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Abstract Background In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda. Methodology This was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks. Results Of 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 – 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 – 19 years (HR 3.2, 95% 1.6 – 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 – 3.1), p < 0.01) prior to second-line ART switch. Conclusion Treatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch.

Abstract Background Several rural public health facilities in East Central Uganda have sub-optimal, below 50%, levels of uptake of cervical cancer screening services among women with HIV. This is attributed to low cervical cancer screening literacy: limited ability to access, understand, appraise, and apply cervical cancer screening information. This research identified multi-level (health facility, community, interpersonal and individual) barriers, and facilitators of accessing, understanding, and applying cervical cancer screening information among rural women with HIV attending rural public health facilities in East Central Uganda to inform interventions. Methods We conducted ten Focus Group Discussions with rural women aged 25–49 years with HIV attending four selected rural public health facilities: thirty women who had ever screened for cervical cancer and thirty women who had never screened for cervical cancer across different age categories. Data was collected using a guide based on the Integrated model of health literacy. Thematic analysis was used for analysis. Competences (accessing, understanding and applying cervical cancer screening information) and categories of factors (health system, community, interpersonal and individual factors) of the integrated model of health literacy were deductively derived whereas barriers and facilitators were deductively derived from women’s statements. Results Lack of communication materials and inability to access information were health facility and individual barriers of accessing cervical cancer screening information respectively. Facilitators of accessing information were access to information at health facility, community, and interpersonal levels and women’s ability to access information. Barriers and facilitators of understanding cervical cancer information were related to communication materials, provision of health education and women’s concentration during health education. Barriers and facilitators of applying cervical cancer screening information were related to communication and provision of cervical cancer screening services at health facility level, and interpersonal level from peers, partners and other family members as well as women’s ability to: understand information and access to cervical cancer screening services at individual level. Conclusions This study emphasizes the influence of multi-level factors on cervical cancer screening literacy among rural women with HIV attending rural public health facilities in East Central Uganda. Improving uptake of cervical cancer screening services among these women requires multi-level interventions.

Abstract Background In clinical practice, Measurement of estimated glomerular filtration rates (eGFR) is the gold standard assessing renal function the glomerular filtration rate often estimated from plasma creatinine. Several studies have shown Cystatin C based eGFR (Cys C) to be a better parameter for the diagnosis of impaired renal function. Cystatin C based eGFR has been proposed as a potential renal function marker but its use in HIV&AIDS patients has not been well evaluated. Methods A cross sectional study was carried out on 914 HIV&AIDS patients on antiretroviral therapy (ART) attending Mildmay Uganda for care and treatment between January to March 2015. Serum Cystatin C based eGFR was measured using the particle enhanced immunoturbidimetric assay. Creatinine was analyzed using enzymatic Creatinine PAP method and creatinine clearance was calculated according to C&G. Results The sensitivity of Cystatin C based eGFR was 15.1% (95% CI = 8.4, 24) with specificity 99.3% (95% CI = 98- 99.7). The positive and negative predictive values were 70.0% (95% CI 45.7–88.1) and 91.2% (95% CI 98.11–92.94) respectively. The positive likelihood ratio was 18.81 and negative likelihood ratio was 0.85. Cystatin C based eGFR had diagnostic accuracy of 90.7 and area under curve was 0.768. Conclusion Cystatin C based eGFR exhibited a high specificity and a high positive likelihood ratio in diagnosis of kidney disease among HIV&AIDS patients. Cystatin C based eGFR can be used as a confirmatory test.

Background: HIV-associated alterations innate and adaptive immune cell compartments are reminiscent of the process of immune aging. Objectives: We described immune aging phenotypes among ART-treated HIV-infected adults relative to age-matched HIV-negative counterparts. Methods: In a cross-sectional comparative study of HIV-infected adults with CD4≥500 cells/μl after at least 12 years of suppressive ART and age-and-gender-matched HIV-negative individuals, immune activation and immune aging phenotypes were measured, using multi-color flowcytometry. Results: ART-treated HIV-infected individuals had higher body mass index (P = 0.004), waist-hip circumference (P = 0.041), hip circumference (P

Abstract Recent efforts to shift the control and leadership of health research on African issues to Africa have led to increased investments for scientific research capacity strengthening (RCS) on the continent and a greater demand for accountability, value for money and demonstration of return on investment. There is limited literature on monitoring and evaluation (M&E) of RCS systems and there is a clear need to further explore whether the M&E frameworks and approaches that are currently used are fit for purpose. The M&E approaches taken by four African RCS consortia funded under the Developing Excellence in Leadership, Training and Science in Africa (DELTAS) I initiative were assessed using several methods, including a framework comparison of the M&E approaches, semi-structured interviews and facilitated discussion sessions. The findings revealed a wide range in the number of indicators used in the M&E plans of individual consortium, which were uniformly quantitative and at the output and outcome levels. Consortia revealed that additional information could have been captured to better evaluate the success of activities and measure the ripple effects of their efforts. While it is beneficial for RCS consortia to develop and implement their own M&E plans, this could be strengthened by routine engagement with funders/programme managers to further align efforts. It is also important for M&E plans to consider qualitative data capture for assessment of RCS efforts. Efforts could be further enhanced by supporting platforms for cross-consortia sharing, particularly when trying to assess more complex effects. Consortia should make sure that processes for developmental evaluation, and capturing and using the associated learning, are in place. Sharing the learning associated with M&E of RCS efforts is vital to improve future efforts. Investing and improving this aspect of RCS will help ensure tracking of progress and impact of future efforts, and ensure accountability and the return on investment. The findings are also likely applicable well beyond health research.

Background: Human herpesvirus 8 (HHV-8) causes Kaposi's sarcoma (KS). Kaposi sarcoma in HIV/AIDS patients is referred to as epidemic KS and is the most common HIV-related malignancy worldwide. The lack of a diagnostic assay to detect latent and early-stage disease has increased disease morbidity and mortality. Serum miRNAs have previously been used as potential biomarkers of normal physiology and disease. In the current study, we profiled unique serum miRNAs in patients with epidemic KS to generate baseline data to aid in developing a miRNA-based noninvasive biomarker assay for epidemic KS. Methods: This was a comparative cross-sectional study involving 27 patients with epidemic KS and 27 HIV-positive adults with no prior diagnosis or clinical manifestation of KS. DNA and RNA were isolated from blood and serum collected from study participants. Nested PCR for circulating HHV-8 DNA was performed on the isolated DNA, whereas miRNA library preparation and sequencing for circulating miRNA were performed on the RNA samples. The miRge2 pipeline and EdgeR were used to analyse the sequencing data. Results: Fifteen out of the 27 epidemic KS-positive subjects (55.6%) tested positive for HHV-8 DNA, whereas only 3 (11.1%) out of the 27 HIV-positive, KS-negative subjects tested positive for HHV-8 DNA. Additionally, we found a unique miRNA expression signature in 49 circulating miRNAs in epidemic KS subjects compared to subjects with no epidemic KS, with 41 miRNAs upregulated and 8 miRNAs downregulated. Subjects with latent KS infection had a differential upregulation of circulating miR-193a compared to HIV-positive, KS-negative subjects for whom circulating HHV-8 DNA was not detected. Further analysis of serum from epidemic KS patients revealed a miRNA signature according to KS tumor status and time since first HIV diagnosis. Conclusions: This study reveals unique circulating miRNA profiles in the serum of patients with epidemic KS versus HIV-infected subjects with no KS, as well as in subjects with latent KS. Many of the dysregulated miRNAs in epidemic KS patients were previously reported to have crucial roles in KS infection and latency, highlighting their promising roles as potential biomarkers of latent or active KS infection.

Background: Research and clinical use of clinical pharmacology laboratories are limited in low- and middle-income countries. We describe our experience in building and sustaining laboratory capacity for clinical pharmacology at the Infectious Diseases Institute, Kampala, Uganda. Intervention: Existing laboratory infrastructure was repurposed, and new equipment was acquired. Laboratory personnel were hired and trained to optimise, validate, and develop in-house methods for testing antiretroviral, anti-tuberculosis and other drugs, including 10 high-performance liquid chromatography methods and four mass spectrometry methods. We reviewed all research collaborations and projects for which samples were assayed in the laboratory from January 2006 to November 2020. We assessed laboratory staff mentorship from collaborative relationships and the contribution of research projects towards human resource development, assay development, and equipment and maintenance costs. We further assessed the quality of testing and use of the laboratory for research and clinical care. Lessons learnt: Fourteen years post inception, the clinical pharmacology laboratory had contributed significantly to the overall research output at the institute by supporting 26 pharmacokinetic studies. The laboratory has actively participated in an international external quality assurance programme for the last four years. For clinical care, a therapeutic drug monitoring service is accessible to patients living with HIV at the Adult Infectious Diseases clinic in Kampala, Uganda. Recommendations: Driven primarily by research projects, clinical pharmacology laboratory capacity was successfully established in Uganda, resulting in sustained research output and clinical support. Strategies implemented in building capacity for this laboratory may guide similar processes in other low- and middle-income countries.

