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.
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.
Alvarez-Martínez
Míriam J
MJ
Hospital Clínic-IDIBAPS (Institut d'Investigació August Pi i Sunyer), Universitat de Barcelona, Barcelona, Spain.
Miró
José M
JM
Valls
Maria Eugenia
ME
Mas
Jordi
J
de la Bellacasa
Jorge Puig
JP
Sued
Omar
O
Solé
Manel
M
Rivas
Paula V
PV
de Lazzari
Elisa
E
Benito
Natividad
N
García
Felipe
F
Agustí
Carlos
C
Wilson
Paul E
PE
Gatell
José M
JM
Jiménez de Anta
Maria Teresa
MT
Meshnick
Steven R
SR
Moreno
Asunción
A
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
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D004094:Dihydropteroate Synthase