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We report a 23% asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) Omicron carriage rate in participants being enrolled into a clinical trial in South Africa, 15-fold higher than in trials before Omicron. We also found lower CD4 + T-cell counts in persons with human immunodeficiency virus (HIV) strongly correlated with increased odds of being SARS-CoV-2 polymerase chain reaction (PCR) positive.

BackgroundWe aimed to determine the extent to which emerging evidence and changing guidelines regarding timing of antiretroviral therapy (ART) among human immunodeficiency virus (HIV)-infected patients with tuberculosis influenced "real-world" clinical practice in Uganda.MethodsWe evaluated ART-naive, HIV-infected adults starting tuberculosis therapy at 2 HIV clinics in Uganda between 26 August 2006 and 29 September 2012. We used multivariate regression to calculate associations between 4 calendar periods reflecting publication of seminal clinical studies or changes in guidelines and timing of ART after tuberculosis therapy initiation.ResultsFor patients with CD4 counts 50 cells/µL starting ART within 60 days increased from 16% to 28%. After adjustment for sociodemographic factors, when comparing the most recent with the earliest calendar period, the rate of ART initiation increased by 4.57-fold (95% confidence interval [CI], 1.76-fold to 11.86-fold) among patients with baseline CD4 counts ≤ 50 cells/µL and by 5.43-fold (95% CI, 3.16- fold to 9.31-fold) among those with baseline CD4 counts >50 cells/µL.ConclusionsWe observed large changes in clinical practice during a period of emerging data and changing guidelines among HIV-infected patients with tuberculosis. Nonetheless, a significant proportion of individuals with higher CD4 cell counts do not start ART within recommended time frames. Targeted dissemination and implementation efforts are still needed to achieve target levels in practice.

: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]

Background: TB preventive therapy (TPT) among people living with HIV (PLHIV) reduces the risk of developing TB disease. In Fort Portal region, data on TPT outcomes among PLHIV are scarce. [...]

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2022 The Author(s).)

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., Competing Interests: Conflict of interest The authors have no competing interests to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

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.

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., Competing Interests: The authors declare they have no competing interests.

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.

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.

Background: Adolescents have gained increased attention because they are the only age group where HIV related mortality is going up. We set out to describe the level and factors associated with adherence to antiretroviral therapy (ART) as well as the 1 year retention in care among adolescents in 10 representative districts in Uganda. In addition, we explored the barriers and facilitators of adherence to ART among adolescents., Methods: The study involved 30 health facilities from 10 representative districts in Uganda. We employed both qualitative and quantitative data collection methods in convergent design. The former involved Focus group discussions with adolescents living with HIV, Key informant interviews with various stakeholders and in depth interviews with adolescents. The quantitative involved using retrospective records review to extract the last recorded adherence level from all adolescents who were active in HIV care. Factors associated with adherence were extracted from the ART cards. For the 1 year retention in care, we searched the hospital records of all adolescents in the 30 facilities who had started ART 1 year before the study to find out how many were still in care., Results: Out of 1824 adolescents who were active on ART, 90.4 % (N = 1588) had ≥95 % adherence recorded on their ART cards at their last clinic visit. Only location in rural health facilities was independently associated with poor adherence to ART (P = 0.008, OR 2.64 [1.28 5.43]). Of the 156 adolescents who started ART, 90 % (N = 141) were still active in care 1 year later. Stigma, discrimination and disclosure issues were the most outstanding of all barriers to adherence. Other barriers included poverty, fatigue, side effects, pill burden, depression among others. Facilitators of adherence mainly included peer support groups, counseling, supportive health care workers, short waiting time and provision of food and transport., Conclusion: Adherence to ART was good among adolescents. Being in rural areas was associated with poor adherence to ART and 1 year retention in care was very good among adolescents who were newly started on ART. Stigma and disclosure issues continue to be the main barriers to adherence among adolescents.

Uganda introduced an HIV Early Infant Diagnosis (EID) program in 2006, and then worked to improve the laboratory, transportation, and clinical elements. Reported here are the activities involved in setting up a prospective analysis in which the Ministry of Health, with its NGO partners, determined it would be more effective and efficient to consolidate the initial eight-laboratory system for EID testing of HIV dried blood samples offered by two nongovernmental partners operating research facilities into a single well-equipped and staffed laboratory within the Ministry. A retrospective analysis confirmed that redesign reduced overhead cost per PCR test of HIV dried blood samples from US$22.20 to an average of $5. Along with the revamped system of sample collection, transportation, and result communication, Uganda has been able to vastly increase the HIV diagnosis of babies and engagement of them and their mothers in clinical care, including antiretroviral therapy. Uganda reduced turnaround times for results reporting to clinicians from more than a month in 2006 to just 2 weeks by 2014, even as samples tested increased dramatically. The next challenge is overcoming loss of babies and mothers to follow up.

Introduction: Uganda scaled-up Early HIV Infant Diagnosis (EID) when simplified methods for testing of infants using dried blood spots (DBS) were adopted in 2006 and sample transport and management was therefore made feasible in rural settings. Before this time only 35% of the facilities that were providing EID services were reached through the national postal courier system, Posta Uganda. The transportation of samples during this scale-up, therefore, quickly became a challenge and varied from facility to facility as different methods were used to transport the samples. This study evaluates a novel specimen transport network system for EID testing., Methods: A retrospective study was done in mid-2012 on 19 pilot hubs serving 616 health facilities in Uganda. The effect on sample-result turnaround time (TAT) and the cost of DBS sample transport on 876 sample-results was analyzed., Results: The HUB network system provided increased access to EID services ranging from 36% to 51%, drastically reduced transportation costs by 62%, reduced turn-around times by 46.9% and by a further 46.2% through introduction of SMS printers., Conclusions: The HUB model provides a functional, reliable and efficient national referral network against which other health system strengthening initiatives can be built to increase access to critical diagnostic and treatment monitoring services, improve the quality of laboratory and diagnostic services, with reduced turn-around times and improved quality of prevention and treatment programs thereby reducing long-term costs.