Use of computer-assisted self-interview in detection of and referral for depression among adolescents living with HIV at an urban HIV treatment clinic in Uganda: a quasi-experimental study.

BACKGROUND: Depression is common among adolescents living with HIV (ALHIV) and impacts their quality of life. However, it is not routinely detected and treated due to a lack of screening tools, coupled with large numbers of clients in the HIV clinics and limited staff. Enabling adolescents to do a self-assessment for depression on a tablet computer could possibly improve the detection of depression in this population. We set out to assess the detection and referral of depression among ALHIV in care in Uganda. METHODS: This was a quasi-experimental study design with a historical control at Baylor College of Medicine of Children's Foundation. We conducted a retrospective chart review of 425 adolescents covering a 3-month period and documented the proportion screened for depression and referred to the clinic counsellors. From July to September 2022, eligible adolescents aged 10-19 years who had assented and consented self-assessed for depression using a Patient Health Questionnaire-Adolescent on a tablet computer-assisted self-interview (CASI). Adolescents who screened positive had a prompt on the tablet computers referring them to the counsellor for mental healthcare. We compared the proportions of participants screened for depression and referred to counsellors from clinic chart review and on the CASI using paired t-tests. RESULTS: Out of 425 medical records reviewed, 54% (231/425) were females and the median age was 15 years. Of the participants who self-assessed on the CASI, 52% (222/425) were males and the median age of all participants was 16 years. Self-assessment on the CASI increased the rate of detection of depression from 0% to 23.3%. Of those referred on the CASI, 15% accessed care at the referral point. CONCLUSION: The use of CASI improves the rate of detection of depression among ALHIV; however, there is a need to address the barriers to effective referral for mental health services.

Predicting mortality within 1 year of ART initiation in children and adolescents living with HIV in sub-Saharan Africa: a retrospective observational cohort study.

BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV. METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable selection and logistic regression were performed to develop predictive models for mortality within 1 year of ART initiation. Probabilities of mortality were generated, compared with true outcomes, internally validated, and evaluated against WHO advanced HIV criteria. FINDINGS: The study population included 16 958 children and adolescents living with HIV and initiated on ART between May 18, 2005, and Dec 18, 2020. Predictive variables for the most accurate model included: age, CD4 percentage, white blood cell count, haemoglobin concentration, platelet count, and BMI Z score as continuous variables, and WHO clinical stage and oedema, abnormal muscle tone and respiratory distress on examination as categorical variables. The area under the curve (AUC) of the predictive model was 0·851 (95% CI 0·839-0·863) in the training set and 0·822 (0·800-0·845) in the test set, compared with 0·606 (0·595-0·617) for the WHO advanced HIV criteria (p<0·0001). INTERPRETATION: This study evaluated a large, multinational population to derive a mortality prediction tool for children and adolescents living with HIV. The model more accurately predicted clinical outcomes than the WHO advanced HIV criteria and has the potential to improve DSD for children and adolescents living with HIV in high-burden settings. FUNDING: National Institute of Health Fogarty International Center.

Patient characteristics and predictors of mortality among children hospitalised with tuberculosis: A six-year case series study in Uganda.

BACKGROUND: The high case-fatality rates among children with tuberculosis (TB) are reportedly driven by in-hospital mortality and severe forms of TB. Therefore, there is need to better understand the predictors of mortality among children hospitalised with TB. We examined the patient clinical profiles, length of hospital stay from date of admission to date of final admission outcome, and predictors of mortality among children hospitalised with TB at two tertiary hospitals in Uganda. METHODS: We conducted a case-series study of children below 15 years of age hospitalised with TB, from January 1st, 2016, to December 31st, 2021. Convenience sampling was done to select TB cases from paper-based medical records at Mulago National Referral Hospital (MNRH) in urban Kampala, and Fort Portal Regional Referral Hospital (FRRH) in rural Fort Portal. We fitted linear and logistic regression models with length of stay and in-hospital mortality as key outcomes. RESULTS: Out of the 201 children hospitalised with TB, 50 were at FRRH, and 151 at MNRH. The male to female ratio was 1.5 with median age of 2.6 years (Interquartile range-IQR 1-6). There was a high prevalence of HIV (67/171, 39%), severe malnutrition reported as weight-for-age Z-score <-3SD (51/168, 30%). Among children with pulmonary TB who initiated anti-tuberculosis therapy (ATT) either during hospitalisation or within seven days prior to hospitalisation; cough (134/143, 94%), fever (111/143, 78%), and dyspnoea (78/143, 55%) were common symptoms. Children with TB meningitis commonly presented with fever (17/24, 71%), convulsions (14/24 58%), and cough (13/24, 54%). The median length of hospital stay was 8 days (IQR 5-15). Of the 199 children with known in-hospital outcomes, 34 (17.1%) died during hospitalisation. TB meningitis was associated with in-hospital mortality (aOR = 3.50, 95% CI = 1.10-11.17, p = 0.035), while male sex was associated with reduced mortality (aOR = 0.33, 95% CI = 0.12-0.95, p = 0.035). Hospitalisation in the urban hospital predicted a 0.48-day increase in natural log-transformed length of hospital stay (ln-length of stay) (95% CI 0.15-0.82, p = 0.005), but not age, sex, HIV, malnutrition, or TB meningitis. CONCLUSIONS: In-hospital mortality was high, and significantly driven almost four times higher by TB meningitis, with longer hospital stay among children in urban hospitals. The high in-hospital mortality and long hospital stay may be reduced by timely TB diagnosis and treatment initiation among children.

