Respiratory support with standard low-flow oxygen therapy, high-flow oxygen therapy or continuous positive airway pressure in adults with acute hypoxaemic respiratory failure in a resource-limited setting: protocol for a randomised, open-label, clinical trial - the Acute Respiratory Intervention StudiEs in Africa (ARISE-AFRICA) study.

RATIONALE: Acute hypoxaemic respiratory failure (AHRF) is associated with high mortality in sub-Saharan Africa. This is at least in part due to critical care-related resource constraints including limited access to invasive mechanical ventilation and/or highly skilled acute care workers. Continuous positive airway pressure (CPAP) and high-flow oxygen by nasal cannula (HFNC) may prove useful to reduce intubation, and therefore, improve survival outcomes among critically ill patients, particularly in resource-limited settings, but data in such settings are lacking. The aim of this study is to determine whether CPAP or HFNC as compared with standard oxygen therapy, could reduce mortality among adults presenting with AHRF in a resource-limited setting. METHODS: This is a prospective, multicentre, randomised, controlled, stepped wedge trial, in which patients presenting with AHRF in Uganda will be randomly assigned to standard oxygen therapy delivered through a face mask, HFNC oxygen or CPAP. The primary outcome is all-cause mortality at 28 days. Secondary outcomes include the number of patients with criteria for intubation at day 7, the number of patients intubated at day 28, ventilator-free days at day 28 and tolerance of each respiratory support. ETHICS AND DISSEMINATION: The study has obtained ethical approval from the Research and Ethics Committee, School of Biomedical Sciences, College of Health Sciences, Makerere University as well as the Uganda National Council for Science and Technology. Patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04693403. PROTOCOL VERSION: 8 September 2023; version 5.

Prediction models for post-discharge mortality among under-five children with suspected sepsis in Uganda: A multicohort analysis.

In many low-income countries, over five percent of hospitalized children die following hospital discharge. The lack of available tools to identify those at risk of post-discharge mortality has limited the ability to make progress towards improving outcomes. We aimed to develop algorithms designed to predict post-discharge mortality among children admitted with suspected sepsis. Four prospective cohort studies of children in two age groups (0-6 and 6-60 months) were conducted between 2012-2021 in six Ugandan hospitals. Prediction models were derived for six-months post-discharge mortality, based on candidate predictors collected at admission, each with a maximum of eight variables, and internally validated using 10-fold cross-validation. 8,810 children were enrolled: 470 (5.3%) died in hospital; 257 (7.7%) and 233 (4.8%) post-discharge deaths occurred in the 0-6-month and 6-60-month age groups, respectively. The primary models had an area under the receiver operating characteristic curve (AUROC) of 0.77 (95%CI 0.74-0.80) for 0-6-month-olds and 0.75 (95%CI 0.72-0.79) for 6-60-month-olds; mean AUROCs among the 10 cross-validation folds were 0.75 and 0.73, respectively. Calibration across risk strata was good: Brier scores were 0.07 and 0.04, respectively. The most important variables included anthropometry and oxygen saturation. Additional variables included: illness duration, jaundice-age interaction, and a bulging fontanelle among 0-6-month-olds; and prior admissions, coma score, temperature, age-respiratory rate interaction, and HIV status among 6-60-month-olds. Simple prediction models at admission with suspected sepsis can identify children at risk of post-discharge mortality. Further external validation is recommended for different contexts. Models can be digitally integrated into existing processes to improve peri-discharge care as children transition from the hospital to the community.

Characterization of Antibiotic Resistance in Select Tertiary Hospitals in Uganda: An Evaluation of 2020 to 2023 Routine Surveillance Data.