Uganda applies the World Health Organization threshold of 1,000 copies/ml to determine HIV viral non-suppression. While there is an emerging concern of low-level viraemia (≥50 to

Self-Medication (SM) involves the utilization of medicines to treat self-recognized symptoms or diseases without consultation and the irrational use of over-the-counter drugs. During the COVID-19 pandemic, the lack of definitive treatment led to increased SM. We aimed to estimate the extent of SM for drugs used to treat COVID-19 symptoms by collecting data from pharmacy sale records. The study was conducted in Kampala, Uganda, where we extracted data from community pharmacies with functional Electronic Health Records between January 2018 and October 2021 to enable a comparison of pre-and post-COVID-19. The data included the number of clients purchasing the following drugs used to treat COVID-19 and its symptoms: Antibiotics included Azithromycin, Erythromycin, and Ciprofloxacin; Supplements included Zinc and vitamin C, while Corticosteroids included dexamethasone. A negative binomial model was used to estimate the incident rate ratios for each drug to compare the effect of COVID-19 on SM. In the pre- COVID-19 period (1st January 2018 to 11th March 2020), 19,285 customers purchased antibiotics which included; Azithromycin (n = 6077), Ciprofloxacin (n = 6066) and Erythromycin (n = 997); health supplements including Vitamin C (430) and Zinc (n = 138); and Corticosteroid including Dexamethasone (n = 5577). During the COVID-19 pandemic (from 15th March 2020 to the data extraction date in October 2021), we observed a 99% increase in clients purchasing the same drugs. The number of clients purchasing Azithromycin increased by 19.7% to 279, Ciprofloxacin reduced by 58.8% to 96 clients, and those buying Erythromycin similarly reduced by 35.8% to 492 clients. In comparison, there were increases of 170%, 181%, and 377% for Vitamin C, Zinc, and Dexamethasone, respectively. The COVID-19 pandemic underscored the extent of SM in Uganda. We recommend future studies with a representation of data from pharmacies located in rural and urban areas to further study pandemics' effect on antimicrobials prescriptions, including obtaining pharmacists' perspectives using mixed methods approaches.

BackgroundUganda's efforts to end the HIV epidemic by 2030 are threatened by the increasing number of PLHIV with low-level viraemia (LLV). We conducted a study to determine the prevalence of LLV and the association between LLV and subsequent viral non-suppression from 2016 to 2020 among PLHIV on ART in Uganda.MethodThis was a retrospective cohort study, using the national viral load (VL) program data from 2016 to 2020. LLV was defined as a VL result of at least 50 copies/ml, but less than 1,000 copies/ml. Multivariable logistic regression was used to determine the factors associated with LLV, and cox proportional hazards regression model was used to determine the association between LLV and viral non-suppression.ResultsA cohort of 17,783 PLHIV, of which 1,466 PLHIV (8.2%) had LLV and 16,317 (91.8%) had a non-detectable VL was retrospectively followed from 2016 to 2020. There were increasing numbers of PLHIV with LLV from 2.0% in 2016 to 8.6% in 2020; and LLV was associated with male sex, second line ART regimen and being of lower age. 32.5% of the PLHIV with LLV (476 out of 1,466 PLHIV) became non-suppressed, as compared to 7.7% of the PLHIV (1,254 out of 16,317 PLHIV) with a non-detectable viral load who became non-suppressed during the follow-up period. PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL (adjusted hazard ratio was 4.1, 95% CI: 3.7 to 4.7, p < 0.001).ConclusionOur study indicated that PLHIV with LLV increased from 2.0% in 2016 to 8.6% in 2020, and PLHIV with LLV had 4.1 times the hazard rate of developing viral non-suppression, as compared to PLHIV with a non-detectable VL. Hence the need to review the VL testing algorithm and also manage LLV in Uganda.

Abstract Background Retention of pregnant and breastfeeding women and their infants in HIV care still remains low in Uganda. Recent literature has shown that the effects of COVID-19 mitigation measures may increase disease burden of common illnesses including HIV, Tuberculosis, Malaria and other key public health outcomes such as maternal mortality. A research program was undertaken to locate disengaged HIV positive women on option B+ and supported them to reengage in care. A 1 year follow up done following the tracing revealed that some women still disengaged from care. We aimed to establish the barriers to and facilitators for reengagement in care among previously traced women on option B+, and how these could have been impacted by the COVID-19 pandemic. Methods This was a cross sectional qualitative study using individual interviews conducted in June and July, 2020, a period when the COVID-19 response measures such as lockdown and restrictions on transport were being observed in Uganda. Study participants were drawn from nine peri-urban and rural public healthcare facilities. Purposive sampling was used to select women still engaged in and those who disengaged from care approximately after 1 year since they were last contacted. Seventeen participants were included. Data was analysed using the content analysis approach. Results Women reported various barriers that affected their reengagement and retention in care during the COVID-19 pandemic. These included structural barriers such as transport difficulties and financial constraints; clinical barriers which included unsupportive healthcare workers, short supply of drugs, clinic delays, lack of privacy and medicine side effects; and psychosocial barriers such as perceived or experienced stigma and non-disclosure of HIV sero-status. Supportive structures such as family, community-based medicine distribution models, and a friendly healthcare environment were key facilitators to retention in care among this group. The COVID-19 pandemic was reported to exacerbate the barriers to retention in care. Conclusions COVID-19 may exacerbate barriers to retention in HIV care among those who have experienced previous disengagement. We recommend community-based models such as drop out centres, peer facilitated distribution and community outreaches as alternative measures for access to ART during the COVID-19 pandemic.

Abstract Background Innate lymphoid cells (ILC) are lymphoid lineage innate immune cells that do not mount antigen-specific responses due to their lack of B and T-cell receptors. ILCs are predominantly found at mucosal surfaces, as gatekeepers against invading infectious agents through rapid secretion of immune regulatory cytokines. HIV associated destruction of mucosal lymphoid tissue depletes ILCs, among other immune dysfunctions. Studies have described limited restoration of ILCs during the first three years of combined antiretroviral therapy (cART). Little is known about restoration of ILCs during long-term cART, particularly in sub-Saharan Africa which hosts increasing numbers of adults with at least a decade of cART. Results We examined phenotypes and function of ILCs from peripheral blood mononuclear cells after 12 years of suppressive cART. We report that ILC1 frequencies (T-BET + CD127 + and CD161 +) were higher in cART-treated HIV-infected relative to age-matched health HIV-negative adults; P = 0.04 whereas ILC precursors (ILCP) were comparable in the two groups (P = 0.56). Interferon gamma (IFN-γ) secretion by ILC1 was higher among cART-treated HIV-infected relative to HIV-negative adults (P = 0.03). Conclusion HIV associated alteration of ILC persisted during cART and may likely affect the quality of host innate and adaptive immune responses during long-term cART.

Attaining viral load (VL) suppression for over 95% of the people living with HIV on antiretroviral therapy is a fundamental step in enabling Uganda and other sub-Saharan African countries to achieve global Sustainable Development Goal targets to end the HIV/AIDS epidemic by 2030. In line with the 2013 World Health Organization recommendations, several sub-Saharan African countries, including Uganda, use a threshold of 1000 HIV viral RNA copies/mL to determine HIV viral non-suppression. The United States Centers for Disease Control and Prevention and the International Association of Providers of AIDS Care deem this threshold very high, and hence recommend using 200 copies/mL to determine viral non-suppression. Using 1000 copies/mL as a threshold ignores people living with HIV who have low-level viraemia (LLV; HIV VL of at least 50 copies/mL but less than 1000 copies/mL). Despite the 2021 World Health Organization recommendations of using intensive adherence counselling for people living with HIV with LLV, several sub-Saharan African countries have no interventions to address LLV. However, recent studies have associated LLV with increased risks of HIV drug resistance, virologic failure and transmission. The purpose of this narrative review is to provide insights on the emerging concern of LLV among people living with HIV receiving antiretroviral therapy in sub-Saharan Africa. The review also provides guidance for Uganda and other sub-Saharan African countries to implement immediate appropriate interventions like intensive adherence counselling, reducing VL thresholds for non-suppression and conducting more research to manage LLV which threatens progress towards ending HIV by 2030.

