Victor Musiime | Makerere University (original) (raw)

Papers by Victor Musiime

We thank all the patients and staff from all the centres partici We thank all the patients and st... more We thank all the patients and staff from all the centres partici We thank all the patients and staff from all the centres participating in the ARROW trial. pating in the ARROW trial.

South Sudan Medical Journal, 2019

Introduction: HIV continues to be a major global health issue. There were approximately 2.1 milli... more Introduction: HIV continues to be a major global health issue. There were approximately 2.1 million infected children aged <15 years in 2017 and most were in sub-Saharan Africa. South Sudan with its low prevention of mother to child transmission (PMTCT) coverage has a greater risk of high transmission rates of HIV from mothers to their children. Objective: To determine the prevalence of HIV infection, the clinical pattern, and the immediate outcomes of children admitted to Al Sabah Children’s Hospital. Method: This was a cross sectional descriptive study, with a longitudinal component for the immediate outcome. A total of 828 children were recruited: 424 aged <18 months and 424 aged ≥ 18 months. HIV rapid tests were done to confirm the HIV infection for children aged ≥18 months, while HIV DNA-PCR was done to confirm the HIV infection for children aged <18 months found to be HIV exposed. Results: Twenty four children tested HIV positive giving an overall HIV prevalence of 2....

Pediatric Hematology and Oncology

Journal of the International AIDS Society, 2015

Sensitive assays are needed for detection of residual HIV in patients with undetectable plasma vi... more Sensitive assays are needed for detection of residual HIV in patients with undetectable plasma viral loads to determine if eradication strategies are effective. The gold standard quantitative viral outgrowth assay (QVOA) underestimates the magnitude of the viral reservoir, while sensitive PCR-based assays lack the ability to distinguish replication competent from defective virus. We sought to determine whether xenograft of leukocytes from HIV-1 infected patients with undetectable plasma viral loads into severely immunocompromised mice would result in viral amplification and measurable viral loads within the aberrant murine host. Methods: We evaluated whether xenograft of 1) peripheral blood mononuclear cells (PBMCs) from five HIV-1' patients on suppressive antiretroviral therapy (ART), 2) PBMCs or purified resting CD4' T cells from 5 HIV-1' elite suppressors (ES), or 3) PBMCs from a Simian Immunodeficiency Virus (SIV)' pigtailed macaque on suppressive ART, all with undetectable plasma viral loads, into NOD. Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG) mice resulted in viral amplification in the mouse. Successful xenograft of mice was confirmed by flow cytometry. Human CD8' T cells were depleted in humanized mice with depleting antibody, and CD4' T cells were activated in a subset of mice with activating anti-CD3. Plasma viral loads in xenografted mice were quantified using qRT-PCR, and compared to plasma viral load and QVOA results from the human or macaque donor. Results: With this murine viral outgrowth assay (MVOA), we amplified HIV-1 from all 10 HIV' subjects with undetectable plasma viral load, including an ES from whom we were unable to recover virus by QVOA. We detected HIV in mice an average of 20 days after xenograft with PBMCs from patients on suppressive ART, and an average of 28 days after xenograft with PBMCs or resting CD4' T cells from ES. For two of the mice xenografted with CD4' T cells from ES, we detected HIV only after activation with anti-CD3. We similarly detected SIV in macaquized mice by seven days post-xenograft. Conclusions: The MVOA has the potential to serve as a powerful tool to identify residual HIV-1 in patients with undetectable viral loads, such as those who have undergone promising cure therapies.

The Lancet. Infectious diseases, 2018

Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes usin... more Millions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings. We analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 ...

Clinical Infectious Diseases, 2013

Frontiers in Pediatrics

BackgroundChildren living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CH... more BackgroundChildren 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 sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among CLHIV/CHEU admitted with severe acute malnutrition.MethodsThis is an open label randomized controlled trial involving 300 children; 76 CLHIV and 224 CHEU. The participants are being randomized to receive 1 week of ceftriaxone (n = 150) or standard-of-care (ampicillin/gentamicin) (n = 150), in addition to other routine care. The trial's primary outcome is in-hospital mortality. Secondary outcomes are: length of hospitalization; weight-for-height, weight-for-age and height-for-age z-scores; and pattern/antimicrobial sensitivity of pathogens....

