Primary prophylaxis for cryptococcosis has been recommended for HIV-infected patients with CD4 cell count <100 cells/mm3 in developing countries due to the survival benefit and high prevalence of cryptococcosis. However, the previous study was conducted prior to the scaling up of antiretroviral therapy (ART). For patients receiving ART, the relevance of this benefit is unclear.
Methods: A prospective observational cohort study was conducted among HIV-infected patients who had CD4 < 100 cells/mm3 and initiated ART in a university hospital. Patients were categorized into fluconazole group (receiving fluconazole 400 mg weekly) and control group (not receiving fluconazole) and followed up for 2 years after ART initiation.
Results: Of 302 patients, 201 were in fluconazole group and 101 in control group. Mean age was 37.9 ±9.2 years and 64.6% were males. Median (IQR) CD4 was 31 (15-54) cells/mm3. Of all, 60.6% of patients had history of opportunistic infections other than cryptococcosis. Demographics, risk of HIV acquisition, history of opportunistic infections, HBV or HCV co-infection, VDRL serostatus, and baseline CD4 cell counts were similar between the two groups (p>0.05). Regarding ART regimens, 91.1% pf patients received NNRTI-based regimens and 8.9% received PI-based regimens. Median (IQR) CD4 cell counts at 1 and 2 years of ART were 184 (129-275) and 271 (202-380) cells/mm3, respectively, and were not different between the two groups (p>0.05). During a 2-year follow-up period, 1 patient in each group died (p=0.619). Five patients (2.5%) in fluconazole group and 5 patients (2.5%) in control group developed cryptococcosis (p=0.311). Kaplan-Meier analysis showed that there was no difference of occurrence of cryptococcosis between the two groups (log-rank test, p=0.221, Figure). Among 10 patients with cryptococcosis, the median (IQR) time to develop cryptococcosis was 4.1 (2.4-8.9) months after ART initiation; 3.5 (2.2-11.7) months in fluconazole group and 4.7 (1.7-8.0) months in control group (p=0.690).
Conclusion: In the settings that ART is widely available and HIV-infected patients with CD4 cell counts < 100 cells/mm3 are initiated ART, primary prophylaxis for cryptococcosis with fluconazole has no survival benefit and may not be necessary. The recommendations in developing countries should be reconsidered.
S. Sungkanuparph, None