Mortality and associated factors among people living with HIV admitted at a tertiary-care hospital in Uganda: a cross-sectional study

Abstract Background Hospital admission outcomes for people living with HIV (PLHIV) in resource-limited settings are understudied. We describe in-hospital mortality and associated clinical-demographic factors among PLHIV admitted at a tertiary-level public hospital in Uganda. Methods We performed a cross-sectional analysis of routinely collected data for PLHIV admitted at Kiruddu National Referral Hospital between March 2020 and March 2023. We estimated the proportion of PLHIV who had died during hospitalization and performed logistic regression modelling to identify predictors of mortality. Results Of the 5,827 hospitalized PLHIV, the median age was 39 years (interquartile range [IQR] 31–49) and 3,293 (56.51%) were female. The median CD4 + cell count was 109 cells/µL (IQR 25–343). At admission, 3,710 (63.67%) were active on antiretroviral therapy (ART); 1,144 (19.63%) had interrupted ART > 3 months and 973 (16.70%) were ART naïve. In-hospital mortality was 26% (1,524) with a median time-to-death of 3 days (IQR 1–7). Factors associated with mortality (with adjusted odds ratios) included ART interruption, 1.33, 95% confidence intervals (CI) 1.13–1.57, p 0.001; CD4 + counts ≤ 200 cells/µL 1.59, 95%CI 1.33–1.91, p  20 km from hospital 1.23, 95%CI 1.04–1.46, p 0.014; hospital readmission 0.7, 95%CI 0.56–0.88, p 0.002; chronic lung disease 0.62, 95%CI 0.41–0.92, p 0.019; and neurologic disease 0.46, 95%CI 0.32–0.68, p < 0.001. Conclusion One in four admitted PLHIV die during hospitalization. Identification of risk factors (such as ART interruption, function impairment, low/undocumented CD4 + cell count), early diagnosis and treatment of co-infections and liver disease could improve outcomes

Empiric TB Treatment of Severely Ill Patients With HIV and Presumed Pulmonary TB Improves Survival

RationaleIn 2007, World Health Organization (WHO) issued emergency recommendations on empiric treatment of sputum acid-fast bacillus smear-negative patients with possible tuberculosis (TB) in HIV-prevalent areas, and called for operational research to evaluate their effectiveness. We sought to determine if early, empiric TB treatment of possible TB patients with abnormal chest radiography or severe illness as suggested by the 2007 WHO guidelines, is associated with improved survival.MethodsWe prospectively enrolled consecutive HIV-seropositive inpatients at Mulago Hospital in Kampala, Uganda, from 2007 to 2011 with cough for ≥2 weeks. We retrospectively examined the effect of empiric TB treatment before discharge on 8-week survival among those with and without a WHO-defined "danger sign," including fever &gt;39°C, tachycardia &gt;120 beats per minute, or tachypnea &gt;30 breaths per minute. We modeled the interaction between empiric TB treatment and danger signs, and their combined effect on 8-week survival, and adjusted for relevant covariates.ResultsAmong 631 sputum smear-negative patients, 322 (51%) had danger signs. Cumulative 8-week survival of patients with danger signs was significantly higher with empiric TB treatment (80%) than without treatment (64%, P &lt; 0.001). After adjusting for duration of cough and concurrent hypoxemia, patients with danger signs who received empiric TB treatment had a 44% reduction in 8-week mortality (risk ratio 0.56, 95% confidence interval: 0.34-0.91, P = 0.020).ConclusionsEmpiric TB treatment of HIV-seropositive, smear-negative, presumed pulmonary TB patients with 1 or more danger signs is associated with improved 8-week survival. Enhanced implementation of the 2007 WHO empiric treatment recommendations should be encouraged whenever and wherever rapid and highly sensitive diagnostic tests for TB are unavailable

Variation in the observed effect of Xpert MTB/RIF testing for tuberculosis on mortality: A systematic review and analysis of trial design considerations.