Antimicrobial resistance (AMR) is a public health concern in Uganda. We sought to conduct an extended profiling of AMR burden at selected Ugandan tertiary hospitals. We analyzed routine surveillance data collected between October 2020 and March 2023 from 10 tertiary hospitals. The analysis was stratified according to the hospital unit, age, gender, specimen type, and time. Up to 2754 isolates were recovered, primarily from pus: 1443 (52.4%); urine: 1035 (37.6%); and blood: 245 (8.9%). Most pathogens were Staphylococcus aureus, 1020 (37%), Escherichia coli, 808 (29.3%), and Klebsiella spp., 200 (7.3%). Only 28% of Escherichia coli and 42% of the other Enterobacterales were susceptible to ceftriaxone, while only 44% of Staphylococcus aureus were susceptible to methicillin (56% were MRSA). Enterococcus spp. susceptibility to vancomycin was 72%. The 5-24-year-old had 8% lower ampicillin susceptibility than the >65-year-old, while the 25-44-year-old had 8% lower ciprofloxacin susceptibility than the >65-year-old. The 0-4-year-old had 8% higher ciprofloxacin susceptibility. Only erythromycin susceptibility varied by sex, being higher in males. Escherichia coli ciprofloxacin susceptibility in blood (57%) was higher than in urine (39%) or pus (28%), as was ceftriaxone susceptibility in blood (44%) versus urine (34%) or pus (14%). Klebsiella spp. susceptibility to ciprofloxacin and meropenem decreased by 55% and 47%, respectively, during the evaluation period. During the same period, Escherichia coli ciprofloxacin susceptibility decreased by 40%, while Staphylococcus aureus gentamicin susceptibility decreased by 37%. Resistance was high across the Access and Watch antibiotic categories, varying with time, age, sex, specimen type, and hospital unit. Effective antimicrobial stewardship targeted at the critical AMR drivers is urgently needed.

Continental concerted efforts to control the seventh outbreak of Ebola Virus disease in Uganda: The first 90 days of the response.

On 20th September 2022, Uganda declared the 7th outbreak of Ebola virus disease (EVD) caused by the Sudan Ebola strain following the confirmation of a case admitted at Mubende Regional Referral Hospital. Upon confirmation, the Government of Uganda immediately activated the national incident management system to initiate response activities. Additionally, a multi-country emergency stakeholder meeting was held in Kampala; convening Ministers of Health from neighbouring Member States to undertake cross-border preparedness and response actions. The outbreak spanned 69 days and recorded 164 cases (142 confirmed, 22 probable), 87 recoveries and 77 deaths (case fatality ratio of 47%). Nine out of 136 districts were affected with transmission taking place in 5 districts but spilling over in 4 districts without secondary transmission. As part of the response, the Government galvanised robust community mobilisation and initiated assessment of medical counter measures including therapeutics, new diagnostics and vaccines. This paper highlights the response actions that contributed to the containment of this outbreak in addition to the challenges faced with a special focus on key recommendations for better control of future outbreaks.

Defining Collective Priorities: Research and Learning Agendas for Family Planning Across 6 Countries.

Evidence should be the foundation for a well-designed family planning (FP) program, but existing evidence is rarely aligned with and/or synthesized to speak directly to FP programmatic needs. Based on our experience cocreating FP research and learning agendas (FP RLAs) in Côte d'Ivoire, Malawi, Mozambique, Nepal, Niger, and Uganda, we argue that FP RLAs can drive the production of coordinated research that aligns with national priorities.To cocreate FP RLAs, stakeholders across 6 countries conducted desk reviews of 349 documents and 106 key informant interviews, organized consultation meetings in each country to prioritize evidence gaps and generate research and learning questions, and, ultimately, formed 6 FP RLAs comprising 190 unique questions. We outline the process for consensus-driven development of FP RLAs and communicate the results of an analysis of the questions in each FP RLA across 4 technical areas: self-care, equity, high impact practices, and youth. Each question was categorized as a learning versus research question, the former indicating an opportunity to synthesize existing evidence and the latter to conduct new research to answer the question. Themes emerging from the data shed light on shared evidence gaps across the 6 countries. We argue that similarities and differences in the questions in each FP RLA reflect the unique implementation experience and context, as well as each country's placement on the FP S-curve. Early uses of the FP RLAs include informing the development of FP costed implementation plans and FP2030 commitments. FP RLAs have also been discussed in multiple thematic working groups. For FP stakeholders, these FP RLAs represent a consensus-based agenda that can guide the generation and synthesis of evidence to answer each country's most pressing questions, ultimately driving progress toward increasingly evidence-based programming and policy.

Mortality after hospital discharge among children younger than 5 years admitted with suspected sepsis in Uganda: a prospective, multisite, observational cohort study.

