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.

Background/AimNeuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings.MethodsWe enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologist's clinical assessment of moderate/severe neuropathy.ResultsThe sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologist's assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS - 83% sensitivity, 71% specificity; Subjective-PNS-total - 83% sensitivity, 83% specificity; Subjective-PNS-max and NSS - 67% sensitivity, 92% specificity; Brief-PNS - 0% sensitivity, 92% specificity; monofilament - 100% sensitivity, 88% specificity; graduated tuning fork - 83% sensitivity, 88% specificity; two-point discrimination - 75% sensitivity, 58% specificity.ConclusionsPilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.

INTRODUCTION Peripheral neuropathy is the most common neurological complication of HIV but is widely under-diagnosed in resource-limited settings. We investigated the utility of screening tools administered by non-physician health care workers (HCW) and quantitative sensory testing (QST) administered by trained individuals for identification of moderate/severe neuropathy. METHODS We enrolled 240 HIV-infected outpatients using two-stage cluster randomized sampling. HCWs administered the several screening tools. Trained study staff performed QST. Tools were validated against a clinical diagnosis of neuropathy. RESULTS Participants were 65% women, mean age 36.4 years, median CD4 324 cells/μL. 65% were taking antiretrovirals, and 18% had moderate/severe neuropathy. The screening tests were 76% sensitive in diagnosing moderate/severe neuropathy with negative predictive values of 84–92%. QST was less sensitive but more specific. DISCUSSION Screening tests administered by HCW have excellent negative predictive values and are promising tools for scale-up in resource-limited settings. QST shows promise for research use.

Purpose Cryptococcal meningitis is a leading cause of mortality among HIV-infected individuals in sub-Saharan Africa but little is known about its treatment and outcomes in decentralized HIV outpatient settings. We assessed adherence to treatment guidelines and determined predictors of survival. Design A computerized laboratory database identified HIV-infected adults with cryptococcal meningitis at Family AIDS Care and Education Services in Nyanza Province, Kenya, between 2005-2009. Medical records were reviewed. Kaplan-Meier survival curves were generated. Bivariate and multivariate Cox proportional hazards models were used to determine associations between key clinical characteristics and survival. Results Medical records were located for 79% (71/90). Mortality was 38% (27/71) over a median follow-up period of 201 days [Inter-quartile range (IQR): 10-705 days]. Adherence to local guidelines for treatment of cryptococcal meningitis was 48% (34/71). Higher BMI was associated with improved survival (HR: 0.82, 95%CI [0.68,0.99]) even after controlling for factors such as age, CD4 cell count, receipt of HAART, and treatment with any anti-fungal therapy. Conclusion Cryptococcal meningitis diagnosed in routine HIV outpatient settings is largely treated as an outpatient and adherence to treatment guidelines is poor. BMI is a critical independent predictor of outcome. Additional research to determine the most effect strategies to reduce premature mortality is urgently needed.