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.

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.

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.