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BackgroundAging in males is associated with lower testosterone levels and a decrease in diurnal variation of testosterone secretion. Cross-sectional studies have shown lower than expected testosterone levels among HIV-infected men, but whether age-related changes in serum testosterone differ by HIV serostatus are not known.MethodsHIV-infected men from the Multicenter AIDS Cohort Study (MACS), age ≥ 45 years at highly active antiretroviral therapy initiation, who had ≥ 2 samples from the subsequent 10 years, were matched to HIV-uninfected men by age, race, MACS site, and calendar time of samples. Linear mixed-effects regression models were used to determine whether free testosterone (FT) and its rate of change differed by HIV serostatus.ResultsOne hundred eighty-two HIV-infected and 267 HIV-uninfected men were included, median age: 48.8 years (interquartile range: 45.8-53.4), median numbers of FT measurements per participant 4 (interquartile range: 3-5), 65% were drawn in the adjusted morning (AM). Mean-adjusted FT levels were lower among HIV-infected than HIV-uninfected men in AM samples {-6.1 ng/dL [95% confidence interval (CI): -9.8 to -2.4], P = 0.001}, but not in afternoon samples [-1.7 ng/dL (-6.0 to 2.6), P = 0.441]. The rate of FT decline with age did not differ by HIV serostatus: 9.2 ng/dL (95% CI: -13.4 to -5.0) per 10 years for HIV-infected vs. 7.9 ng/dL (95% CI: -10.2 to -5.5) for HIV-uninfected men, P = 0.578.ConclusionsFT decreased similarly with increasing age regardless of HIV serostatus. The lower AM, but not adjusted afternoon, FT levels among HIV-infected men compared with HIV-uninfected men suggest a loss of diurnal variation in FT levels among HIV-infected men.

ContextAbnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.ObjectiveTo determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.DesignCross-sectional study nested within the Multicenter AIDS Cohort Study.SettingFour US academic medical centers.ParticipantsThere were 578 HIV-infected and 344 HIV-uninfected men.Main outcome measuresCoronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.ResultsOPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.ConclusionsOPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.

ObjectiveThe aim of this article is to determine whether HIV-infected (HIV+) men have either higher incidence or more rapid progression of coronary artery calcium (CAC) compared with HIV-uninfected (HIV-) controls.DesignProspective observational study.SettingMulticenter study in four US academic research centers: University of Pittsburgh, Johns Hopkins University, University of California Los Angeles, and Northwestern University.ParticipantsEight hundred and twenty-five men (541 HIV+ and 284 HIV-) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study who underwent serial cardiac computed tomography (CT) imaging during a mean follow-up of 5 years (range, 2-8 years).Main outcome measuresIncidence and progression of CAC assessed by cardiac CT.ResultsDuring follow-up, 21% of HIV+ men developed incident CAC compared with 16% of HIV- men. This association persisted after adjustment for traditional and HIV-associated risk factors: hazard ratio 1.64 (1.13-3.14). However, there was no association between HIV serostatus and CAC progression among men with CAC present at baseline. Current smoking and increased insulin resistance, both modifiable risk factors, were independently associated with increased incidence of CAC. No evidence supporting an elevated risk for either CAC progression or incidence was found for either dyslipidemia or long-term usage of antiretroviral therapy.ConclusionIn this large study of HIV+ and HIV- men who underwent serial cardiac CT scan imaging, HIV+ men were at significantly higher risk for development of CAC: hazard ratio 1.64 (1.13-3.14). In addition, two important and modifiable risk factors were identified for increased incidence of CAC. Taken together, these findings underscore the potential importance for smoking cessation and interventions to improve insulin resistance among HIV+ men.