BackgroundDental caries is a multifactorial disease that affects many people. Even though microorganisms play a crucial role in causing dental caries, diagnosis is routinely macroscopic. In order to improve early detection especially in HIV patients who are disproportionately affected, there is need to reconcile the macroscopic and microscopic characteristics of dental caries. Therefore, the aim of this study was to characterize the oral microbiota profile along the decayed, missing, filled teeth (DMFT) index using amplicon sequencing data.MethodsAmplicon sequencing of the V6-V8 region of the 16S rRNA gene was done on DNA recovered from whole unstimulated saliva of 59 HIV positive and 29 HIV negative individuals. The microbial structure, composition and co-occurrence networks were characterized using QIIME-2, Phyloseq, Microbiome-1.9.2 and Metacoder in R.ResultsWe characterized the oral microbiota into 2,093 operational taxonomic units (OTUs), 21 phyla and 239 genera from 2.6 million high quality sequence reads. While oral microbiota did not cluster participants into distinct groups that track with the DMFT index, we observed the following: (a) The proportion of accessory microbiota was highest in the high DMFT category while the core size (∼50% of richness) remained relatively stable across all categories. (b) The abundance of core genera such as Stomatobaculum, Peptostreptococcus and Campylobacter was high at onset of dental caries, (c) A general difference in oral microbial biomass. (d) The onset of dental caries (low DMFT) was associated with significantly lower oral microbial entropy.ConclusionsAlthough oral microbial shifts along the DMFT index were not distinct, we demonstrated the potential utility of microbiota dynamics to characterize oral disease. Therefore, we propose a microbial framework using the DMFT index to better understand dental caries among HIV positive people in resource limited settings.

Abstract Background Research on the management of complications of chemotherapy is important in facilitating the growing approaches to individualized patient management. Hence the need to document patient’s perspectives about chemotherapy-induced mucositis and the support they need from cancer care teams. Methods We carried out a qualitative study using in-depth interviews (IDI) and focus group discussions (FGD). We collected patient’s experiences on chemotherapy-induced mucositis by conducting 5 FGD and 13 IDIs. Results One glaring improvement that we need to make is the provision of information and counseling before, during, and after chemotherapy. Additionally, we need to explore inexpensive mucositis preventive strategies to aid our patients as they undergo treatment. Conclusion As a country, we must move away from taking cancer patients’ needs as those of common tropical diseases. This will allow us to provide that extra help needed outside the usual diagnosis and administration of medication.

Abstract Background Translational research is a process of applying knowledge from basic biology and clinical trials to techniques and tools that address critical medical needs. Translational research is less explored in the Ugandan health system, yet, it is fundamental in enhancing human health and well-being. With the current high disease burden in Uganda, there are many opportunities for exploring, developing and utilising translational research. Main body In this article, we described the current state, barriers and opportunities for translational research in Uganda. We noted that translational research is underutilised and hindered by limited funding, collaborations, laboratory infrastructure, trained personnel, equipment and research diversity. However, with active collaborations and funding, it is possible to set up and develop thriving translational research in Uganda. Researchers need to leverage existing international collaborations to enhance translational research capacity development. Conclusion Expanding the integration of clinical and translational research in Uganda health care system will improve clinical care.

Abstract Background Chest X-ray (CXR) interpretation remains a central component of the current World Health Organization recommendations as an adjuvant test in diagnosis of smear-negative tuberculosis (TB). With its low specificity, high maintenance and operational costs, utility of CXR in diagnosis of smear-negative TB in high HIV/TB burden settings in the Xpert MTB/RIF era remains unpredictable. We evaluated accuracy and additive value of CXR to Xpert MTB/RIF in the diagnosis of TB among HIV-positive smear-negative presumptive TB patients. Methods HIV co-infected presumptive TB patients were recruited from the Infectious Diseases Institute outpatient clinic and in-patient medical wards of Mulago Hospital, Uganda. CXR films were reviewed by two independent radiologists using a standardized evaluation form. CXR interpretation with regard to TB was either positive (consistent with TB) or negative (normal or unlikely TB). Sensitivity, specificity and predictive values of CXR and CXR combined with Xpert MTB/RIF for diagnosis of smear-negative TB in HIV-positive patients were calculated using sputum and/or blood mycobacterial culture as reference standard. Results Three hundred sixty-six HIV co-infected smear-negative participants (female, 63.4%; hospitalized, 68.3%) had technically interpretable CXR. Median (IQR) age was 32 (28–39) years and CD4 count 112 (23–308) cells/mm3. Overall, 22% (81/366) were positive for Mycobacterium tuberculosis (Mtb) on culture; 187/366 (51.1%) had CXR interpreted as consistent with TB, of which 55 (29.4%) had culture-confirmed TB. Sensitivity and specificity of CXR interpretation in diagnosis of culture-positive TB were 67.9% (95%CI 56.6–77.8) and 53.7% (95%CI 47.7–59.6) respectively, while Xpert MTB/RIF sensitivity and specificity were 65.4% (95%CI 54.0–75.7) and 95.8% (95%CI 92.8–97.8) respectively. Addition of CXR to Xpert MTB/RIF had overall sensitivity and specificity of 87.7% (95%CI 78.5–93.9) and 51.6% (95%CI 45.6–57.5) respectively; 86.2% (95%CI 75.3–93.5) and 48.1% (95%CI 40.7–55.6) among inpatients and 93.8% (95%CI 69.8–99.8) and 58.0% (95%CI 47.7–67.8) among outpatients respectively. Conclusion In this high prevalence TB/HIV setting, CXR interpretation added sensitivity to Xpert MTB/RIF test at the expense of specificity in the diagnosis of culture-positive TB in HIV-positive individuals presenting with TB symptoms and negative smear. CXR interpretation may not add diagnostic value in settings where Xpert MTB/RIF is available as a TB diagnostic tool.

Abstract Background Nephrotic syndrome is the most common glomerulopathy among children aged 2–18 years and high dose corticosteroids are the backbone of its management. Potentially blinding ocular complications often result from nephrotic syndrome and/or its treatment. We conducted a study to determine the prevalence and predictors of ocular complications among children undergoing nephrotic syndrome treatment at Mulago National Referral Hospital. Methods This was a cross-sectional study conducted for three [3] months at the pediatric renal unit of Mulago National Referral Hospital (MNRH). Data from a consecutive sample of 100 children was collected using a semi-structured questionnaire, entered into Epi-data 4.4.2 and exported to STATA 14 for analysis at univariate, bivariate and multivariate levels. A robust Poisson regression model was used to identify predictors of ocular complications. Results Out of 100 patients examined, 80(80%) had ocular complications. The median age was 10 (IQR: 7–12) and 52 (52%) were girls. The most frequent complications were hypertrichosis and refractive errors in 71% (95%CI 61.1–79.6) and 56% (95%CI 45.7–65.9) of the patients respectively. Age above 10 years was the predictor for ocular complications with a RR = 1.37 (95%CI:1.14–1.64) p = 0.001. Conclusions We found a high prevalence of ocular complications among children with nephrotic syndrome in this tertiary hospital. The predictor of ocular complications was age greater than 10 years. We recommend that all children with nephrotic syndrome undergo a baseline ocular examination prior to commencement of treatment and be reviewed periodically by an ophthalmologist.

IntroductionThe burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa with untreated hypertension being a major contributing factor. Understanding the magnitude of the problem and risk factors associated with HIV and long-term antiretroviral therapy (ART) is critically important for designing effective programs for diagnosing and treating hypertension in Kenya.MethodsIn this cross-sectional study, we enrolled 300 persons with HIV (PWH) on long term ART (≥6 months) and 298 HIV-negative adults seeking care at the Kisumu County Hospital between September 2017 and May 2018. Hypertension was defined as blood pressure of ≥140/90mmHg or a previous hypertension diagnosis. Multivariate regression was used to assess the association between hypertension and HIV adjusting for age, sex, and known CVD risk factors.ResultsOverall prevalence of hypertension was 22%. PWH had a lower prevalence of hypertension than HIV-negative persons (16% vs 27% respectively; p40 years, body mass index (BMI) >25 kg/m2 and low-density lipoproteins ≥130mg/dL. Among PWH, being older than 40 years and higher BMI >30 kg/m2 were associated with hypertension.ConclusionPrevalence of hypertension was high, affecting nearly one in every 4 adults, and associated with older age, higher BMI and high low-density lipoproteins. PWH on long-term ART had significantly lower prevalence of hypertension compared to HIV-negative individuals, potentially due to increased access to healthcare services and interaction with prevention messaging. Interventions to increase screening for and prevention of hypertension in the community for all adults are warranted.

