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.