Frank J. Palella

Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection

BACKGROUND AND METHODS National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. RESULTS Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. CONCLUSIONS The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.

Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study.

Background: AIDS-related death and disease rates have declined in the highly active antiretroviral therapy (HAART) era and remain low; however, current causes of death in HAART-treated patients remain ill defined. Objective: To describe mortality trends and causes of death among HIV-infected patients in the HAART era. Design: Prospective, multicenter, observational cohort study of participants in the HIV Outpatient Study who were treated from January 1996 through December 2004. Measurements: Rates of death, opportunistic disease, and other non-AIDS-defining illnesses (NADIs) determined to be primary or secondary causes of death. Results: Among 6945 HIV-infected patients followed for a median of 39.2 months, death rates fell from 7.0 deaths/100 person-years of observation in 1996 to 1.3 deaths/100 person-years in 2004 (P = 0.008 for trend). Deaths that included AIDS-related causes decreased from 3.79/100 person-years in 1996 to 0.32/100 person-years in 2004 (P = 0.008). Proportional increases in deaths involving liver disease, bacteremia/sepsis, gastrointestinal disease, non-AIDS malignancies, and renal disease also occurred (P = <0.001, 0.017, 0.006, <0.001, and 0.037, respectively.) Hepatic disease was the only reported cause of death for which absolute rates increased over time, albeit not significantly, from 0.09/100 person-years in 1996 to 0.16/100 person-years in 2004 (P = 0.10). The percentage of deaths due exclusively to NADI rose from 13.1% in 1996 to 42.5% in 2004 (P < 0.001 for trend), the most frequent of which were cardiovascular, hepatic, and pulmonary disease, and non-AIDS malignancies in 2004. Mean CD4 cell counts closest to death (n = 486 deaths) increased from 59 cells/&mgr;L in 1996 to 287 cells/&mgr;L in 2004 (P < 0.001 for trend). Patients dying of NADI causes were more HAART experienced and initiated HAART at higher CD4 cell counts than those who died with AIDS (34.5% vs 16.8%, respectively, received HAART for 4 of more years, P < 0.0001; 22.4% vs 7.8%, respectively, initiated HAART with CD4 cell counts of more than 350 cells/&mgr;L, P < 0.001). Conclusions: Although overall death rates remained low through 2004, the proportion of deaths attributable to non-AIDS diseases increased and prominently included hepatic, cardiovascular, and pulmonary diseases, as well as non-AIDS malignancies. Longer time spent receiving HAART and higher CD4 cell counts at HAART initiation were associated with death from non-AIDS causes. CD4 cell count at time of death increased over time.

Guidelines for the Management of Chronic Kidney Disease in HIV-Infected Patients: Recommendations of the HIV Medicine Association of the Infectious Diseases Society of America

Samir K. Gupta, Joseph A. Eustace, Jonathan A. Winston, Ivy I. Boydstun, Tejinder S. Ahuja, Rudolph A. Rodriguez, Karen T. Tashima, Michelle Roland, Nora Franceschini, Frank J. Palella, Jeffrey L. Lennox, Paul E. Klotman, Sharon A. Nachman, Stephen D. Hall, and Lynda A. Szczech Divisions of Infectious Diseases and Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis; Division of Nephrology, Johns Hopkins University, School of Medicine and Department of Epidemiology, Bloomberg School of Public Health, Baltimore, Maryland; Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, and Division of Nephrology and Hypertension and Division of Infectious Diseases, Department of Pediatrics, State University of New York, Stony Brook; Division of Nephrology, Department of Medicine, University of Texas Medical Branch, Galveston; Division of Nephrology, Department of Medicine, San Francisco General Hospital and Positive Health Program at San Francisco General Hospital and the UCSF AIDS Research Institute, Department of Medicine, University of California at San Francisco; Division of Infectious Diseases, Department of Medicine, The Miriam Hospital, Brown Medical School, Providence, Rhode Island; Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina at Chapel Hill, and Duke Clinical Research Institute and the Division of Nephrology, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; and Grady Infectious Disease Program, Division of Infectious Diseases, Department of Medicine, Emory University, Atlanta, Georgia

Clinical assessment of Hiv-associated lipodystrophy in an ambulatory population

ObjectiveTo identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients. DesignEvaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics. SettingEight clinics specializing in the care of HIV-1 infected patients. PatientsA total of 1077 patients were evaluated for signs of fat maldistribution. InterventionsA standardized set of questions and specific clinical signs were assessed. Demographic, clinical and pharmacological data for each patient were also included in the analysis. Main outcome measuresDemographic, immunologic, virologic, clinical, laboratory, and drug treatment factors were assessed in stratified and multivariate analyses for their relationship to the presence and severity of fat accumulation and atrophy. ResultsIndependent factors for moderate/severe lipoatrophy for 171 patients were increasing age, any use of stavudine, use of indinavir for longer than 2 years, body mass index (BMI) loss, and measures of duration and severity of HIV disease. Independent risk factors for moderate/severe fat accumulation for 104 patients were increasing age, BMI gain, measures of amount and duration of immune recovery, and duration of antiretroviral therapy (ART). The number of non-drug risk factors substantially increased the likelihood of lipoatrophy. If non-drug risk factors were absent, lipoatrophy was unusual regardless of the duration of drug use. ConclusionsHIV-associated lipodystrophy is associated with several host, disease, and drug factors. While prevalence of lipoatrophy increased with the use of stavudine and indinavir, and lipoaccumulation was associated with duration of ART, other non-drug factors were strongly associated with both fat atrophy and accumulation.

