NRU :: Browsing by Author "Musiime, Victor"

Browsing by Author "Musiime, Victor"

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Bacteremia, Causative Agents and Antimicrobial Susceptibility Among HIV-1–infected Children on Antiretroviral Therapy in Uganda and Zimbabwe
(The Pediatric infectious disease journal, 2013) Musiime, Victor; Cook, Adrian; Bakeera-Kitaka, Sabrina; Vhembo, Tichaona; Lutakome, Joseph; Keishanyu, Rosette; Prendergast, Andrew J.; Lubwama, Sam; Robertson, Val; Hughes, Peter; Nathoo, Kusum; Munderi, Paula; Klein, Nigel; Musoke, Philippa; Gibb, Diana M.
Bacteremia is common in HIV-infected children in Africa, including after start of antiretroviral therapy (ART), but there are limited data on causative pathogens and their antimicrobial sensitivity patterns in this population. Methods: We analyzed data on blood cultures taken from HIV-infected children developing acute febrile illness after enrollment to the Antiretroviral Research for Watoto (ARROW) clinical trial in Uganda and Zimbabwe. Patterns of bacterial pathogens and their antimicrobial susceptibilities were determined and bacteremia rates calculated over time from ART initiation. Results: A total of 848 blood cultures were obtained from 461 children, of which 123 (14.5%) from 105 children (median age 3.5 years, 51% girls) were culture positive, including 75 (8.8%) with clearly pathogenic organisms. The event rates for positive cultures with clearly pathogenic organisms after 0–1, 2–3, 4–11 and ≥12 months on ART were 13.3, 11.4, 2.1 and 0.3 per 1000 person-months of follow-up, respectively. The pathogens isolated (n; %) were Streptococcus pneumoniae (36; 28.3%), Staphylococcus aureus (11; 8.7%), Klebsiella pneumoniae (6; 4.7%), Pseudomonas aeruginosa (6; 4.7%), Salmonella spp (6; 4.7%), Escherichia coli (5; 3.9%), Haemophilus influenzae (1; 0.8%) and fungal spp (4; 3.1%). Other bacteria of doubtful pathogenicity (n = 52; 42%) were also isolated. Most isolates tested were highly (80–100%) susceptible to ceftriaxone, cefotaxime and ciprofloxacin; very few (~5%) were susceptible to cotrimoxazole; S. pneumoniae had high susceptibility to amoxicillin/ampicillin (80%). Conclusions: Rates of proven bacteremia were >20-fold higher immediately after starting ART compared with 12 months later in African HIV-infected children. S. pneumoniae was most commonly isolated, suggesting need for pneumococcal vaccination and effective prophylactic antibiotics.
Barriers to Initiation of Pediatric HIV Treatment in Uganda: A Mixed-Method Study
(AIDS research and treatment, 2012) Boender, T. Sonia; Sigaloff, Kim C. E.; Kayiwa, Joshua; Musiime, Victor; Calis, Job C. J.; Katumba, Lillian Nakatudde; Khauda, Elizabeth; Mukuye, Andrew; Ditai, James; Mugyenyi, Peter; Rinke deWit, Tobias F.; Kityo, Cissy
Although the advantages of early infant HIV diagnosis and treatment initiation are well established, children often present late to HIV programs in resource-limited settings. We aimed to assess factors related to the timing of treatment initiation among HIV-infected children attending three clinical sites in Uganda. Clinical and demographic determinants associated with early disease (WHO clinical stages 1-2) or late disease (stages 3-4) stage at presentation were assessed using multilevel logistic regression. Additionally, semistructured interviews with caregivers and health workers were conducted to qualitatively explore determinants of late disease stage at presentation. Of 306 children initiating first-line regimens, 72% presented late. Risk factors for late presentation were age below 2 years old (OR 2.83, ), living without parents (OR 3.93, ), unemployment of the caregiver (OR 4.26, ), lack of perinatal HIV prophylaxis (OR 5.66, ), and high transportation costs to the clinic (OR 2.51, ). Forty-nine interviews were conducted, confirming the identified risk factors and additionally pointing to inconsistent referral from perinatal care, caregivers’ unawareness of HIV symptoms, fear, and stigma as important barriers. The problem of late disease at presentation requires a multifactorial approach, addressing both health system and individual-level factors.
