background Many aspects of microbial dissemination appear to vary with host cholesterol levels. Since neonatal septicemia remains a leading cause of newborn admissions and mortality in resource-limited settings, the contribution of abnormal cholesterol levels in maternal and/or newborn blood to the risk of neonatal septicemia and outcome requires e...

The phase 3 HESTIA3 study assessed the efficacy and safety of the reversible P2Y12 inhibitor ticagrelor versus placebo in preventing vaso-occlusive crises in pediatric patients with sickle cell disease (SCD). Patients aged 2 to 17 years were randomly assigned 1:1 to weight-based doses of ticagrelor or matching placebo. The primary endpoint was the...

Although 23 antiretroviral drugs are approved for use in adults, only six are approved by regulatory authorities for use in term neonates born to women with HIV, with even fewer options for preterm neonates. A major hurdle for approvals is the delay in the generation of pharmacokinetic and safety data for antiretrovirals in neonates. The median tim...

Background Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicen...

Background Pneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35–40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB...

Background Children living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CHEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in CLHIV/CHEU. This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensit...

Background Sickle cell anemia (SCA) leads to chronic end organ damage including the thyroid gland. This is postulated to be due to recurrent hemolysis leading to iron overload, vaso - occlusive crises, micro-vasculature obstruction due to red cell entrapment and frequent transfusions. Hypothyroidism has been reported at a prevalence of 6% in childr...

Background: Hunger and malnutrition are rampant among refugees and displaced populations, many of whom are infants and children. We sought to determine the prevalence and factors associated with thinness among children aged 5-17 years living in Nakivale refugee settlement, Isingiro district, southwestern Uganda. Methods: This was a cross sectional...

Background Clinical trial investigators may need to evaluate treatment effects in a specific subgroup (or subgroups) of participants in addition to reporting results of the entire study population. Such subgroups lack power to detect a treatment effect, but there may be strong justification for borrowing information from a larger patient group with...

Despite the great strides that have been made in prevention of mother to child transmission (PMTCT), children continue to acquire HIV. The reduction in transmission is variable, for example in Africa, great gains have been made in Eastern and Southern Africa, but critical gaps remain in West and Central Africa. These gaps are also observed in the t...

Objective: In this study, we aim to investigate the relationship between particulate matter, a common proxy indicator for air pollution, and markers of inflammation, monocyte activation, and subclinical vascular disease. Design: A cross sectional study. Methods: Adolescents with perinatally acquired HIV (PHIV) and HIV-uninfected adolescents be...

Background Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). Methods We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non–dolutegravir-based ART) in children...

Background Heme oxygenase-1 (HO-1) is a cytoprotective enzyme with potent anti-inflammatory, and anti-oxidant effects. The HO-1 response is modulated by functional polymorphisms (a dinucleotide (GT)n repeat length variation) in the HO-1 gene promoter region which have been associated with cardiovascular disease (CVD) susceptibility in adults. HO-1...

Background Pneumonia is the primary cause of death among HIV-infected children in Africa, with mortality rates as high as 35-40% in infants hospitalized with severe pneumonia. Bacterial pathogens and Pneumocystis jirovecii are well known causes of pneumonia-related death, but other important causes such as cytomegalovirus (CMV) and tuberculosis (TB...

Abstract Background HIV infection is associated with significant neurocognitive deficits making maximization of cognitive function among children receiving antiretroviral therapy (ART) a public health imperative. Non-protease inhibitors (non-PIs) achieve higher drug levels in the cerebral spinal fluid (CSF) compared to PIs, potentially leading to b...

Background Uganda has an imbalanced distribution of the health workforce, which may be influenced by the specialty career preferences of medical students. In spite of this, there is inadequate literature concerning the factors influencing specialty career preferences. We aimed to determine the specialty career preferences and the factors influencin...

Objective: To determine the impact of virological control on inflammation and cluster of differentiation 4 depletion among HIV-infected children initiating antiretroviral therapy (ART) in sub-Saharan Africa. Design: Longitudinal cohort study. Methods: In a sub-study of the ARROW trial (ISRCTN24791884), we measured longitudinal HIV viral loads,...

Background: Globally there is a high burden of low serum vitamin D levels, with children being more at risk, due to low intake in breastmilk, few available foods and inadequate cutaneous synthesis of vitamin D. Even in countries with abundant sunshine, Vitamin D deficiency (VDD) remains a problem. The classical clinical effect of severe vitamin D d...

Background: Air pollution is known to induce systemic inflammation and contribute to cardiovascular disease. The effects of ambient air pollution on adolescents living with perinatally acquired HIV (PHIV) in Africa has been understudied. In this study, we aim to investigate the relationship between particulate matter, a common proxy indicator for a...