Bedaquiline and Linezolid improve anti-TB treatment outcome in drug-resistant TB patients with HIV: A systematic review and meta-analysis

Pharmacol Res. 2022 Aug:182:106336. doi: 10.1016/j.phrs.2022.106336. Epub 2022 Jun 30.

Abstract

Objectives: We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing multiple chemotherapy regimens, to provide a basis for evidence-based practice.

Methods: We searched three electronic databases (PubMed, Web of Science and Cochrane) for related English studies published since 2010. A random-effect model was used to estimate the pooled result for the treatment outcomes. Subgroup analysis based on possible factors, such as ART, baseline CD4 T-cell count, treatment regimens, and profiles of drug resistance, was also conducted to assess factors for favorable outcome. Outcomes were treatment success and mortality.

Results: 38 studies, 40 cohorts with 9279 patients were included. The pooled treatment success, mortality, treatment failure, and default rates were 57.5 % (95 % CI 53.1-61.9), 21 % (95 % CI 17.8-24.6), 4.8 % (95 % CI 3.5-6.5), and 10.7 % (95 % CI 8.7-13.1), respectively, in patients with DR-TB and HIV co-infection. Subgroup analysis showed that BDQ and LZD based regimen, and ≥ 2 Group A drugs were associated with a higher treatment success rate. Besides, higher CD4 T-cell count at baseline was also correlated with higher treatment success rate, too.

Conclusions: Suboptimal anti-TB outcomes underlining the need to expand the application of effective drugs and better regimen in high HIV setting. BDQ and LZD based all-oral regimen and early ART could contribute to higher treatment success, particularly among XDR-TB-HIV patients. Given that all included studies were observational, our findings emphasize the need for high-quality studies to further investigate the optimal treatment regimen for DR-TB-HIV.

Keywords: All-oral regimen; Bedaquiline (PubChem CID: 5388906); Drug-resistant tuberculosis; Group A drugs; HIV; Levofloxacin (PubChem CID: 149096); Linezolid (PubChem CID: 441401); Meta-analysis; Moxifloxacin (PubChem CID: 152946); Outcome.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / therapeutic use
  • Diarylquinolines
  • Extensively Drug-Resistant Tuberculosis* / complications
  • Extensively Drug-Resistant Tuberculosis* / drug therapy
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Humans
  • Linezolid / adverse effects
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant* / complications
  • Tuberculosis, Multidrug-Resistant* / drug therapy

Substances

  • Antitubercular Agents
  • Diarylquinolines
  • bedaquiline
  • Linezolid