Acta Scientific Medical Sciences, 2021

Background: Malaria remains a serious infectious disease causing a high rate of morbidity and mor... more Background: Malaria remains a serious infectious disease causing a high rate of morbidity and mortality. Whereas cerebral malaria and other neurological sequelae have been described among under-fives and adults, a case of delayed cerebellar ataxia has not been published among adolescents in Uganda. Case Presentation: A 10-year-old, HIV-negative girl who initially presented with severe headache and new-onset seizures, who developed severe cerebellar ataxia and vertigo on Day 14 after treatment. Notably, she had no other risk factors for cerebellar ataxia and had a normal cerebrospinal fluid and a normal CT-scan report. She was treated with anti-malarial medication, anti-convulsant therapy and antihistamines. She was discharged home in a stable condition. Conclusion: We describe a case of delayed cerebellar ataxia in a 10 year-old HIV negative adolescent girl after completing her course of anti-malarial treatment. This case highlights the need of immediate follow-up of adolescents with cerebral malaria since they may present with delayed cerebellar ataxia.

Pediatrics, 2020

Purpose: Mortality among children under five years of age admitted to malnutrition units in sub S... more Purpose: Mortality among children under five years of age admitted to malnutrition units in sub Saharan Africa remains high. Anecdotal reports from the malnutrition unit our country’s National Referral Hospital (NRH) indicate that there is high mortality among patients with severe acute malnutrition (SAM) in routine care. The burden of HIV infection, a major risk factor for mortality among patients with SAM, has reduced due to …

Journal of Medical Case Reports, 2020

Background Fanconi–Bickel syndrome is an autosomal recessive disorder of glucose metabolism. It i... more Background Fanconi–Bickel syndrome is an autosomal recessive disorder of glucose metabolism. It is an extremely rare disorder. Most cases have been reported in consanguineous communities. None of the cases have been reported in Black Africans in sub-Saharan Africa. This case was diagnosed 3 years after initial presentation due to diagnostic challenges and limited awareness of similar metabolic syndromes in our setting. Case presentation We report the case of a 4-year-old boy, born to non-consanguineous Black African parents, who presented with failure to thrive and rachitic features in infancy. Clinical, laboratory, and radiological features were indicative of Fanconi–Bickel syndrome. No genetic testing was done. The diagnosis was made 3 years after the initial presentation due to diagnostic challenges. He showed clinical improvement with the institution of a galactose-free diet. Conclusion Fanconi–Bickel syndrome occurs even in non-consanguineous Black African populations. Therefor...

Pilot and Feasibility Studies, 2020

Background Young adults with perinatally acquired HIV (PAH) face several challenges, including ad... more Background Young adults with perinatally acquired HIV (PAH) face several challenges, including adhering to antiretroviral therapy (ART), managing the risk of onward HIV transmission and maintaining positive well-being. Sharing one’s HIV status with others (onward HIV disclosure) may assist with these challenges by facilitating emotional and practical support. Rates of HIV status sharing are, however, low in this population. There are no existing interventions focused on sharing one’s HIV status for young adults living with PAH. The HEADS-UP study is designed to develop and test the feasibility of an intervention to help the sharing of HIV status for young adults with PAH. Methods The study is a 30-month multi-site randomised feasibility study across both a high-income/low-HIV prevalence country (UK) and a low-income/high-HIV prevalence country (Uganda). Phase 1 (12 months) will involve developing the intervention using qualitative interviews with 20 young people living with PAH (ten...

Open Journal of Pediatrics, 2021

Background: Globally there is a high burden of low serum vitamin D deficiency (VDD) with children... more Background: Globally there is a high burden of low serum vitamin D deficiency (VDD) with children being acknowledged at risk due to low vitamin D content in both breastmilk and available foods and inadequate cutaneous synthesis of vitamin D. Even in countries with abundant sunshine, vitamin D deficiency (VDD) remains a problem. There is little characterization of the status of vitamin D among infants in East Africa. This study aimed to determine the prevalence and factors associated with vitamin D deficiency among infants attending the Reproductive and Child Health (RCH) Clinic in Arusha, Tanzania. Methods: A cross-sectional study of 304 infants aged 6 weeks to 12 months was conducted at Arusha Lutheran Medical Centre (ALMC). Infants were enrolled during the warm season between November 2018 and January 2019. A pre-coded questionnaire was used to collect data on sociodemographic characteristics of the infant with consent from their caretakers. Physical examination was done for anthropometric measures and signs of rickets. Blood was drawn for assessment of serum 25-hydroxyvitamin D 25(OH)D, calcium, phosphorus and alkaline phosphate. Vitamin D deficiency was defined as 25(OH)D level below 20 ng/ml (<50 nmol/L) and Vitamin D insufficiency defined as a 25(OH)D level 20-30 ng/ml (50-75 nmol/L). Statistical analysis was performed using STATA 14 version and factors associated with VDD explored with multivariate analysis. Results: The mean serum 25(OH)D among infants was 34.51 ng/ml (±15.53). Vitamin D deficiency was found in 67/304 (22%) infants and Vitamin D insufficiency in 50 (16.5%

