BACKGROUND: Perinatal mortality (newborn deaths in the first week of life and stillbirths) continues to be a significant global health threat, particularly in resource-constrained settings. Low-tech, innovative solutions that close the quality-of-care gap may contribute to progress toward the Sustainable Development Goals for health by 2030. From 2012 to 2018, the Saving Mothers, Giving Life Initiative (SMGL) implemented the Birth weight and Age-at-Death Boxes for Intervention and Evaluation System (BABIES) matrix in Western Uganda. The BABIES matrix provides a simple, standardized way to track perinatal health outcomes to inform evidence-based quality improvement strategies. METHODS: In November 2017, a facility-based qualitative evaluation was conducted using in-depth interviews with 29 health workers in 16 health facilities implementing BABIES in Uganda. Data were analyzed using directed content analysis across five domains: 1) perceived ease of use, 2) how the matrix was used, 3) changes in behavior or standard operating procedures after introduction, 4) perceived value of the matrix, and 5) program sustainability. RESULTS: Values in the matrix were easy to calculate, but training was required to ensure correct data placement and interpretation. Displaying the matrix on a highly visible board in the maternity ward fostered a sense of accountability for health outcomes. BABIES matrix reports were compiled, reviewed, and responded to monthly by interprofessional teams, prompting collaboration across units to fill data gaps and support perinatal death reviews. Respondents reported improved staff communication and performance appraisal, community engagement, and ability to track and link clinical outcomes with actions. Midwives felt empowered to participate in the problem-solving process. Respondents were motivated to continue using BABIES, although sustainability concerns were raised due to funding and staff shortages. CONCLUSIONS: District-level health systems can use data compiled from the BABIES matrix to inform policy and guide implementation of community-centered health practices to improve perinatal heath. Future work may consider using the Conceptual Framework on Use of the BABIES Matrix for Perinatal Health as a model to operationalize concepts and test the impact of the tool over time.

On behalf of the Saving Mothers, Giving Life (SMGL) Technical Working Group, we would like to thank Holt and Simpson1 for their valuable insights. We also appreciate their interest in finding out more about the planning and implementation process of the initiative, the challenges encountered, and the adaptations needed to account for contextual factors in each country. | | We agree with the authors on the importance of bringing attention to the valuable experiences and lessons learned during the implementation and course of the SMGL activities, including the activities directly related to health systems strengthening (HSS). We generally agree with the points raised regarding a lesser focus on the evaluation of the process of implementation of the SMGL initiative in the supplement in favor of highlighting the outcomes and impacts of the initiative on maternal and newborn health. However, we beg to differ that the implementation experiences of SGML are “not well documented.” | | The articles constituting the supplement do not represent an exhaustive account of all aspects of the SMGL initiative. The select articles published in the supplement have largely focused on the outcomes of the initiative at its conclusion after 5 years of implementation. They add to already published accounts about the initial planning, implementation, and monitoring and evaluation of the SMGL interventions, including a comprehensive external evaluation of inputs and processes undertaken during the first year of the initiative.2 They also add to the article by Kruk and colleagues that focused on the effects of the SMGL on the health systems in Uganda and Zambia during Phase 1.3

BACKGROUND: Saving Mothers, Giving Life (SMGL) is a 5-year initiative implemented in participating districts in Uganda and Zambia that aimed to reduce deaths related to pregnancy and childbirth by targeting the 3 delays to receiving appropriate care: seeking, reaching, and receiving. Approaches to addressing the third delay included adequate health facility infrastructure, specifically sufficient equipment and medications; trained providers to provide quality evidence-based care; support for referrals to higher-level care; and effective maternal and perinatal death surveillance and response. METHODS: SMGL used a mixed-methods approach to describe intervention strategies, outcomes, and health impacts. Programmatic and monitoring and evaluation data-health facility assessments, facility and community surveillance, and population-based mortality studies-were used to document the effectiveness of intervention components. RESULTS: During the SMGL initiative, the proportion of facilities providing emergency obstetric and newborn care (EmONC) increased from 10% to 25% in Uganda and from 6% to 12% in Zambia. Correspondingly, the delivery rate occurring in EmONC facilities increased from 28.2% to 41.0% in Uganda and from 26.0% to 29.1% in Zambia. Nearly all facilities had at least one trained provider on staff by the endline evaluation. Staffing increases allowed a higher proportion of health centers to provide care 24 hours a day/7 days a week by endline-from 74.6% to 82.9% in Uganda and from 64.8% to 95.5% in Zambia. During this period, referral communication improved from 93.3% to 99.0% in Uganda and from 44.6% to 100% in Zambia, and data systems to identify and analyze causes of maternal and perinatal deaths were established and strengthened. CONCLUSION: SMGL's approach was associated with improvements in facility infrastructure, equipment, medication, access to skilled staff, and referral mechanisms and led to declines in facility maternal and perinatal mortality rates. Further work is needed to sustain these gains and to eliminate preventable maternal and perinatal deaths.

