Mutations in the human-derived Pneumocystis carinii dihydropteroate synthase (DHPS) gene have been reported with increasing frequency and have been linked to prior sulfa prophylaxis and possible ...emergence of sulfa resistance. This study was done to examine the prevalence and clinical significance of P. carinii DHPS mutations in Italian patients. A previously described singlestrand conformation polymorphism technique was used to identify P. carinii DHPS mutations in 107 patients with acquired immunodeficiency syndrome. Overall prevalence (8%) was low compared with that in other reports. Mutations were observed in 19% (6/31) of patients exposed to sulfa prophylaxis, compared with 4% (3/76) of patients not exposed to sulfa prophylaxis (P = .017). No significant association was observed between the presence of DHPS mutations and mortality, CD4 cell count, or demographic factors. The study confirms the association between DHPS mutations and prior sulfa prophylaxis and shows that the prevalence of DHPS mutations in an Italian patient population is lower than that in other populations.
The introduction of protease inhibitors (PIs) gave a dramatic drop in AIDS-related opportunistic events, mainly due to induced immune reconstitution. Discontinuation of prophylaxis against ...Pneumocystis carinii is considered safe when CD4 > 200 cells/mm3. Ideally, we should have specific functional tests for HIV-1-related decisions. We examined viro-immunological profiles, clinical outcome and lymphocyte proliferation (LP) to P. carinii and other antigens in 108 subjects: 28 AIDS presenters with P. carinii pneumonia (PCP) (CD4 < 200 cells/mm3), 22 untreated asymptomatic HIV-1-infected patients (CD4 > 200 cells/mm3), 44 HIV-1-infected patients immune-reconstituted on antiretroviral regimens and 14 HIV-1-uninfected healthy controls. As regards viral load, there was no significant difference in therapy duration, nadir, or actual CD4, CD8, natural killer or B cell counts in immune-reconstituted patients receiving protease inhibitor (PI)-based versus those receiving PI-sparing antiretroviral regimens. Among subjects showing abnormally low P. carinii-specific LP, three patients receiving a non-nucleoside reverse transcriptase inhibitor (nNRTI) developed PCP despite having CD4 > 250 cells/mm3. P. carinii-specific LP could be considered for doubtful situations, i.e. for a safer clinical decision of discontinuing or restarting prophylaxis in patients with a low CD4 nadir or experiencing a sudden CD4 decrease under highly active antiretroviral therapy (HAART). HIV-1 PIs, having in vitro aspecific effects against Pneumocystis, could play a clinically significant anti-opportunistic role, thus offering a further benefit in heavily immunosuppressed patients during early stages of antiretroviral therapy.
Mutations in the human-derived Pneumocystis carinii dihydropteroate synthase (DHPS) gene have been reported with increasing frequency and have been linked to prior sulfa prophylaxis and possible ...emergence of sulfa resistance. This study was done to examine the prevalence and clinical significance of P. carinii DHPS mutations in Italian patients. A previously described single-strand conformation polymorphism technique was used to identify P. carinii DHPS mutations in 107 patients with acquired immunodeficiency syndrome. Overall prevalence (8%) was low compared with that in other reports. Mutations were observed in 19% (6/31) of patients exposed to sulfa prophylaxis, compared with 4% (3/76) of patients not exposed to sulfa prophylaxis (P=.017). No significant association was observed between the presence of DHPS mutations and mortality, CD4 cell count, or demographic factors. The study confirms the association between DHPS mutations and prior sulfa prophylaxis and shows that the prevalence of DHPS mutations in an Italian patient population is lower than that in other populations.
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