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

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.

Prevalence, risk factors, and impact on outcome of cytomegalovirus replication in serum of Cambodian HIV-infected patients (2004-2007).

BACKGROUND: In developing countries, the study of cytomegalovirus (CMV) coinfection in HIV-infected patients remains neglected. Quantitative CMV polymerase chain reaction (PCR) is the gold standard diagnostic tool for analyzing serum CMV replication and for predicting CMV disease. We estimated the prevalence of replicating CMV in sera of newly diagnosed HIV-infected Cambodian patients and examined its impact on mortality. METHODS: This cohort study was based on 2 highly active antiretroviral therapy treatment programs in Cambodia between 2004 and 2007. Quantitative CMV PCR was performed on baseline serum samples of 377 HIV-infected patients. RESULTS: The prevalence of serum CMV DNA was 55.2% (150 of 272) in patients with CD4 count <100/mm. In multivariate analysis, hemoglobin <9 g/dL, CD4 count <100/mm, and Karnofsky index <50 were independently associated with positive serum CMV DNA at baseline. During a 3-year follow-up period, CMV viral load >or=3.1 log10 copies per milliliter was significantly associated with death independently of CD4 count, other opportunistic infections, and highly active antiretroviral therapy. CONCLUSIONS: As in industrialized countries, serum CMV replication is highly prevalent among HIV-infected Cambodian patients and is associated with increased mortality. This underscores the importance of diagnostic CMV infection by PCR in sera of HIV-infected patients with CD4 count <100/mm and treating this opportunistic infection to reduce its associated mortality.

Prevalence, determinants of positivity, and clinical utility of cryptococcal antigenemia in Cambodian HIV-infected patients.

OBJECTIVES: To determine the prevalence, determinants ofpositivity, and clinical utility of serum cryptococcal polysaccharide (CPS) antigen testing among HIV-infected patients in 2004 in Cambodia, an area highly endemic for cryptococcosis. METHODS: All HIV-infected patients with a CD4+ count <200 cells/mm3 attending 1 of 2 Phnom Penh hospitals for the first time were systematically screened for serum CPS. Patients with positive test results were further investigated to identify those with cryptococcal meningitis (CM), pulmonary cryptococcosis, or isolated positive cryptococcal antigenemia (IPCA). RESULTS: The median (interquartile range [IQR]) CD4+ count of 327 enrolled patients was 24 (IQR: 8 to 65) cells/mm3. The prevalence of cryptococcal infection was 59 (18.0%) of 327 cases, of which 41 were CM and 10 were IPCA. In the absence of serum CPS detection, 17 (28.8%) of 59 cryptococcal infections would have been missed on the day of consultation. In patients with no specific symptoms of meningoencephalitis, the prevalence of positive serum CPS detection was 32 (10.8%) of 295 cases. Countryside residence (adjusted odds ratio [AOR] = 3.6), headache (AOR = 3.2), body mass index <15.4 kg/m2 (AOR = 3.4), CD4+ count <50 cells/mm3 (AOR = 4.0), and male gender (marginally, AOR = 2.1) were all independently associated with a positive test results. CONCLUSION: Serum CPS screening among AIDS patients with a CD4+ count <100 cells/mm3 is useful in areas highly endemic for cryptococcosis, allowing early diagnosis and treatment of this opportunistic infection.