High prevalence of low high-density lipoprotein cholesterol and insulin resistance among children and adolescents living with HIV in Uganda: harbinger for metabolic syndrome?

BACKGROUND: Antiretroviral therapy-associated adverse effects and comorbidities are still pervasive in people living with HIV, especially metabolic syndrome (MetS). We investigated the age-dependent prevalence of components of MetS and insulin resistance in children and adolescents living with HIV (CALWH). METHODS: A cross-sectional pilot study of CALWH treated at the Baylor Uganda Clinical Centre of Excellence in Kampala, Uganda, May to August 2021. The primary outcome of MetS was defined by both the International Diabetes Federation (IDF) and the Adult Treatment Panel (ATP III) criteria. We estimated the prevalence of MetS and its components for all participants and by the stratification factors. RESULTS: We enrolled 90 children and adolescents, aged 6 to <10 years (n = 30), 10 to <16 years (n = 30), and ≥ 16 to <19 years (n = 30). Fifty-one percent were females. The estimated prevalence of MetS was 1.11% (1 of 90) using either IDF or ATPIII criteria for all participants, and 3.33% in the oldest age group. Notably, while only one among study participants met the criterion based on having central obesity or blood pressure, over 55% of participants had one or more IDF component, with 47% having low high-density lipoprotein (HDL) cholesterol. Two participants (6.67%) in the group aged 10 to <16 years met one of the definitions for insulin resistance (IR) using the Homeostatic Model Assessment (HOMA-IR) index. For every 1-year increase in age, HOMA-IR index increased by 0.04 (95% confidence interval: 0.01-0.08; p = 0.02). CONCLUSIONS: With increasing survival of CALWH into adulthood, lifetime exposure to ART, the frequency of MetS in this population may rise, increasing the lifetime risk for associated health problems. There is a need to study the natural history of MetS in CALWH to inform preventative and treatment interventions as needed.

Rift valley fever outbreak in Sembabule District, Uganda, December 2020.

BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that can cause severe haemorrhagic fevers in humans and high mortality rates and abortions in livestock. On 10 December 2020, the Uganda Ministry of Health was notified of the death of a 25-year-old male who tested RVF-positive by reverse-transcription polymerase chain reaction (RT-PCR) at the Uganda Virus Research Institute. We investigated to determine the scope of the outbreak, identify exposure factors, and institute control measures. METHODS: A suspected case was acute-onset fever (or axillary temperature > 37.5 °C) and ≥ 2 of: headache, muscle or joint pain, unexpected bleeding, and any gastroenteritis symptom in a resident of Sembabule District from 1 November to 31 December 2020. A confirmed case was the detection of RVF virus nucleic acid by RT-PCR or serum IgM antibodies detected by enzyme-linked immunosorbent assay (ELISA). A suspected animal case was livestock (cattle, sheep, goats) with any history of abortion. A confirmed animal case was the detection of anti-RVF IgM antibodies by ELISA. We took blood samples from herdsmen who worked with the index case for RVF testing and conducted interviews to understand more about exposures and clinical characteristics. We reviewed medical records and conducted an active community search to identify additional suspects. Blood samples from animals on the index case's farm and two neighbouring farms were taken for RVF testing. RESULTS: The index case regularly drank raw cow milk. None of the seven herdsmen who worked with him nor his brother's wife had symptoms; however, a blood sample from one herdsman was positive for anti-RVF-specific IgM and IgG. Neither the index case nor the additional confirmed case-patient slaughtered or butchered any sick/dead animals nor handled abortus; however, some of the other herdsmen did report high-risk exposures to animal body fluids and drinking raw milk. Among 55 animal samples collected (2 males and 53 females), 29 (53%) were positive for anti-RVF-IgG. CONCLUSIONS: Two human RVF cases occurred in Sembabule District during December 2020, likely caused by close interaction between infected cattle and humans. A district-wide animal serosurvey, animal vaccination, and community education on infection prevention practices campaign could inform RVF exposures and reduce disease burden.

