HIV-1 and recurrence, relapse, and reinfection of tuberculosis after cure:a cohort study in South African mineworkers

Background The proportion of recurrent tuberculosis cases attributable to r elapse or reinfection and the risk factors associated with these different mechanisms are poorly understood. We followed up a cohort of 326 South Afri can mineworkers, who had successfully completed treatment for pulmonary tub erculosis in 1995, to determine the rate and mechanisms of recurrence. Methods Patients were examined 3 and 6 months after cure, and then were mon itored by the routine tuberculosis surveillance system until December, 1998 . IS6110 DNA fingerprints from initial and subsequent episodes of tuberculo sis were compared to determine whether recurrence was due to relapse or rei nfection All patients gave consent for HIV-1 testing. Findings During follow-up (median 25.1 months, IQR 13.2-33.4), 65 patients (20%) had a recurrent episode of tuberculosis, a recurrence rate of 10.3 ep isodes per 100 person-years at risk (PYAR)-16.0 per 100 PYAR in HIV-1-posit ive patients and 6.4 per 100 PYAR in HIV-1-negative patients. Paired DNA fi ngerprints were available in 39 of 65 recurrences: 25 pairs were identical (relapse) and 14 were different (reinfection). 93% (13/14) of recurrences w ithin the first 6 months were attributable to relapse compared with 48% (12 /25) of later recurrences. HIV-1 infection was a risk factor for recurrence (hazard ratio 2.4, 95% CI 1.5-4.0), due to its strong association with dis ease caused by reinfection (18.7 2.4-143), but not relapse (0.58; 0.24-1.4) . Residual cavitation and increasing years of employment at the mine were r isk factors for relapse. Interpretation In a setting with a high risk of tuberculous Infection, HIV- 1 increases the risk of recurrent tuberculosis because of an Increased risk of reinfection. Interventions to prevent recurrent disease, such as lifelo ng chemoprophylaxis in HIV-1-positive tuberculosis patients, should be furt her assessed.