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AIDSInfo-at-a-glance

Issue No. 18 | May 07, 2010
A Service of the U.S. Department of Health and Human ServicesView HTML version
News and Features 

Study Suggests Thymic Selection of the T-cell Repertoire of HLA Class I Alleles is Associated with Control of HIV Infection

“Without therapy, most people infected with human immunodeficiency virus (HIV) ultimately progress to AIDS. Rare individuals ('elite controllers') maintain very low levels of HIV RNA without therapy, thereby making disease progression and transmission unlikely. Certain HLA class I alleles are markedly enriched in elite controllers, with the highest association observed for HLA-B57. ... Because HLA molecules present viral peptides that activate CD8(+) T cells, an immune-mediated mechanism is probably responsible for superior control of HIV. Here we describe how the peptide-binding characteristics of HLA-B57 molecules affect thymic development such that, compared to other HLA-restricted T cells, a larger fraction of the naive repertoire of B57-restricted clones recognizes a viral epitope, and these T cells are more cross-reactive to mutants of targeted epitopes. Our calculations predict that such a T-cell repertoire imposes strong immune pressure on immunodominant HIV epitopes and emergent mutants, thereby promoting efficient control of the virus. Supporting these predictions, in a large cohort of HLA-typed individuals, our experiments show that the relative ability of HLA-B alleles to control HIV correlates with their peptide-binding characteristics that affect thymic development. Our results provide a conceptual framework that unifies diverse empirical observations, and have implications for vaccination strategies.”

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Study Suggests Adherence to HAART Does Not Decrease Over Time

“We aimed to investigate long-term trends in highly active antiretroviral therapy (HAART) adherence to identify the main predictors and to evaluate whether participants experience periods of low adherence (<or=60%). …Participants in the Royal Free Clinic Cohort were followed from the date of start of HAART until the end of the last recorded ART prescription or death. Follow-up was divided into 6-month periods, and for each period, a value of adherence, measured as the percentage of days in the 6-month period covered by a valid prescription for at least three antiretroviral drugs, was calculated. … There was evidence of a slight increase in adherence over time [adjusted odds ratio (OR) of >95% adherence = 1.02 per year; 95% confidence interval (CI) 1.01-1.04; P = 0.0053]. Independent predictors of adherence were age, demographic group, calendar year period, drug regimen and previous virologic failures. The overall rate of at least one period of low adherence was 0.12 per person-year, but this rate decrease[d] markedly over time to 0.01 in 2007/2008. … Adherence, as measured by drug coverage, does not decrease on average over more than a decade from start of HAART. This is encouraging, because it shows that patients could potentially maintain viral suppression for many years.”

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