Despite advances in the treatment of HIV disease, the incidence and mortality of 
invasive cryptococcal disease remain significant. A matched, case-control study 
was performed to examine the impact of highly active antiretroviral therapy 
(HAART) and azole use on the incidence of invasive cryptococcal disease in 
HIV-infected patients. The study was performed at a metropolitan hospital with a 
large indigent population and an incidence of seven cases of cryptococcal 
disease per 1000 persons with AIDS. Bivariate analysis, matched on CD4 count, 
revealed that both HAART use [odds ratio (OR) 0.43; 95% confidence interval (CI) 
0.23-0.99] and azole use (OR 0.14; 95% CI 0.06-0.34) had a protective effect. 
Conditional logistic regression stratified on CD4 lymphocyte count revealed a 
protective role for azole use (OR 0.15; 95% CI 0.06-0.40) but not for HAART use 
(OR 0.47; 95% CI 0.18-1.26). Of note, the prevalence of HAART use was low in 
both cases and controls, with only 12% of cases and 23% of controls on HAART. 
The results of this study support previous evidence that azole use prevents 
invasive cryptococcal disease. Although current guidelines for the prophylaxis 
of opportunistic infections do not suggest routine prophylaxis for cryptococcal 
infection, this issue should be reconsidered, especially in populations that 
have a low prevalence of HAART use.