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Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis.

ABSTRACT: BACKGROUND: Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood. METHODS: Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was used to control for potential confounding. Stratification and covariate adjustment for PS and not PS-based multivariable Cox models were also performed. RESULTS: A total of 1,609 (7.52%) patients had active pulmonary TB at the start of ART. TB patients had higher proportions of being male, suffering from AIDS-defining illnesses, having World Health Organization (WHO) disease stage III or IV, and having lower CD4 cell counts at baseline (p?

SUBMITTER: Chu R

PROVIDER: S-EPMC3716897 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis.

Chu Rong R Mills Edward J EJ Beyene Joseph J Pullenayegum Eleanor E Bakanda Celestin C Nachega Jean B JB Devereaux P J PJ Thabane Lehana L

AIDS research and therapy 20130713 1

<h4>Background</h4>Tuberculosis (TB) disease affects survival among HIV co-infected patients on antiretroviral therapy (ART). Yet, the magnitude of TB disease on mortality is poorly understood.<h4>Methods</h4>Using a prospective cohort of 22,477 adult patients who initiated ART between August 2000 and June 2009 in Uganda, we assessed the effect of active pulmonary TB disease at the initiation of ART on all-cause mortality using a Cox proportional hazards model. Propensity score (PS) matching was ...[more]

PMID: 23849301

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Project description:Background:Evidence regarding potential adverse neuropsychiatric effects of efavirenz is conflicting, and data from sub-Saharan Africa, where 70% of persons living with HIV (PLHIV) reside and efavirenz is used as first-line therapy, are limited. Objective:To estimate associations between efavirenz use and depression and suicidal ideation among PLHIV in Uganda. Design:Prospective observational cohort study. (ClinicalTrials.gov: NCT01596322). Setting:Mbarara, Uganda. Participants:Adult PLHIV enrolled at the start of antiretroviral therapy (ART) and observed every 3 to 4 months from 2005 to 2015. Measurements:The exposure of interest was time-varying efavirenz use, defined as use during the 7 days and in 60 or more of the 90 days before a study visit, compared with nevirapine use. Self-reported outcomes were depression, defined as a mean score greater than 1.75 on the Hopkins Symptom Checklist depression subscale, and suicidal ideation. Multivariable-adjusted generalized estimating equations (GEE) logistic regression, Cox proportional hazards regression, and marginal structural models were fit to estimate the association between efavirenz use and the risk for depression and suicidal ideation. Results:694 participants (median age, 33 years; median pretreatment CD4+ count, 1.8 × 109 cells/L) contributed 1200 person-years of observation (460 person-years receiving efavirenz). No baseline differences in depression or suicidal ideation were found between patients ever exposed to efavirenz and those never exposed to efavirenz and receiving nevirapine (P > 0.80 for both). Of 305 participants ever-exposed to efavirenz, 61 (20.0%) and 19 (6.2%) had depression and suicidal ideation, respectively, on at least 1 follow-up visit, compared with 125 (32.1%) and 47 (12.1%) of the 389 who received nevirapine. In adjusted GEE models, efavirenz use was associated with decreased odds of depression compared with nevirapine use (adjusted odds ratio, 0.62 [95% CI, 0.40 to 0.96]) and was not significantly associated with suicidal ideation (adjusted odds ratio, 0.61 [CI, 0.30 to 1.25]). Time-to-event and marginal structural models yielded similar estimates. Limitation:Nonrandom assignment to treatment and substantial differences between the efavirenz and nevirapine groups. Conclusion:No evidence was found that use of efavirenz in first-line ART increased the risk for depression or suicidal ideation compared with nevirapine use among PLHIV in Uganda. Primary Funding Source:National Institutes of Health.