Survival Benefit of Initiating Antiretroviral Therapy in HIV-Infected Persons in Different CD4+ Cell Strata

Context When to start antiretroviral therapy (ART) for HIV infection is controversial. Starting too early exposes patients to side effects and uncertain benefits. Starting too late deprives patients of benefits. Contribution In this cohort study, HIV-infected patients with baseline CD4+ cell counts between 0.201 and 0.350 109 cells/L who began ART immediately had lower mortality rates than those who started therapy after their CD4+ cell count decreased to less than 0.201 109 cells/L. Optimal timing of therapy is unclear when the CD4+ cell count is greater than 0.350 109 cells/L. Cautions A randomized, controlled trial is the best way to identify the optimal timing of ART. The Editors Optimal timing of antiretroviral therapy (ART) initiation for persons with HIV infection is of great clinical and public health importance. Therapy reduces HIV-related mortality and morbidity for patients with substantial CD4+ cell depletion (<0.100 109 cells/L) who initiate treatment (1). Although data demonstrate the viral suppressive and immunologic (CD4+ cell count) benefits of therapy in persons with higher CD4+ cell counts (2-8), long-term improvements in disease-associated morbidity and mortality with earlier therapy are less clear (9, 10). In such patients, the potential benefits of ART and highly active ART (HAART) will probably be weighed against possible untoward sequelae of earlier treatment, including the development of metabolic abnormalities; emergence of drug-resistant virus, with resultant exhaustion of effective remaining therapies; cost; and access (9, 11-13). Current treatment guidelines allowing for the delay of ART until a lower CD4+ thresholdusually 0.350 109 cells/L or, for some patients, 0.200 109 cells/Lreflect a lack of consensus on the benefits of earlier initiation of therapy (13, 14). Sparse data exist on which to base specific recommendations for the initiation of ART relative to CD4+ cell count. Longitudinal data comparing ART recipients to appropriate comparison groups not receiving ART (especially patients with CD4+ cell counts > 0.200 109 cells/L) are limited (10, 15). Analyses that include extended follow-up data on such patients are critical because these patients are unlikely to develop or die of an HIV-related condition over the short term, in contrast to those who start therapy with lower CD4+ cell counts. Another challenge is related to the relatively brief time that HAART has been available (since early 1996), making comparative longitudinal studies of sufficient duration difficult. We compare mortality rates among ambulatory HIV-infected patients who initiated ART and those who delayed ART in various CD4+ strata. Patients were enrolled in the HIV Outpatient Study (HOPS), a dynamic cohort of ambulatory HIV-infected patients demographically representative of treated HIV-infected patients in the United States. Methods HOPS HOPS is an ongoing prospective observational cohort study into which patients have been continuously recruited and followed since 1993 (1, 16). Study sites are 10 clinics (8 private, 2 public) in 8 U.S. cities that provide care for more than 2400 HIV-infected patients per year. Participating physicians have extensive experience treating HIV-infected patients. Information is abstracted from outpatient charts at each visit and entered electronically by trained staff; it is then compiled centrally and reviewed and edited before being analyzed. Information abstracted includes demographic characteristics and risk factors for HIV infection; symptoms; diagnosed diseases (both definitive and presumptive); medications prescribed, including dose and duration; and laboratory values, including CD4+ cell counts and measurements of plasma HIV-1 RNA (viral load). Selection of Patients for Analysis We identified HOPS participants who had at least two CD4+ measurements and reliable data on ART initiation and use for at least 30 consecutive days from January 1994 through March 2001. We defined HAART as the use of at least three drugs simultaneously, including one protease inhibitor or non-nucleoside reverse-transcriptase inhibitor, or any regimen with at least two full-dose protease inhibitors. Three patient subgroups were analyzed: those observed to have a pre-ART CD4+ cell count of 0.501 to 0.750 109 cells/L, those with a pre-ART CD4+ cell count of 0.351 to 0.500 109 cells/L, and those with a pre-ART CD4+ cell count of 0.201 to 0.350 109 cells/L. Patients could be in more than one subgroup if they had a pre-ART CD4+ cell count in more than one of the defined ranges. Thus, analyses within a subgroup are distinct from analyses in other subgroups. We then stratified patients in each subgroup into one of three treatment groups: those who began ART while still in the same CD4+ subgroup range (subsequently called patients who initiated ART), those who began ART after their CD4+ cell count decreased to less than the CD4+ subgroup range (subsequently called patients who delayed ART), and those who never received ART (untreated patients). The closest (in time) CD4+ cell count available within 6 months before or 2 weeks after ART initiation was used to define the CD4+ cell count at the start of therapy. By definition, because patients who delayed ART had to have at least 1 additional CD4+ measurement during follow-up, patients who initiated ART and those who were untreated were also required to have at least 1 additional CD4+ measurement during follow-up