Background. The majority of patients with retinoblastoma, the most common intraocular cancer of childhood, are found in low-and middle-income countries (LMICs), with leukocoria being the most common initial presenting sign and indication for referral. Findings from the current study serve to augment earlier findings on the clinical presentation and outcomes of children with retinoblastoma in Uganda. Methods. This was a retrospective study in which we reviewed records of children admitted with a diagnosis of retinoblastoma at the Uganda Cancer Institute from January 2009 to February 2020. From the electronic database, using admission numbers, files were retrieved. Patient information was recorded in a data extraction tool. Results. A total of 90 retinoblastoma patients were studied, with a mean age at the first Uganda Cancer Institute (UCI) presentation of 36.7 months. There were more males (57.8%) than females, with a male to female ratio of 1.37 : 1. The majority (54.4%) had retinoblastoma treatment prior to UCI admission. The most common presenting symptoms were leukocoria (85.6%), eye reddening (64.4%), and eye swelling (63.3%). At 3 years of follow-up after index admission at UCI, 36.7% of the patients had died, 41.1% were alive, and 22.2% had been lost to follow-up. The median 3-year survival for children with retinoblastoma in our study was 2.18 years. Significant predictors of survival in the multivariate analysis were follow-up duration (P̲

IntroductionDiabetic retinopathy (DR) is one of the major complications of diabetes mellitus and is a significant cause of blindness worldwide. In Uganda, the prevalence of diabetes is approximately 2.7% of the urban population and 1% in rural areas. Many diabetics cannot access an eye exam due to the lack of less costly and user-friendly equipment that primary eye workers can use. Smartphone-based fundus photography allows for a cheap and mobile fundus examination. The study aimed to determine the sensitivity and specificity of the Portable Eye Examination Kit (PEEK) retina compared to a standard ophthalmic fundus camera (Zeiss Visucam 200) for the diagnosis of DR.MethodsFrom January-March 2020, 286 people with diabetes (type 1 & 2) patients were seen at Kiruddu National referral hospital diabetes clinic. All participants had funduscopy with PEEK retina and the standard ophthalmic fundus camera following ophthalmic examination and pupillary dilation. The PEEK retina's sensitivity, specificity and reliability were determined using an ophthalmic fundus camera as the gold standard.ResultsThe participants' mean age was 51 with a standard deviation of ±11years, 213 (74.5%) were females, and the majority (93.4%) had Type 2 diabetes. The overall Sensitivity of PEEK retina for DR was 84% (95% CI 70.9-83.5), while the specificity was 79.9% (95% CI 76-83.5) with a positive predictive value (PPV) of 30.9% (95% CI 23.2-39.4) and a negative predictive value (NPV) of 97.9% (95% CI 95.9-99.1).ConclusionsPEEK retina has high sensitivity and specificity, making it suitable for screening and diagnostic purposes. Therefore, we recommend the integration of the PEEK retina in the screening and diagnosis of DR in resource-limited settings.

BackgroundHIV testing uptake remains low among men in sub-Saharan Africa. HIV self-testing (HIVST) at the workplace is a novel approach to increase the availability of, and access to, testing among men. However, both access and linkage to posttest services remain a challenge. ObjectiveThe aim of this protocol is to describe a cluster randomized trial (CRT)—Workplace-Based HIV Self-testing Among Men (WISe-Men)—to evaluate the effect of HIVST in workplace settings on the uptake of HIV testing services (HTS) and linkage to treatment and prevention services among men employed in private security services in Uganda. MethodsThis is a two-arm CRT involving men employed in private security services in two Ugandan districts. The participants in the intervention clusters will undergo workplace-based HIVST using OraQuick test kits. Those in the control clusters will receive routine HTS at their work premises. In addition to HTS, participants in both the intervention and control arms will undergo other tests and assessments, which include blood pressure assessment, blood glucose and BMI measurement, and rapid diagnostic testing for syphilis. The primary outcome is the uptake of HIV testing. The secondary outcomes include HIV status reporting, linkage into HIV care and confirmatory testing following HIVST, initiation of antiretroviral therapy following a confirmatory HIV test, the uptake of voluntary medical male circumcision, consistent condom use, and the uptake of pre-exposure prophylaxis by the most at-risk populations. ResultsParticipant enrollment commenced in February 2020, and the trial is still recruiting study participants. Follow-up for currently enrolled participants is ongoing. Data collection and analysis is expected to be completed in December 2021. ConclusionsThe WISe-Men trial will provide information regarding whether self-testing at worksites increases the uptake of HIV testing as well as the linkage to care and prevention services at male-dominated workplaces in Uganda. Additionally, the findings will help us propose strategies for improving men’s engagement in HTS and ways to improve linkage to further care following a reactive or nonreactive HIVST result. Trial RegistrationClinicalTrials.gov NCT04164433; https://clinicaltrials.gov/ct2/show/NCT04164433 International Registered Report Identifier (IRRID)DERR1-10.2196/25099

Onchocerciasis is known to cause skin lesions and blindness, but there is also epidemiological evidence that onchocerciasis is associated with epilepsy, including nodding syndrome. We carried out ocular exams in persons with epilepsy in Mahenge, an onchocerciasis endemic area with a high prevalence of epilepsy in Tanzania. We recruited 278 consecutive persons with epilepsy attending the epilepsy clinic at Mahenge hospital and satellite clinics in rural villages. They underwent a general physical and a detailed ocular examination and were tested for onchocerciasis Ov16 IgG4 antibodies. Glaucoma was defined by a raised intraocular pressure above 21 mmHg with evidence of typical glaucomatous disc changes in one or both eyes. Among the 278 participants, median age 27 (IQR 21–38) years, 55.4% were female; 151/210 (71.9%) (95% CI: 65.3–77.9) were Ov16 positive. The most frequent ophthalmic lesions were glaucoma (33.1%), vitreous opacities (6.5%) and cataracts (2.9%). In multivariate analysis, glaucoma (adjusted IRR = 1.46; 95% CI: 1.24–1.70) and age (adjusted IRR = 1.01; 95% CI: 1.01–1.02) were significantly associated with onchocerciasis. In conclusion, a high prevalence of glaucoma was observed among Ov16 positive persons with epilepsy. Persons with epilepsy with O. volvulus infection should undergo screening for glaucoma to prevent one of the causes of preventable blindness.

Introduction: Partnerships are essential to creating effective global health leadership training programs. Global pandemics, including the HIV/AIDS pandemic, and more recently the COVID-19 pandemic, have tested the impact and stability of healthcare systems. Partnerships must be fostered to prepare the next generation of leaders to collaborate effectively and improve health globally. Objectives: We provide key matrices that predict success of partnerships in building global health leadership capacity. We highlight opportunities and challenges to building effective partnerships and provide recommendations to promote development of equitable and mutually beneficial partnerships. Findings: Critical elements for effective partnership when building global health leadership capacity include shared strategic vision, transparency and excellent communication, as well as intentional monitoring and evaluation of the partnership, not just the project or program. There must be recognition that partnerships can be unpredictable and unequal, especially if the end is not defined early on. Threats to equitable and effective partnerships include funding and co-funding disparities between partners from high-income and low-income countries, inequalities, unshared vision and priorities, skewed decision-making levels, and limited flexibility to minimize inequalities and make changes. Further, imbalances in power, privilege, position, income levels, and institutional resources create opportunities for exploitation of partners, particularly those in low-income countries, which widens the disparities and limits success and sustainability of partnerships. These challenges to effective partnering create the need for objective documentation of disparities at all stages, with key milestones to assess success and the environment to sustain the partnerships and their respective goals. Conclusions: Developing effective and sustainable partnerships requires a commitment to equality from the start by all partners and an understanding that there will be challenges that could derail otherwise well-intended partnerships. Guidelines and training on evaluation of partnerships exist and should be used, including generic indicators of equity, mutual benefit, and the added value of partnering. Key Takeaways Effective partnerships in building global health leadership capacity require shared strategic vision and intentional monitoring and evaluation of goals Inequalities in partnerships may arise from disparities in infrastructure, managerial expertise, administrative and leadership capacity, as well as limited mutual benefit and mutual respect To promote equitable and effective partnerships, it is critical to highlight and monitor key measures for success of partnerships at the beginning of each partnership and regularly through the lifetime of the partnership. We recommend that partnerships should have legal and financial laws through executed memoranda of understanding, to promote accountability and facilitate objective monitoring and evaluation of the partnership itself. More research is needed to understand better the contextual predictors of the broader influence and sustainability of partnership networks in global health leadership training.

