Recurrence of tuberculosis in HIV-1-infected adults treated after rifamycin-based treatment and highly active antiretroviral therapy.

To the Editor: Tuberculosis (TB) and HIV infection may cause mutually detrimental effects in patients with coinfection: TB may accelerate the progression of HIV infection by increasing HIV replication and may be associated with a higher mortality rate and a shorter survival, while HIV-infected patients have an increased risk for development of active TB and TB recurrence compared with HIVuninfected patients. In HIV-infected patients, the risk for TB recurrence increases with background TB incidence and shorter durations of rifampin-based treatment. Although highly active antiretroviral therapy (HAART) has resulted in declines in morbidity and mortality in Western countries, whether the introduction of HAART may provide a benefit in reducing the recurrence rate of TB remains unclear because most previously reported studies were performed in the pre-HAART era or in regions with limited access to HAART. In view of the massive challenge imposed by the HIV pandemic on global TB control, concurrent treatment of TB and HIV infection may provide a survival benefit and reduction in the risk for occurrence and recurrence of TB. Such an argument can be supported by an increasing number of studies of HIVinfected patients with access to HAART, which have demonstrated that the incidence and recurrence rate of TB and the mortality rate among patients with TB and HIV coinfection are declining and survival rates are improving. In addition, the rate of anti-TB drug resistance may be declining for patients with access to HAART. To further understand the recurrence rate of TB among patients with late-stage HIV infection who are receiving HAART and rifamycin (rifampin or rifabutin)–based treatment, we analyzed the data of a prospective observational study of patients with TB and HIV coinfection at a university hospital in Taiwan between June 1994 and June 2003, where the estimated TB incidence was 76 cases per 100,000 population in 2000 and the seroprevalence of HIV infection was 16.84 cases per 100,000 population in 2002. The major route of HIV transmission in Taiwan was sexual, which accounted for >90% of cases, while intravenous drug use accounted for only 1.78% of cases. Patients were provided free access to HIV care and HAART at designated hospitals since April 1997, before which time only 2 nucleoside reverse transcriptase inhibitors were given. As of July 31, 2003, 126 patients (17.6%) developed 135 episodes of TB after a median follow-up of 889 days (range, 5–3214 days); 90 patients had 99 episodes of culture-proven TB. Their clinical characteristics are shown in Table 1. Most TB patients had a baseline CD4 lymphocyte count of 200/mm, and nearly one-third had concurrent AIDS-defining opportunistic illnesses within 1 month of the TB diagnosis. Of the first episodes of TB, 109 were pulmonary TB, 65 were extrapulmonary TB, and 48 were both pulmonary and extrapulmonary TB. Of the 66 Mycobacterium tuberculosis isolates saved from the first episodes of TB, 11 were resistant to isoniazid, 4 were resistant to rifampin, and 2 were resistant to both rifampin and isoniazid (ie, multidrug-resistant M. tuberculosis). Only 1 isolate was primary multidrug-resistant M. tuberculosis. TB treatment for HIV-infected patients in the era of HAART consisted of rifamycin-based treatment combined with indinavir or efavirenz. The median duration of anti-TB therapy was 9 months (range, 1–24 months); 83.8% of patients received rifamycin-based treatment for 6 months. Only 2 patients (1.6%) received anti-TB therapy not containing rifamycins because of recurrent severe skin rashes and drug fevers due to both rifabutin and rifampin. Approximately four fifths (80.2%) of the patients received HAART. Overall, 8 patients developed 9 episodes of recurrent TB; 8 of these episodes were culture proven. The median interval from TB diagnosis to the date of TB recurrences was 1065 days (range, 210–1307 days). The overall incidence of recurrent TB was 2.50 cases per 100 patient-years (95% confidence interval, 2.34–2.67). Among the 90 patients with culture-proven TB, the recurrence rate was 3.32 cases per 100 patient-years (95% confidence interval, 3.11–3.50). The median plasma HIV RNA load measured by reverse transcriptase–polymerase chain reaction analysis (Amplicor version 1.5; Roche, Branchburg, NJ) at recurrence was 5.06 log10 copies/mL (range, 2.60–5.18 log10), and the median CD4 cell count at recurrence was 75/mm. The latest median CD4 cell count had increased to 230/mm, and the plasma HIV RNA load was 2.60 log10 copies/mL (range, 2.60–5.88 log10); 70% of patients had plasma HIV RNA loads of <2.60 log10 (<400 copies/mL). As compared with findings of other studies, our results suggest that the recurrence rate of TB may not be improved to a significant extent by concurrent treatment of TB and HIV infection with HAART and a longer duration ( 6 months) of rifamycin-based treatment in a region with moderate background TB incidence. The insignificant improvement may be because most of our TB patients had late-stage HIV infection. Whether earlier diagnosis of HIV infection and initiation of HAART will reduce the risk for TB recurrence remains to be studied, although HAART has been shown to reduce the incidence of HIV-1– associated TB, especially in