my personal edition > aids and hiv > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Fluconazole Prophylaxis Can Prevent Cryptococcal Disease in HIV-Positive Treatment-Naive African Patients: Presented at BHIVA

By Evelyn Harvey

LIVERPOOL, United Kingdom -- April 6, 2009 -- Invasive cryptcoccal disease can be prevented in HIV-positive (+) patients using fluconazole prophylaxis, according to a study presented here at the 15th Annual Conference of the British HIV Association (BHIVA).

Although no effects on mortality were seen in the Cryptococcal Prophylaxis (CRYPTOPRO) study, the researchers suggest that fluconazole prophylaxis could reduce mortality in standard African clinical practice.

"This is the first large-scale trial of fluconazole prophylaxis in Africa," said Rosalind Parkes-Ratanshi, MD, Imperial College London, London, United Kingdom, in a presentation on April 3. "Our objective was to determine the effects of fluconazole on survival and cryptococcal disease in HIV-infected Ugandan adults."

The study included 1,519 patients who were cryptococcal antigen (CrAg)-negative -- with no prior history of cryptococcal disease -- and treatment-naive, with a CD4 count of <200 cells/uL.

Patients were randomised to receive fluconazole 200 mg 3 times per week (n = 760) or placebo (n = 759). Baseline demographics and CD4 counts were similar between groups. Patients were followed up at 4 weeks, then reviewed every 8 weeks and given hospital treatment if unwell.

All patients were referred for antiretroviral therapy (ART), and 88% began therapy during the trial (median time to ART 11 weeks). Patients also received cotrimoxazole prophylaxis as per Ugandan care guidelines.

Administration of fluconazole was continued until CD4 counts reached 200 cells/mm³, after which patients dropped out of the trial. Patients participated in the study for a median of 5 months.

Fluconazole prophylaxis significantly reduced invasive cryptococcal infection in HIV-positive patients (P = .0001). During the course of the study, 19 cryptococcal infections were recorded, of which only 1 occurred in the fluconazole group.

Looking at the effect of fluconazole in conjunction with ART, rates of cryptococcal disease remained significantly higher in the placebo group (7 infections) even after the introduction of ART (P = .0001). Cryptococcal infections were more frequent in patients with low baseline CD4 counts.

All 7 patients who died from cryptococcal disease were in the placebo group. However, these deaths did not translate into a statistically significant effect on all-cause mortality, with 100 deaths overall in the fluconazole group and 98 in the placebo group.

Rates of oesophageal (P < .0001) and oropharyngeal and vaginal (both P < .001) candida infections were significantly lower for patients in the fluconazole group than in the placebo group, independently of ART.

No significant differences in discontinuation because of adverse events were found between groups. After starting ART, no adverse interactions between fluconazole and ARVs, including nevirapine, were observed.

"[S]ince CrAg testing and crypotococcal treatments are not widely available in African clinical settings, we believe that widespread use of fluconazole prophylaxis would be likely to reduce mortality in addition to morbidity," said Dr. Parkes-Ratanshi. "This study strengthens the argument for fluconazole prophylaxis in resource-poor settings, particularly those with <100% ART coverage."

Funding for this study was provided by the UK Medical Research Council.

[Presentation title: Successful Primary Prevention of Cryptococcal Disease Using Fluconazole Prophylaxis in HIV-Infected Ugandan Adults (CRYPTOPRO). Abstract O26]

E-Mail this DGDispatch to a colleague

To print, use this version