Abstract Background Male partner involvement has been shown to increase mothers’ uptake of Prevention of Mother-to-Child Transmission of HIV (PMTCT) and improve maternal and infant HIV treatment outcomes. Currently, male involvement in PMTCT is measured primarily through men’s attendance at HIV testing and counselling which may not be a true reflection of their engagement. This study therefore set out to explore the meaning of male partner involvement and propose a definition and theoretical model of this concept in PMTCT in Uganda. Methods Eight focus group discussions and five in-depth interviews were conducted with couples at three public health facilities and community members in the health facility catchment areas in Uganda. The study employed a grounded theory approach underpinned by the pragmatic philosophical paradigm. Data were analyzed using the constant comparative method, performing three levels of open, axial, and selective coding. Results Of the 61 participants, 29 (48%) were male and the majority 39 (63.9%) were in long term marital relationships, while about half were self-employed 29 (47.5%). Three themes emerged for the meaning of male involvement in PMTCT (a) HIV treatment support (b) economic support and (c) psychosocial support. HIV treatment support included adherence support, couples’ HIV counseling and testing, and clinic attendance during and after pregnancy. Participants expressed that men were engaged in PMTCT when they offered economic support by providing basic needs and finances or when they included their female partners in financial planning for the family. Psychosocial support arose from the female participants who defined male involvement as family support, perceived societal recognition and emotional support. Emotional support also included the absence of harm resulting from women’s disclosure of HIV test results to their male partner. Conclusions This study proposes a new definition for male partner involvement in PMTCT in Uganda. The definition extends beyond men’s clinic attendance and HIV testing and counselling. Further research should seek to develop and validate tools to accurately measure male partner involvement as the next step in the development of interventions to improve PMTCT outcomes.

Abstract Background Chronic Human Immunodeficiency Virus (HIV) infection is associated with reduced saliva flow rate due to infiltration of HIV and proliferation of CD8 lymphocytes in salivary glands. It is unclear whether HIV infection and antiretroviral therapy (ART) increase caries risk. This study aimed to determine the prevalence and factors associated with dental caries in HIV infected adults attending the Mulago Immune Suppression Syndrome (ISS) clinic in Uganda. Methods A cross-sectional study was conducted among HIV infected persons. Dental examinations were performed by two calibrated dentists using the WHO Radke’s caries classification criteria and reported using the decayed (D), missing (M), filled (F), teeth (DMFT) index. The prevalence and factors associated with dental caries was examined through linear regression analyses. Results Overall, 748 participants (females = 491, 65.6%) with a mean age of 39 ± 9.4 years were included in the final analysis; of whom 83.7% had caries (DMFT> 0), with a significantly (p 2 years but 5 years 6.6 ± 6.0 p

Abstract Background Of the estimated 130,000 children living with HIV in Uganda, 47% are receiving ART. Only 39.3% have suppressed HIV-1 viral load to levels below 50 copies per ml. Caregivers are key drivers of adherence to achieve viral suppression in children. We investigated the challenges and potential support required by caregivers of ART-treated children. Methods A qualitative study was conducted within the Infectious Diseases Institute paediatric ART program in Kampala and Hoima districts. Caregivers of children with viral loads above 1000 copies were purposively sampled and engaged in five focus group discussions (FGD). The FGD guide highlighted questions on challenges that caregivers face and the kind of support they required to improve children’s ART adherence. Thematic analysis using the inductive approach was used. All the transcripts were read, coded and emergent themes determined. Results Overall, 37 caregivers participated in five FGD, of whom 29 (78%) were female, 28 (76%) were HIV-infected and 25 (68%) were biological parents of the children. The elicited challenges were either in failure to attend the counselling sessions or in supporting adherence to medication. Individual and health system challenges such as competing priorities, logistics, poor quality of counselling and lack of reminders prevented attendance at counselling sessions. Five themes emerged as challenges to supporting adherence: i) environmental (school activities, working away from home), ii) personal (non-disclosure, stigma), iii) psychological (guilt), iv) financial (lack of food and transport) and v) child-related (fatigue and peer influence). Three major themes emerged for the support that caregivers needed namely: a) health system reforms (clinic appointments outside school hours, minimize ART drug stock outs and improve quality of counselling), b) psychosocial support (support with disclosure of HIV status to children and their families, more frequent peer support groups and parenting classes) and c) economic empowerment (training in vocational skills, school fees support and opportunities to initiate income generating activities). Discussion and conclusion To achieve viral suppression, ART programs require targeted efforts to provide specific health facility requirements, psychological and economic needs of ART-treated children and their caregivers. Integration of HIV treatment with programs for orphans and vulnerable children may improve viral suppression rates.

Abstract Background The estimated number of people living with human immunodeficiency virus (HIV) (PLHIV) in Uganda is 1.5 million (7.3%). As of June 2016, 60% (898,197) of PLHIV were enrolled and receiving antiretroviral therapy (ART). In scientific literature, the effect of HIV and ART on dental caries remains equivocal. At the Prosthetics Clinic of the Department of Dentistry, Makerere University College of Health Sciences, we have seen a number of PLHIV who require replacement of missing teeth with partial or complete dentures as a result of extensive caries. Here we report a case of an HIV positive female patient with extensive dental caries resulting in complete edentulous jaws, associated with psychological stress and stigmatization. Case presentation A 52-year-old patient, HIV positive for fourteen (14) years and receiving antiretroviral therapy (ART) for the last four years wanted to replace her missing teeth for effective feeding and cosmetic reasons. A diagnosis of partially edentulous maxillary and mandibular arches, cervical caries of tooth # 12, 15, 25, 34 and retained roots of tooth # 11, 13, 22 and 35 was made. Following oral health education and mouth preparation, this patient received a set of removable acrylic full upper and lower dentures. Conclusion This case may represent the long-term effects of HIV and ART on oral health status especially tooth surfaces in some PLHIV. Further evaluation is required to ascertain if this was an isolated case or it is a common finding among HIV positive adult patients receiving long-term ART in sub-Saharan Africa. Information emerging from these studies would establish the magnitude of dental caries among PLHIV and guide the development of appropriate oral health care guidelines in the management of people living with HIV.

Expansion of Antiretroviral Therapy (ART) programs in sub-Saharan Africa (SSA) has increased the number of people accessing treatment. However, the number of males accessing and being retained along the human immunodeficiency virus (HIV) care cascade is significantly below the UNAIDS target. Male gender has been associated with poor retention in HIV care programs, and little is known about strategies that reduce attrition of men in ART programs. This review aimed to summarize any studies on strategies to improve retention of heterosexual males in HIV care in SSA. An electronic search was conducted through Ovid® for three databases (MEDLINE®, Embase and Global Health). Studies reporting interventions aimed at improving retention among heterosexual men along the HIV care cascade were reviewed. The inclusion criteria included randomized-controlled trials (RCTs), prospective or retrospective cohort studies that studied adult males (≥15years of age), conducted in SSA and published between January 2005 and April 2019 with an update from 2019 to 2020. The search returned 1958 articles, and 14 studies from eight countries met the inclusion criteria were presented using the PRISMA guidelines. A narrative synthesis was conducted. Six studies explored community-based adherence support groups while three compared use of facility versus community-based delivery models. Three studies measured the effect of national identity cards, disclosure of HIV status, six-monthly clinic visits and distance from the health center. Four studies measured risk of attrition from care using hazard ratios ranging from 1.2-1.8, four studies documented attrition proportions at an average of 40.0% and two studies an average rate of attrition of 43.4/1000PYs. Most (62%) included studies were retrospective cohorts, subject to risk of allocation and outcome assessment bias. A pooled analysis was not performed because of heterogeneity of studies and outcome definitions. No studies have explored heterosexual male- centered interventions in HIV care. However, in included studies that explored retention in both males and females, there were high rates of attrition in males. More male-centered interventions need to be studied preferably in RCTs. Registry number: PROSPERO2020 CRD42020142923 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020142923.