BACKGROUND: Maternal and perinatal mortality is a global development priority that continues to present major challenges in sub-Saharan Africa. Saving Mothers, Giving Life (SMGL) was a multipartner initiative implemented from 2012 to 2017 with the goal of improving maternal and perinatal health in high-mortality settings. The initiative accomplished this by reducing delays to timely and appropriate obstetric care through the introduction and support of community and facility evidence-based and district-wide health systems strengthening interventions. METHODS: SMGL-designated pilot districts in Uganda and Zambia documented baseline and endline maternal and perinatal health outcomes using multiple approaches. These included health facility assessments, pregnancy outcome monitoring, enhanced maternal mortality detection in facilities, and district population-based identification and investigation of maternal deaths in communities. RESULTS: Over the course of the 5-year SMGL initiative, population-based estimates documented a 44% reduction in the SMGL-supported district-wide maternal mortality ratio (MMR) in Uganda (from 452 to 255 maternal deaths per 100,000 live births) and a 41% reduction in Zambia (from 480 to 284 maternal deaths per 100,000 live births). The MMR in SMGL-supported health facilities declined by 44% in Uganda and by 38% in Zambia. The institutional delivery rate increased by 47% in Uganda (from 45.5% to 66.8% of district births) and by 44% in Zambia (from 62.6% to 90.2% of district births). The number of facilities providing emergency obstetric and newborn care (EmONC) rose from 10 to 26 in Uganda and from 7 to 13 in Zambia, and lower- and mid-level facilities increased the number of EmONC signal functions performed. Cesarean delivery rates increased by more than 70% in both countries, reaching 9% and 5% of all births in Uganda and Zambia districts, respectively. Maternal deaths in facilities due to obstetric hemorrhage declined by 42% in Uganda and 65% in Zambia. Overall, perinatal mortality rates declined, largely due to reductions in stillbirths in both countries; however, no statistically significant changes were found in predischarge neonatal death rates in predischarge either country. CONCLUSIONS: MMRs fell significantly in Uganda and Zambia following the introduction of the SMGL interventions, and SMGL's comprehensive district systems-strengthening approach successfully improved coverage and quality of care for mothers and newborns. The lessons learned from the initiative can inform policy makers and program managers in other low- and middle-income settings where similar approaches could be used to rapidly reduce preventable maternal and newborn deaths.