Baseline Inflammatory Biomarkers Identify Subgroups of HIV-Infected African Children With Differing Responses to Antiretroviral Therapy
(The Journal of infectious diseases, 2016) Prendergast, Andrew J.; Szubert, Alexander J.; Berejena, Chipo; Pimundu, Godfrey; Pala, Pietro; Shonhai, Annie; Musiime, Victor; Bwakura-Dangarembizi, Mutsa; Poulsom, Hannah; Hunter, Patricia; Musoke, Philippa; Kihembo, Macklyn; Munderi, Paula; Gibb, Diana M.; Spyer, Moira; Walker, A. Sarah; Klein, Nigel
Background. Identifying determinants of morbidity and mortality may help target future interventions for human immunodeficiency virus (HIV)–infected children. Methods. CD4+ T-cell count, HIV viral load, and levels of biomarkers (C-reactive protein, tumor necrosis factor α [TNF-α], interleukin 6 [IL-6], and soluble CD14) and interleukin 7 were measured at antiretroviral therapy (ART) initiation in the ARROW trial (case-cohort design). Cases were individuals who died, had new or recurrent World Health Organization clinical stage 4 events, or had poor immunological response to ART. Results. There were 115 cases (54 died, 45 had World Health Organization clinical stage 4 events, and 49 had poor immunologicalresponse) and 485 controls. Before ART initiation, the median ages of cases and controls were 8.2 years (interquartile range [IQR], 4.4–11.4 years) and 5.8 years (IQR, 2.3–9.3 years), respectively, and the median percentages of lymphocytes expressing CD4were 4% (IQR, 1%–9%) and 13% (IQR, 8%–18%), respectively. In multivariable logistic regression, cases had lower age-associatedCD4+ T-cell count ratio (calculated as the ratio of the subject’s CD4+ T-cell count to the count expected in healthy individuals of thesame age; P < .0001) and higher IL-6 level (P = .002) than controls. Clustering biomarkers and age-associated CD4+ and CD8+ T-cellcount ratios identified 4 groups of children. Group 1 had the highest frequency of cases (41% cases; 16% died) and profoundimmunosuppression; group 2 had similar mortality (23% cases; 15% died), but children were younger, with less profound immunosuppression and high levels of inflammatory biomarkers and malnutrition; group 3 comprised young children with moderate immunosuppression, high TNF-α levels, and high age-associated CD8+ T-cell count ratios but lower frequencies of events (12% cases; 7% died); and group 4 comprised older children with low inflammatory biomarker levels, lower HIV viral loads, and good clinical outcomes (11% cases; 5% died). Conclusions. While immunosuppression is the major determinant of poor outcomes during ART, baseline inflammation is an additional important factor, identifying a subgroup of young children with similar mortality. Antiinflammatory interventions may help improve outcomes.
Cardiac Dysfunction Among Ugandan HIV-Infected Children on Antiretroviral Therapy
(The Pediatric infectious disease journal, 2016) Namuyonga, Judith; Lubega, Sulaiman; Musiime, Victor; Lwabi, Peter; Lubega, Irene
Despite effective antiretroviral therapy (ART), HIV-infected children on treatment have been observed to have cardiac abnormalities. We sought to determine the prevalence, types and factors associated with cardiac abnormalities among HIV-infected Ugandan children on combination ART. Methods—We carried out a cross-sectional study from July 2012 to January 2013, at Joint Clinical Research Centre among HIV infected children aged 1 to 18 years. Cardiac abnormalities were assessed using electrocardiography (EKG) and echocardiography. CD4 counts, viral load and complete blood count were performed at enrollment. The prevalence of cardiac abnormalities was determined using simple proportions with the associated factors ascertained using logistic regression. Results—Among 285 children recruited, the median (IQR) age was 9 (6, 13) years, 54% were female; 72% were on first line cART. Their mean (±sd) CD4 count was 1092 (±868.7) cells/mm3; median (IQR) viral load was 20 (20, 76) copies/ml. 94% had adherence to ART of more than 95%. Cardiac abnormalities were detected in 39 (13.7%) children. The most common abnormalities by EKG and echocardiography were non specific T-wave changes (4.6%) and pericardial disease (thickened pericardium with or without pericardial effusion) (2.8%), respectively. No factor assessed was found to be significantly associated occurrence of cardiac dysfunction. Conclusions—The prevalence of cardiac dysfunction among the HIV-infected children on ART was 13.7 % which was high, with non specific T wave changes and pericardial disease being the most frequent abnormalities observed. No factor assessed was found to be associated with cardiac dysfunction.
A Case of Cryptococcal Lymphadenitis in an HIV-Infected Child
(AIDS research and human retroviruses, 2011) Natukunda, Eva; Musiime, Victor; Ssali, Francis; Kizito, Hilda; Kityo, Cissy; Mugyenyi, Peter
An 8-year-old HIV-positive antiretroviral therapy-naive child developed severe headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG) test was positive, the histology on the lymph node biopsy revealed budding yeast cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal fluid. He was treated with intravenous amphotericin B followed by oral fluconazole with a good response. Therefore cryptococcal lymphadenitis should be considered in the differential diagnosis of children presenting with lymphadenopathy and a positive serum CRAG.
