title: Prevalence of dihydropteroate synthase genotypes before and after the introduction of combined antiretroviral therapy and their influence on the outcome of Pneumocystis pneumonia in HIV-1-infected patients.
abstract: The objective of this study was to determine whether the prevalence of Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations has changed since the introduction of combined antiretroviral therapy (cART) and whether the mutations are associated with poor outcome in Spanish HIV-1-infected patients with Pneumocystis pneumonia (PcP). We studied 167 PcP episodes in HIV-1-infected patients diagnosed during the pre-cART (1989-1995) and cART (2001-2004) periods. Molecular genotyping of DHPS was successfully performed in 98 patients (43 pre-cART and 55 cART). Seventeen patients (17/98, 17%; 95% confidence interval [CI], 10-25%) had mutations in the DHPS gene: 14 patients (14/43, 33%; 95% CI, 19-49%) from the pre-cART period and 3 patients (3/55, 5.5%; 95% CI, 1.3-16%) from the cART period (P < 0.01). In the multivariate analysis, the pre-cART period, previous PcP prophylaxis with sulfa drugs, and homosexuality as an HIV risk factor were found to be associated with a higher risk of presenting DHPS mutations. Overall, 95% of patients were treated with trimethoprim and sulfamethoxazole (TMP-SMX). In-hospital mortality was similar in patients with (out) mutations (6% versus 11%, P = 0.84). DHPS gene mutations were more common during the pre-cART period and were associated with previous sulfa exposure and homosexuality. However, their presence did not worsen prognosis of PcP. The response to TMP-SMX with therapeutic doses was successful in most cases.
authors: Hospital Clínic-IDIBAPS (Institut d'Investigació August Pi i Sunyer), Universitat de Barcelona, Barcelona, Spain.
authors: Míriam J
authors: MJ
authors: Alvarez-Martínez
authors: José M
authors: JM
authors: Miró
authors: Maria Eugenia
authors: ME
authors: Valls
authors: Jordi
authors: J
authors: Mas
authors: Jorge Puig
authors: JP
authors: de la Bellacasa
authors: Omar
authors: O
authors: Sued
authors: Manel
authors: M
authors: Solé
authors: Paula V
authors: PV
authors: Rivas
authors: Elisa
authors: E
authors: de Lazzari
authors: Natividad
authors: N
authors: Benito
authors: Felipe
authors: F
authors: García
authors: Carlos
authors: C
authors: Agustí
authors: Paul E
authors: PE
authors: Wilson
authors: José M
authors: JM
authors: Gatell
authors: Maria Teresa
authors: MT
authors: Jiménez de Anta
authors: Steven R
authors: SR
authors: Meshnick
authors: Asunción
authors: A
authors: Moreno
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology / Q000401:mortality; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000627:therapeutic use; D004094:Dihydropteroate Synthase / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D017052:Hospital Mortality; D006801:Humans; D009154:Mutation; D045363:Pneumocystis carinii / Q000201:enzymology* / Q000235:genetics; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality*; D015995:Prevalence; D013030:Spain; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004094:Dihydropteroate Synthase