Outcomes of Multi-Drug Resistant Tuberculosis (MDR-TB) among a Cohort of South African Patients with High HIV Prevalence

Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access.We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status.Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55-5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05).In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed

Baseline Demographic Characteristics by HIV Status.

<p>∧ Interval between culture positive diagnosis at initial evaluation to time of treatment initiation in MDR-TB Hospital *All (100%) of patients had a positive culture on initial evaluation and referral to the study. The numbers presented here reflect repeat testing on cohort enrollment.</p

Competing Risk Model of Failure, Default and Death.

<p>AIC =  4854.266.</p><p>-2 Log L =  4812.266.</p><p>Test of Weight Group 1 vs 2: Wald = 3.5642 p = 0.0590 Wald = 0.5475 p = 0.4593 Wald = 17.6184.</p><p>Test of DxTx^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020436#nt107" target="_blank">*</a>} Group 1 vs 2: Wald = 2.9411 p = 0.0863 Wald = 0.0155 p = 0.9011 Wald = 0.9187.</p><p>*DxTx is the time from culture diagnosis to treatment initiation.</p

Cumulative Incidence of Treatment Outcomes by HIV status and weight group.

<p>A =  Failure; B =  Default; C =  Died.</p