Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: implications for future treatment options

Article approval pendingDrug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy

Enhancing science preparedness for health emergencies in Africa through research capacity building.

Editorial (no available abstract)

Comparison of a Clinical Prediction Rule and a LAM Antigen-Detection Assay for the Rapid Diagnosis of TBM in a High HIV Prevalence Setting

Background/Objective: The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB (R)) using cerebrospinal fluid (CSF).Methods: Patients with suspected TBM were classified as definite-TBM(CSF culture or PCR positive), probable-TBM and non-TBM.Results: Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/mu l). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95% CI) was 31% (17; 48) and 94% (85; 99), respectively (cut-point >= 0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4200 cells/mu l; p = 0.03). The sensitivity and specificity in those with a CD4= 6 derived from multivariate analysis had a sensitivity and specificity (95% CI) of 47% (31; 64) and 98% (90; 100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47; 68) and specificity remained high at 93% (82; 98).Conclusions: Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression

Comparative performance outcomes of the clinical prediction rule, LAM, and a combination of LAM and the clinical prediction rule for the diagnosis of definite TB meningitis.

<p>*One patient did not have lymphocyte count and was excluded.</p>†<p>Clinical prediction rule.</p>‡<p>p value comparing sensitivity of the clinical prediction rule alone (47%) vs. the clinical prediction rule plus the LAM result (63%) = 0.07.</p><p>#p value comparing sensitivity LAM 31% vs. clinical prediction rule combined with LAM (63%) <0.001.</p><p>Sens  =  sensitivity, Spec  =  specificity, PPV  =  positive predictive value, NPV  =  negative predictive value.</p

Summary flow chart of patient categorisation and investigations performed at recruitment.

<p>Summary flow chart of patient categorisation and investigations performed at recruitment.</p

Univariable and multivariable analysis for the prediction of definite TB meningitis.

<p>Univariable and multivariable analysis for the prediction of definite TB meningitis.</p

LAM performance outcomes in definite TBM and non-TBM patients when stratified by HIV status and CD4 count.

<p>*Comparison between HIV positive and HIV negative patients was not significant; p value was 0.3.</p>†<p>Expressed as percentages.</p>‡<p>Comparison between sensitivity values for CD4 counts <100 with ≥100, the p value was 0.01.</p><p>#Comparison between sensitivity values for CD4counts <200 with ≥200, the p value was 0.03.</p><p>Note: HIV status was unknown for 1 patient in the definite TBM group and 1 patient in the non TBM group.</p