Prevalence and factors associated with sexual and reproductive health literacy among youth living with HIV in Uganda: a cross-sectional study.

BACKGROUND: Adequate sexual and reproductive health literacy (SRHL) among young people has been linked to informed sexual behaviours. Studies on SRHL have largely been conducted among the general adolescent population. Little is known about youth aged 15-24 years living with human immunodeficiency virus (YLHIV). There is a possible lack of SRHL in this population, considering the high rate of teenage pregnancies and unprotected sex reported by YLHIV. This study aimed to assess the prevalence and associated personal and environmental factors for SRHL among YLHIV at a high-volume urban HIV Clinic in Uganda. METHODS: Through a cross-sectional survey, YLHIV receiving routine HIV care services at Baylor-Uganda HIV Clinic were interviewed using an adapted European Health Literacy Survey (HLS-EU). Using simple random sampling, eligible youth who received HIV care services between August and November 2019 were enrolled in the study. SRHL scores were computed using the HLS-EU index method; and individuals whose scores ranged from 34 to 50 were considered health literate. We used descriptive statistics to determine the prevalence. Potential associated personal and environmental factors (p<0.05) were identified by performing two-step inferential statistics, bivariate analysis and binary logistic regression. Odds ratios were calculated to estimate the likelihood of youth being health literate on sexual and reproductive health (SRH) issues in comparison with the reference categories, and 95% confidence intervals were determined to establish whether the relationships were statistically significant. RESULTS: Of the 267 YLHIV interviewed at Baylor-Uganda HIV Clinic, 167 (62.5%) were female with a mean age of 18.9 years (SD± 2.8), and the majority (242; 90.6%) were vertically infected with HIV. Only 52 (19.5%) were health literate on SRH issues. At the multivariate level, YLHIV who never had difficulty accessing SRH information were 0.391 times less likely to be health literate on SRH issues than their counterparts with challenges in accessing SRH information (Adjusted Odds Ratio [AOR] = 0.391, 95% CI =0.178 to 0.860; p= 0.019). YLHIV who did not find it easy to access SRH care service points were 2.929 times more likely to be literate in SRH than those who found it easy to access such services (Adjusted Odds Ratio [AOR] = 2.929, 95% CI =1.241 to 6.917; p=0.014). Additionally, YLHIV who did not listen to radio health talks were 2.406 times more likely to be health literate on SRH issues than those who did (AOR = 2.406, 95% CI =1.133 to 5.112; p=0.022). CONCLUSIONS: SRHL is an unmet need among YLHIV; only 19.5% were health literate on SRH issues. This could complicate the achievement of the UNAIDS sustainable development goal (SDG) of an HIV/AIDS-free generation by 2030 because low health literacy (HL) skills can affect the efficacy of almost all HIV disease prevention and health promotion efforts. Inaccessible SRH care service points and not listening to radio health talks were positively associated with SRHL, while having access to SRH information was negatively associated with SRHL.

Community dialogue meetings among district leaders improved their willingness to receive COVID-19 vaccines in Western Uganda, May 2021.