Saving Mothers, Giving Life (SMGL), a 5-year initiative implemented in selected districts in Uganda and Zambia, was designed to reduce deaths related to pregnancy and childbirth by targeting the 3 delays to receiving appropriate care at birth. While originally the "Three Delays" model was designed to focus on curative services that encompass emergency obstetric care, SMGL expanded its application to primary and secondary prevention of obstetric complications. Prevention of the "first delay" focused on addressing factors influencing the decision to seek delivery care at a health facility. Numerous factors can contribute to the first delay, including a lack of birth planning, unfamiliarity with pregnancy danger signs, poor perceptions of facility care, and financial or geographic barriers. SMGL addressed these barriers through community engagement on safe motherhood, public health outreach, community workers who identified pregnant women and encouraged facility delivery, and incentives to deliver in a health facility. SMGL used qualitative and quantitative methods to describe intervention strategies, intervention outcomes, and health impacts. Partner reports, health facility assessments (HFAs), facility and community surveillance, and population-based mortality studies were used to document activities and measure health outcomes in SMGL-supported districts. SMGL's approach led to unprecedented community outreach on safe motherhood issues in SMGL districts. About 3,800 community health care workers in Uganda and 1,558 in Zambia were engaged. HFAs indicated that facility deliveries rose significantly in SMGL districts. In Uganda, the proportion of births that took place in facilities rose from 45.5% to 66.8% (47% increase); similarly, in Zambia SMGL districts, facility deliveries increased from 62.6% to 90.2% (44% increase). In both countries, the proportion of women delivering in facilities equipped to provide emergency obstetric and newborn care also increased (from 28.2% to 41.0% in Uganda and from 26.0% to 29.1% in Zambia). The districts documented declines in the number of maternal deaths due to not accessing facility care during pregnancy, delivery, and the postpartum period in both countries. This reduction played a significant role in the decline of the maternal mortality ratio in SMGL-supported districts in Uganda but not in Zambia. Further work is needed to sustain gains and to eliminate preventable maternal and perinatal deaths.

BACKGROUND: Cesarean section (CS) is an important intervention in complicated births when the safety of the mother or baby is compromised. Despite worldwide concerns about the overutilization of CS in recent years, many African women and their newborns still die because of limited or no access to CS services. We evaluated temporal and spatial trends in CS births in Uganda and modeled future trends to inform programming. METHODS: We performed secondary analysis of total births data from the Uganda National Health Management Information System (HMIS) reports during 2012-2016. We reviewed data from 3461 health facilities providing basic, essential obstetric and emergency obstetric care services in all 112 districts. We defined facility-based CS rate as the proportion of cesarean deliveries among total live births in facilities, and estimated the population-based CS rate using the total number of cesarean deliveries as a proportion of annual expected births (including facility-based and non-facility-based) for each district. We predicted CS rates for 2021 using Generalised Linear Models with Poisson family, Log link and Unbiased Sandwich Standard errors. We used cesarean deliveries as the dependent variable and calendar year as the independent variable. RESULTS: Cesarean delivery rates increased both at facility and population levels in Uganda. Overall, the CS rate for live births at facilities was 9.9%, increasing from 8.5% in 2012 to 11% in 2016. The overall population-based CS rate was 4.7%, and increased from 3.2 to 5.9% over the same period. Health Centre IV level facilities had the largest annual rate of increase in CS rate between 2012 and 2016. Among all 112 districts, 80 (72%) had a population CS rate below 5%, while 38 (34%) had a CS rate below 1% over the study period. Overall, Uganda's facility-based CS rate is projected to increase by 36% (PRR 1.36, 95% CI 1.35-1.36) in 2021 while the population-based CS rate is estimated to have doubled (PRR 2.12, 95% CI 2.11-2.12) from the baseline in 2016. CONCLUSION: Cesarean deliveries are increasing in Uganda. Health center IVs saw the largest increases in CS, and while there was regional heterogeneity in changes in CS rates, utilization of CS services is inadequate in most districts. We recommend expansion of CS services to improve availability.