Children Living with HIV: A Narrative review of Recent Advances in Paediatric HIV Research and their Implications for Clinical Practice
(Therapeutic Advances in Infectious Disease, 2022) Nalwanga, Damalie; Musiime, Victor
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 treatment of children living with HIV. Although there is increased access to lifesaving antiretroviral therapy (ART), management of pediatric HIV infection continues to be a challenge to clinicians in low-income countries where the disease burden is disproportionately high. On the contrary, recent advances in ART drug types and formulations provide great hope. In this narrative review, we present key updates in HIV care and promising ART research among children and adolescents living with HIV. We particularly highlight the dolutegravir (DTG) research which informed the change of the World Health Organization (WHO) ART guidelines in this age group. Significant gaps remain around management of children presenting with advanced disease to minimize mortality and in the long-term care and treatment of adolescents living with HIV. Research to address these sensitive areas is crucial for the realization of global, regional, and national pediatric HIV targets.
The cost-effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa
(John Wiley & Sons Ltd, 2020) Walker, Simon M.; Cox, Edward; Revill, Paul; Musiime, Victor; Bwakura-Dangarembizi, Mutsa; Mallewa, Jane; Cheruiyot, Priscilla; Maitland, Kathryn; Ford, Nathan; Gibb, Diana M; Walker, Sarah A.; Soares, Marta
Many HIV-positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced-prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost-effectiveness of this enhanced-prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision-analytic model was developed to estimate the cost-effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard-prophylaxis, enhanced-prophylaxis, standard-prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced-prophylaxis (CrAg-positive) or standard-prophylaxis (CrAg-negative), the second to enhanced-prophylaxis (CrAg-positive) or enhanced-prophylaxis without fluconazole (CrAg-negative) and the third to standardprophylaxis with fluconazole (CrAg-positive) or without fluconazole (CrAg-negative). The model estimated costs, life-years and quality-adjusted life-years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced-prophylaxis was cost-effective at cost-effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost-effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhancedprophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US $722 per QALY). Results were sensitive to prices of the enhanced-prophylaxis components. Enhanced-prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced-prophylaxis still conveyed health gains in CrAg-negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost-effective unless the price of CrAg testing fell below US$2.30. Conclusions: The REALITY enhanced-prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost-effective. Efforts should continue to ensure that components are accessed at lowest available prices.
Differences in body circumference, skin fold thickness and lipid profile measurements among HIV-infected children on and not on stavudine-based therapy in Uganda and Zambia in the CHAPAS-3 clinical trial
(Joint Clinical Research Centre, 2013) Musiime, Victor; Cook, Adrian.; Kayiwa, Joshua; Zangata, Dorothy; Gibb, Diana M.; Kityo, Cissy; Kekitiinwa, Adeodata; Mulenga, Veronica; Nansubuga, Carol; Arach, Beatrice; Kenny, Julia; Wavamunno, Priscilla; Kabamba, Desiree; Asiimwe, Alice R.; Abongomera, George
Lipodystrophy is a major side effect of antiretroviral therapy (ART) especially in adults, and although there have been some reports among HIV-infected children [1,2], paediatric data are limited Stavudine (d4T) has particularly been associated with lipodystrophy among HIVinfected adults owing to intracellular accumulation of the drug and its metabolites In HIV-infected children, d4T clearance is enhanced, potentially protecting them from these effects [3]. In addition, the relative d4T dose in paediatric fixed dosecombination “baby” tablets is lower than used in adults, and is also lower compared to the 4mg/kg licensed dose for children [4] Features of lipodystrophy have been observed to reverse when children have been switched from d4T-containing regimens [5]; however, clinical lipodystrophy ismore difficult to diagnose in growing children than in adults We compared body circumferences, skin-fold thickness (SFT) and lipid levels, as objective measures of lipodystrophy, among HIV-infected ART naïve vs experienced children at enrolment into the CHAPAS-3 trial, and in HIV-uninfected
Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial
(The lancet HIV, 2018) Mallewa, Jane; Szubert, Alexander J.; Mugyenyi, Peter; Chepkorir, Priscilla; Abongomera, George; Baleeta, Keith; Etyang, Anthony; Warambwa, Colin; Mudzingwa, Shepherd; Agutu, Clara; Nkomani, Sanele; Musiime, Victor; Lugemwa, Abbas; Bwakura-Dangarembizi, Mutsa; on behalf of the REALITY trial team
In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing ready-to-use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only.We did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks' of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5–12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] <16–18 kg/m2 or BMI-for-age Z scores <–3 for children). We did the randomisation with computer-generated, sequentially numbered tables with different block sizes incorporated within an online database. Randomisation was stratified by centre, age, and two other factorial randomisations, to 12 week adjunctive raltegravir and enhanced anti-infection prophylaxis (reported elsewhere). Clinic visits were scheduled at weeks 2, 4, 8, 12, 18, 24, 36, and 48, and included nurse assessment of vital status and symptoms and dispensing of all medication including ART and RUSF. The primary outcome was mortality at week 24, analysed by intention to treat. Secondary outcomes included absolute changes in weight, BMI, and mid-upper-arm circumference (MUAC). Safety was analysed in all randomly assigned participants. Follow-up was 48 weeks. This trial is registered with ClinicalTrials.gov (NCT01825031) and the ISRCTN registry (43622374).Between June 18, 2013, and April 10, 2015, we randomly assigned 1805 participants to treatment: 897 to RUSF and 908 to no-RUSF. 56 (3%) were lost-to-follow-up. 96 (10·9%, 95% CI 9·0–13·1) participants allocated to RUSF and 92 (10·3%, 8·5–12·5) to no-RUSF died within 24 weeks (hazard ratio 1·05, 95% CI 0·79–1·40; log-rank p=0·75), with no evidence of interaction with the other randomisations (both p>0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious adverse events in both groups (p=0·81), and 181 had grade 4 adverse events in the RUSF group compared with 172 in the non-RUSF group (p=0·45).In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised HIV-infected individuals starting ART is therefore not warranted at present.