BACKGROUND: Substantial mortality occurs after hospital discharge in children younger than 5 years with suspected sepsis, especially in low-income countries. A better understanding of its epidemiology is needed for effective interventions to reduce child mortality in these countries. We evaluated risk factors for death after discharge in children admitted to hospital for suspected sepsis in Uganda, and assessed how these differed by age, time of death, and location of death. METHODS: In this prospective, multisite, observational cohort study, we recruited and consecutively enrolled children aged 0-60 months admitted with suspected sepsis from the community to the paediatric wards of six Ugandan hospitals. Suspected sepsis was defined as the need for admission due to a suspected or proven infectious illness. At admission, trained study nurses systematically collected data on clinical variables, sociodemographic variables, and baseline characteristics with encrypted study tablets. Participants were followed up for 6 months after discharge by field officers who contacted caregivers at 2 months and 4 months after discharge by telephone and at 6 months after discharge in person to measure vital status, health-care seeking after discharge, and readmission details. We assessed 6-month mortality after hospital discharge among those discharged alive, with verbal autopsies conducted for children who had died after hospital discharge. FINDINGS: Between July 13, 2017, and March 30, 2020, 16 991 children were screened for eligibility. 6545 children (2927 [44·72%] female children and 3618 [55·28%] male children) were enrolled and 6191 were discharged from hospital alive. 6073 children (2687 [44·2%] female children and 3386 [55·8%] male children) completed follow-up. 366 children died in the 6-month period after discharge (weighted mortality rate 5·5%). Median time from discharge to death was 28 days (IQR 9-74). For the 360 children for whom location of death was documented, deaths occurred at home (162 [45·0%]), in transit to care (66 [18·3%]), or in hospital (132 [36·7%]) during a subsequent readmission. Death after hospital discharge was strongly associated with weight-for-age Z scores less than -3 (adjusted risk ratio [aRR] 4·7, 95% CI 3·7-5·8 vs a Z score of >-2), discharge or referral to a higher level of care (7·3, 5·6-9·5), and unplanned discharge (3·2, 2·5-4·0). Hazard ratios (HRs) for severe anaemia (<7g/dL) increased with time since discharge, from 1·7 (95% CI 0·9-3·0) for death occurring in the first time tertile to 5·2 (3·1-8·5) in the third time tertile. HRs for some discharge vulnerabilities decreased significantly with increasing time since discharge, including unplanned discharge (from 4.5 [2·9-6·9] in the first tertile to 2·0 [1·3-3·2] in the third tertile) and poor feeding status (from 7·7 [5·4-11·0] to 1·84 [1·0-3·3]). Age interacted with several variables, including reduced weight-for-age Z score, severe anaemia, and reduced admission temperature. INTERPRETATION: Paediatric mortality following hospital discharge after suspected sepsis is common, with diminishing, although persistent, risk during the first 6 months after discharge. Efforts to improve outcomes after hospital discharge are crucial to achieving Sustainable Development Goal 3.2 (ending preventable childhood deaths under age 5 years). FUNDING: Grand Challenges Canada, Thrasher Research Fund, BC Children's Hospital Foundation, and Mining4Life.

Uptake of reproductive, maternal and child health services during the first year of the COVID-19 pandemic in Uganda: A mixed methods study.

Use of reproductive health (RH), maternal, newborn and child health (MNCH) services in Uganda is suboptimal. Reasons for this are complex; however, service-delivery factors such as availability, quality, staffing, and supplies, contribute substantially to low uptake. The COVID-19 pandemic threatened to exacerbate existing challenges to delivery and use of high-quality RH and MNCH services. We conducted a mixed methods study, combining secondary analysis of routine electronic health management information system (eHMIS) data with exploratory key informant interviews (KII) to examine changes in health service uptake over the course of the pandemic and to understand service delivery adaptations implemented in response. We analyzed eHMIS data for four services (family planning, facility-based deliveries, antenatal visits, and immunization for children by one year), comparing them across four time periods: pre-COVID-19, partial lockdown, total lockdown and post lockdown. Additionally, KIIs were used to document adaptations made for continuity of health services. Use of services declined substantially during total lockdown; however, rebounded quickly to earlier observed levels, during the post lockdown for all four services, especially for immunization for children by one year. KIIs identified several health services delivery adaptations. At the community level, these included: community outreaches, training some mothers as community liaisons to encourage others to seek health services, and support from local leaders to create call centers to facilitate clients transport during travel restrictions. Health facilities creatively used space to accommodate social distancing and shifted providers' roles. District leadership reassigned health workers to facilities closest to their homes, provided vehicle passes to staff, and ambulances to transport pregnant women in critical need. WhatsApp groups facilitated communication at district level and enabled redistribution of supplies. Ministry of Health produced critical guidelines for continuity of health services. Implementing partners provided and redistributed commodities and personal protective equipment, and provided technical support, training and transport.

