The impact of routine cryptococcal antigen screening on survival among HIV‐infected individuals with advanced immunosuppression in Kenya

Abstract

Objectives We hypothesized that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV-infected individuals with low CD4 cell counts. Methods Newly enrolled patients at Family AIDS Care and Education Services (FACES) in Kenya with CD4≤100 cells/μl were tested for serum Cryptococcal antigen (sCrAg). Individuals with sCrAg titer≥1:2 were treated with high-dose fluconazole. Cox proportional hazard models of Kaplan-Meier curves were used to compare survival among individuals with CD4≤100 cells/μl in the intervention and historical control groups. Results The median age was 34 years [IQR: 29,41], 54% were female, and median CD4 was 43 cells/μl [IQR: 18,71]. Follow-up time was 1224 person-years. In the intervention group 66% (514/782) were tested for sCrAg; of whom 11% (59/514) were sCrAg positive. Mortality was 25% (196/782) in the intervention group and 25% (191/771) in the control group. There was no significant difference between the intervention and control group in overall survival [Hazard Ratio(HR): 1.1 (95%CI:0.9,1.3)] or three-month survival [HR: 1.0 (95%CI:0.8,1.3)]. Within the intervention group, sCrAg positive individuals had borderline lower survival rates than sCrAg negative individuals [HR:1.8 (95%CI: 1.0, 3.0)]. Conclusions A screening and treatment intervention to identify sCrAg positive individuals and treat them with high-dose fluconazole did not significantly improve overall survival among HIV-infected individuals with CD4 counts≤100 cells/μl as compared to a historical control. Potential explanations include intervention uptake rates or poor efficacy of high-dose oral fluconazole. Future studies to identify the best treatments for early cryptococcal infection and improve uptake of the intervention are critical.

Cryptococcal Antigenaemia among Treatment-Naïve Adult HIV-Infected Nigerian Patients

“…Our observed overall low cryptococcal antigenaemia of 1.6% among treatment naïve HIV positive patients is comparable with previous reports from Shika in Nigeria 2.2 % [17], Tanzania 3% [18] and USA 2.9% [19]. However our overall prevalence value in this study is lower than some reports from Nnewi 13.1% [20] South east, and Benin12.7% [12] South south part of Nigeria as well as Kenya 11% [21], Uganda 5.7% [22], Indonesia 7.1% [23] and Thailand 9.2% [24]. The observed differences in prevalence rates of cryptoccocal antigen positivity among HIV infected persons in the various studies cited may be explained by differences in sample sizes as well as varying sensitivities and specificities with differing methodologies of used kits.…”

Cryptococcal meningitis: epidemiology and therapeutic options

“…A management algorithm is shown in Figure 5 154. However, deployment of preventive screening and therapy strategies is operationally difficult, and an implementation study in Kenya achieved effective fluconazole administration for only 52% of eligible patients 155. The benefit of presumptive therapy for asymptomatic antigenemia will depend on the logistics of integrating this strategy into routine practice at ART clinics.…”

Estimated burden of fungal infections in Kenya

“…6 /L [15,16]. The vast majority of these patients progress to meningitis, if they don't have meningitis when tested.…”

“…The vast majority of these patients progress to meningitis, if they don't have meningitis when tested. We have assumed a conservative rate of 7% in those with CD4+ cell counts <100×10 6 /L [15,16]. In Uganda it was 1.1% of all HIV patients [17] and 12% in all HIV Sub Saharan Africa [18][19][20].…”