BACKGROUND: Widespread COVID-19 vaccine uptake can facilitate epidemic control. A February 2021 study in Uganda suggested that public vaccine uptake would follow uptake among leaders. In May 2021, Baylor Uganda led community dialogue meetings with district leaders from Western Uganda to promote vaccine uptake. We assessed the effect of these meetings on the leaders' COVID-19 risk perception, vaccine concerns, perception of vaccine benefits and access, and willingness to receive COVID-19 vaccine. METHODS: All departmental district leaders in the 17 districts in Western Uganda, were invited to the meetings, which lasted approximately four hours. Printed reference materials about COVID-19 and COVID-19 vaccines were provided to attendees at the start of the meetings. The same topics were discussed in all meetings. Before and after the meetings, leaders completed self-administered questionnaires with questions on a five-point Likert Scale about risk perception, vaccine concerns, perceived vaccine benefits, vaccine access, and willingness to receive the vaccine. We analyzed the findings using Wilcoxon's signed-rank test. RESULTS: Among 268 attendees, 164 (61%) completed the pre- and post-meeting questionnaires, 56 (21%) declined to complete the questionnaires due to time constraints and 48 (18%) were already vaccinated. Among the 164, the median COVID-19 risk perception scores changed from 3 (neutral) pre-meeting to 5 (strong agreement with being at high risk) post-meeting (p < 0.001). Vaccine concern scores reduced, with medians changing from 4 (worried about vaccine side effects) pre-meeting to 2 (not worried) post-meeting (p < 0.001). Median scores regarding perceived COVID-19 vaccine benefits changed from 3 (neutral) pre-meeting to 5 (very beneficial) post-meeting (p < 0.001). The median scores for perceived vaccine access increased from 3 (neutral) pre-meeting to 5 (very accessible) post-meeting (p < 0.001). The median scores for willingness to receive the vaccine changed from 3 (neutral) pre-meeting to 5 (strong willingness) post-meeting (p < 0.001). CONCLUSION: COVID-19 dialogue meetings led to district leaders' increased risk perception, reduced concerns, and improvement in perceived vaccine benefits, vaccine access, and willingness to receive the COVID-19 vaccine. These could potentially influence public vaccine uptake if leaders are vaccinated publicly as a result. Broader use of such meetings with leaders could increase vaccine uptake among themselves and the community.

High blood pressure and associated factors among HIV-infected young persons aged 13 to 25 years at selected health facilities in Rwenzori region, western Uganda, September-October 2021.

BACKGROUND: High blood pressure (HBP), including hypertension (HTN), is a predictor of cardiovascular events, and is an emerging challenge in young persons. The risk of cardiovascular events may be further amplified among people living with HIV (PLHIV). We determined the prevalence of HBP and associated factors among PLHIV aged 13 to 25 years in Rwenzori region, western Uganda. METHODS: We conducted a cross-sectional study among PLHIV aged 13 to 25 years at nine health facilities in Kabarole and Kasese districts during September 16 to October 15, 2021. We reviewed medical records to obtain clinical and demographic data. At a single clinic visit, we measured and classified BP as normal (< 120/ < 80 mmHg), elevated (120/ < 80 to 129/ < 80), stage 1 HTN (130/80 to 139/89), and stage 2 HTN (≥ 140/90). We categorized participants as having HBP if they had elevated BP or HTN. We performed multivariable analysis using modified Poisson regression to identify factors associated with HBP. RESULTS: Of the 1,045 PLHIV, most (68%) were female and the mean age was 20 (3.8) years. The prevalence of HBP was 49% (n = 515; 95% confidence interval [CI], 46%-52%), the prevalence of elevated BP was 22% (n = 229; 95% CI, 26%-31%), and the prevalence of HTN was 27% (n = 286; 95% CI, 25%-30%), including 220 (21%) with stage 1 HTN and 66 (6%) with stage 2 HTN. Older age (adjusted prevalence ratio [aPR], 1.21; 95% CI, 1.01-1.44 for age group of 18-25 years vs. 13-17 years), history of tobacco smoking (aPR, 1.41; 95% CI, 1.08-1.83), and higher resting heart rate (aPR, 1.15; 95% CI, 1.01-1.32 for > 76 beats/min vs. ≤ 76 beats/min) were associated with HBP. CONCLUSIONS: Nearly half of the PLHIV evaluated had HBP, and one-quarter had HTN. These findings highlight a previously unknown high burden of HBP in this setting's young populations. HBP was associated with older age, elevated resting heart rate, and ever smoking; all of which are known traditional risk factors for HBP in HIV-negative persons. To prevent future cardiovascular disease epidemics among PLHIV, there is a need to integrate HBP/HIV management.

Realizing the Promise of Dolutegravir in Effectively Treating Children and Adolescents Living With HIV in Real-world Settings in 6 Countries in Eastern and Southern Africa.