Journal of the International AIDS Society, 2020

Introduction: Sustaining optimal adherence is the major challenge facing adolescents living with ... more Introduction: Sustaining optimal adherence is the major challenge facing adolescents living with HIV (ALHIV), particularly in low-resource settings, where "second-line" is often the last accessible treatment option. We explored the knowledge and skills adolescents need in order to maintain improved adherence behaviours, and the specific ways clinicians and caregivers may support young people to do so more independently. Methods: We conducted individual, in-depth interviews with 20 ALHIV aged 10 to 18 years in Uganda in 2017 to 2018. All participants had recently commenced second-line treatment as part of a clinical trial. We used thematic qualitative analysis to examine adherence experiences and challenges while on first-line therapy, as well as specific supports necessary to optimise treatment-taking longer-term. Results: Adherence difficulties are exacerbated by relatively rapid shifts from caregiver-led approaches during childhood, to an expectation of autonomous treatment-taking with onset of adolescence. For many participants this shift compounded their ongoing struggles managing physical side effects and poor treatment literacy. Switching to second-line typically prompted reversion back to supervised adherence, with positive impacts on self-reported adherence in the immediate term. However, this measure is unlikely to be sustainable for caregivers due to significant caregiver burden (as on first line), and provided little opportunity for clinicians to guide and develop young people's capacity to successfully adopt responsibility for their own treatment-taking. Conclusions: As ALHIV in sub-Saharan Africa are attributed increasing responsibility for treatment adherence and HIV management, they must be equipped with the core knowledge and skills required for successful, self-directed care. Young people need to be relationally supported to develop necessary "adherence competencies" within the supportive framework of a gradual "transition" period. Clinic conversations during this period should be adolescent-focussed and collaborative, and treatment-taking strategies situated within the context of their lived environments and support networks, to facilitate sustained adherence. The disclosure of adherence difficulties must be encouraged so that issues can be identified and addressed prior to treatment failure.

BMC Pediatrics, 2020

Background Prematurity is the leading cause of mortality in children under 5 years of age globall... more Background Prematurity is the leading cause of mortality in children under 5 years of age globally and is also frequently associated with postnatal growth failure (PGF). Although most preterm births occur in low resource settings, little is known about their postnatal growth outcomes especially in rural areas. We evaluated the incidence and factors associated with PGF among preterm infants managed at a rural hospital in Uganda. Methods Retrospective cohort study of preterm infants discharged from Kiwoko Hospital neonatal intensive care unit (NICU) from July 2017 to June 2018. Inclusion criteria included gestational age 26 up to but not including 37 weeks, admission within 24 h of birth and at least 7 days hospital stay. Exclusion criteria included major congenital anomalies and missing gestational age or birth weight. Birth and discharge weights from clinical notes were plotted on Fenton 2013 growth charts. Gestation age was determined by last normal menstruation period (LNMP), extr...

Clinical Infectious Diseases, 2019

BackgroundChildren with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lif... more BackgroundChildren 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.MethodsThis 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.ResultsThe 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...

Journal of the Association of Nurses in AIDS Care, 2018

Self-management of HIV is a desirable goal for the millions of adolescent persons living with HIV... more Self-management of HIV is a desirable goal for the millions of adolescent persons living with HIV (PLWH). Adolescent PLWH continue to experience poor HIV care outcomes, primarily due to poor rates of medication adherence and retention in care, highlighting a need to develop adolescent self-management skills. The aim of our study was to examine adolescent, caregiver, and health care provider perceptions of adolescent PLWH self-management roles, barriers, and facilitators. Swendeman et al.'s self-management framework for chronic diseases guided the analyses. Participant narratives highlighted perceptions of their responsibilities and related challenges with regard to self-management of HIV by adolescents. Our findings highlighted the complexity of HIV self-management for adolescents and underscored the need for multifaceted programs to strengthen adolescent-caregiver-health care provider partnerships in order to improve adolescent PLWH health and wellbeing.

European Journal of Preventive Cardiology, 2018

Air pollution has a great impact on health, representing one of the leading causes of death world... more Air pollution has a great impact on health, representing one of the leading causes of death worldwide. Previous experimental and epidemiological studies suggested the role of pollutants as risk factors for cardiovascular diseases. For this reason, international guidelines included specific statements regarding the contribution of particulate matter exposure to increase the risk of these events. In this review, we summarise the main evidence concerning the mechanisms involved in the processes linking air pollutants to the development of cardiovascular diseases.