BackgroundIndividuals infected with human immunodeficiency virus (HIV) live longer as a result of effective treatment, but long-term consequences of infection, treatment, and immunological dysfunction are poorly understood.MethodsWe prospectively examined 1011 women (74% HIV-infected) in the Women's Interagency HIV Study and 811 men (65% HIV-infected) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. Outcomes included changes in right common carotid artery intima-media thickness (CCA-IMT) and new focal carotid artery plaque formation (IMT >1.5 mm) over median 7 years. We assessed the association between HIV serostatus and progression of subclinical atherosclerosis, adjusting for demographic, behavioral, and cardiometabolic risk factors.ResultsUnadjusted mean CCA-IMT increased (725 to 752 µm in women, 757 to 790 µm in men), but CCA-IMT progression did not differ by HIV serostatus, either in combined or sex-specific analyses. Focal plaque prevalence increased from 8% to 15% in women and 25% to 34% in men over 7 years. HIV-infected individuals had 1.6-fold greater risk of new plaque formation compared with HIV-uninfected individuals (relative risk [RR] 1.61, 95% CI, 1.12-2.32), adjusting for cardiometabolic factors; the association was similar by sex. Increased plaque occurred even among persistently virologically suppressed HIV-infected individuals compared with uninfected individuals (RR 1.56, 95% CI, 1.07-2.27). HIV-infected individuals with baseline CD4+ ≥ 500 cells/µL had plaque risk not statistically different from uninfected individuals.ConclusionsHIV infection is associated with greater increases in focal plaque among women and men, potentially mediated by factors associated with immunodeficiency or HIV replication at levels below current limits of detection.

ObjectivePositive remodeling (PR), a coronary artery characteristic associated with risk for myocardial infarction (MI), may be more prevalent in HIV-infected (HIV+) people. We evaluated the prevalence of PR using coronary CT angiography (CCTA) in HIV+ and HIV-uninfected (HIV-) men.MethodsMen enrolled in the Multicenter AIDS Cohort Study underwent CCTA if they were 40-70 years, had normal kidney function and no history of coronary revascularization. Multivariable logistic regression models were used to estimate the odds ratio (OR) of PR by HIV serostatus, adjusting for demographics and coronary artery disease (CAD) risk factors. Analysis of PR among atherosclerotic segments further adjusted for plaque type and stenosis.ResultsThe prevalence of PR was 8.4% versus 12.1% (p = 0.10) for HIV- and HIV + men, respectively. After demographic adjustment, HIV + men had twice the odds of PR [OR 2.01(95% CI 1.20-3.38)], which persisted after CAD risk factor adjustment [1.76(1.00-3.10)]. Higher systolic blood pressure, total cholesterol, diabetes medication use, older age, segment number with plaque present, mixed and non-calcified plaque, and stenosis>50%, were associated with increased odds of PR, while higher HDL cholesterol, higher nadir CD4 count, and black race were associated with lower PR odds. Among atherosclerotic segments, the association between HIV infection and PR persisted, but was not statistically significantly.ConclusionHIV+ men have more positively remodeled arterial segments, which may be due to more coronary segments with atherosclerosis or HIV-related immunosuppression. Further studies are needed to evaluate whether PR contributes to higher rates of MI in HIV+ individuals.

BackgroundHeightened immune activation among human immunodeficiency virus (HIV)-infected persons may contribute to atherosclerosis. We assessed associations of serologic markers of monocyte activation, soluble CD163 (sCD163) and soluble CD14 (sCD14), and monocyte chemoattractant protein 1 (CCL2) with subclinical atherosclerosis among men with and those without HIV infection in the Multicenter AIDS Cohort Study.MethodsWe performed noncontrast computed tomography on 906 men (566 HIV-infected men and 340 HIV-uninfected men), 709 of whom also underwent coronary computed tomographic angiography. Associations between each biomarker and the prevalence of coronary plaque, the prevalence of stenosis of ≥50%, and the extent of plaque were assessed by logistic and linear regression, adjusting for age, race, HIV serostatus, and cardiovascular risk factors.ResultsLevels of all biomarkers were higher among HIV-infected men, of whom 81% had undetectable HIV RNA, and were associated with lower CD4(+) T-cell counts. In the entire population and among HIV-infected men, higher biomarker levels were associated with a greater prevalence of coronary artery stenosis of ≥50%. Higher sCD163 levels were also associated with greater prevalences of coronary artery calcium, mixed plaque, and calcified plaque; higher CCL2 levels were associated with a greater extent of noncalcified plaque.ConclusionssCD163, sCD14, and CCL2 levels were elevated in treated HIV-infected men and associated with atherosclerosis. Monocyte activation may increase the risk for cardiovascular disease in individuals with HIV infection.

