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15th Annual Conference of the British HIV Association1-3 April 2009, Liverpool, UK |
SUCCESSFUL PRIMARY PREVENTION OF CRYPTOCOCCAL DISEASE USING FLUCONAZOLE PROPHYLAXIS IN HIV-INFECTED UGANDAN ADULTS (CRYPTOPRO)
HIV Med 2009 Apr 1-3 (Suppl 1);15:12 (abstract no. O26)
R Parkes-Ratanshi1, K Wakeham2, A Kamali2, J Levin2, A Coutinho3, J Whitworth4, H Grosskurth2 and D Lalloo5
1Imperial College, London, UK, 2MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda, 3Institute of Infectious Diseases, Kampala, Uganda, 4Wellcome Trust, London, UK, 5Liverpool School of Tropical Medicine, Liverpool, UK
BACKGROUND: Cryptococcal disease remains a significant cause of morbidity and mortality in HIV infected individuals in tropical settings, despite the introduction of antiretroviral therapy (ART). No large trial of fluconazole as primary prophylaxis has been done in Africa.
METHODS: We performed a prospective, double blind randomized controlled trial comparing 200 mg fluconazole 3· per week to identical placebo in rural Uganda. 1519 ART naïve adults with CD4 counts <200 were enrolled. Patients were excluded if baseline cryptococcal antigen (CrAg) was positive. Participants were reviewed every 8 weeks and seen in clinic if unwell. 1335 (88%) participants started ART. Trial drug was continued until CD4 counts rose to 200. Primary end points were invasive cryptoccocal disease and all cause mortality. Survival and time to end points were assessed in intention to treat Kaplan-Meier survival analyses. Cox’s proportional hazard regression models analyses were used to adjust for ART and CD4 count.
RESULTS: Seven hundred and sixty participants received fluconazole and 759 received placebo. 19 participants developed definite cryptococcal disease, one on fluconazole and 18 on placebo (log rank X2 15.36 P=0.0001) with an adjusted Hazard Ratio (aHR) of 0.053 (95% CI 0.007–0.4 P=0.004). 12 developed cryptococcus before starting ART (11 on placebo) and 7 whilst on ART (all placebo); fluconazole was effective both pre ART (log rank X2=8.02 P=0.0046) and post ART (log rank X2=7.45 P=0.0064). 7 participants died of cryptococcal disease. There was no difference in all cause mortality between fluconazole (n=100) and placebo (n=98) arms. Fluconazole reduced oesphageal candida (aHR=0.14, 95% CI 0.067–0.30 P ≤0.0001), oropharyngeal and vaginal candida (aHR=0.15, 95% CI 0.097–0.22 P≤0.001). Elevated transaminases (>5·upper limit) were similar in both arms (aHR=0.94, 95% CI 0.65–1.35 P≤0.47).
CONCLUSIONS: Fluconazole proved to be safe and effective prophylaxis against cryptococcal disease, both before starting ART and during early ART.
2009-04-01
O26
Copyright © 2009 - British HIV Association (BHIVA) Reproduction of this abstract (other than one copy for personal reference) must be cleared through the BHIVA Organising Secretariat 1 Mountview Court, 310 Friern Barnet Lane, London N20 0LD