Respiratory Support Techniques for COVID-19-Related ARDS in a Sub-Saharan African Country: A Multicenter Observational Study.

BACKGROUND: Limited data from low-income countries report on respiratory support techniques in COVID-19-associated ARDS. RESEARCH QUESTION: Which respiratory support techniques are used in patients with COVID-19-associated ARDS in Uganda? STUDY DESIGN AND METHODS: A multicenter, prospective, observational study was conducted at 13 Ugandan hospitals during the pandemic and included adults with COVID-19-associated ARDS. Patient characteristics, clinical and laboratory data, initial and most advanced respiratory support techniques, and 28-day mortality were recorded. Standard tests, log-rank tests, and logistic regression analyses were used for statistical analyses. RESULTS: Four hundred ninety-nine patients with COVID-19-associated ARDS (mild, n = 137; moderate, n = 247; and severe, n = 115) were included (ICU admission, 38.9%). Standard oxygen therapy (SOX), high-flow nasal oxygen (HFNO), CPAP, noninvasive ventilation (NIV), and invasive mechanical ventilation (IMV) was used as the first-line (most advanced) respiratory support technique in 37.3% (35.3%), 10% (9.4%), 11.6% (4.8%), 23.4% (14.4%), and 17.6% (36.6%) of patients, respectively. The first-line respiratory support technique was escalated in 19.8% of patients. Twenty-eight-day mortality was 51.9% (mild ARDS, 13.1%; moderate ARDS, 62.3%; severe ARDS, 75.7%; P < .001) and was associated with respiratory support techniques as follows: SOX, 19.9%; HFNO, 31.9%; CPAP, 58.3%; NIV 61.1%; and IMV, 83.9% (P < .001). Proning was used in 79 patients (15.8%; 59 of 79 awake) and was associated with lower mortality (40.5% vs 54%; P = .03). The oxygen saturation to Fio2 ratio (OR, 0.99; 95% CI, 0.98-0.99; P < .001) and respiratory rate (OR, 1.07; 95% CI, 1.03-1.12; P = .002) at admission and NIV (OR, 6.31; 95% CI, 2.29-17.37; P < .001) or IMV (OR, 8.08; 95% CI, 3.52-18.57; P < .001) use were independent risk factors for death. INTERPRETATION: SOX, HFNO, CPAP, NIV, and IMV were used as respiratory support techniques in patients with COVID-19-associated ARDS in Uganda. Although these data are observational, they suggest that the use of SOX and HFNO therapy as well as awake proning are associated with a lower mortality resulting from COVID-19-associated ARDS in a resource-limited setting.

Building Critical Care Capacity in a Low-Income Country.

Critical illness is common throughout the world and is associated with high costs of care and resource intensity. The Corona virus disease 2019 (COVID-19) pandemic created a sudden surge of critically ill patients, which in turn led to devastating effects on health care systems worldwide and more so in Africa. This narrative report describes how an attempt was made at bridging the existing gaps in quality of care for critically ill patients at national and regional levels for COVID and the postpandemic era in a low income country.

Hypoxaemia prevalence and management among children and adults presenting to primary care facilities in Uganda: A prospective cohort study.