BackgroundHuman immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks.MethodsUsing data from the North American AIDS Cohort Collaboration for Research and Design from January 2000 to December 2009, we validated 286 incident ESRD cases using abstracted medical evidence of dialysis (lasting >6 months) or renal transplant. A total of 38 354 HIV-infected adults aged 18-80 years contributed 159 825 person-years (PYs). Age- and sex-standardized incidence ratios (SIRs) were estimated by race. Poisson regression was used to identify predictors of ESRD.ResultsHIV-infected ESRD cases were more likely to be of black race, have diabetes mellitus or hypertension, inject drugs, and/or have a prior AIDS-defining illness. The overall SIR was 3.2 (95% confidence interval [CI], 2.8-3.6) but was significantly higher among black patients (4.5 [95% CI, 3.9-5.2]). ESRD incidence declined from 532 to 303 per 100 000 PYs and 138 to 34 per 100 000 PYs over the time period for blacks and nonblacks, respectively, coincident with notable increases in both the prevalence of viral suppression and the prevalence of ESRD risk factors including diabetes mellitus, hypertension, and hepatitis C virus coinfection.ConclusionsThe risk of ESRD remains high among HIV-infected individuals in care but is declining with improvements in virologic suppression. HIV-infected black persons continue to comprise the majority of cases, as a result of higher viral loads, comorbidities, and genetic susceptibility.

BackgroundExisting data suggest that human immunodeficiency virus (HIV)-infected African Americans carrying 2 copies of the APOL1 risk alleles have greater risk of kidney disease than noncarriers. We sought to determine whether HIV RNA suppression mitigates APOL1-related kidney function decline among African Americans enrolled in the Multicenter AIDS Cohort Study.MethodsWe genotyped HIV-infected men for the G1 and G2 risk alleles and ancestry informative markers. Mixed-effects models were used to estimate the annual rate of estimated glomerular filtration rate (eGFR) decline, comparing men carrying 2 (high-risk) vs 0-1 risk allele (low-risk). Effect modification by HIV suppression status (defined as HIV type 1 RNA level 90% of follow-up time) was evaluated using interaction terms and stratified analyses.ResultsOf the 333 African American men included in this study, 54 (16%) carried the APOL1 high-risk genotype. Among HIV-infected men with unsuppressed viral loads, those with the high-risk genotype had a 2.42 mL/minute/1.73 m(2) (95% confidence interval [CI], -3.52 to -1.32) faster annual eGFR decline than men with the low-risk genotype. This association was independent of age, comorbid conditions, baseline eGFR, ancestry, and HIV-related factors. In contrast, the rate of decline was similar by APOL1 genotype among men with sustained viral suppression (-0.16 mL/minute/1.73 m(2)/year; 95% CI, -.59 to .27; P for interaction

BackgroundThere is limited evidence that among HIV-infected patients haemoglobin A1c (HbA1c) values may not accurately reflect glycaemia. We assessed HbA1c discordance (observed HbA1c - expected HbA1c) and associated factors among HIV-infected participants in the Multicenter AIDS Cohort Study (MACS).MethodsFasting glucose (FG) and HbA1c were measured at each semi-annual MACS visit since 1999. All HIV-infected and HIV-uninfected men for whom at least one FG and HbA1c pair measurement was available were evaluated. Univariate median regression determined the association between HbA1c and FG by HIV serostatus. The relationship between HbA1c and FG in HIV-uninfected men was used to determine the expected HbA1c. Generalized estimating equations determined factors associated with the Hb1Ac discordance among HIV-infected men. Clinically significant discordance was defined as observed HbA1c - expected HbA1c ≤-0.5%.ResultsOver 13 years, 1500 HIV-uninfected and 1357 HIV-infected men were included, with a median of 11 visits for each participant. At an FG of 125 mg/dL, the median HbA1c among HIV-infected men was 0.21% lower than among HIV-uninfected men and the magnitude of this effect increased with FG >126 mg/dL. Sixty-three percent of HIV-infected men had at least one visit with clinically significant HbA1c discordance, which was independently associated with: low CD4 cell count (