Effect of ready-to-use supplementary food on mortality in severely immunocompromised HIV-infected individuals in Africa initiating antiretroviral therapy (REALITY): an open-label, parallel-group, randomised controlled trial
(Elsevier Ltd., 2018) Mallewa, Jane.; Berkley, James A; Szubert, Alexander J.; Mugyenyi, Peter; Chidziva, Ennie; Thomason, Margaret J; Walker, Sarah A.; Chepkorir, Priscilla; Abongomera, George; Baleeta, Keith; Etyang, Anthony; Warambwa, Colin; Melly, Betty; Gibb, Diana M; Prendergast, Andrew J; Mudzingwa, Shepherd; Kelly, Christine; Agutu, Clara; Wilkes, Helen; Nkomani, Sanele; Musiime, Victor; Lugemwa, Abbas; Pett, Sarah L; Bwakura-Dangarembizi, Mutsa
In sub-Saharan Africa, severely immunocompromised HIV-infected individuals have a high risk of mortality during the first few months after starting antiretroviral therapy (ART). We hypothesise that universally providing readyto- use supplementary food (RUSF) would increase early weight gain, thereby reducing early mortality compared with current guidelines recommending ready-to-use therapeutic food (RUTF) for severely malnourished individuals only. Methods We did a 2 × 2 × 2 factorial, open-label, parallel-group trial at inpatient and outpatient facilities in eight urban or periurban regional hospitals in Kenya, Malawi, Uganda, and Zimbabwe. Eligible participants were ART-naive adults and children aged at least 5 years with confirmed HIV infection and a CD4 cell count of fewer than 100 cells per μL, who were initiating ART at the facilities. We randomly assigned participants (1:1) to initiate ART either with (RUSF) or without (no-RUSF) 12 weeks’ of peanut-based RUSF containing 1000 kcal per day and micronutrients, given as two 92 g packets per day for adults and one packet (500 kcal per day) for children aged 5–12 years, regardless of nutritional status. In both groups, individuals received supplementation with RUTF only when severely malnourished (ie, body-mass index [BMI] <16–18 kg/m² or BMI-for-age Z scores <–3 for children). We did the randomisation with computer-generated, sequentially numbered tables with different block sizes incorporated within an online database. Randomisation was stratified by centre, age, and two other factorial randomisations, to 12 week adjunctive raltegravir and enhanced anti-infection prophylaxis (reported elsewhere). Clinic visits were scheduled at weeks 2, 4, 8, 12, 18, 24, 36, and 48, and included nurse assessment of vital status and symptoms and dispensing of all medication including ART and RUSF. The primary outcome was mortality at week 24, analysed by intention to treat. Secondary outcomes included absolute changes in weight, BMI, and mid-upper-arm circumference (MUAC). Safety was analysed in all randomly assigned participants. Follow-up was 48 weeks. This trial is registered with ClinicalTrials.gov (NCT01825031) and the ISRCTN registry (43622374). Findings Between June 18, 2013, and April 10, 2015, we randomly assigned 1805 participants to treatment: 897 to RUSF and 908 to no-RUSF. 56 (3%) were lost-to-follow-up. 96 (10·9%, 95% CI 9·0–13·1) participants allocated to RUSF and 92 (10·3%, 8·5–12·5) to no-RUSF died within 24 weeks (hazard ratio 1·05, 95% CI 0·79–1·40; log-rank p=0·75), with no evidence of interaction with the other randomisations (both p>0·7). Through 48 weeks, adults and adolescents aged 13 years and older in the RUSF group had significantly greater gains in weight, BMI, and MUAC than the no-RUSF group (p=0·004, 0·004, and 0·03, respectively). The most common type of serious adverse event was specific infections, occurring in 90 (10%) of 897 participants assigned RUSF and 87 (10%) of 908 assigned no-RUSF. By week 48, 205 participants had serious adverse events in both groups (p=0·81), and 181 had grade 4 adverse events in the RUSF group compared with 172 in the non-RUSF group (p=0·45). Interpretation In severely immunocompromised HIV-infected individuals, providing RUSF universally at ART initiation, compared with providing RUTF to severely malnourished individuals only, improved short-term weight gain but not mortality. A change in policy to provide nutritional supplementation to all severely immunocompromised HIV-infected individuals starting ART is therefore not warranted at present. Funding Joint Global Health Trials Scheme (UK Medical Research Council, UK Department for International Development, and Wellcome Trust).
