Objectives To investigate the impact of HAART-induced HIV suppression on levels of 24 serological biomarkers of inflammation and immune activation. Design Prospective cohort study. Methods Biomarkers were measured with multiplex assays in centralized laboratories using stored serum samples contributed by 1,697 men during 8,903 person-visits in the Multicenter AIDS Cohort Study (MACS) from 1984–2009. Using generalized gamma models, we compared biomarker values across three groups, adjusting for possible confounders: HIV-uninfected (NEG); HIV+, HAART-naïve (NAI); and HAART-exposed with HIV RNA suppressed to <50 copies/mL plasma (SUP). We also estimated changes in biomarker levels associated with duration of HIV suppression, using splined generalized gamma regression with a knot at one year. Results Most biomarkers were relatively normalized in the SUP group relative to the NAI group; however, 12 biomarkers in the SUP group were distinct (p<0.002) from NEG values: CXCL10, CRP, sCD14, sTNFR2, TNF-α, sCD27, sGP130, IL-8, CCL13, BAFF, GM-CSF, and IL-12p70. Thirteen biomarkers exhibited significant changes in the first year after viral suppression, but none changed significantly after that time. Conclusions Biomarkers of inflammation and immune activation moved toward HIV-negative levels within the first year after HAART-induced HIV suppression. Although several markers of T cell activation returned to levels present in HIV-negative men, residual immune activation, particularly monocyte/macrophage activation, was present. This residual immune activation may represent a therapeutic target to improve the prognosis of HIV-infected individuals receiving HAART.

These results identify NF-kappaB activation as a molecular pathway by which sleep disturbance may influence leukocyte inflammatory gene expression and the risk of inflammation-related disease.

Some autoimmune disorders are increasingly recognized as risk factors for nonHodgkin lymphoma (NHL) overall, but large-scale systematic assessments of risk of NHL subtypes are lacking. We performed a pooled analysis of selfreported autoimmune conditions and risk of NHL and subtypes, including 29 423 participants in 12 case-control studies. We computed pooled odds ratios (OR) and 95% confidence intervals (

BACKGROUND:The incidence of Kaposi sarcoma (KS) and non‐Hodgkin lymphoma (NHL) among human immunodeficiency virus (HIV)‐infected individuals declined after the introduction of highly active antiretroviral therapy (HAART) in the mid‐1990s, but the cancer risk associated with HIV infection during the HAART era remains to be clarified.METHODS:Cancer incidence among HIV‐infected and HIV‐uninfected participants in the Multicenter AIDS (acquired immunodeficiency syndrome) Cohort Study (MACS) between 1984 and 2007 was compared with the expected incidence using US population‐based data from the Surveillance, Epidemiology, and End Results (SEER) program. Age‐ and race‐adjusted cancer incidence rates were also compared HIV by status and over time within the MACS. Exact statistical methods were used for all analyses.RESULTS:A total of 933 incident cancers were observed during 77,320 person‐years of follow‐up. Compared with SEER, MACS HIV‐infected men had significantly (P < .05) elevated rates of KS (standardized incidence ratio [SIR], 139.10), NHL (SIR, 36.80), Hodgkin lymphoma (HL)(SIR, 7.30), and anal cancer (SIR, 25.71). Within MACS, HIV infection was found to be independently associated with each of these cancers across the entire follow‐up period, and KS (incidence rate ratio [IRR], 54.93), NHL (IRR, 11.18), and anal cancer (IRR, 18.50) were each found to be significantly elevated among HIV‐infected men during the HAART era. Among these men, the incidence of KS and NHL declined (IRR, 0.13 and 0.23, respectively), the incidence of anal cancer increased (IRR, 5.84), and the incidence of HL remained statistically unchanged (IRR, 0.75) from the pre‐HAART to the HAART era.CONCLUSIONS:Cancer risk remains elevated among HIV‐infected men who have sex with men, highlighting the continuing need for appropriate cancer screening in this population. Cancer 2010. © 2010 American Cancer Society.

The concentrations of cytokines in human serum and plasma can provide valuable information about in vivo immune status, but low concentrations often require high-sensitivity assays to permit detection. The recent development of multiplex assays, which can measure multiple cytokines in one small sample, holds great promise, especially for studies in which limited volumes of stored serum or plasma are available. Four high-sensitivity cytokine multiplex assays on a Luminex (Bio-Rad, BioSource, Linco) or electrochemiluminescence (Meso Scale Discovery) platform were evaluated for their ability to detect circulating concentrations of 13 cytokines, as well as for laboratory and lot variability. Assays were performed in six different laboratories utilizing archived serum from HIV-uninfected and -infected subjects from the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) and commercial plasma samples spanning initial HIV viremia. In a majority of serum samples, interleukin-6 (IL-6), IL-8, IL-10, and tumor necrosis factor alpha were detectable with at least three kits, while IL-1␤ was clearly detected with only one kit. No single multiplex panel detected all cytokines, and there were highly significant differences (P < 0.001) between laboratories and/or lots with all kits. Nevertheless, the kits generally detected similar patterns of cytokine perturbation during primary HIV viremia. This multisite comparison suggests that current multiplex assays vary in their ability to measure serum and/or plasma concentrations of cytokines and may not be sufficiently reproducible for repeated determinations over a long-term study or in multiple laboratories but may be useful for longitudinal studies in which relative, rather than absolute, changes in cytokines are important.