BACKGROUND: Despite encouraging results from clinical trials and in high-income countries, large-scale data on the effectiveness and safety of dolutegravir (DTG) in children and adolescents living with HIV (CALHIV) are lacking in low- and middle-income countries (LMICs). METHODS: Retrospective analysis was performed among CALHIV 0-19 years old and weighing greater than or equal to 20 kg who received DTG from 2017 to 2020 at sites in Botswana, Eswatini, Lesotho, Malawi, Tanzania and Uganda to determine effectiveness, safety and predictors of viral load suppression (VLS) among CALHIV using DTG, including through single drug substitutions (SDS). RESULTS: Among 9419 CALHIV using DTG, 7898 had a documented post-DTG VL, and VLS post-DTG was 93.4% (7378/7898). VLS for antiretroviral therapy (ART) initiations was 92.4% (246/263), and VLS was maintained for the ART-experienced [92.9% (7026/7560) pre- vs. 93.5% (7071/7560) post-DTG; P = 0.14). Among previously unsuppressed, 79.8% (426/534) achieved VLS with DTG. Only 5 patients reported a Grade 3 or 4 adverse event (0.057 per 100 patient-years) requiring DTG discontinuation. History of protease inhibitor-based ART [odds ratio (OR) = 1.53; 95% confidence interval (CI): 1.16-2.03], care in Tanzania (OR = 5.45; 95% CI: 3.41-8.70), and being 15-19 years old (OR = 1.31; 95% CI: 1.03-1.65) were associated with gain of VLS post-DTG. Predictors of VLS on DTG included VLS before DTG (OR = 3.87; 95% CI: 3.03-4.95) and using the once-daily, single tab tenofovir-lamivudine-DTG regimen (OR = 1.78; 95% CI: 1.43-2.22). SDS maintained VLS [95.9% (2032/2120) pre- vs. 95.0% (2014/2120) post-SDS with DTG; P = 0.19], and 83.0% (73/88) of unsuppressed gained VLS using SDS with DTG. CONCLUSIONS: We found DTG to be highly effective and safe within our cohort of CALHIV in LMICs. These findings can empower clinicians to prescribe DTG confidently to eligible CALHIV.

Risk factors and prognostic significance of platelet count abnormalities in children with HIV infection on antiretroviral therapy.

OBJECTIVES: To establish the incidence, risk factors and correlation with survival of thrombocytopenia and thrombocytosis (T/T) among children with HIV infection (CWH). DESIGN: A retrospective nested case control study of patients 0-18 years in five Baylor International Pediatric AIDS Initiative (BIPAI) centers in sub-Sahara Africa, 2004-2014. METHODS: Clinical and laboratory variables including complete blood counts (CBC) were extracted from the BIPAI electronic medical record system. Incident cases of T/T were identified and frequency-matched on follow-up time with controls with normal platelets. We calculated the prevalence and incidence density of T/T and used conditional logistic regression to evaluate their association with selected clinical variables. We constructed Kaplan-Meier curves and a Cox proportional hazards model to evaluate the impact of T/T on survival. RESULTS: Two thousand, one hundred and nine children were sampled. The incidence density of thrombocytopenia was 1 per 57.9 (95% confidence interval [CI] 50.3-66.8) CWH-years. Thrombocytopenia was higher in children with WHO Stage III/IV, lower in children on zidovudine, and had no association with use of lamivudine or nevirapine, CD4 + suppression, age, and nutrition status. Thrombocytopenia was independently associated with 2.2-fold higher mortality (95% CI 1.62-3.08). The incidence density of thrombocytosis was 1 per 11.4 (95% CI 10.7-12.1) CWH-years. Thrombocytosis was associated with higher CD4 + cell count, younger age, and use of lamivudine or nevirapine, and did not impact survival. CONCLUSIONS: Platelet count is a clinically valuable biomarker of HIV clinical progression and mortality. Laboratory studies are necessary to elucidate the mechanisms of T/T.

Using Population Mobility Patterns to Adapt COVID-19 Response Strategies in 3 East Africa Countries.

The COVID-19 pandemic spread between neighboring countries through land, water, and air travel. Since May 2020, ministries of health for the Democratic Republic of the Congo, Tanzania, and Uganda have sought to clarify population movement patterns to improve their disease surveillance and pandemic response efforts. Ministry of Health-led teams completed focus group discussions with participatory mapping using country-adapted Population Connectivity Across Borders toolkits. They analyzed the qualitative and spatial data to prioritize locations for enhanced COVID-19 surveillance, community outreach, and cross-border collaboration. Each country employed varying toolkit strategies, but all countries applied the results to adapt their national and binational communicable disease response strategies during the pandemic, although the Democratic Republic of the Congo used only the raw data rather than generating datasets and digitized products. This 3-country comparison highlights how governments create preparedness and response strategies adapted to their unique sociocultural and cross-border dynamics to strengthen global health security.

Individual and household risk factors for COVID-19 infection among household members of COVID-19 patients in home-based care in western Uganda, 2020.

