HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease.

Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females.

Aims HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore, exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk. We aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. Methods and results Prospective multinational cohort study. The data set included 22 625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection on Adverse Effects of Anti-HIV Drugs Study. Using cross-validation methods, separate models were developed to predict the risk of myocardial infarction, coronary heart disease, and a composite CVD endpoint. Model performance was compared with the Framingham score. The models included age, sex, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, HDL cholesterol and indinavir, lopinavir/r and abacavir exposure. The models performed well with area under the receiver operator curve statistics of 0.783 (range 0.642-0.820) for myocardial infarction, 0.776 (0.670-0.818) for coronary heart disease and 0.769 (0.695-0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. Conclusion Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters and exposure to individual antiretroviral therapy drugs, might be more useful in estimating CVD risks in HIV-infected persons than conventional risk prediction models. Eur J Cardiovasc Prev Rehabil 00:000-000

HIV infection results in CD4

Context Evidence regarding the impact of minority, or low frequency, HIV-1 drug-resistant variants on the effectiveness of first-line antiretroviral treatment (ART) is conflicting. Objective To evaluate the association of pre-existing HIV-1 minority drug-resistant variants with risk of first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral virologic failure. Data Sources We searched published and unpublished studies in MEDLINE (1966 through December, 2010), EMBASE (1974 through December, 2010), conference abstracts, and article references. Authors of all studies were contacted for detailed laboratory, ART, and adherence data. Study Selection and Data Abstraction Studies involving ART-naive participants initiating NNRTI-based regimens were included. Participants were included if all drugs in their ART regimen were fully active by standard HIV population sequencing. Cox proportional hazard models using pooled patient-level data were used to estimate the risk of virologic failure based on a Prentice weighted case-cohort analysis stratified by study. Data Synthesis Individual data from 10 studies and 985 participants were available for the primary analysis. Minority HIV-1 drug resistance mutations were associated with an increased risk of virologic failure (HR 2.3 [95% CI, 1.7–3.3], P<0.001) after controlling for medication adherence, ethnicity, baseline CD4 cell count and plasma HIV-1 RNA levels. The increased risk of virologic failure was most strongly associated with minority variants resistant to NNRTIs (HR 2.6 [95% CI, 1.9–3.5], P<0.001). Among participants from the cohort studies, 35% of those with detectable minority variants experienced virologic failure as compared to 15% of those without minority variants. The presence of minority variants was associated with 2.5–3 times the risk of virologic failure at either ≥95% or <95% overall medication adherence. A dose-dependent increased risk of virologic failure was found in participants with a higher proportion or quantity of drug-resistant variants. Conclusion In this pooled analysis, minority HIV-1 resistance mutations, particularly involving NNRTI-resistance, were significantly associated with a dose-dependent increased risk of virologic failure with first-line ART.

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Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating, follicular disease of the skin. Despite a high prevalence in the general population, the physiopathology of HS remains poorly understood. The use of antibiotics and immunosuppressive agents for therapy suggests a deregulated immune response to microflora. Using cellular and gene expression analyses, we found an increased number of infiltrating CD4(+) T cells secreting IL-17 and IFN-γ in perilesional and lesional skin of patients with HS. By contrast, IL-22-secreting CD4(+) T cells are not enriched in HS lesions contrasting with increased number of those cells in the blood of patients with HS. We showed that keratinocytes isolated from hair follicles of patients with HS secreted significantly more IL-1β, IP-10, and chemokine (C-C motif) ligand 5 (RANTES) either constitutively or on pattern recognition receptor stimulations. In addition, they displayed a distinct pattern of antimicrobial peptide production. These findings point out a functional defect of keratinocytes in HS leading to a balance prone to inflammatory responses. This is likely to favor a permissive environment for bacterial infections and chronic inflammation characterizing clinical outcomes in patients with HS.