Previous studies demonstrated that blacks have less coronary artery calcification (CAC) than whites. We evaluated racial differences in plaque composition and stenosis in the Multicenter AIDS Cohort Study. HIV-positive and HIV-negative men underwent noncontrast cardiac computed tomography (CT) if they were aged 40 to 70 years, weighed 50% on CTA. The association of presence and extent of plaque with race was determined after adjustment for HIV serostatus, cardiovascular risk factors, and measures of socioeconomic status. The prevalences of any plaque on CTA and noncalcified plaque were not different between black and white men; however, black men had lower prevalences of CAC (prevalence ratio [PR] 0.79, p = 0.01), calcified plaque (PR 0.69, p = 0.002), and stenosis >50% (PR 0.59, p = 0.009). There were no associations between black race and extent of plaque in fully adjusted models. Using log-linear regression, black race was associated with a lower extent of any plaque on CTA in HIV-positive men (estimate = -0.24, p = 0.051) but not in HIV-negative men (0.12, p = 0.50, HIV interaction p = 0.005). In conclusion, a lower prevalence of CAC in black compared with white men appears to reflect less calcification of plaque and stenosis rather than a lower overall prevalence of plaque.

ObjectiveCytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and antiretroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine whether HIV infection is associated with greater epicardial fat and whether epicardial fat is associated with subclinical coronary atherosclerosis.DesignWe studied 579 HIV-infected and 353 HIV-uninfected men aged 40-70 years with noncontrast computed tomography to measure epicardial adipose tissue (EAT) volume and coronary artery calcium (CAC). Total plaque score (TPS) and plaque subtypes (noncalcified, calcified, and mixed) were measured by coronary computed tomography angiography in 706 men.MethodsWe evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race, and serostatus and with additional cardiovascular risk factors and tested for modifying effects of HIV serostatus.ResultsHIV-infected men had greater EAT than HIV-uninfected men (P=0.001). EAT was positively associated with duration of antiretroviral therapy (P=0.02), specifically azidothymidine (P

ObjectivesHuman immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase the risk of fatty liver disease. We determined the prevalence of and risk factors for fatty liver by comparing HIV-infected men with HIV-uninfected men who have sex with men in the Multicenter AIDS Cohort Study (MACS).MethodsIn 719 MACS participants who consumed less than three alcoholic drinks daily, fatty liver was defined as a liver-to-spleen attenuation ratio

BackgroundCoronary artery disease (CAD) has been associated with HIV infection, but data are not consistent.ObjectiveTo determine whether HIV-infected men have more coronary atherosclerosis than uninfected men.DesignCross-sectional study.SettingMulticenter AIDS Cohort Study.ParticipantsHIV-infected (n = 618) and uninfected (n = 383) men who have sex with men who were aged 40 to 70 years, weighed less than 136 kg (200 lb), and had no history of coronary revascularization.MeasurementsPresence and extent of coronary artery calcium (CAC) on noncontrast cardiac computed tomography (CT) and of any plaque; noncalcified, mixed, or calcified plaque; or stenosis on coronary CT angiography.Results1001 men had noncontrast CT, of whom 759 had coronary CT angiography. After adjustment for age, race, CT scanning center, and cohort, HIV-infected men had a greater prevalence of CAC (prevalence ratio [PR], 1.21 [95% CI, 1.08 to 1.35]; P = 0.001) and any plaque (PR, 1.14 [CI, 1.05 to 1.24]; P = 0.001), including noncalcified (PR, 1.28 [CI, 1.13 to 1.45]; P < 0.001) and mixed (PR, 1.35 [CI, 1.10 to 1.65]; P = 0.004) plaque, than uninfected men. Associations between HIV infection and any plaque or noncalcified plaque remained significant (P < 0.005) after CAD risk factor adjustment. HIV-infected men had a greater extent of noncalcified plaque after CAD risk factor adjustment (P = 0.026). They also had a greater prevalence of coronary artery stenosis greater than 50% (PR, 1.48 [CI, 1.06 to 2.07]; P = 0.020), but not after CAD risk factor adjustment. Longer duration of highly active antiretroviral therapy (PR, 1.09 [CI, 1.02 to 1.17]; P = 0.007) and lower nadir CD4+ T-cell count (PR, 0.80 [CI, 0.69 to 0.94]; P = 0.005) were associated with coronary stenosis greater than 50%.LimitationCross-sectional observational study design and inclusion of only men.ConclusionCoronary artery plaque, especially noncalcified plaque, is more prevalent and extensive in HIV-infected men, independent of CAD risk factors.Primary funding sourceNational Heart, Lung, and Blood Institute and National Institute of Allergy and Infectious Diseases.