Objective: To investigate factors associated with COVID-19 among household members of patients in home-based care (HBC) in western Uganda. Methods: We conducted a case-control and cohort study. Cases were reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 diagnosed 1-30 November 2020 among persons in HBC in Kasese or Kabarole districts. We compared 78 case-households (≥1 secondary case) with 59 control-households (no secondary cases). The cohort included all case-household members. Data were captured by in-person questionnaire. We used bivariate regression to calculate odds and risk ratios. Results: Case-households were larger than control-households (mean 5.8 vs 4.3 members, P<0.0001). Having ≥1 household member per room (adjusted odds ratio (aOR)=4.5, 95% CI 2.0-9.9), symptom development (aOR=2.3, 95% CI 1.1-5.0), or interaction with primary case-patient (aOR=4.6, 95% CI 1.4-14.7) increased odds of case-household status. Households assessed for suitability for HBC reduced odds of case-household status (aOR=0.4, 95% CI=0.2-0.8). Interacting with a primary case-patient increased the risk of individual infection among household members (adjusted risk ratio=1.7, 95% CI 1.1-2.8). Conclusion: Household and individual factors influence secondary infection risk in HBC. Decisions about HBC should be made with these in mind.

Risk factors and prognostic significance of anemia in children with HIV infection on antiretroviral therapy.

OBJECTIVES: To establish the incidence, risk factors and prognostic effect of anemia in children living with HIV (CLWH). DESIGN: Retrospective nested case-control study of patients 0-18 years in five centers in sub-Saharan Africa, 2004-2014. METHODS: Incident cases of anemia were identified from electronic records and matched with CLWH without anemia. We calculated the incidence density of anemia and used conditional logistic regression to evaluate its association with risk factors, stratified by severity and type of anemia. We used a Cox proportional hazards model to evaluate the impact of anemia on survival. RESULTS: Two thousand, one hundred and thirty-seven children were sampled. The incidence density of anemia was 1 per 6.6 CLWH-years. Anemia was moderate in 31.8% and severe in 17.3% of anemia cases, which had 10-year mortality hazards of 3.4 and 4.5, respectively. Microcytic anemia (36% cases) was associated with 2.3-fold hazard of 10-year mortality, and with malnutrition and CD4 + suppression. Normocytic anemia (50.5% cases) was associated with 2.6-fold hazards of 10-year mortality, and with more severe malnutrition, CD4 + suppression, and WHO stage, but inversely associated with lamivudine and nevirapine therapy. Macrocytic anemia (13.5% cases) was neither associated with higher 10-year mortality nor with severe malnutrition or CD4 + suppression but was associated with WHO stage II/III and negatively associated with lamivudine therapy. CONCLUSION: This large multicountry study of CLWH found a high incidence density of anemia. Higher severity, normocytic and microcytic types of anemia were independently associated with long-term mortality. Laboratory studies are needed to decipher the mechanisms of anemia and how it impacts mortality in CLWH.

Investigation of possible preventable causes of COVID-19 deaths in the Kampala Metropolitan Area, Uganda, 2020-2021.

BACKGROUND: Identifying preventable causes of COVID-19 deaths is key to reducing mortality. We investigated possible preventable causes of COVID-19 deaths over a six-month period in Uganda. METHODS: A case-patient was a person testing reverse transcription polymerase chain reaction-positive for SARS-CoV-2 who died in Kampala Metropolitan Area hospitals from August 2020 to February 2021. We reviewed records and interviewed health workers and case-patient caretakers. RESULTS: We investigated 126 (65%) of 195 reported COVID-19 deaths during the investigation period; 89 (71%) were male, and the median age was 61 years. A total of 98 (78%) had underlying medical conditions. Most (118, 94%) had advanced disease at admission to the hospital where they died. A total of 44 (35%) did not receive a COVID-19 test at their first presentation to a health facility despite having consistent symptoms. A total of 95 (75%) needed intensive care unit admission, of whom 45 (47%) received it; 74 (59%) needed mechanical ventilation, of whom 47 (64%) received it. CONCLUSION: Among hospitalized patients with COVID-19 who died in this investigation, early opportunities for diagnosis were frequently missed, and there was inadequate intensive care unit capacity. Emphasis is needed on COVID-19 as a differential diagnosis, early testing, and care-seeking at specialized facilities before the illness reaches a critical stage. Increased capacity for intensive care is needed.

Association between Antiretroviral Therapy and Cancers among Children Living with HIV in Sub-Saharan Africa.

