Cost‐Effectiveness of Serum Cryptococcal Antigen Screening to Prevent Deaths among HIV‐Infected Persons with a CD4⁺Cell Count ⩽100 Cells/μL Who Start HIV Therapy in Resource‐Limited Settings

Abstract

Background Cryptococcal meningitis (CM) remains a common AIDS-defining illness in Africa and Asia. Sub-clinical cryptococcal antigenemia is frequently unmasked with antiretroviral therapy (ART). We sought to define the cost-effectiveness of serum cryptococcal antigen (CRAG) screening to identify persons with sub-clinical cryptococcosis and the efficacy of preemptive fluconazole. Methods 609 ART-naïve adults with AIDS initiating ART in Kampala, Uganda had a serum CRAG prospectively measured during 2004–2006. The number needed to test/treat (NNT) with a positive CRAG was assessed for ≥30-month outcomes. Results In the overall cohort, 50 persons (8.2%) were serum CRAG positive when starting ART. Of 295 people with CD4+ ≤ 100cells/μL and without prior CM, 26 (8.8%: 95% CI: 5.8–12.6%) were CRAG positive of whom 21 were promptly treated with fluconazole (200–400mg) for 2–4 weeks. Clinical CM developed in 3 fluconazole-treated persons, and 30-month survival was 71% (95% CI: 48%–89%). In the 5 CRAG positive persons with CD4+≤ 100 cell/μL treated with ART but did not fluconazole, all died within 2 months of ART initiation. The NNT with CRAG screening and fluconazole to prevent one CM case is 11.3 (95%CI: 7.9–17.1) at costs of $190 (95%CI: $132–$287). The NNT to save one life is 15.9 (95%CI: 11.1–24.0) at costs of $266 (95% CI: $185–$402). The cost per disability-adjusted life year (DALY) saved is $21 (95%CI: $15 to $32). Conclusions Integrating CRAG screening into HIV care, specifically targeting people with severe immunosuppression (CD4+≤ 100 cells/μL) should be implemented in treatment programs in resource-limited settings. ART alone is insufficient treatment for CRAG-positive persons.

Causes and outcome of hospitalization among HIV-infected adults receiving antiretroviral therapy in Mulago hospital, Uganda

“…It is likely that some of the causes of hospitalization were due to IRIS following ART initiation; however we were unable to determine this using our study design. Screening and treatment for opportunistic diseases pre-ART initiation reduces the morbidity related to IRIS [30][31][32][33] . All HIV-infected patients should be screened for TB prior to ART initiation because TB affects HIV infected patients across all CD4 count strata.…”

Cryptococcal neorformans Antigenemia among HIV-Infected Patients in North Eastern Nigeria

“…This is because screening for serum cryptococcal antigen is highly sensitive, specific and cost effective in preventing death in HIV-infected patients with CD4 counts of 100 cells/mm 3 or less. In a study on cost effectiveness analysis in Uganda the findings suggest that the number needed to test and treat with CrAg screening and fluconazole treatment to prevent one cryptococcal meningitis case is 11.3 (95% CI 7.9-17.1) at a cost of US$190 (95% CI, $132-$287) while the number needed to test and treat to save one life is 15.9 (95% CI 11.1-24.0) at a cost of $266 (95% CI $185-$402) [33,34].…”

Management of HIV-associated cryptococcal disease in South Africa

“…[12] The screen-and-treat intervention has been shown to be cost-effective in several settings. [9,22] Based on recent estimates, approximately 2% of asymptomatic SA persons with a CD4 + count <100 cells/µL and no prior diagnosis of CM have cryptococcal antigenaemia. [23] The updated Southern African HIV Clinicians Society (SAHIVCS) guidelines recommend that HIV-infected ART-naive adults with a CD4 + count <100 cells/µL should be screened for cryptococcal disease before ART is started and screening for cryptococcal antigenaemia should occur by reflex laboratory or clinician-initiated testing (Fig.…”