ObjectiveTo examine whether altered levels of adipokines, adipose-derived peptides associated with myocardial infarction in the general population, may contribute to subclinical coronary atherosclerosis in HIV-infected persons.DesignNested cohort study.MethodsWe studied HIV-infected (HIV+) and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study with noncontrast computed tomography (CT) to measure coronary artery calcium and regional adiposity; 75% additionally underwent coronary CT angiography to measure plaque composition and stenosis. Adiponectin and leptin levels were assessed. Multiple regression models were used to assess associations between adipokine levels and HIV disease parameters, regional adiposity, and plaque adjusted for age, race, HIV serostatus, and cardiovascular disease (CVD) risk factors.ResultsSignificant findings were limited to adiponectin. HIV-positive men (n=493) had lower adiponectin levels than HIV-negative men (n=250) after adjusting for CVD risk factors (P

ObjectiveDiabetes and hypertension, common conditions in antiretroviral-treated HIV-infected individuals, are associated with glomerular hyperfiltration, which precedes the onset of proteinuria and accelerated kidney function decline. In the Multicenter AIDS Cohort Study, we examined the extent to which hyperfiltration is present and associated with metabolic, cardiovascular, HIV and treatment risk factors among HIV-infected men.DesignCross-sectional cohort using direct measurement of glomerular filtration rate by iohexol plasma clearance for 367 HIV-infected men and 241 HIV-uninfected men who were free of chronic kidney disease.MethodsHyperfiltration was defined as glomerular filtration rate above 140-1 ml/min per 1.73 m per year over age 40. Multivariate logistic regression was used to estimate the odds ratios (ORs) of prevalent hyperfiltration for metabolic, cardiovascular, HIV and cumulative antiretroviral exposure factors.ResultsAmong individuals without chronic kidney disease, the prevalence of hyperfiltration was higher for HIV-infected participants (25%) compared to uninfected participants (17%; P = 0.01). After adjustment, HIV infection remained associated with hyperfiltration [OR 1.70, 95% confidence interval (CI) 1.11-2.61] and modified the association between diabetes and hyperfiltration, such that the association among HIV-uninfected men (OR 2.56, 95% CI 1.33-5.54) was not observed among HIV-infected men (OR 1.19, 95% CI 0.69-2.05). These associations were independent of known risk factors for hyperfiltration. Indicators of hyperglycemia and hypertension were also associated with hyperfiltration as was cumulative zidovudine exposure.ConclusionHyperfiltration, a potential modifiable predictor of kidney disease progression, is significantly higher among antiretroviral-treated HIV-infected men. Furthermore, HIV-infection nullifies the association of diabetes and hyperfiltration present in HIV-uninfected men.