Approximately 91% of the world's children living with HIV (CLWH) are in sub-Saharan Africa (SSA). Living with HIV confers a risk of developing HIV-associated cancers. To determine the incidence and risk factors for cancer among CLWH, we conducted a nested case-control study of children 0-18 years from 2004-2014 at five centers in four SSA countries. Incident cases of cancer and HIV were frequency-matched to controls with HIV and no cancer. We calculated the incidence density by cancer type, logistic regression, and relative risk to evaluate risk factors of cancer. The adjusted incidence density of all cancers, Kaposi sarcoma, and lymphoma were 47.6, 36.6, and 8.94 per 100,000 person-years, respectively. Delayed ART until after 2 years of age was associated with cancer (OR = 2.71, 95% CI 1.51, 4.89) even after adjusting for World Health Organization clinical stage at the time of enrolment for HIV care (OR = 2.85, 95% CI 1.57, 5.13). The relative risk of cancer associated with severe CD4 suppression was 6.19 (p = 0.0002), 2.33 (p = 0.0042), and 1.77 (p = 0.0305) at 1, 5, and 10 years of ART, respectively. The study demonstrates the high risk of cancers in CLWH and the potential benefit of reducing this risk by the early initiation of ART.

Uganda's "EID Systems Strengthening" model produces significant gains in testing, linkage, and retention of HIV-exposed and infected infants: An impact evaluation.

INTRODUCTION: A review of Uganda's HIV Early Infant Diagnosis (EID) program in 2010 revealed poor retention outcomes for HIV-exposed infants (HEI) after testing. The review informed development of the 'EID Systems Strengthening' model: a set of integrated initiatives at health facilities to improve testing, retention, and clinical care of HIV-exposed and infected infants. The program model was piloted at several facilities and later scaled countrywide. This mixed-methods study evaluates the program's impact and assesses its implementation. METHODS: We conducted a retrospective cohort study at 12 health facilities in Uganda, comprising all HEI tested by DNA PCR from June 2011 to May 2014 (n = 707). Cohort data were collected manually at the health facilities and analyzed. To assess impact, retention outcomes were statistically compared to the baseline study's cohort outcomes. We conducted a cross-sectional qualitative assessment of program implementation through 1) structured clinic observation and 2) key informant interviews with health workers, district officials, NGO technical managers, and EID trainers (n = 51). RESULTS: The evaluation cohort comprised 707 HEI (67 HIV+). The baseline study cohort contained 1268 HEI (244 HIV+). Among infants testing HIV+, retention in care at an ART clinic increased from 23% (57/244) to 66% (44/67) (p < .0001). Initiation of HIV+ infants on ART increased from 36% (27/75) to 92% (46/50) (p < .0001). HEI receiving 1st PCR results increased from 57% (718/1268) to 73% (518/707) (p < .0001). Among breastfeeding HEI with negative 1st PCR, 55% (192/352) received a confirmatory PCR test, a substantial increase from baseline period. Testing coverage improved significantly: HIV+ pregnant women who brought their infants for testing after birth increased from 18% (67/367) to 52% (175/334) (p < .0001). HEI were tested younger: mean age at DBS test decreased from 6.96 to 4.21 months (p < .0001). Clinical care for HEI was provided more consistently. Implementation fidelity was strong for most program components. The strongest contributory interventions were establishment of 'EID Care Points', integration of clinical care, longitudinal patient tracking, and regular health worker mentorship. Gaps included limited follow up of lost infants, inconsistent buy-in/ownership of health facility management, and challenges sustaining health worker motivation. DISCUSSION: Uganda's 'EID Systems Strengthening' model has produced significant gains in testing and retention of HEI and HIV+ infants, yet the country still faces major challenges. The 3 core concepts of Uganda's model are applicable to any country: establish a central service point for HEI, equip it to provide high-quality care and tracking, and develop systems to link HEI to the service point. Uganda's experience has shown the importance of intensively targeting systemic bottlenecks to HEI retention at facility level, a necessary complement to deploying rapidly scalable technologies and other higher-level initiatives.

Retention outcomes and drivers of loss among HIV-exposed and infected infants in Uganda: a retrospective cohort study.