Background: Protecting healthcare workers against COVID-19 disease is crucial, and COVID-19 vaccination is the most effective method to do so. Eye healthcare workers provide routine care in proximity, increasing infection risk, hence their need for full vaccination. This study determined COVID-19 vaccine acceptance and barriers to its uptake among eye healthcare workers practicing in Uganda. Methods: This was a cross-sectional online and telephone survey based on the health belief model (HBM), conducted in June–August 2021. A modified Poisson regression model with robust standard errors was used to determine the factors associated with COVID-19 vaccine acceptance. Results: In total, 300 (85%) of the 357 eye healthcare workers participated in the study with mean age 43 ± 8 years and 182 (60.7%) were men. Overall, 97.6% (95% CI: 95.9–99.4) had accepted and/or were willing to take the COVID-19 vaccine, 65.3% had received a shot of the COVID-19 vaccine, and 97 (32.3%) reported the intention to accept the vaccine when it became available. Among the HBM constructs, high perceived susceptibility and high perceived benefits were significantly associated with COVID-19 vaccine acceptance. Conclusions: The acceptance of the COVID-19 vaccine among eye healthcare workers in Uganda is very high. There is a dire need to make vaccines available to developing nations like Uganda.

Background: The Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) is a collaborative programme supporting excellence in Infection and Immunity (I&I) research in Uganda. Set up in 2008, MUII aims to produce internationally competitive Ugandan and East African I&I research leaders, and develop human and infrastructural resources to support research and training excellence. We undertook an internal evaluation of MUII’s achievements, challenges and lessons learned between 08-2008 and 12-2019, to inform programmes seeking to build Africa’s health research expertise. Methods: Quantitative data were abstracted from programme annual reports. Qualitative data were obtained in 03-04/2019: a cross-sectional evaluation was undertaken among a purposefully selected representative sample of 27 trainees and two programme staff. Qualitative data was analysed according to pre-determined themes of achievements, challenges, lessons learned and recommendations for improvement. Results: By 12-2019, MUII had supported 68 fellowships at master’s-level and above (50% female: 23 Masters, 27 PhD, 15 post-doctoral, three group-leaders) and over 1,000 internships. Fellows reported career advancement, mentorship by experts, and improved research skills and outputs. Fellows have published over 300 papers, secured grants worth over £20m, established over 40 international collaborations, and taken on research and academic leadership positions in the country. Key lessons were: i) Efficient administration provides a conducive environment for high quality research; ii) Institutions need supportive policies for procurement, including provisions for purchases of specific biological research reagents from international manufacturers; iii) Strong international and multi-disciplinary collaboration provides a critical mass of expertise to mentor researchers in development; and iv) Mentorship catalyses young scientists to progress from graduate trainees to productive academic researchers, relevant to society’s most pressing health challenges. Conclusions: Sustainable academic productivity can be achieved through efficient operational support, global collaboration and mentorship to provide solutions to Africa’s health challenges.

Background: The Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) is a collaborative programme supporting excellence in Infection and Immunity (I&I) research in Uganda. Set up in 2008, MUII aims to produce internationally competitive Ugandan and East African I&I research leaders, and develop human and infrastructural resources to support research and training excellence. We undertook an internal evaluation of MUII’s achievements, challenges and lessons learned between August 2008 and December 2019, to inform programmes seeking to build Africa’s health research expertise. Methods: Quantitative data were abstracted from programme annual reports. Qualitative data were obtained in March and April 2019: a cross-sectional evaluation was undertaken among a purposefully selected representative sample of 27 trainees and two programme staff. Qualitative data was analysed according to pre-determined themes of achievements, challenges, lessons learned and recommendations for improvement. Results: By December 2019, MUII had supported 68 fellowships at master’s-level and above (50% female: 23 Masters, 27 PhD, 15 post-doctoral, three group-leader fellows) and over 1,000 internships. Fellows reported career advancement, mentorship by experts, and improved research skills and outputs. Fellows have published over 300 papers, secured grants worth over £20m, established over 40 international collaborations, and taken on research and academic leadership positions in the country. Key lessons for success include the following: efficient administration provides an enabling environment; institutions need supportive policies for procurement, including provisions for purchases of specific biological research reagents from international manufacturers; strong international, multi-disciplinary collaboration provides a critical mass of expertise to mentor researchers in development; and mentorship catalyses young scientists to progress from graduate trainees to productive academic researchers, relevant to society’s most pressing health challenges. Conclusions: Sustainable academic productivity can be achieved through efficient operational support, global collaboration and mentorship to provide solutions to Africa’s health challenges.

Dental caries is still a major public health problem owing to its high prevalence and incidence in several regions. Planning and development of effective preventive and treatment modalities for the management of dental caries demand information on disease pattern and treatment needs of the populations. However, there is a paucity of this information in Uganda. The aim of the present study was to identify the dental caries pattern and treatment needs among Ugandan adolescent students. This was a descriptive cross-sectional study conducted among 11- to 19-year-old adolescents attending two secondary schools in Kampala and Mukono districts of Uganda. At both schools, random sampling was used to select the participating classes and the adolescents. Decayed teeth and treatment needs were recorded using the World Health Organization Basic Oral Health Survey criteria. A total of 406 adolescents comprising of 249 female and 157 male students participated in the study. Data were analysed using STATA, version 12.0. The prevalence of decayed teeth (DT) was expressed as a percentage of individuals with DT score ≥1. The treatment needs were categorised into three groups. Associations between dependent and independent variables were evaluated using cross-tabulation, chi-square test, and Poisson regression analysis. The overall prevalence of decayed teeth was 62.6% and mean DT was 1.7 ± 2.3. A total of 696 decayed teeth were observed, and the molar teeth, particularly the second molar (50.6%), were the most significantly affected. The prevalence of caries was higher in the mandible (51.4%) compared to the maxilla though the difference was not statistically significant. Decayed teeth were significantly (p

Abstract Background The UNAIDS 90–90-90 strategy clearly stipulates that 90% of all people on antiretroviral therapy (ART) should have a suppressed viral load. Intensified adherence counselling (IAC) was recently recommended by WHO to improve viral suppression among ART-treated paediatric and adolescent clients with virological failure. This paper describes the implementation and outcomes of IAC in the first year of implementation in a public ART program, to inform strategic interventions to reach the “third 90” among children. Methods A retrospective chart review was conducted for all children aged 9 months to 19 years with HIV viral loads (VL) ≥ 1000 copies/ml at 15 public health facilities from June 2015–December 2016. Data on initial VL test results, IAC sessions, repeat VL test results, and ART regimen switch were abstracted and analysed for completion of IAC and viral suppression after IAC. Results A total of 449 children had a detectable viral load above 1000 copies/ml, after an average of 3.5 years (SD 5.8) years of ART. 192 (43%) were 10–20 years of age, and 320 (71%) were receiving Nevirapine-based ART regimen. Out of 345 (77%) who completed the recommended three IAC sessions, 62 (23%) achieved viral suppression following IAC. The mean time from 1st to 3rd IAC session was 113 (SD 153) days and 172 (50%) of the children had completed the three sessions within 200 days. Conclusion Suppression rates were low among ART-treated children with virological failure that completed the recommended three IAC sessions. As we move towards having 90% of ART-treated children and adolescents achieve and maintain viral suppression, there is need to re-evaluate the implementation of IAC among children and adolescents to consider both psychosocial and biological factors such as resistance testing for those with multiple detectable viral loads.

Abstract Background Tuberculosis (TB) is the major cause of death in Human Immunodeficiency Virus (HIV)-infected individuals. However, diagnosis of TB in HIV remains challenging particularly when HIV infection is advanced. Several gene signatures and serum protein biomarkers have been identified that distinguish active TB from latent infection. Our study was designed to assess if gene expression signatures and cytokine levels would distinguish active TB in advanced HIV. Methods We conducted a case-control study of whole blood RNA-Seq and plasma cytokine/chemokine analysis in HIV-infected with CD4+ T cell count of ≤ 100 cells/μl, with and without active TB. Next, the overlap of the differentially expressed genes (DEG) with the published signatures was performed and then receiver operator characteristic (ROC) analysis was done on small gene discriminators to determine their performance in distinguishing TB in advanced HIV. ELISA was performed on plasma to evaluate cytokine and chemokine levels. Results Hierarchical clustering of the transcriptional profiles showed that, in general, HIV-infected individuals with TB (TB-HIV) clustered separately from those without TB. IPA indicated that the TB-HIV signature was characterized by an increase in inflammatory signaling pathways. Analysis of overlaps between DEG in our data set with published TB signatures revealed that significant overlap was seen with one TB signature and one TB-IRIS signature. ROC analysis revealed that transcript levels of FcGR1A (AUC = 0.85) and BATF2 (AUC = 0.82), previously reported as consistent single gene classifiers of active TB irrespective of HIV status, performed successfully even in advanced HIV. Plasma protein levels of IFNγ, a stimulator of FcGR1A and BATF2, and CXCL10, also up-regulated by IFNγ, accurately classified active TB (AUC = 0.98 and 0.91, respectively) in advanced HIV. Neither of these genes nor proteins distinguished between TB and TB-IRIS. Conclusions Gene expression of FcGR1A and BATF2, and plasma protein levels of IFNγ and CXCL10 have the potential to independently detect TB in advanced HIV. However, since other lung diseases were not included in this study, these final candidates need to be validated as specific to TB in the advanced HIV population with TB.