Hypoxaemia (low blood oxygen) is common among hospitalised patients, increasing the odds of death five-fold and requiring prompt detection and treatment. However, we know little about hypoxaemia prevalence in primary care and the role for pulse oximetry and oxygen therapy. This study assessed the prevalence and management of hypoxaemia at primary care facilities in Uganda. We conducted a cross sectional prevalence study and prospective cohort study of children with hypoxaemia in 30 primary care facilities in Uganda, Feb-Apr 2021. Clinical data collectors used handheld pulse oximeters to measure blood oxygen level (SpO2) of all acutely unwell children, adolescents, and adults. We followed up a cohort of children aged under 15 years with SpO2<93% by phone after 7 days to determine if the patient had attended another health facility, been admitted, or recovered. Primary outcome: proportion of children under 5 years of age with severe hypoxaemia (SpO2<90%). Secondary outcomes: severe (SpO2<90%) and moderate hypoxaemia (SpO2 90-93%) prevalence by age/sex/complaint; number of children with hypoxaemia referred, admitted and recovered. We included 1561 children U5, 935 children 5-14 years, and 3284 adolescents/adults 15+ years. Among children U5, the prevalence of severe hypoxaemia was 1.3% (95% CI 0.9 to 2.1); an additional 4.9% (3.9 to 6.1) had moderate hypoxaemia. Performing pulse oximetry according to World Health Organization guidelines exclusively on children with respiratory complaints would have missed 14% (3/21) of severe hypoxaemia and 11% (6/55) of moderate hypoxaemia. Hypoxaemia prevalence was low among children 5-14 years (0.3% severe, 1.1% moderate) and adolescents/adults 15+ years (0.1% severe, 0.5% moderate). A minority (12/27, 44%) of severely hypoxaemic patients were referred; 3 (12%) received oxygen. We followed 87 children aged under 15 years with SpO2<93%, with complete data for 61 (70%), finding low rates of referral (6/61, 10%), hospital attendance (10/61, 16%), and admission (6/61, 10%) with most (44/61, 72%) fully recovered at day 7. Barriers to referral included caregiver belief it was unnecessary (42/51, 82%), cost (8/51, 16%), and distance or lack of transport (3/51, 6%). Hypoxaemia is common among acutely unwell children under five years of age presenting to Ugandan primary care facilities. Routine pulse oximetry has potential to improve referral, management and clinical outcomes. Effectiveness, acceptability, and feasibility of pulse oximetry and oxygen therapy for primary care should be investigated in implementation trials, including economic analysis from health system and societal perspectives.

Efficacy of convalescent plasma for treatment of COVID-19 in Uganda.

RATIONALE: Convalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited. OBJECTIVE: In this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda. MEASUREMENTS: Patients with a positive SARS-CoV-2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalised and randomised to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. The primary outcome was time to viral clearance, defined as having two consecutive RT-PCR-negative tests by day 28. Secondary outcomes included time to symptom resolution, clinical status on the modified WHO Ordinal Clinical Scale (≥1-point increase), progression to severe/critical condition (defined as oxygen saturation <93% or needing oxygen), mortality and safety. MAIN RESULTS: A total of 136 patients were randomised, 69 to CCP+SOC and 67 to SOC only. The median age was 50 years (IQR: 38.5-62.0), 71.3% were male and the median duration of symptom was 7 days (IQR=4-8). Time to viral clearance was not different between the CCP+SOC and SOC arms (median of 6 days (IQR=4-11) vs 4 (IQR=4-6), p=0.196). There were no statistically significant differences in secondary outcomes in CCP+SOC versus SOC: time to symptom resolution (median=7 (IQR=5-7) vs 7 (IQR=5-10) days, p=0.450), disease progression (9 (22.0%) vs 7 (24.0%) patients, p=0.830) and mortality (10 (14.5%) vs 8 (11.9%) deaths, p=0.476). CONCLUSION: In this African trial, CCP therapy did not result in beneficial virological or clinical improvements. Further trials are needed to determine subgroups of patients who may benefit from CCP in Africa.Trial registration number NCT04542941.

Solar-powered oxygen delivery for the treatment of children with hypoxemia: protocol for a cluster-randomized stepped-wedge controlled trial in Uganda.