Project description:BACKGROUND:In sub-Saharan Africa, diagnosis and management of extrapulmonary tuberculosis (EPTB) in people living with HIV (PLHIV) remains a major challenge. This study aimed to characterize the epidemiology and risk factors for poor outcome of extrapulmonary tuberculosis in people living with HIV (PLHIV) in a rural setting in Tanzania. METHODS:We included PLHIV >18 years of age enrolled into the Kilombero and Ulanga antiretroviral cohort (KIULARCO) from 2013 to 2017. We assessed the diagnosis of tuberculosis by integrating prospectively collected clinical and microbiological data. We calculated prevalence- and incidence rates and used Cox regression analysis to evaluate the association of risk factors in extrapulmonary tuberculosis (EPTB) with a combined endpoint of lost to follow-up (LTFU) and death. RESULTS:We included 3,129 subjects (64.5% female) with a median age of 38 years (interquartile range [IQR] 31-46) and a median CD4+ cell count of 229/?l (IQR 94-421) at baseline. During the median follow-up of 1.25 years (IQR 0.46-2.85), 574 (18.4%) subjects were diagnosed with tuberculosis, whereof 175 (30.5%) had an extrapulmonary manifestation. Microbiological evidence by Acid-Fast-Bacillus stain (AFB-stain) or Xpert® MTB/RIF was present in 178/483 (36.9%) patients with pulmonary and in 28/175 (16.0%) of patients with extrapulmonary manifestations, respectively. Incidence density rates for pulmonary Tuberculosis (PTB and EPTB were 17.9/1000person-years (py) (95% CI 14.2-22.6) and 5.8/1000 py (95% CI 4.0-8.5), respectively. The combined endpoint of death and LTFU was observed in 1058 (33.8%) patients, most frequently in the subgroup of EPTB (47.2%). Patients with EPTB had a higher rate of the composite outcome of death/LTFU after TB diagnosis than with PTB [HR 1.63, (1.14-2.31); p = 0.006]. The adjusted hazard ratios [HR (95% CI)] for death/LTFU in EPTB patients were significantly increased for patients aged >45 years [HR 1.95, (1.15-3.3); p = 0.013], whereas ART use was protective [HR 0.15, (0.08-0.27); p <0.001]. CONCLUSIONS:Extrapulmonary tuberculosis was a frequent manifestation in this cohort of PLHIV. The diagnosis of EPTB in the absence of histopathology and mycobacterial culture remains challenging even with availability of Xpert® MTB/RIF. Patients with EPTB had increased rates of mortality and LTFU despite early recognition of the disease after enrollment.

Project description:BACKGROUND:Identifying characteristics of HIV-infected adults likely to have poor treatment outcomes can be useful for targeting interventions efficiently. Research in economics and psychology suggests that individuals' intertemporal time preferences, which indicate the extent to which they trade-off immediate vs. future cost and benefits, can influence various health behaviors. While there is empirical support for the association between time preferences and various non-HIV health behaviors and outcomes, the extent to which time preferences predict outcomes of those receiving antiretroviral therapy (ART) has not been examined previously. METHODS:HIV-infected adults initiating ART were enrolled at a health facility in Kenya. Participants' time preferences were measured at enrollment and used to classify them as having either a low or high discount rate for future benefits. At 48 weeks, we assessed mortality and ART adherence, as measured by Medication Event Monitoring System (MEMS). Logistic regression models adjusting for socio-economic characteristics and risk factors were used to determine the association between time preferences and mortality as well as MEMS adherence ?90%. RESULTS:Overall, 44% (96/220) of participants were classified as having high discount rates. Participants with high discount rates had significantly higher 48-week mortality than participants with low discount rates (9.3% vs. 3.1%; adjusted odds ratio 3.84; 95% CI 1.03, 14.50). MEMS adherence ?90% was similar for participants with high vs. low discount rates (42.3% vs. 49.6%, AOR 0.70; 95% CI 0.40, 1.25). CONCLUSION:High discount rates were associated with significantly higher risk of mortality among HIV-infected patients initiating ART. Greater use of time preference measures may improve identification of patients at risk of poor clinical outcomes. More research is needed to further identify mechanisms of action and also to build upon and test the generalizability of this finding.

Dataset Information

Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis.

Publications

Impact of tuberculosis on mortality among HIV-infected patients receiving antiretroviral therapy in Uganda: a prospective cohort analysis.

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