Abstract HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery.

Abstract Background Cataracts occur earlier among HIV-infected adults and this is attributed to various intraocular inflammatory processes that result in early degeneration. In this study we purposed to investigate whether HIV infected individuals with cataracts develop heightened intraocular inflammatory processes compared to their HIV negative counterparts by determining the concentration of 8 cytokines in the aqueous humour of HIV-positive adults with cataracts and their HIV-negative counterparts. Methods A cross-sectional study was conducted among consecutive adults with cataracts that were operated in an ophthalmology surgical camp in western Uganda. We determined levels of Granulocyte macrophage stimulating factor (GM-CSF), interleukin 6 (IL-6), interleukin 8 (IL-8), tumour necrotic factor alpha (TNF-a), interferon gamma (IFN-g), interleukin 4 (IL-4), interleukin 2 (IL-2), and interleukin (IL-10) in the aqueous fluid using a multiplexed cytokine analysis. Data was entered in the SPSS version 10 and analyzed using STATA statistical software version 7.0. Categorical and continuous variables were compared using the χ2 test, Fisher’s exact test and the Student’s t-test. Bonferroni correction was used to cater for multiple comparison of p values for the various cytokines. Results The 50 adults that underwent cataract surgery were outdoor peasants with similar exposure hours to UV radiation. The HIV-positive patients were younger {median age 43 years (SD 11.741)} compared to the HIV -negative patients {median age 66.5 years (SD 21.4)}. The mean CD4+ T cell count of the HIV-positive patients was 161 cells /mm3, and 12(48%) had started anti-retroviral therapy (ART). Pro inflammatory cytokines, GM-CSF, IL-8 and IL-10 were significantly higher among HIV-positive individuals (p = 0.001, 0.030,

Abstract Background In the last decade, Makerere University College of Health Sciences (MakCHS) has taken strides in research and training to improve healthcare through collaborative training and research programs. However, there is limited data on the trends of MakCHS faculty contributions to research and on faculty growth to take leading roles in health research. This paper reviews MakCHS faculty research publications over 15.5 years and outlines possible strategies to enhance faculty research outputs. Methods We used a mixed methods approach. A systematic review of research publications by faculty at MakCHS (PubMed and Google Scholar from January 1, 2000, to June 30, 2015) to quantify the number of research articles, areas researched, authorship contribution by MakCHS faculty, source of funding, as well as affiliated local and international collaborations. Graphs were used to shown trends in publications and leadership of authorship by faculty. Annual individual faculty research productivity was presented as publication per capita. Qualitative data on high priority needs to improve research outputs was collected through focus group discussions (FGDs) with faculty members, and analysed manually into emerging themes. Results Of 298 faculty at MakCHS at 2015, 89 (30%) were female and 229 (77%) were junior and mid-level faculty (senior lecturer and below). The PubMed and Google Scholar searches yielded 6927 published articles, of which 3399 (49%) full-text articles were downloaded for analysis, 426/3825 (11%) available as titles/abstracts only, and 598/4423 (14%) were excluded. Only 614 articles were published in 2014, giving a publication per capita of 2.1 for any authorship, and 0.3 for first and last authorship positions. MakCHS faculty increasingly contributed as first, second, third, and last authors. Up to 57% of research was in infectious diseases, followed by non-communicable diseases (20%) and non-communicable maternal child health (11%). Priority needs to improve research outputs, as expressed by faculty, were (1) an institutionally led faculty career development program, (2) skills building in research methods and scientific writing, (3) protected time for research related activities, (4) opportunities for collaborative research, and (5) use of individual development plans. Conclusion Faculty research productivity was low and dominated by infectious diseases and non-communicable disease research. There is a need for structured institutional support to optimise faculty research outputs. Only with increased research productivity will MakCHS and other academic institutions be able to make a significant contribution in addressing national health challenges.

Background. Combination antiretroviral therapy (cART) initiation in hospital settings, where individuals often present with undiagnosed, untreated, advanced HIV disease, is not well understood. Methods. A cross-sectional study was conducted to determine a period prevalence of cART initiation within two weeks of eligibility, as determined at hospitalization. Using a pretested and precoded data extraction tool, data on cART initiation status and reason for not initiating cART was collected. Phone calls were made to patients that had left the hospital by the end of the two-week period. Delayed cART initiation was defined as failure to initiate cART within two weeks. Sociodemographic characteristics, WHO clinical stage, CD4 count, cART initiation status, and reasons for delayed cART initiation were extracted and analyzed. Results. Overall, 386 HIV-infected adults were enrolled, of whom 289/386 (74.9%) had delayed cART initiation, 77/386 (19.9%) initiated cART, and 20/386 (5.2%) were lost-to-follow-up, within two weeks of cART eligibility. Of 289 with delayed ART initiation, 94 (32.5%) died within two weeks of cART eligibility. Patients with a CD4 cell count≥ 50 cells/μl and who resided in ≥8 kilometers from the hospital were more likely to have delayed cART initiation [adjusted odds ratio (AOR) 2.34, 95% CI: 1.33-4.10, p value 0.003; and AOR 1.92, 95% CI: 1.09-3.40, p value 0.025; respectively]. Conclusion. Up to 75% of hospitalized HIV-infected, cART-naïve, cART-eligible patients did not initiate cART and had a 33% pre-ART mortality rate within two weeks of eligibility for cART. Hospital based strategies to hasten cART initiation during hospitalization and electronic patient tracking systems could promote active linkage to HIV treatment programs, to prevent HIV/AIDS-associated mortality in resource-limited settings.

Abstract Background Disclosure of parental HIV status is associated with a number of positive outcomes such as improved adherence to clinic appointments, lower levels of parental anxiety and depression, and mutual emotional support between parents and their children. Very few studies in low-resource settings have addressed the issues of parental disclosure of their HIV status to their children. Methods A cross-sectional study was conducted among adult parents attending HIV/AIDS prevention, care and treatment clinic at Makerere University Infectious Diseases Institute (IDI), Kampala, Uganda. Participants were interviewed using the Parent Disclosure Interview (PDI) questionnaire which is a standard tool developed specifically for HIV infected parents. Data were analyzed using STATA version 13.1. Results Of 344 participants, only 37 % had told at least one of their children that they were HIV positive. Barriers to disclosure were fear that children may tell other people about the parent’s HIV status, desire not to worry or upset children and perceptions that children may not understand. Age of the parent, religion and having someone committed to care of the children were positively associated with parental disclosure of their HIV positives status. Attainment of tertiary level of education was negatively associated with parental disclosure of their HIV status. Conclusions Parental disclosure of a positive HIVstatus to their children is still low in urban Kampala. There is therefore need to develop locally relevant interventions so as to increase rates of parental disclosure of a positive HIV status to their children and thus promote open and honest discussions about HIV/AIDS at family level.

Limited data are available on the experiences of parental HIV disclosure to children in Uganda. We conducted a qualitative study comprising sixteen in-depth interviews and four focus group discussions with parents receiving highly active antiretroviral therapy. Analysis was done using Atlas.ti qualitative research software. Back-and-forth triangulation was done between transcripts of the in-depth interviews and focus group discussions, and themes and subthemes were developed. Barriers to parents’ disclosure included perceptions that children are too young to understand what HIV infection means and fears of secondary disclosure by the children. Immediate outcomes of disclosure included children getting scared and crying, although such instances often gave way to more enduring positive experiences for the parents, such as support in adherence to medical care, help in household chores, and a decrease in financial demands from the children. Country-specific interventions are needed to improve the process of parental HIV disclosure to children and this should encompass preparation on how to deal with the immediate psychological challenges associated with the parent’s disclosure.

