Implementing the screen and treat strategy for prevention of cryptococcal disease in Botswana: An efficacy and costing study (study protocol V1.5 16th March 2017)

Adult HIV prevalence in Botswana is estimated at 25%. In 2013, despite widespread availability of antiretroviral therapy (ART), an estimated one-quarter of patients did not initiate ART until their CD4 count was below 147 cells/microL. The early mortality rate in these individuals is high, and cryptococcal meningitis is a leading contributor to this mortality, particularly for those with CD4 counts below 100 cell/microL. In ART-naïve adults, cryptococcal antigenemia predicts incident cryptococcal meningitis and all-cause mortality during this early treatment period. Pre-emptive antifungal therapy may prevent cryptococcal meningitis and decrease overall mortality and the World Health Organization now recommends screening and antifungal therapy for cryptococcal antigen (CrAg)-positive patients along with ART in areas with high cryptococcal antigenaemia (3% prevalence). In our recent pilot screening programme of 1,781 unique patients who received CD4 count testing at the Ministry of Health / Botswana-Harvard HIV Reference Laboratory found to have CD4 100 cells/microL, prevalence of cryptococcal antigenaemia was 5.8% (95% confidence interval [CI]: 4.8-7.0%). CrAg screening and targeted pre-emptive antifungal therapy has subsequently been implemented in the Botswana 2016 Integrated HIV Clinical Care Guidelines. Building on this recent pilot CrAg screening programme, we propose a study to: (1) Determine the outcomes of CrAg-positive patients treated according to WHO and Botswana national guidelines by prospectively monitoring ART-naïve, CrAg-positive adults given pre-emptive fluconazole treatment prior to ART; and compare their 6-month cryptococcal meningitis and all-cause mortality rate with a CrAg-negative, CD4-matched control group starting ART alone; and (2) Use a micro-costing approach to estimate treatment cost of cryptococcal meningitis from the provider perspective and the costs of cryptococcal antigen screening and fluconazole pre-emptive therapy.