Background: Most studies evaluating the effect of Xpert MTB/RIF testing for tuberculosis (TB) concluded that it did not reduce overall mortality compared to usual care. We conducted a systematic review to assess whether key study design and execution features contributed to earlier identification of patients with TB and decreased pre-treatment loss to follow-up, thereby reducing the potential impact of Xpert MTB/RIF testing. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Scopus for literature published from 1 st January 2009 to February 2019. We included all primary intervention studies that had evaluated the effect of Xpert MTB/RIF on mortality compared to usual care in participants with presumptive pulmonary TB. We critically reviewed features of included studies across: Study setting and context, Study population, Participant recruitment and enrolment, Study procedures, and Study follow-up. Results: We included seven randomised and one non-randomised study.  All included studies demonstrated relative reductions in overall mortality in the Xpert MTB/RIF arm ranging from 6% to 40%. However, mortality reduction was reported to be statistically significant in two studies. Study features that could explain the lack of observed effect on mortality included: the higher quality of care at study sites; inclusion of patients with a higher pre-test probability of TB leading to higher than expected empirical rates; performance of additional diagnostic testing not done in usual care leading to increased TB diagnosis or empiric treatment initiation; the recruitment of participants likely to return for follow-up; and involvement of study staff in ensuring adherence with care and follow-up. Conclusion: Most studies of Xpert MTB/RIF were designed and conducted in a manner that resulted in more patients being diagnosed and treated for TB, minimising the potential difference in mortality Xpert MTB/RIF testing could have achieved compared to usual care

Increased uptake of tuberculosis preventive therapy (TPT) among people living with HIV following the 100-days accelerated campaign: A retrospective review of routinely collected data at six urban public health facilities in Uganda

Tuberculosis preventive therapy (TPT) effectively decreases rates of developing active tuberculosis disease in people living with HIV (PLHIV) who are at increased risk. The Uganda Ministry of Health launched a 100-day campaign to scale-up TPT in PLHIV in July 2019. We sought to examine the effect of the campaign on trends of TPT uptake and characteristics associated with TPT uptake and completion among persons in HIV care. We retrospectively reviewed routinely collected data from 2016 to 2019 at six urban public health facilities in Uganda. HIV care database and paper-based TPT registers at six public health facilities in Kampala, Uganda were retrospectively reviewed. Estimated trends of TPT (given as Isoniazid monotherapy) uptake and completion across the 4 years, among PLHIV aged 15 years and above, and factors associated, were examined using Poisson regression model with robust standard errors using generalized estimating equation (GEE) models. On average, a total of 39,774 PLHIV aged 15 years and above were eligible for TPT each calendar year at the six health facilities. Across all 4 years, more than 70% were females (range: 73.5% -74.6%) and the median age ranged from 33 to 34 years. From 2016 quarter one to 2019 quarter two, TPT uptake was consistently below 25%, but, as expected, the uptake significantly increased by about 3-folds from 22.1% to 61.2%, in 2019 quarter two (i.e. before the roll-out of the 100-day accelerated TPT intervention) and quarter three (i.e. after the roll-out of the 100-day accelerated TPT intervention) respectively. This increase remained highly significant even after adjusting for patients’ baseline characteristics (adjusted prevalence ratio [aPR] = 2.58 [95%CI 2.45, 2.72], P-value<0.001). TPT completion was consistently high at above 70% at most of the time, but, it increased significantly among those initiated during 2018 quarter four and in the subsequent two quarters after the roll-out of the 100-day accelerated TPT intervention (i.e. TPT completion was: 83.2%, 95.3%, and 97.1% among individuals initiated during 2018 quarter4, and 2019 quarters 1 and 2, respectively). The increase in TPT completion during this period remained significant even after adjusting for patients’ baseline characteristics (aPR [95%CI] = 1.09 [1.04, 1.14], P value<0.001, and 1.10 [1.05,1.15], P value<0.001, for individuals initiated during 2019 quarter 1, and 2, respectively compared to those initiated during 2018 quarter 4). Not on ART or newly started on ART compared to ART experienced, and pregnant at TPT initiation compared to not pregnant were associated with poor TPT completion, whereas older age (≥25 years versus 15–24 years) was associated with higher TPT completion. The targeted 100-day campaign dramatically increased TPT uptake and completion among PLHIV suggesting a viable catch up strategy to meet WHO guidelines. Future analysis with additional years of data post 100-days TPT intervention is required to evaluate the sustainability of the observed gains

