Cost-effectiveness of primary prophylaxis of AIDS associated cryptococcosis in Cambodia

Abstract

Background: Cryptococcal infection is a frequent cause of mortality in Cambodian HIV-infected patients with CD4+ count ≤100 cells/µl. This study assessed the cost-effectiveness of three strategies for cryptococcosis prevention in HIV-infected patients.

Methods: A MARKOV DECISION TREE WAS USED TO COMPARE THE FOLLOWING STRATEGIES AT THE TIME OF HIV DIAGNOSIS: no intervention, one time systematic serum cryptococcal antigen (CRAG) screening and treatment of positive patients, and systematic primary prophylaxis with fluconazole. The trajectory of a hypothetical cohort of HIV-infected patients with CD4+ count ≤100 cells/µl initiating care was simulated over a 1-year period (cotrimoxazole initiation at enrollment; antiretroviral therapy within 3 months). Natural history and cost data (US$ 2009) were from Cambodia. Efficacy data were from international literature.

Results: In a population in which 81% of patients had a CD4+ count ≤50 cells/ µl and 19% a CD4+ count between 51-100 cells/µl, the proportion alive 1 year after enrollment was 61% (cost $ 472) with no intervention, 70% (cost $ 483) with screening, and 72% (cost $ 492) with prophylaxis. After one year of follow-up, the cost-effectiveness of screening vs. no intervention was US$ 180/life year gained (LYG). The cost-effectiveness of prophylaxis vs. screening was $ 511/LYG. The cost-effectiveness of prophylaxis vs. screening was estimated at $1538/LYG if the proportion of patients with CD4+ count ≤50 cells/µl decreased by 75%.

Conclusion: In a high endemic area of cryptococcosis and HIV infection, serum CRAG screening and prophylaxis are two cost effective strategies to prevent AIDS associated cryptococcosis in patients with CD4+ count ≤100 cells/µl, at a short-term horizon, screening being more cost-effective but less effective than prophylaxis. Systematic primary prophylaxis may be preferred in patients with CD4+ below 50 cells/µl while systematic serum CRAG screening for early targeted treatment may be preferred in patients with CD4+ between 51-100 cells/µl.

Figure 1. Model structure for no intervention or primary prophylaxis intervention (A), and CRAG screening intervention for treatment of positive cases (B).

The probabilities of transition were stratified according to CD4+ count categories (0–50 and 51–100 cells/µl). At the end of one cycle (i.e., after 3 months), patient was back to start of cycle state within the same CD4 cell count strata or a higher CD4 cell count based on cART efficacy or was remaining alive in the model (without occurrence of new OI) because of death or CD4 cell count >100 cells/µl thanks to cART efficacy. Pulm. Crypto.: pulmonary cryptococcosis; CM: cryptococcal meningitis; OI: opportunistic infections other than cryptococcosis; +: positive serum CRAG screening; −: negative serum CRAG screening; Isolated CrAG+: Asymptomatic positive serum CRAG. Non-response to cART was included in the transition probabilities.