Handbook on Counselling and Psychosocial Care for Children and Adolescents Living with and Affected by HIV in Africa
(African Network for the Care of Children Affected by HIV/AIDS – ANECCA, 2013) Nasaba, Rosemary; Tindyebwa, Denis; Musiime, Victor; Iriso, Robert; Ingabire, Resty; Nansera, Denis; Etima-Kizito, Monica; Kasule, Joseylee; Duffy, Malia
In 2013, the Joint United Nations Programme on HIV/AIDS (UNAIDS) proposed the ambitious “fasttrack” goals to end the global HIV epidemic by 2030, including reducing new HIV infections among children and adolescents from 500,000 annually to 200,000 annually (2014). Donor- and countrydriven investments have dramatically strengthened the HIV response around the world. Despite these major commitments and advances, HIV incidence is on the rise in young people; and in Africa, AIDS remains a leading cause of death in adolescents. The proportion of HIV-positive children and adolescents receiving HIV services, including ART, has also continued to lag well behind that of adults. Evidence of this gap from the World Health Organization (WHO) shows that 52% of children compared to 59% of adults were on ART in 2017 (2018). Controlling the epidemic, within countries and globally, must include preventing, testing for, and treating HIV in children and adolescents, including addressing psychosocial issues experienced by these populations to enhance their ability to manage the disease and live positively. To improve access to HIV services, several African countries have decentralised HIV care to primary health facilities. However, health care providers (HCPs) in many primary care settings do not have access to up-to-date clinical resources to build their knowledge so they can provide comprehensive HIV care for children and adolescents. HIV care for children and adolescents is complex, and requires not only addressing their medical needs, but also caring for their psychological wellbeing— to keep them healthy, retain them in care, and enable them to live positively. HCPs often have limited skills to counsel and provide psychosocial support (PSS) to children and adolescents living with HIV. While there have been specific in-service training courses designed to address this challenge, high staff turnover reduces their impact. The Handbook on Counselling and Psychosocial Care for Children and Adolescents Living with and Affected by HIV in Africa seeks to address this gap and serves as a comprehensive reference to provide HCPs with practical information to provide effective counselling and PSS for children and adolescents living with and affected by HIV.
HIV prevalence among children admitted with severe acute malnutrition and associated factors with mother-to-child HIV transmission at Mulago Hospital, Uganda: A mixed methods study
(Public Library of Science, 2024-04) Musiime, Victor; Rujumba, Joseph; Kakooza, Lawrence; Namisanvu, Henriator; Atuhaire, Loice; Naguti, Erusa; Beinomugisha, Judith; Kiggwe, Andrew; Nkinzi, Sharafat; Segawa, Ivan; Matsiko, Nicholas; Babirekere-Iriso, Esther; Musoke, Philippa
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 associated with HIV-infection, and explored factors leading to HIV-infection among a subset of the mother-child dyads that tested positive. We conducted a cross-sectional evaluation within the REDMOTHIV (Reduce mortality in HIV) clinical trial that investigated strategies to reduce mortality among HIV-infected and HIV-exposed children admitted with SAM at the Nutrition Unit. From June 2021 to December 2022, we consecutively tested children aged 1 month to 5 years with SAM for HIV, and the mothers who were available, using rapid antibody testing upon admission to the unit. HIV-antibody positive children under 18 months of age had a confirmatory HIV-DNA PCR test done. In-depth interviews (IDIs) were conducted with mothers of HIV positive dyads, to explore the individual, relationship, social and structural factors associated with MTCT, until data saturation. Quantitative data was analyzed using descriptive statistics and logistic regression in STATAv14, while a content thematic approach was used to analyze qualitative data. Of 797 children tested, 463(58.1%) were male and 630(79.1%) were [less than or equal to]18months of age; 76 (9.5%) tested positive. Of 709 mothers, median (IQR) age 26 (22, 30) years, 188(26.5%) were HIV positive. Sixty six of the 188 mother-infant pairs with HIV exposure tested positive for HIV, an MTCT rate of 35.1% (66/188). Child age >18 months was marginally associated with HIV-infection (crude OR = 1.87,95% CI: 1.11-3.12, p-value = 0.02; adjusted OR = 1.72, 95% CI: 0.96, 3.09, p-value = 0.068). The IDIs from 16 mothers revealed associated factors with HIV transmission at multiple levels. Individual level factors: inadequate information regarding prevention of MTCT(PMTCT), limited perception of HIV risk, and fear of antiretroviral drugs (ARVs). Relationship level factors: lack of family support and unfaithfulness (infidelity) among sexual partners. Health facility level factors: negative attitude of health workers and missed opportunities for HIV testing. Community level factors: poverty and health service disruptions due to the COVID-19 pandemic. In this era of universal antiretroviral therapy for PMTCT, a 10% HIV prevalence among severely malnourished children is substantially high. To eliminate vertical HIV transmission, more efforts are needed to address challenges mothers living with HIV face intrinsically and within their families, communities and at health facilities.
Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic
(AIDS research and therapy, 2013) Sebunya, Robert; Musiime, Victor; Kitaka, Sabrina Bakeera; Ndeezi, Grace
Early recognition of antiretroviral therapy (ART) failure in resource limited settings is a challenge given the limited laboratory facilities and trained personnel. This study aimed at describing the incidence, risk factors and the resistance associated mutations (RAMs) of first line treatment failure among HIV-1-infected children attending the Joint Clinical Research Centre (JCRC), Kampala, Uganda.
Is fat mass a better predictor of 6-month survival than muscle mass among African children aged 6–59 months with severe pneumonia?
(BioMed Central, 2024-09) Nalwanga, Damalie; Musiime, Victor; Kiguli, Sarah; Olupot-Olupot, Peter; Alaroker, Florence;; Opoka, Robert;; Tagoola, Abner; Mnjalla, Hellen; Mogaka, Christabel; Nabawanuka, Eva; Giallongo, Elisa; Karamagi, Charles; Briend, André; Maitland, Kathryn
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-area (AMA), and arm-muscle-circumference (AMC) could be useful predictors. To compare the ability of fat and muscle mass indices to predict 6-month survival among children with severe pneumonia. This prospective cohort study was nested in the COAST-Nutrition trial (ISRCTN10829073, 06/06/2018) conducted between June 2020 and October 2022 in Uganda and Kenya. We included children aged 6-59 months hospitalized for severe pneumonia with hypoxemia. Children with severe malnutrition, known chronic lung or cardiac diseases were excluded. Anthropometry and clinical status were assessed at enrolment and at follow-up to day 180. We examined Receiver Operator Characteristic (ROC) curves of fat and muscle mass indices with 6-month survival as the outcome, and compared the areas under the curve (AUCs) using chi-square tests. Cox survival analysis models assessed time-to-mortality. We included 369 participants. The median age was 15-months (IQR 9, 26), and 59.4% (219/369) of participants were male. The baseline measurements were: median MUAC 15.0 cm (IQR 14.0,16.0); arm-fat-area 5.6cm (IQR 4.7, 6.8); arm-muscle-area 11.4cm (IQR 10.0, 12.7); and arm-muscle-circumference 12.2 cm (IQR 11.5, 12.9). Sixteen (4.3%) participants died and 4 (1.1%) were lost-to-follow-up. The AUC for Arm-Fat-Area was not significantly higher than that for Arm-Muscle-Area and Arm-Muscle-Circumference [AUC 0.77 (95%CI 0.64-0.90) vs. 0.61 (95%CI 0.48-0.74), p = 0.09 and 0.63 (95%CI 0.51-0.75), p = 0.16 respectively], but was not statistically different from MUAC (AUC 0.73 (95%CI 0.62-0.85), p = 0.47). Increase in Arm-Fat-Area and Arm-Muscle-Circumference significantly improved survival [aHR 0.40 (95%CI 0.24-0.64), p = < 0.01 and 0.59 (95%CI 0.36-1.06), p = 0.03 respectively]. Survival prediction using Arm-Fat-Area was not statistically different from that of MUAC (p = 0.54). Muscle mass did not predict 6-month survival better than fat mass in children with severe pneumonia. Fat mass appears to be a better predictor. Effects of fat and muscle could be considered for prognosis and targeted interventions. PubMed
Mortality Among Children Under Five Years Admitted For Routine Care Of Severe Acute Malnutrition: A Prospective Cohort Study From Kampala, Uganda
(BMC pediatrics, 2020) Nalwanga, Damalie; Musiime, Victor; Kizito, Samuel; Kiggundu, John Baptist; Batte, Anthony; Musoke, Philippa; Tumwine, James K.