Oral antimicrobial rinse to reduce mycobacterial culture contamination among tuberculosis suspects in Uganda: a prospective study.

RationaleContamination by bacterial or fungal organisms reduces the effectiveness of mycobacterial culture for diagnosis of pulmonary tuberculosis (TB). We evaluated the effect of an anti-microbial and an anti-fungal oral rinse prior to expectoration on culture-contamination rates.MethodsWe enrolled a consecutive random sample of adults with cough for ≥ 2 weeks and suspected TB admitted to Mulago Hospital (Kampala, Uganda) between October 2008 and June 2009. We randomly assigned patients to oral rinse (60 seconds with chlorhexidine followed by 60 seconds with nystatin) vs. no oral rinse prior to initial sputum collection. Uganda National Tuberculosis Reference Laboratory technicians blinded to the method of sputum collection (with or without oral rinse) processed all sputum specimens for smear microscopy (direct Ziehl-Neelsen) and mycobacterial culture (Lowenstein-Jensen media).ResultsOf 220 patients enrolled, 177 (80%) were HIV-seropositive (median CD4-count 37 cells/uL, IQR 13-171 cells/uL). Baseline characteristics were similar between patients in the oral-rinse (N = 110) and no oral-rinse (N = 110) groups. The proportion of contaminated cultures was significantly lower in the oral-rinse group compared to the no oral-rinse group (4% vs. 15%, risk difference -11%, 95% CI -18 to -3%, p = 0.005). Oral rinse significantly reduced the proportion of contaminated cultures among HIV-infected patients (3% vs. 18%, risk difference -14%, 95% CI -23 to -6%, p = 0.002) but not HIV-uninfected (6% vs. 4%, risk difference 2%, 95% CI -12 to +15%, p = 0.81) patients. However, the proportion of smear-positive specimens (25% vs. 35%, p = 0.10) and culture-positive specimens (48% vs. 56%, p = 0.24) were lower in the oral-rinse compared to the no oral-rinse group, although the differences were not statistically significant.ConclusionsOral rinse prior to sputum expectoration is a promising strategy to reduce mycobacterial culture contamination in areas with high HIV prevalence, if strategies can be devised to reduce the adverse impact of oral rinse on smear- and culture-positivity

Integrated Strategies to Optimize Sputum Smear Microscopy: A Prospective Observational Study

Rationale: Smear-positive tuberculosis (TB) case detection rates are far below targets in most low-income countries. The standard approach to smear microscopy involves sputum collection over multiple days and examination of sputum smears by light microscopy (LM), an insensitive and time-consuming technique

Impact of Xpert MTB/RIF testing on tuberculosis management and outcomes in hospitalized patients in Uganda.

RationaleThe clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown.ObjectiveTo determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects.MethodsWE PROSPECTIVELY ENROLLED CONSECUTIVE, HOSPITALIZED, UGANDAN TB SUSPECTS IN TWO PHASES: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase.Results477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73-84%) and specificity (190/199, 96%, 95% CI: 92-98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31-54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0-26] vs. 0 [IQR 0-1], p&lt;0.001), and for smear-negative TB (35 [IQR 22-55] vs. 22 [IQR 0-33], p=0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0-5] vs. 0 [IQR 0-2], p=0.06) and for smear-negative TB (7 [IQR 3-53] vs. 6 [IQR 1-61], p=0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: -21% to +27%, p=0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: -34 to +46%, p=0.77).ConclusionsXpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases