Characterization of CD4+ T cell subsets and HIV susceptibility in the inner and outer foreskin of Ugandan men.

PROBLEM: Biological mechanisms of foreskin HIV acquisition are poorly defined. The inner foreskin is preferentially infected in explant models, so we hypothesized that this site would be enriched for HIV-susceptible CD4+ T cells and proinflammatory/chemoattractant cytokines. METHOD OF STUDY: A total of 42 HIV-uninfected Ugandan men without genital symptoms provided foreskin tissues and swabs at the time of elective penile circumcision. The immune phenotype of foreskin-derived CD4+ T cells and entry of a CCR5-tropic HIV pseudovirus was characterized, and specific cytokine levels assayed by multiplexed chemiluminescent ELISA. RESULTS: Unexpectedly, outer foreskin CD4+ T cells more frequently expressed CCR5 (median 29.2% vs 22.9%, P = 0.01) and CD69 (median 36.5% vs 15%, P < 0.01), and on a per-cell basis, HIV entry was higher. However, overall CD4+ T cell density was approximately twofold higher in the inner foreskin, and several highly susceptible T cell subsets were increased at this site, including Th17 cells (20.0% vs 14.1%, P = 0.0021). Specific pro-inflammatory cytokine levels were also higher on the inner foreskin surface (IL-17, IL-8, RANTES and IL-1ß; all P < 0.05). CONCLUSION: There was marked heterogeneity in CD4+ T cell populations and immune milieu between inner and outer foreskin tissues. Despite higher per-cell viral entry into CD4+ T cells from the outer foreskin, the higher target cell density and enriched pro-inflammatory cytokines of the inner foreskin suggest that this may be a preferential site for HIV acquisition.

Field Performance of PIMA Point-of-Care Machine for CD4 Enumeration Under a Mobile HIV Counseling and Testing Program in Remote Fishing Communities of Lake Victoria, Uganda.

Uganda is among the most HIV/AIDS-afflicted countries, and many HIV-infected persons live in remote areas with poor access to health care. The success of HIV care programs relies in part on patient monitoring using CD4 T cell counts. We conducted an evaluation of the point-of-care PIMA test using BD FACSCount as a gold standard. One hundred fifty-one participants were enrolled, provided venous blood and samples tested at the point of care with the Alere PIMA™ CD4 Analyzer and the BD FACSCount in the UVRI-IAVI main laboratory. Correlation between the methods was assessed, as was the ability of the Pima Analyzer to predict values <200, <350, and ≥500 CD4 cells/mm3 when compared with BD FACSCount as the gold standard. A near-perfect positive Pearson correlation coefficient (r = 0.948; p < .0001) between the two methods was observed. The Alere PIMA Analyzer had a mean bias of -32.5 cells/mm3. The sensitivity and specificity, for PIMA to predict CD4 lymphocyte count less than 200 cells/mm3, were 71.4% and 100%, respectively; less than 350 cells/mm3 were 84.6% and 94.6%, respectively; and at CD4 count less than 500 cells/mm3 were 94.4% and 100%. The Alere Pima Analyzer provides reliable CD4 cell count measurement and is suitable for monitoring and screening eligible HIV patients in hard-to-reach settings.