Mortality among children under 5 years of age admitted to malnutrition units in sub-Saharan Africa remains high. The burden of HIV infection, a major risk factor for mortality among patients with severe acute malnutrition (SAM), has reduced due to concerted prevention and treatment strategies. None the less, anecdotal reports from the malnutrition unit at Uganda’s National Referral Hospital (NRH) indicate that there is high mortality among patients with severe acute malnutrition (SAM) in routine care. Uganda has recently adopted the revised World Health Organization (WHO) treatment guidelines for SAM to improve outcomes. The mortality among children with SAM in routine care has not been recently elucidated. We report the magnitude and factors associated with mortality among children under 5 years of age admitted to the NRH for routine care of SAM.This was a cohort study of all severely malnourished children admitted to the NRH between June and October 2017. The primary outcome was two-week mortality. Mortality was calculated using simple proportions and Cox regression analysis was used to determine factors associated with time to mortality. Data was entered into Epidata and analysed using Stata v14.Two-hundred-sixty (98.5%) children: 59.6% male; mean age 14.4 (SD 9.4) months, completed two weeks of follow-up. Of these, 25.2% (95% CI 19.9–30.4%) died. In-hospital mortality was 20.7% (95% CI15.9–25.6%). The prevalence of HIV infection was 12.2%. Factors associated with mortality included: positive HIV status (AHR 2.2, (95% CI; 1.2–4.2), p = 0.014), bacteraemia (AHR 9 (95% CI 3.4–23.0), p < 0.001, and low glomerular filtration rate (eGFR), AHR 3.2; (95% CI 1.7–6.3), p = 0.001).A 25% mortality among children with severe malnutrition remains unacceptably high despite significant reduction in HIV prevalence. Children with SAM who are HIV infected, have eGFR below 60 mL/min/1.73m2 or have bacteraemia, are more likely to die. Further studies to explore the relationship between eGFR and mortality among children with SAM are needed. Studies to establish efficacious antibiotics are urgently required to inform treatment guidelines for children with SAM.
Neurocognitive Function Among Hivinfected Children On Protease Inhibitor -Based Versus Non-Protease Inhibitor Based Antiretroviral Therapy In Uganda: A Pilot Study
(BMC pediatric, 2021) Nalwanga, Damalie; Musiime, Victor; Bangirana, Paul; Nishiguchi, Erika Phelps; Kiggwe, Andrew; Ssesanga, Titus; Ssenkusu, John M.; Musoke, Philippa; Cusick, Sarah E.
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 better neurocognitive function by reducing CSF viral load and inflammation. ART that maximises children’s neurodevelopment and school achievement could result in improved quality of life and productivity as adults, but little research to date has examined whether non-PI ART is associated with better neurocognitive outcomes. We compared the neurocognitive function between children living with HIV receiving PI-based and non PI-based ART.We recruited a consecutive sample of clinically stable Ugandan children living with HIV aged 5–12 years who received PI-based or non PI-based ART for ≥ 1 year (viral load < 1000 copies). Neurocognitive function was assessed using the Kaufman Assessment Battery for Children, the Test of Variables of Attention, and Bruininks-Oseretsky Test of Motor Proficiency. Age-adjusted neurocognitive z-scores for the two groups were compared using linear regression models in STATA version 13. The Hommel’s method was used to adjust for multiple testing.We enrolled 76 children living with HIV; 34 on PI ART and 42 on non-PI ART. Mean (±SD) age was greater in the non-PI vs. PI group (9.5 ± 1.9 vs. 8.5 ± 2.0) years (p = 0.03). Children in the non-PI group had lower socioeconomic scores (5.7 ± 3.3 vs. 7.4 ± 2.8, p = 0.02). There was no difference in neurocognitive function between the groups (adjusted p > 0.05) for KABC and TOVA. Children in the PI group had better total BOT scores than their counterparts (46.07 ± 1.40) vs. 40.51 (1.24), p = 0.03).We detected no difference in neurocognitive function among children on PI and non PI-based ART therapy based on KABC and TOVA tests. Children on PI based ART had better motor function than their counterparts. We recommend a prospective study with a larger sample size.
Prevalence and Factors associated with Hypothyroidism in Children with Sickle Cell Anemia aged 6 months −17 years attending the Sickle Cell Clinic, Mulago Hospital, Uganda; a cross-sectional study
(BMC Endocrine Disorders, 2023) Kaudha, Gloria; Piloya, Thereza; Musiime, Victor; Kuteesa, Mary Goretty; Namugerwa, Shamimu; Owomugisha, Gloria; Wachepa, Stella Alinafe; Lubwama, Sanyu Kirabo; Kiguli, Sarah; Tumwine, James K.
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. A cross-sectional study was conducted among children aged 6 months − 17 years with a confirmed diagnosis of Sickle Cell Anemia, with no prior diagnosis of hypothyroidism and in steady state attending the Sickle Cell Clinic in Mulago hospital. Data was collected using a structured questionnaire and a blood sample was used to measure thyroid stimulating hormone and free thyroxine. Of the 332 children enrolled, sixty (18.1%) participants had sub-clinical hypothyroidism (95% CI: 14.3 — 22.6). Factors associated with hypothyroidism included constipation [adjusted odds ratio: 3.1, 95% CI:1.0 — 9.0, p = 0.043] and male sex [adjusted odds ratio:2.0, 95% CI:1.1— 3.5, p = 0.025]. Approximately 1 in 5 children (18.1%) had sub-clinical hypothyroidism. Males and children who presented with constipation were more likely to have sub-clinical hypothyroidism.