BACKGROUND: Uganda's HIV Early Infant Diagnosis (EID) program rapidly scaled up testing of HIV-exposed infants (HEI) in its early years. However, little was known about retention outcomes of HEI after testing. Provision of transport refunds to HEI caregivers was piloted at 3 hospitals to improve retention. This study was conducted to quantify retention outcomes of tested HEI, identify factors driving loss-to-follow-up, and assess the effect of transport refunds on HEI retention. METHODS: This mixed-methods study included 7 health facilities- retrospective cohort review at 3 hospitals and qualitative assessment at all facilities. The cohort comprised all HEI tested from September-2007 to February-2009. Retention data was collected manually at each hospital. Qualitative methods included health worker interviews and structured clinic observation. Qualitative data was synthesized, analyzed and triangulated to identify factors driving HEI loss-to-follow-up. RESULTS: The cohort included 1268 HEI, with 244 testing HIV-positive. Only 57% (718/1268) of tested HEI received results. The transport refund pilot increased the percent of HEI caregivers receiving test results from 54% (n = 763) to 58% (n = 505) (p = .08). HEI were tested at late ages (Mean = 7.0 months, n = 1268). Many HEI weren't tested at all: at 1 hospital, only 18% (67/367) of HIV+ pregnant women brought their HEI for testing after birth. Among HIV+ infants, only 40% (98/244) received results and enrolled at an ART Clinic. Of enrolled HIV+ infants, only 43% (57/98) were still active in chronic care. 36% (27/75) of eligible HIV+ infants started ART. Our analysis identified 6 categories of factors driving HEI loss-to-follow-up: fragmentation of EID services across several clinics, with most poorly equipped for HEI care/follow-up; poor referral mechanisms and data management systems; inconsistent clinical care; substandard counseling; poor health worker knowledge of EID; long sample-result turnaround times. DISCUSSION: The poor outcomes for HEI and HIV+ infants have highlighted an urgent need to improve retention and linkage to care. To address the identified gaps, Uganda's Ministry of Health and the Clinton Health Access Initiative developed a new implementation model, shifting EID from a lab-based diagnostic service to an integrated clinic-based chronic care model. This model was piloted at 21 facilities. An evaluation is needed.

Impact of a Family Clinic Day intervention on paediatric and adolescent appointment adherence and retention in antiretroviral therapy: A cluster randomized controlled trial in Uganda.

BACKGROUND: In 2013, Uganda adopted a test-and-treat policy for HIV patients 15 years or younger. Low retention rates among paediatric and adolescent antiretroviral therapy (ART) initiates could severely limit the impact of this new policy. This evaluation tested the impact of a differentiated care model called Family Clinic Day (FCD), a family-centered appointment scheduling and health education intervention on patient retention and adherence to monthly appointment scheduling. METHODS: We conducted a cluster randomized controlled trial, from October 2014 to March 2015. Forty-six facilities were stratified by implementing partner and facility type and randomly assigned to the control or intervention arm. Primary outcomes included the proportion of patients retained in care at 6 months and the proportion adherent to their appointment schedule at last study period scheduled visit. Data collection occurred retrospectively in May 2015. Six patient focus group discussions and 17 health workers interviews were conducted to understand perspectives on FCD successes and challenges. RESULTS: A total of 4,715 paediatric and adolescent patient records were collected, of which 2,679 (n = 1,319 from 23 control facilities and 1,360 from 23 intervention facilities) were eligible for inclusion. The FCD did not improve retention (aOR 1.11; 90% CI 0.63-1.97, p = 0.75), but was associated with improved adherence to last appointment schedule (aOR 1.64; 90% CI 1.27-2.11, p<0.001). Qualitative findings suggested that FCD patients benefited from health education and increased psychosocial support. CONCLUSION: FCD scale-up in Uganda may be an effective differentiated care model to ensure patient adherence to ART clinic appointment schedules, a key aspect necessary for viral load suppression. Patient health outcomes may also benefit following an increase in knowledge based on health education, and peer support. Broad challenges facing ART clinics, such as under-staffing and poor filing systems, should be addressed in order to improve patient care.

Pediatric Treatment Scale-Up: The Unfinished Agenda of the Global Plan.

Five million children have died of AIDS-related causes since the beginning of the epidemic. In 2011, the Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan) created the political environment to catalyze both the resources and commitment to end pediatric AIDS. Implementation and scale-up have encountered substantial hurdles, however, which have resulted in slow progress. Reasons include a lack of emphasis on testing outside of prevention of mother-to-child transmission services, an overall lack of integration and coordination with other services, a lack of training among providers, low confidence in caring for children living with HIV, and a lack of appropriate formulations for pediatric antiretrovirals. During the Global Plan period, we have learned that simplification is essential to successful decentralization, integration, and task shifting of services; that innovations require careful planning; and that the family is an important unit for delivering HIV care and treatment services. The post-Global Plan phase presents a number of noteworthy challenges that all stakeholders, national programs, and communities must tackle to guarantee universal treatment for children living with HIV. Accelerated action is essential in ensuring that HIV diagnosis and linkage to treatment happen as quickly and effectively as possible. As fewer infants are infected because of effective prevention of mother-to-child transmission interventions and the population of children living with HIV will age into adolescence adapting service delivery models to the epidemic context, and engaging the community will be critical to finding new efficiencies and allowing us to realize a true HIV-free generation-and to end AIDS by 2030.