Effect of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of P carinii pneumonia in patients with HIV-1: a prospective study

Lancet. 2001 Aug 18;358(9281):545-9. doi: 10.1016/S0140-6736(01)05705-1.

Abstract

Background: Investigators have reported that patients infected with Pneumocystis carinii containing mutations in the DHPS (dihydropteroate synthase) gene have a worse outcome than those infected with P carinii containing wild-type DHPS. We investigated patients with HIV-1 infection and P carinii pneumonia to determine if DHPS mutations were associated with poor outcomes in these patients.

Methods: We compared presence of mutations at the DHPS locus with survival and response of patients to co-trimoxazole or other drugs.

Findings: For patients initially given co-trimoxazole, nine (14%) of 66 with DHPS mutant died, compared with nine (25%) of 36 with wild type (risk ratio50.55 [95% CI=0.24-1.25]; p=0.15). Ten (15%) of 66 patients with a DHPS mutant did not respond to treatment, compared with 13 (36%) of 36 patients with the wild type (0.42 [0.20-0.86]; p=0.02). For patients aged 40 years or older, four (14%) of 29 with the mutant and nine (56%) of 16 with the wild type died (0.25 [0.09-0.67]; p=0.005).

Interpretation: These results, by contrast with those of previous studies, suggest that patients with wild-type P carinii do not have a better outcome than patients with the mutant when given co-trimoxazole. Our results suggest that presence of a DHPS mutation should be only one of several criteria guiding the choice of initial drug treatment of P carinii pneumonia in patients with HIV-1 infection.

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy
  • AIDS-Related Opportunistic Infections / genetics*
  • AIDS-Related Opportunistic Infections / mortality
  • Adult
  • Anti-Infective Agents / therapeutic use
  • Dapsone / therapeutic use
  • Dihydropteroate Synthase / genetics*
  • Drug Resistance, Microbial
  • Genotype
  • HIV-1
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pneumocystis / drug effects
  • Pneumocystis / enzymology*
  • Pneumocystis / genetics
  • Pneumonia, Pneumocystis / drug therapy
  • Pneumonia, Pneumocystis / genetics*
  • Pneumonia, Pneumocystis / mortality
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • Trimethoprim / therapeutic use
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use

Substances

  • Anti-Infective Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination
  • Dapsone
  • Trimethoprim
  • Dihydropteroate Synthase