Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA–viral peptide interaction as the major factor modulating durable control of HIV infection.

Patients switched to EFV + TDF/FTC maintained virologic suppression and the regimen was well tolerated. Patients reported increased satisfaction with treatment and fewer were bothered by side effects.

IntroductionThe use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals.Materials and MethodsA set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed.ResultsNone of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count.DiscussionNo associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Adults infected with HIV live longer when they receive regular medical care, yet many adults are not retained in care. Providers measure retention in order to evaluate interventions to improve retention and quality of HIV care. However, multiple measures for retention exist. This study compares two methods of operationalizing retention and evaluates the contribution of individual characteristics on the likelihood of retention. A chart review was performed for a random sample of 212 active clients of an urban HIV primary care clinic. Data on clinic utilization, sex, age, race, mental illness, substance use, AIDS diagnosis, language, and housing were collected for each participant. Clinic utilization data were used to classify participants for retention status and to score them by frequency of visits. Binary logistic regression analysis was compared with ordinal logistic regression analysis, using distinct retention measures as outcome variables. In the binary model, those with a history of substance use were about half as likely to be retained (OR 0.52, 95% CI 0.29-0.94) and those with an AIDS diagnosis were more than twice as likely to be retained (OR 2.18, 95% CI 1.17-4.09). These characteristics were significant predictors in the ordinal model, with the additional finding that those reporting English as a primary language were less likely to have higher retention scores (OR 0.40, 95% CI 0.19-0.84). An ordinal score for retention can identify unexpected predictors, but a dichotomous measure of retention may be easier to use and interpret for providers involved in retention-related quality improvement activities.