Prevalence of latent rheumatic heart disease among HIV-infected children in Kampala, Uganda
(Journal of acquired immune deficiency syndromes, 2016) Gleason, Brigette; Mirembe, Grace; Namuyonga, Judith; Okello, Emmy; Lwabi, Peter; Lubega, Irene; Lubega, Sulaiman; Musiime, Victor; Kityo, Cissy; Salata, Robert A.; Longenecker, Chris T.
Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained settings around the world, including countries with high rates of HIV/AIDS. Although both are immune-mediated diseases, it is unknown whether HIV modifies the risk or progression of RHD. We performed screening echocardiography to determine the prevalence of latent rheumatic heart disease in 488 HIV-infected children aged 5-18 in Kampala, Uganda. The overall prevalence of borderline/definite RHD was 0.82% (95% CI 0.26% to 2.23%) which is lower than the published prevalence rates of 1.5-4% among Ugandan children. There may be protective factors that decrease the risk of RHD in HIV-infected children.
Virologic Response to First-Line Efavirenz- or Nevirapine-Based Anti-Retroviral Therapy in HIV-Infected African Children
(The Pediatric infectious disease journal, 2017) Kekitiinwa, Adeodata; Szubert, Alexander J.; Katuramu, Richard; Musiime, Victor; Kitaka, Sabrina Bakeera; Walker, Ann Sarah; Senfuma, Oscar; Gibb, Diana M.
Poorer virologic response to nevirapine vs efavirenz-based antiretroviral therapy (ART) has been reported in adult systematic reviews and pediatric studies. We compared drug discontinuation and viral load (VL) response in ART-naïve Ugandan/Zimbabwean children ≥3 years of age initiating ART with clinician-chosen nevirapine vs efavirenz in the ARROW trial. Predictors of suppression <80, <400 and <1000 copies/ml at 36, 48 and 144 weeks were identified using multivariable logistic regression with backwards elimination (p=0.1).
Virological Response and Resistance Among HIV-Infected Children Receiving Long-Term Antiretroviral Therapy Without Virological Monitoring in Uganda and Zimbabwe: Observational Analyses Within the Randomised ARROW Trial
(PLoS medicine, 2017) Szubert, Alexander J.; Prendergast, Andrew J.; Musiime, Victor; Musoke, Philippa; Bwakura-Dangarembizi, Mutsa; Nahirya-Ntege, Patricia; Thomason, Margaret J.; Nkanya, Immaculate; Senfuma, Oscar; Mudenge, Boniface; Walker, A. Sarah
Although WHO recommends viral load (VL) monitoring for those on antiretroviral therapy (ART), availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring. In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine) with a non-nucleoside reverse transcriptase inhibitor (NNRTI) or 3 NRTIs as long-term ART. All children had VL assayed retrospectively after a median of 4 years on ART; those with >1,000 copies/ml were genotyped. Three hundred and sixteen children had VL and genotypes assayed longitudinally (at least every 24 weeks). Overall, 67 (6%) switched to second-line ART and 54 (4%) died. In children randomised to WHO-recommended 2NRTI+NNRTI long-term ART, 308/378 (81%) monitored with CD4 counts versus 297/375 (79%) without had VL <1,000 copies/ml at 4 years (difference = +2.3% [95% CI −3.4% to +8.0%]; P = 0.43), with no evidence of differences in intermediate/high-level resistance to 11 drugs. Among children with longitudinal VLs, only 5% of child-time post–week 24 was spent with persistent low-level viraemia (80–5,000 copies/ml) and 10% with VL rebound ≥5,000 copies/ml. No child resuppressed <80 copies/ml after confirmed VL rebound ≥5,000 copies/ml. A median of 1.0 (IQR 0.0,1.5) additional NRTI mutation accumulated over 2 years’ rebound. Nineteen out of 48 (40%) VLs 1,000–5,000 copies/ml were immediately followed by resuppression <1,000 copies/ml, but only 17/155 (11%) VLs ≥5,000 copies/ml resuppressed (P < 0.0001). Main study limitations are that analyses were exploratory and treatment initiation used 2006 criteria, without pre-ART genotypes. In this study, children receiving first-line ART in sub-Saharan Africa without real-time VL monitoring had good virological and resistance outcomes over 4 years, regardless of CD4 monitoring strategy. Many children with detectable low-level viraemia spontaneously resuppressed, highlighting the importance of confirming virological failure before switching to second-line therapy. Children experiencing rebound ≥5,000 copies/ml were much less likely to resuppress, but NRTI resistance increased only slowly. These results are relevant to the increasing numbers of HIV-infected children receiving first-line ART in sub-Saharan Africa with limited access to virological monitoring.

Browsing by Author "Musiime, Victor"

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