Treatment of Pneumocystis jirovecii pneumonia in HIV-infected patients: a review

Expert Rev Anti Infect Ther. 2017 Sep;15(9):873-892. doi: 10.1080/14787210.2017.1364991. Epub 2017 Aug 21.

Abstract

Pneumocystis pneumonia is a potentially life-threatening pulmonary infection that occurs in immunocompromised individuals and HIV-infected patients with a low CD4 cell count. Trimethoprim-sulfamethoxazole has been used as the first-line agent for treatment, but mutations within dihydropteroate synthase gene render potential resistance to sulfamide. Despite advances of combination antiretroviral therapy (cART), Pneumocystis pneumonia continues to occur in HIV-infected patients with late presentation for cART or virological and immunological failure after receiving cART. Areas covered: This review summarizes the diagnosis and first-line and alternative treatment and prophylaxis for Pneumocystis pneumonia in HIV-infected patients. Articles for this review were identified through searching PubMed. Search terms included: 'Pneumocystis pneumonia', 'Pneumocystis jirovecii pneumonia', 'Pneumocystis carinii pneumonia', 'trimethoprim-sulfamethoxazole', 'primaquine', 'trimetrexate', 'dapsone', 'pentamidine', 'atovaquone', 'echinocandins', 'human immunodeficiency virus infection', 'acquired immunodeficiency syndrome', 'resistance to sulfamide' and combinations of these terms. We limited the search to English language papers that were published between 1981 and March 2017. We screened all identified articles and cross-referenced studies from retrieved articles. Expert commentary: Trimethoprim-sulfamethoxazole will continue to be the first-line agent for Pneumocystis pneumonia given its cost, availability of both oral and parenteral formulations, and effectiveness or efficacy in both treatment and prophylaxis. Whether resistance due to mutations within dihydropteroate synthase gene compromises treatment effectiveness remains controversial. Continued search for effective alternatives with better safety profiles for Pneumocystis pneumonia is warranted.

Keywords: Interstitial pneumonitis; alternative therapy; combination antiretroviral therapy; prophylaxis; trimethoprim-sulfamethoxazole.

Publication types

  • Review

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / immunology
  • AIDS-Related Opportunistic Infections / virology
  • Anti-Bacterial Agents / therapeutic use*
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • CD4 Lymphocyte Count
  • Dihydropteroate Synthase / genetics
  • Dihydropteroate Synthase / metabolism
  • Drug Resistance, Bacterial / genetics
  • HIV-1 / drug effects
  • HIV-1 / immunology
  • HIV-1 / pathogenicity
  • Humans
  • Immunocompromised Host*
  • Mutation
  • Pneumocystis carinii / drug effects
  • Pneumocystis carinii / genetics
  • Pneumocystis carinii / pathogenicity
  • Pneumonia, Pneumocystis / drug therapy*
  • Pneumonia, Pneumocystis / immunology
  • Pneumonia, Pneumocystis / microbiology
  • Treatment Outcome
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*

Substances

  • Anti-Bacterial Agents
  • Anti-HIV Agents
  • Bacterial Proteins
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Dihydropteroate Synthase