BACKGROUND: Between January and June, 2015, a large typhoid fever outbreak occurred in Kampala, Uganda, with 10,230 suspected cases. During the outbreak, area surgeons reported a surge in cases of typhoid intestinal perforation (TIP), a complication of typhoid fever. We conducted an investigation to characterize TIP cases and identify modifiable risk factors for TIP. METHODS: We defined a TIP case as a physician-diagnosed typhoid patient with non-traumatic terminal ileum perforation. We identified cases by reviewing medical records at all five major hospitals in Kampala from 2013 to 2015. In a matched case-control study, we compared potential risk factors among TIP cases and controls; controls were typhoid patients diagnosed by TUBEX TF, culture, or physician but without TIP, identified from the outbreak line-list and matched to cases by age, sex and residence. Cases and controls were interviewed using a standard questionnaire from 1st -23rd December 2015. We used conditional logistic regression to assess risk factors for TIP and control for confounding. RESULTS: Of the 88 TIP cases identified during 2013-2015, 77% (68/88) occurred between January and June, 2015; TIPs sharply increased in January and peaked in March, coincident with the typhoid outbreak. The estimated risk of TIP was 6.6 per 1000 suspected typhoid infections (68/10,230). The case-fatality rate was 10% (7/68). Cases sought care later than controls; Compared with 29% (13/45) of TIP cases and 63% (86/137) of controls who sought treatment within 3 days of onset, 42% (19/45) of cases and 32% (44/137) of controls sought treatment 4-9 days after illness onset (ORadj = 2.2, 95%CI = 0.83-5.8), while 29% (13/45) of cases and 5.1% (7/137) of controls sought treatment ≥10 days after onset (ORadj = 11, 95%CI = 1.9-61). 68% (96/141) of cases and 23% (23/100) of controls had got treatment before being treated at the treatment centre (ORadj = 9.0, 95%CI = 1.1-78). CONCLUSION: Delay in seeking treatment increased the risk of TIPs. For future outbreaks, we recommended aggressive community case-finding, and informational campaigns in affected communities and among local healthcare providers to increase awareness of the need for early and appropriate treatment.

Podoconiosis, a noninfectious elephantiasis, is a disabling neglected tropical disease. In August 2015, an elephantiasis case-cluster was reported in Kamwenge District, western Uganda. We investigated to identify the disease's nature and risk factors. We defined a suspected podoconiosis case as onset in a Kamwenge resident of bilateral asymmetrical lower limb swelling lasting >= 1 month, plus >= 1 of the following associated symptoms: skin itching, burning sensation, plantar edema, lymph ooze, prominent skin markings, rigid toes, or mossy papillomata. A probable case was a suspected case with negative microfilaria antigen immunochromatographic card test (ruling out filarial elephantiasis). We conducted active case-finding. In a case-control investigation, we tested the hypothesis that the disease was caused by prolonged foot skin exposure to irritant soils, using 40 probable case-persons and 80 asymptomatic village control-persons, individually matched by age and sex. We collected soil samples to characterize irritants. We identified 52 suspected (including 40 probable) cases with onset from 1980 to 2015. Prevalence rates increased with age; annual incidence (by reported onset of disease) was stable over time at 2.9/100,000. We found that 93% (37/40) of cases and 68% (54/80) of controls never wore shoes at work (Mantel-Haenszel odds ratio [ORMH] = 7.7; 95% [confidence interval] CI = 2.0-30); 80% (32/40) of cases and 49% (39/80) of controls never wore shoes at home (ORMH = 5.2; 95% CI = 1.8-15); and 70% (27/39) of cases and 44% (35/79) of controls washed feet at day end (versus immediately after work) (OR = 11; 95% CI = 2.1-56). Soil samples were characterized as rich black-red volcanic clays. In conclusion, this reported elephantiasis is podoconiosis associated with prolonged foot exposure to volcanic soil. We recommended foot hygiene and universal use of protective shoes.

INTRODUCTION: While four in ten female sex workers (FSWs) in sub-Saharan Africa are infected with HIV, only a small proportion is enrolled in HIV care. We explored facilitators and barriers to linkage to HIV care among FSWs receiving HIV testing services at a community-based organization in periurban Uganda. METHODS: The cross-sectional qualitative study was conducted among 28 HIV positive FSWs from May to July 2014. Key informant interviews were conducted with five project staff and eleven peer educators. Data were collected on facilitators for and barriers to linkage to HIV care and manually analyzed following a thematic framework approach. RESULTS: Facilitators for linkage to HIV care included the perceived good quality of health services with same-day results and immediate initiation of treatment, community peer support systems, individual's need to remain healthy, and having alternative sources of income. Linkage barriers included perceived stigma, fear to be seen at outreach HIV clinics, fear and myths about antiretroviral therapy, lack of time to attend clinic, and financial constraints. CONCLUSION: Linkage to HIV care among FSWs is influenced by good quality friendly services and peer support. HIV service delivery programs for FSWs should focus on enhancing these and dealing with barriers stemming from stigma and misinformation.