Current U.S. guidelines recommend integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) as initial treatment for people with HIV (PWH). We assessed long-term effects of INSTI use on lipid profiles in routine HIV care. We analyzed medical record data from the HIV Outpatient Study's participants in care from 2007 to 2021. Hyperlipidemia was defined based on clinical diagnoses, treatments, and laboratory results. We calculated hyperlipidemia incidence rates and rate ratios (RRs) during initial ART and assessed predictors of incident hyperlipidemia by using Poisson regression. Among 349 eligible ART-naïve PWH, 168 were prescribed INSTI-based ART (36 raltegravir (RAL), 51 dolutegravir (DTG), and 81 INSTI-others (elvitegravir and bictegravir)) and 181 non-INSTI-based ART, including 68 protease inhibitor (PI)-based ART. During a median follow-up of 1.4 years, hyperlipidemia rates were 12.8, 22.3, 22.7, 17.4, and 12.6 per 100 person years for RAL-, DTG-, INSTI-others-, non-INSTI-PI-, and non-INSTI-non-PI-based ART, respectively. In multivariable analysis, compared with the RAL group, hyperlipidemia rates were higher in INSTI-others (RR = 2.25; 95% confidence interval (CI): 1.29–3.93) and non-INSTI-PI groups (RR = 1.89; CI: 1.12–3.19) but not statistically higher for the DTG (RR = 1.73; CI: 0.95–3.17) and non-INSTI-non-PI groups (RR = 1.55; CI: 0.92–2.62). Other factors independently associated with hyperlipidemia included older age, non-Hispanic White race/ethnicity, and ART without tenofovir disoproxil fumarate. PWH using RAL-based regimens had lower rates of incident hyperlipidemia than PWH receiving non-INSTI-PI-based ART but had similar rates as those receiving DTG-based ART, supporting federal recommendations for using DTG-based regimens as the initial therapy for ART-naïve PWH. [ABSTRACT FROM AUTHOR]

Chronic kidney disease and HIV infection both independently increase the risk of anemia. It is not known if individuals with both HIV infection and kidney dysfunction are at greater than expected risk of anemia resulting from the combined effect of these factors. Men from the Multicenter AIDS Cohort Study with AIDS-free time after 1996 were included in the analysis if they had an initial hemoglobin value greater than 13 g/dl and available serum creatinine measurements for the estimation of glomerular filtration rate. Hemoglobin data were fit parametrically using a linear mixed effects model and effects of medication use on hemoglobin levels were removed using censoring methods. The effect of both HIV infection and glomerular filtration rate less than 60 ml/min/1.73 m(2) on the mean hemoglobin value was assessed. The risk of having anemia (hemoglobin level falling below 13 g/dl) was estimated. There were 862 HIV-infected and 1,214 HIV-uninfected men who contributed to the analysis. Hemoglobin values across all 17,341 person-visits, adjusting for age, were generally lower in HIV-infected AIDS-free men with impaired kidney function by -0.22 g/dl (95% CI: -0.42, -0.03) compared to men with either HIV infection or impaired kidney function, but not both. HIV-infected AIDS-free men with impaired kidney function have a higher risk of anemia by 1.2% compared to HIV-uninfected men with normal kidney function. Comorbid conditions and medication use did not explain this increase in risk. HIV infection and impaired kidney function have a combined impact on lowering hemoglobin levels, resulting in a higher risk of anemia.

ObjectiveChronic inflammation and B-cell hyperactivation are seen in HIV infection, contributing to an increased risk for the accrual of genetic errors that may result in B-cell lymphoma. The primary objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) on serum levels of molecules that are associated with immune activation and/or inflammation, including several that are associated with B-cell activation, specifically IL-6, sCD30, sCD27, IgG, IgA, CXCL13 (B lymphocyte chemoattractant, BLC), a B-lymphocyte chemokine involved in B-cell trafficking, as well as C-reactive protein, an acute-phase protein.DesignWe used a retrospective cohort study design, measuring serum levels of these markers at each of four 1-year intervals, 2 years before and 2 years after HAART initiation, in a subgroup of 290 HIV-infected men enrolled in the Multicenter AIDS Cohort Study (MACS).MethodsSerum levels of immune activation-associated molecules were measured by ELISA and multiplexed immunometric assays. Reference values were determined by the 5th to 95th percentiles from a sample of 109 HIV-uninfected MACS men.ResultsHAART use was associated with a reduction, but not normalization, of most biomarkers tested. Serum levels of IL-6 and C-reactive protein appeared to be unaffected by HAART.ConclusionsThese results suggest a partial normalization of serum cytokine levels post HAART. However, a chronic state of B-cell hyperactivation continues 2-3 years after HAART initiation. These findings may explain, in part, the excess incidence of lymphoma still occurring in HIV-infected persons in the post-HAART era.