Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited.
Xpert MTB/RIF is a major advance for TB diagnostics, especially for multidrug-resistant (MDR) TB and HIV-associated TB. But implementation concerns including cost, technical support requirements, and challenging demands of providing second-line TB drugs for diagnosed MDR-TB cases call for gradual, careful introduction based on country circumstances.
Background
Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with bedaquiline and delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+).
Methods
We prospectively determined the effectiveness and safety of combining 2 new drugs with 2 repurposed drugs—bedaquiline, delamanid, linezolid, and clofazimine—for 24–36 weeks in adults with pulmonary MDR-TBFQ+ and/or MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as 2 consecutive negative cultures taken 4 weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during the treatment period.
Results
Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: 4 deaths, 7 treatment changes, 2 bacteriological failures, and 1 withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500 ms. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority.
Conclusions
After 24–36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully.
Clinical Trials Registration. ClinicalTrials Registry of India (CTRI/2019/01/017310).
To determine the risk of active tuberculosis associated with HIV infection, we retrospectively studied a cohort of HIV-seropositive and HIV-seronegative women participating in an HIV perinatal transmission study in Kinshasa, Zaire. After a median follow-up of 32 months, new cases of proven pulmonary or clinically diagnosed tuberculosis occurred in 19 of the 249 HIV-seropositive women (7.6%, 3.1 cases per 100 person-years) compared with 1 of the 310 HIV-seronegative women (0.3%, 0.12 cases per 100 person-years), for a relative risk of 26 (95% confidence interval, 5 to 125). Proven pulmonary tuberculosis was diagnosed in 7 HIV-seropositive women (2.8%, 1.2 cases per 100 person-years) and 1 HIV-seronegative woman (0.3%, 0.12 cases per 100 person-years), for a relative risk of 10 (95% confidence interval, 1.5 to 47). We estimated that 66 cases of proven pulmonary tuberculosis in 100,000 person-years of follow-up in women of childbearing age could be attributed to HIV; this is 35% of their estimated total incidence of proven pulmonary tuberculosis. Among those followed for 2 yr, 27 (11%) of 243 HIV-seropositive women died during 2 yr of follow-up compared with none of 296 HIV-seronegative women (p less than 0.001). In HIV-seropositive women with proven or clinically diagnosed tuberculosis mortality was even higher: 5 (26%) of the 19 HIV-seropositive women with proven pulmonary or clinically diagnosed tuberculosis died during follow-up compared with 22 (10%) of the 224 HIV-seropositive women not diagnosed as having tuberculosis (relative risk 2.7; 95% confidence interval, 1.1 to 6.3).(ABSTRACT TRUNCATED AT 250 WORDS)
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