BACKGROUND: Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance. METHODS: Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient. RESULTS: A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR = 1.34, 95% CI 1.20-1.50, p < 0.001), having a temperature ≥38.0 degrees C vs < 37.0 degrees C (RR = 1.19, 95% CI 1.05-1.35, p = 0.007) and having a parasite density >20,000/muL vs <4,000/muL (RR = 3.37, 95% CI 2.44-4.49, p < 0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected. CONCLUSIONS: Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy. TRIAL REGISTRATION: Current Controlled Trials Identifier NCT00527800.

BACKGROUND: Cotrimoxazole prophylaxis prolongs survival and prevents opportunistic infections, malaria, and diarrhea in persons infected with human immunodeficiency virus (HIV). Many countries recommend that individuals taking antiretroviral therapy (ART) discontinue cotrimoxazole when CD4 counts are >200 cells/mcL. However, this practice has not been evaluated in sub-Saharan Africa. METHODS: Patients in the Home-Based AIDS Care program in eastern Uganda initiated ART if they had a CD4 cell count ≤250 cells/mcL or World Health Organization stage III or IV HIV disease. In the program's fourth year, patients with CD4 counts >200 cells/mcL were randomly assigned, by household, to continue or discontinue cotrimoxazole. Consenting participants were followed for episodes of malaria and diarrhea. RESULTS: At randomization, 836 eligible patients had been receiving ART for a mean of 3.7 years, with a median CD4 count of 489 cells/mcL; 94% had a viral load <400 copies/mL. Among those continuing (n = 452) vs discontinuing (n = 384) cotrimoxazole, 0.4 vs 12.2%, respectively, had at least 1 episode of malaria (P < .001), and 14% vs 25%, respectively, had at least 1 episode of diarrhea (P < .001). Compared to those remaining on cotrimoxazole, patients who discontinued had a relative risk of malaria of 32.5 (95% confidence interval [CI], 8.6-275.0; P < .001) and of diarrhea of 1.8 (95% CI, 1.3-2.4; P < .001). CONCLUSIONS: HIV-infected adults on ART with CD4 counts >200 cells/mcL who live in a malaria-endemic area of sub-Saharan Africa and who abruptly discontinue cotrimoxazole prophylaxis have an increased incidence of malaria and diarrhea compared with those who continue prophylaxis. CLINICAL TRIALS REGISTRATION: NCT00119093.

BACKGROUND: Clinical outcomes for patients with Kaposi's sarcoma (KS) using nonnucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART) in resource-limited settings have not previously been described. METHODS: We evaluated HIV-infected patients aged ≥18 years, who initiated HAART in the Home-Based AIDS Care (HBAC) project in Tororo, Uganda, between May 2003 and February 2008 and were diagnosed with KS at baseline or during follow-up. We examined independent risk factors for having either prevalent or incident KS and risk factors for death among patients with KS. RESULTS: Of 1121 study subjects, 17 (1.5%) were diagnosed with prevalent KS and 18 (1.6%) with incident KS over a median of 56.1 months of follow-up. KS was associated with male sex [adjusted odds ratio (AOR) 2.41; 95% confidence interval (CI) 1.20-4.86] and baseline CD4 cell count < 50 cells/mcL (AOR 3.25; 95% CI 1.03-10.3). Eleven (65%) of 17 patients with prevalent KS and 13 (72%) of 18 patients with incident KS experienced complete regression (P = 0.137). Eighteen (64%) of 28 patients who remained on NNRTI-based HAART experienced regression of their KS and six (86%) of seven patients who were switched to protease inhibitor-containing HAART regimens had regression of their KS (P = 0.23). Mortality among those with KS was significantly associated with visceral disease (hazard ratio 19.22; 95% CI 2.42-152). CONCLUSION: Prevalent or incident KS was associated with 30% mortality. The resolution of KS lesions among individuals who initiated HAART with NNRTI-based regimens was similar to that found in studies using only protease inhibitor-based HAART.

