The protective effect of circumcision on HIV incidence in rural low-risk men circumcised predominantly by traditional circumcisers in Kenya: two-year follow-up of the Kericho HIV Cohort Study.

BACKGROUND: Three randomized controlled trials (RCTs) have demonstrated that male circumcision prevents female-to-male HIV transmission in sub-Saharan Africa. Data from prospective cohort studies are helpful in considering generalizability of RCT results to populations with unique epidemiologic/cultural characteristics. METHODS: Prospective observational cohort sub-analysis. A total of 1378 men were evaluated after 2 years of follow-up. Baseline sociodemographic and behavioral/HIV risk characteristics were compared between 270 uncircumcised and 1108 circumcised men. HIV incidence rates (per 100 person-years) were calculated, and Cox proportional hazards regression analyses estimated hazard rate ratios (HRs). RESULTS: Of the men included in this study, 80.4% were circumcised; 73.9% were circumcised by traditional circumcisers. Circumcision was associated with tribal affiliation, high school education, fewer marriages, and smaller age difference between spouses (P < 0.05). After 2 years of follow-up, there were 30 HIV incident cases (17 in circumcised and 13 in uncircumcised men). Two-year HIV incidence rates were 0.79 (95% confidence interval [CI]: 0.46 to 1.25) for circumcised men and 2.48 (95% CI: 1.33 to 4.21) for uncircumcised men corresponding to a HR = 0.31 (95% CI: 0.15 to 0.64). In one model controlling for sociodemographic factors, the HR increased and became non-significant (HR = 0.55; 95% CI: 0.20 to 1.49). CONCLUSIONS: Circumcision by traditional circumcisers offers protection from HIV infection in adult men in rural Kenya. Data from well-designed prospective cohort studies in populations with unique cultural characteristics can supplement RCT data in recommending public health policy.

Long-term efficacy of routine access to antiretroviral-resistance testing in HIV type 1-infected patients: results of the clinical efficacy of resistance testing trial.

The long-term efficacy of making resistance testing routinely available to clinicians has not been established. We conducted a clinical trial at 6 US military hospitals in which volunteers infected with human immunodeficiency virus type-1 were randomized to have routine access to phenotype resistance testing (PT arm), access to genotype resistance testing (GT arm), or no access to either test (VB arm). The primary outcome measure was time to persistent treatment failure despite change(s) in antiretroviral therapy (ART) regimen. Overall, routine access to resistance testing did not significantly increase the time to end point. Time to end point was significantly prolonged in the PT arm for subjects with a history of treatment with > or =4 different ART regimens or a history of treatment with nonnucleoside reverse-transcriptase inhibitors before the study, compared with that in the VB arm. These results suggest that routine access to resistance testing can improve long-term virologic outcomes in HIV-infected patients who are treatment experienced but may not impact outcome in patients who are naive to or have had limited experience with ART.

Comprehensive screening for human immunodeficiency virus type 1 subtype-specific CD8 cytotoxic T lymphocytes and definition of degenerate epitopes restricted by HLA-A0207 and -C(W)0304 alleles.

For this report, the rapid identification and characterization of human immunodeficiency virus type 1 (HIV-1)-derived broadly cross-subtype-reactive CD8 cytotoxic T lymphocyte (CTL) epitopes were performed. Using a gamma interferon (IFN-gamma) Elispot assay-based approach and a panel of recombinant vaccinia viruses expressing gag, env, pol, and nef genes representing the seven most predominant subtypes and one circulating recombinant form of HIV-1, the subtype specificity and cross-subtype reactivity of a CD8 response were directly measured from circulating peripheral blood mononuclear cells (PBMC). Enhanced sensitivity of detection of CD8 responses from cryopreserved PBMC was achieved using autologous vaccinia virus-infected B-lymphoblastoid cell lines as supplemental antigen-presenting cells. Of eleven subjects studied, six exhibited broadly cross-subtype-reactive CD8-mediated IFN-gamma production (at least seven of eight subtypes recognized) to at least one major gene product from HIV-1. Screening of subjects showing broadly cross-subtype-specific responses in the vaccinia virus-based enzyme-linked immunospot (Elispot) assay using a panel of overlapping peptides resulted in the identification of cross-subtype responses down to the 20-mer peptide level in less than 3 days. Three subjects showed broad cross-subtype reactivity in both the IFN-gamma Elispot assay and the standard chromium release cytotoxicity assay. Fine mapping and HLA restriction analysis of the response from three subjects demonstrated that this technique can be used to define epitopes restricted by HLA-A, -B, and -C alleles. In addition, the ability of all three epitopes to be processed from multiple subtypes of their parent proteins and presented in the context of HLA class I molecules following de novo synthesis is shown. While all three minimal epitopes mapped here had previously been defined as HIV-1 epitopes, two are shown to have novel HLA restriction alleles and therefore exhibit degenerate HLA binding capacity. These findings provide biological validation of HLA supertypes in HIV-1 CTL recognition and support earlier studies of cross-subtype CTL responses during HIV-1 infection.