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BackgroundDetection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia.MethodsParticipants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture.ResultsTB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm3, this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm3. Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics.ConclusionsPreviously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

Among HIV-infected, antiretroviral therapy (ART)–naive adults with positive World Health Organization tuberculosis (TB) symptom screening, clinical scoring could categorize patients for the risk of TB. This strategy would reduce the proportion of patients requiring TB testing before starting ART.

Abstractobjective To assess the diagnostic performance of urine lipoarabinomannan (LAM) detection for TB screening in HIV-positive adults in Ethiopia.methods Testing for LAM was performed using the Determine TB-LAM lateral flow assay on urine samples from participants in a prospective cohort with baseline bacteriological categorisation for active TB in sputum. Characteristics of TB patients with regard to LAM status were determined. Participants were followed for 6 months to evaluate survival, retention in care and incident TB.results Positive LAM results were found in 78/757 participants. Among 128 subjects with definite (confirmed by culture and/or Xpert MTB/RIF) TB, 33 were LAM-positive (25.8%); the respective figure for clinically diagnosed cases was 2/20 (10%). Five of the remaining 43 LAM-positive individuals had died during the 6-month follow-up period, whereas 38 remained in care without clinical signs of TB. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 25.8%, 92.9%, 42.3% and 86.0%, respectively. Among TB patients, LAM positivity was associated with higher WHO clinical stage, lower body mass index (BMI), CD4 cell and haemoglobin levels, and with increased mortality. A combination algorithm of urine LAM testing and sputum smear microscopy detected 49 (38.2%) of definite TB cases; among those with CD4 count ≤100 cells/mm 3 , this proportion was 66.7%.conclusions The performance of urine LAM testing for TB detection was poor in this population. However, this was improved among subjects with CD4 count ≤100 cells/mm 3 . In combination with sputum microscopy urine, LAM could be considered for targeted TB screening in this subgroup.

Rates of virological suppression after 6 months of ART were high in a cohort of 678 HIV-positive adults managed in Ethiopian health centers, with no significant difference with regard to concomitant tuberculosis at baseline (TB 135; non-TB 543).

BackgroundAccess to second-line antiretroviral therapy (ART) for HIV-positive patients remains limited in sub-Saharan Africa. Furthermore, outcomes of second-line ART may be compromised by mortality and loss to follow-up (LTFU).ObjectiveTo determine retention in care among patients receiving second-line ART in a public hospital in Ethiopia, and to investigate factors associated with LTFU among adults and adolescents.DesignHIV-positive persons with documented change of first-line ART to a second-line regimen were retrospectively identified from hospital registers, and data were collected at the time of treatment change and subsequent clinic visits. Baseline variables for adults and adolescents were analyzed using multivariate Cox proportional hazards models comparing subjects remaining in care and those LTFU (defined as a missed appointment of ≥90 days).ResultsA total of 383 persons had started second-line ART (330 adults/adolescents; 53 children) and were followed for a median of 22.2 months (the total follow-up time was 906 person years). At the end of study follow-up, 80.5% of patients remained in care (adults and adolescents 79.8%; children 85.7%). In multivariate analysis, LTFU among adults and adolescents was associated with a baseline CD4 cell count <100 cells/mm3 and a first-line regimen failure that was not confirmed by HIV RNA testing.ConclusionsAlthough retention in care during second-line ART in this cohort was satisfactory, and similar to that reported from first-line ART programs in Ethiopia, our findings suggest the benefit of earlier recognition of patients with first-line ART failure and confirmation of suspected treatment failure by viral load testing.

Background Traditional models to predict intensive care outcomes do not perform well in COVID‐19. We undertook a comprehensive study of factors affecting mortality and functional outcome after severe COVID‐19. Methods In this prospective multicentre cohort study, we enrolled laboratory‐confirmed, critically ill COVID‐19 patients at six ICUs in the Skåne Region, Sweden, between May 11, 2020, and May 10, 2021. Demographics and clinical data were collected. ICU burden was defined as the total number of ICU‐treated COVID‐19 patients in the region on admission. Surviving patients had a follow‐up at 90 days for assessment of functional outcome using the Glasgow Outcome Scale‐Extended (GOSE), an ordinal scale (1–8) with GOSE ≥5 representing a favourable outcome. The primary outcome was 90‐day mortality; the secondary outcome was functional outcome at 90 days. Results Among 498 included patients, 74% were male with a median age of 66 years and a median body mass index (BMI) of 30 kg/m 2 . Invasive mechanical ventilation was employed in 72%. Mortality in the ICU, in‐hospital and at 90 days was 30%, 38% and 39%, respectively. Mortality increased markedly at age 60 and older. Increasing ICU burden was independently associated with a two‐fold increase in mortality. Higher BMI was not associated with increased mortality. Besides age and ICU burden, smoking status, cortisone use, P a CO 2 >7 kPa, and inflammatory markers on admission were independent factors of 90‐day mortality. Lower GOSE at 90 days was associated with a longer stay in the ICU. Conclusion In critically ill COVID‐19 patients, the 90‐day mortality was 39% and increased considerably at age 60 or older. The ICU burden was associated with mortality, whereas a high BMI was not. A longer stay in the ICU was associated with unfavourable functional outcomes at 90 days.

BackgroundIn order to increase treatment coverage, antiretroviral treatment (ART) is provided through primary health care in low-income high-burden countries, where tuberculosis (TB) co-infection is common. We investigated the long-term outcome of health center–based ART, with regard to concomitant TB.MethodsART-naïve adults were included in a prospective cohort at Ethiopian health centers and followed for up to 4 years after starting ART. All participants were investigated for active TB at inclusion. The primary study outcomes were the impact of concomitant TB on all-cause mortality, loss to follow-up (LTFU), and lack of virological suppression (VS). Kaplan-Meier survival estimates and Cox proportional hazards models with multivariate adjustments were used.ResultsIn total, 141/729 (19%) subjects had concomitant TB, 85% with bacteriological confirmation (median CD4 count TB, 169 cells/mm3; IQR, 99–265; non-TB, 194 cells/mm3; IQR, 122–275). During follow-up (median, 2.5 years), 60 (8%) died and 58 (8%) were LTFU. After ≥6 months of ART, 131/630 (21%) had lack of VS. Concomitant TB did not influence the rates of death, LTFU, or VS. Male gender and malnutrition were associated with higher risk of adverse outcomes. Regardless of TB co-infection status, even after 3 years of ART, two-thirds of participants had CD4 counts below 500 cells/mm3.ConclusionsConcomitant TB did not impact treatment outcomes in adults investigated for active TB before starting ART at Ethiopian health centers. However, one-third of patients had unsatisfactory long-term treatment outcomes and immunologic recovery was slow, illustrating the need for new interventions to optimize ART programs.