OBJECTIVE: To examine the cost and cost effectiveness of quarterly CD4 cell count and viral load monitoring among patients taking antiretroviral therapy (ART). DESIGN: Cost effectiveness study. SETTING: A randomised trial in a home based ART programme in Tororo, Uganda. PARTICIPANTS: People with HIV who were members of the AIDS Support Organisation and had CD4 cell counts <250 x10(6) cells/L or World Health Organization stage 3 or 4 disease. MAIN OUTCOME MEASURES: Outcomes calculated for the study period and projected 15 years into the future included costs, disability adjusted life years (DALYs), and incremental cost effectiveness ratios (ICER; $ per DALY averted). Cost inputs were based on the trial and other sources. Clinical inputs derived from the trial; in the base case, we assumed that point estimates reflected true differences even if non-significant. We conducted univariate and multivariate sensitivity analyses. INTERVENTIONS: Three monitoring strategies: clinical monitoring with quarterly CD4 cell counts and viral load measurement (clinical/CD4/viral load); clinical monitoring and quarterly CD4 counts (clinical/CD4); and clinical monitoring alone. RESULTS: With the intention to treat (ITT) results per 100 individuals starting ART, we found that clinical/CD4 monitoring compared with clinical monitoring alone increases costs by $20,458 ( GBP 12,780, EUR 14 ,707) and averts 117.3 DALYs (ICER=$174 per DALY). Clinical/CD4/viral load monitoring compared with clinical/CD4 monitoring adds $142,458, and averts 27.5 DALYs ($5181 per DALY). The superior ICER for clinical/CD4 monitoring is robust to uncertainties in input values, and that strategy is dominant (less expensive and more effective) compared with clinical/CD4/viral load monitoring in one quarter of simulations. If clinical inputs are based on the as treated analysis starting at 90 days (after laboratory monitoring was initiated), then clinical/CD4/viral load monitoring is dominated by other strategies. CONCLUSIONS: Based on this trial, compared with clinical monitoring alone, monitoring of routine CD4 cell count is considerably more cost effective than additionally including routine viral load testing in the monitoring strategy and is more cost effective than ART.

OBJECTIVE: To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. DESIGN: Randomised clinical trial SETTING: A home based ART programme in rural Uganda. PARTICIPANTS: All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells x 10(6)/L or World Health Organization stage 3 or 4 disease. INTERVENTIONS: Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). MAIN OUTCOME MEASURES: Serious morbidity (newly diagnosed AIDS defining illness) and mortality. RESULTS: 1094 participants started ART; median CD4 count at baseline was 129 cells x 10(6)/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P=0.002) or the CD4 arm (1.49, P=0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P=0.31). CONCLUSION: In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.

BACKGROUND: Up to 20% of people initiating antiretroviral therapy (ART) in sub- Saharan Africa die during the first year of treatment. Understanding the clinical conditions associated with mortality could potentially lead to effective interventions to prevent these deaths. METHODS: We examined data from participants aged ≥18 years in the Home-Based AIDS Care project in Tororo, Uganda, to describe mortality over time and to determine clinical conditions associated with death. Survival analysis was used to examine variables associated with mortality at baseline and during follow-up. RESULTS: A total of 112 (9.4%) deaths occurred in 1,132 subjects (73% women) during a median of 3.0 years of ART. Mortality was 15.9 per 100 person-years (PYR) during the first 3 months and declined to 0.3 per 100 PYR beyond 24 months after ART initiation. Tuberculosis (TB) was the most common condition associated with death (21% of deaths), followed by Candida disease (15%). In 43% of deaths no specific clinical diagnosis was identified. Deaths within 3 months after ART initiation were associated with WHO clinical stage III or IV at baseline, diagnosis of TB at baseline, a diagnosis of a non-TB opportunistic infection (OI) in follow-up and a body mass index (BMI) ≤ 17 kg/m during follow-up. Mortality after 3 months of ART was associated with CD4 cell counts <200 cells/mcL, a diagnosis of TB or other OI, adherence to therapy <95%, and low hemoglobin levels during follow-up. CONCLUSION: Potentially remediable conditions and preventable infections were associated with mortality while receiving ART in Uganda.