BACKGROUND: Child mortality due to pneumonia is a major global health problem and is associated with hypoxemia. Access to safe and continuous oxygen therapy can reduce mortality; however, low-income countries may lack the necessary resources for oxygen delivery. We have previously demonstrated proof-of-concept that solar-powered oxygen (SPO2) delivery can reliably provide medical oxygen remote settings with minimal access to electricity. This study aims to demonstrate the efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness across Uganda. METHODS: Objectives: Demonstrate efficacy of SPO2 in children hospitalized with acute hypoxemic respiratory illness. STUDY DESIGN: Multi-center, stepped-wedge cluster-randomized trial. SETTING: Twenty health facilities across Uganda, a low-income, high-burden country for pediatric pneumonia. Site selection: Facilities with pediatric inpatient services lacking consistent O2 supply on pediatric wards. PARTICIPANTS: Children aged < 5 years hospitalized with hypoxemia (saturation < 92%) warranting hospital admission based on clinical judgement. Randomization methods: Random installation order generated a priori with allocation concealment. Study procedure: Patients receive standard of care within pediatric wards with or without SPO2 system installed. OUTCOME MEASURES: Primary: 48-h mortality. Secondary: safety, efficacy, SPO2 system functionality, operating costs, nursing knowledge, skills, and retention for oxygen administration. Statistical analysis of primary outcome: Linear mixed effects logistic regression model with 48-h mortality (dependent variable) as a function of SPO2 treatment (before versus after installation), while adjusting for confounding effects of calendar time (fixed effect) and site (random effect). SAMPLE SIZE: 2400 patients across 20 health facilities, predicted to provide 80% power to detect a 35% reduction in mortality after introduction of SPO2, based on a computer simulation of > 5000 trials. DISCUSSION: Overall, our study aims to demonstrate mortality benefit of SPO2 relative to standard (unreliable) oxygen delivery. The innovative trial design (stepped-wedge, cluster-randomized) is supported by a computer simulation. Capacity building for nursing care and oxygen therapy is a non-scientific objective of the study. If successful, SPO2 could be scaled across a variety of resource-constrained remote or rural settings in sub-Saharan Africa and beyond. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03851783. Registered on 22 February 2019.

Immunovirological response to combined antiretroviral therapy and drug resistance patterns in children: 1- and 2-year outcomes in rural Uganda.

BACKGROUND: Children living with HIV continue to be in urgent need of combined antiretroviral therapy (ART). Strategies to scale up and improve pediatric HIV care in resource-poor regions, especially in sub-Saharan Africa, require further research from these settings. We describe treatment outcomes in children treated in rural Uganda after 1 and 2 years of ART start. METHODS: Cross-sectional assessment of all children treated with ART for 12 (M12) and 24 (M24) months was performed. CD4 counts, HIV RNA levels, antiretroviral resistance patterns, and non-nucleoside reverse transcriptase inhibitor (NNRTI) plasma concentrations were determined. Patient adherence and antiretroviral-related toxicity were assessed. RESULTS: Cohort probabilities of retention in care were 0.86 at both M12 and M24. At survey, 71 (83%, M12) and 32 (78%, M24) children remained on therapy, and 84% participated in the survey. At ART start, 39 (45%) were female; median age was 5 years. Median initial CD4 percent was 11% [IQR 9-15] in children < 5 years old (n = 12); CD4 count was 151 cells/mm(3) [IQR 38-188] in those ≥ 5 years old (n = 26). At M12, median CD4 gains were 11% [IQR 10-14] in patients < 5 years old, and 206 cells/mm(3) [IQR 98-348] in ≥ 5 years old. At M24, median CD4 gains were 11% [IQR 5-17] and 132 cells/mm(3) [IQR 87-443], respectively. Viral suppression (< 400 copies/mL) was achieved in 59% (M12) and 33% (M24) of children. Antiretroviral resistance was found in 25% (M12) and 62% (M24) of children. Overall, 29% of patients had subtherapeutic NNRTI plasma concentrations. CONCLUSIONS: After one year of therapy, satisfactory survival and immunological responses were observed, but nearly 1 in 4 children developed viral resistance and/or subtherapeutic plasma antiretroviral drug levels. Regular weight-adjustment dosing and strategies to reinforce and maintain ART adherence are essential to maximize duration of first-line therapy in children in resource-limited countries.

Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda.

BACKGROUND: Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART) treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. METHODS: Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/ml) and subtherapeutic antiretroviral (ARV) concentrations were investigated with multiple logistic regression. RESULTS: At 12 and 24 months of ART, 72% (n = 701) and 70% (n = 369) of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (<400 copies/ml). Risk factors for virological failure (>1,000 copies/ml) were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. CONCLUSION: Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.