Introduction. The presentation of acute coronary syndrome (ACS) in young HIV patients may be atypical with different pathophysiological and clinical features. Acute coronary thrombosis, as a presentation of acute coronary syndrome in young patients with HIV, raises diagnostic and treatment challenges. Case Presentation. We describe a case of a 33-year-old African man, without traditional atherosclerotic risk factors, who presented with chest pain of acute onset. Emergent coronary angiography revealed extensive thrombus in the left anterior descending coronary artery with no evidence of atherosclerosis in this or other coronary vessels. Plaque and/or thrombus prolapse through the stent was noted following percutaneous coronary intervention (PCI). Resolution of chest pain and improvement in ST-segment elevation was noted after the procedure. A diagnosis of HIV infection was made during the workup for HIV infection. Conclusion. In young patients without traditional risk factors, HIV infection is a possible etiological factor for spontaneous coronary artery thrombosis. Percutaneous coronary intervention in patients with this presentation may be compounded with atherothrombotic complications. The likely pathophysiological pathway is superficial endothelial cell denudation as a result of chronic inflammation and immune activation.

The existing World Health Organization diagnostic algorithms for smear-negative TB perform poorly in HIV-infected individuals. New TB diagnostics such as urine TB lipoarabinomannan (LAM) could improve the accuracy and reduce delays in TB diagnosis in HIV-infected smear-negative presumptive TB. We sought to determine predictors for MTB culture-positivity among these patients.This study was nested into a prospective evaluation of HIV-infected outpatients and inpatients clinically suspected to have TB who were screened by smear-microscopy on two spot sputum samples. Data on socio-demographics, clinical symptoms, antiretroviral therapy, CXR, CD4 count, mycobacterial sputum and blood cultures and TB-LAM were collected. Logistic regression and conditional inference tree analysis were used to determine the most predictive indicators for MTB culture-positivity.Of the 418 smear-negative participants [female, 64%; median age (IQR) 32 (28-39) years, median CD4 106 (IQR 22 - 298) cells/mm3], 96/418 (23%) were sputum and/ or blood culture-positive for Mycobacterium tuberculosis (MTB) complex. Abnormal CXR (aOR 3.68, 95% CI 1.76- 7.71, p=0.001) and positive urine TB-LAM (aOR 6.21, 95% CI 3.14-12.27, p< 0.001) were significantly associated with MTB culture-positivity. Previous TB treatment (aOR 0.41, 95% CI 0.17-0.99, p=0.049) reduced the likelihood of a positive MTB culture. A conditional inference tree analysis showed that positive urine TB-LAM and abnormal CXR were the most predictive indicators of MTB culture-positivity. A combination of urine TB-LAM test and CXR had sensitivity and specificity of 50% and 86.1% respectively overall, and 70.8% and 84.1% respectively among those with CD4

The increased immune activation and inflammation of chronic HIV-infection and the characteristic dyslipidemias associated with HIV infection and antiretroviral therapy (ART) contribute to an increased risk of atherosclerotic vascular disease among HIV-infected adults. There is an emerging need to understand determinants of cardiovascular disease (CVD) among individuals aging with HIV in sub-Saharan Africa. We determined the prevalence of subclinical atherosclerosis [carotid intima media thickness (CIMT) ≥ 0.78 mm] and its correlation with traditional CVD risk factors among HIV-infected adults.In a cross-sectional study, HIV-infected adults (ART-naïve and ART-treated) were consecutively selected from patients' enrollment registers at two large HIV clinics at Mulago Hospital, Kampala, Uganda. We measured traditional CVD risk factors including age, biophysical profile, fasting blood sugar and serum lipid profile as well as biomarkers of inflammation. High resolution ultrasound was used to measure common carotid CIMT.Of 245 patients, Median age [Interquartile range (IQR)] 37 years (31-43), 168 (69%) were females; and 100 (41%) were ART-treated for at least 7 years. Overall, 34/186 (18%) had subclinical atherosclerosis; of whom 15/108 (14%) were ART-naïve whereas 19/78 (24%) were ART-treated. Independent predictors of subclinical atherosclerosis included age [odds ratio (OR) 1.83 per 5-year increase in age; 95% confidence interval (CI) 1.24-2.69; p = 0.002], body mass index (BMI); OR 1.15; CI 1.01-1.31; p = 0.041 and high low density lipoprotein (LDL) [OR 2.99; CI 1.02-8.78, p = 0.046]. High sensitivity C-reactive protein (hsCRP) was positively correlated with traditional cardio-metabolic risk factors including waist circumference (r = 0.127, p = 0.05), triglycerides (r = 0.19, p = 0.003) and Total Cholesterol: High Density Lipoprotein ratio (TC:LDL) (r = 0.225, p

Linkage of HIV-infected pregnant women to HIV care remains critical for improvement of maternal and child outcomes through prevention of maternal-to-child transmission of HIV (PMTCT) and subsequent chronic HIV care. This study determined proportions and factors associated with intra-facility linkage to HIV care and Early Infant Diagnosis care (EID) to inform strategic scale up of PMTCT programs.A cross-sectional review of records was done at 2 urban and 3 rural public health care facilities supported by the Infectious Diseases Institute (IDI). HIV-infected pregnant mothers, identified through routine antenatal care (ANC) and HIV-exposed babies were evaluated for enrollment in HIV clinics by 6 weeks post-delivery.Overall, 1,025 HIV-infected pregnant mothers were identified during ANC between January and June, 2012; 267/1,025 (26%) in rural and 743/1,025 (74%) in urban facilities. Of these 375/1,025 (37%) were linked to HIV clinics [67/267(25%) rural and 308/758(41%) urban]. Of 636 HIV-exposed babies, 193 (30%) were linked to EID. Linkage of mother-baby pairs to HIV chronic care and EID was 16% (101/636); 8/179 (4.5%)] in rural and 93/457(20.3%) in urban health facilities. Within rural facilities, ANC registration

The existing diagnostic algorithms for sputum smear-negative tuberculosis (TB) are complicated, time-consuming, and often difficult to implement. The decision to initiate TB treatment in resource-limited countries is often largely based on clinical predictors. We sought to determine the clinical predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum smear-negative TB suspects using sputum culture as a reference standard.Out-patient HIV-TB integrated urban clinic in Kampala, Uganda.HIV-infected TB suspects were screened using sputum smear microscopy, and mycobacterial sputum liquid and solid cultures were performed. Smear results were made available to the clinician who made a clinical decision on empiric TB treatment initiation for sputum smear-negative patients. Clinic records were reviewed for patients whose sputum smears were negative to collect data on socio-demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB treatment initiation.Of 253 smear-negative TB suspects, 56% (142/253) were females, median age 38 IQR (31-44) years, with a median CD4 cell count of 291 IQR (150-482) cells/mm(3). Of the 85 (33.6%) smear-negative patients empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture positive compared to only 18 (10.7%) of the 168 untreated patients (p

Malnutrition is common among HIV-infected individuals and is often accompanied by low serum levels of micronutrients. Vitamin B-12 deficiency has been associated with various factors including faster HIV disease progression and CD4 depletion in resource-rich settings. To describe prevalence and factors associated with sub-optimal vitamin B-12 levels among HIV-infected antiretroviral therapy (ART) naïve adults in a resource-poor setting, we performed a cross-sectional study with a retrospective chart review among individuals attending either the Mulago-Mbarara teaching hospitals' Joint AIDS Program (MJAP) or the Infectious Diseases Institute (IDI) clinics, in Kampala, Uganda. Logistic regression was used to determine factors associated with sub-optimal vitamin B-12. The mean vitamin B-12 level was 384 pg/ml, normal range (200-900). Sub-optimal vitamin B-12 levels (

Background Stavudine is no longer recommended as part of first‐line therapy for patients initiating antiretroviral therapy (ART) in Uganda. Most patients are currently initiated on zidovudine‐containing regimens, which can induce anaemia. We investigated the risk factors for early severe anaemia in the first six months of ART initiation. Methods We defined baseline (ART initiation) anaemia as haemoglobin (Hb) ≤9.5 g/dL, baseline severe anaemia as Hb ≤8 g/dL, and early severe anaemia as Hb ≤8 g/dL within six months of ART initiation. Risk factors for the development of early severe anaemia were analyzed using a multivariable logistic regression model. Results In total, 5494 patients initiated ART, 821 (15%) had baseline anaemia, and 296 (5%) had baseline severe anaemia. Early severe anaemia occurred in 109 (4%) of 3105 patients who had at least one Hb measurement in the first six months on ART. Patients with baseline anaemia had a larger increase in Hb (median g/dL [IQR]) within the first six months compared with non‐anaemic patients (2.9 [1.7, 4.6] vs. 0.7 [‐0.2, 1.7], p < 0.0001). Having a new tuberculosis episode OR 3.69 (95% CI 1.64 ‐ 8.32), MCV