to reduce potential bias in the analysis as a result of differential time under observation. For all treatment groups, time under observation began with the date of the earliest CD4+ cell count within the CD4+ stratum in which the patient was analyzed. Patients included in the analyses of the CD4+ subgroups of 0.201 to 0.350 109 cells/L and 0.351 to 0.500 109 cells/L were those whose earliest CD4+ cell count within the subgroup-defined range was observed after 1 January 1994. The analysis of the CD4+ subgroup of 0.501 to 0.750 109 cells/L was limited to those whose earliest CD4+ cell count within this range was observed between January 1994 and December 1995. This allowed longer elapsed time to observe clinical events. For analysis, the observation period for each patient ended at 6 months after the last contact with a HOPS clinic or at death. We analyzed all deaths, including those not directly due to AIDS or indirectly from conditions exacerbated by HIV infection (such as hepatic, renal, or cardiac disease). Causes of death were ascertained through review of clinic and hospital charts, death certificates, and national AIDS surveillance data. Deaths from suicide (one patient in the CD4+ subgroup of 0.201 to 0.350 109 cells/L who delayed ART and one patient in the CD4+ subgroup of 0.501 to 0.750 109 cells/L who initiated treatment) were treated as censored. Statistical Analysis We used SAS software, version 8.0 (SAS Institute, Inc., Cary, North Carolina), for all analyses. Patient characteristics were compared by chi-square test or the Fisher exact test for categorical variables and the Wilcoxon rank-sum test or t-test for continuous variables. We analyzed mortality rates per 1000 person-years and calculated the relative risk for death, 95% CIs, and approximate two-sided P values for each subgroup (17). Cox proportional-hazards regression was used to estimate hazard ratios, adjusted for age, sex, race, insurance status, viral load (log scale) at time of first ART (a dummy variable was used to include patients missing viral load data), receipt of HAART, and CD4+ cell count at the time of first observation within each stratum. Role of the Funding Source The funding source participated in the design, conduct, analysis, and reporting of the study and in the decision to submit the manuscript for publication. Results We evaluated data from 1464 HIV-infected HOPS participants. Of these patients, 596 who initiated ART had at least one additional CD4+ measurement after ART initiation, and 175 who delayed ART had at least one additional recorded CD4+ cell count in a higher stratum before ART initiation. We compared the demographic and baseline characteristics of patients described in this report to those of the larger overall group of HOPS participants and found no meaningful differences (data not shown). We analyzed data from 399 patients (340 who initiated and 59 who delayed ART) with pre-ART CD4+ cell counts between 0.201 and 0.350 109 cells/L, 327 patients (240 who initiated and 87 who delayed ART) with pre-ART CD4+ cell counts between 0.351 and 0.500 109 cells/L, and 122 patients (55 who initiated and 67 who delayed ART) with pre-ART CD4+ cell counts between 0.501 and 0.750 109 cells/L. Median years of follow-up for patients who initiated and those who delayed ART, by CD4+ subgroup, were as follows: 3.8 and 3.9 years for the subgroup of 0.201 to 0.350 109 cells/L, 4.1 and 4.2 years for the subgroup of 0.351 to 0.500 109 cells/L, and 5.4 and 5.3 years for the subgroup of 0.501 to 0.750 109 cells/L, respectively. Table 1 shows the demographic, immunologic, virologic, and care characteristics of patients who initiated ART and those who delayed ART, by CD4+ subgroup. Across subgroups, at least 69% of patients were men, 64% were younger than 40 years of age, 62% were white, and 35% had private health care insurance. Patients who initiated ART and those who delayed ART did not differ significantly except for the following: Patients in the CD4+ subgroup of 0.351 to 0.500 109 cells/L with private insurance tended to initiate rather than delay ART, and men in the CD4+ subgroup of 0.501 to 0.750 109 cells/L tended to delay therapy. Table 1. Characteristics of the HIV Outpatient Study Patients Who Initiated or Delayed Antiretroviral Therapy, by Preantiretroviral CD4+ Cell Count Stratum In general, most patients in a CD4+ subgroup who delayed ART initiated therapy in the next lowest CD4+ subgroup, that is, those who did not start in one subgroup started approximat

Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study

Objective:To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls. Design:Prospective cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicenter AIDS Cohort Study evaluated at 6-month intervals between 1999 and 2003. Methods:Recent ART exposure was assessed by type of treatment in the preceding 6 months [i.e., no ART, monotherapy, combination ART, or highly active antiretroviral therapy (HAART) with and without a protease inhibitor (PI)]. Cumulative exposure was determined for the three major ART classes and for individual medications within each class. Two endpoints, a modified QUICKI index, 100 × 1/[log10(glucose) + log10(insulin)] and fasting hyperinsulinemia (insulin > 15 μU/ml), were assessed. All statistical models were adjusted for age, body mass index, race, nadir CD4 cell count, hepatitis C serostatus and family history of diabetes mellitus. Results:Each of the HIV-infected groups had higher odds of hyperinsulinemia and lower mean QUICKI than the HIV-seronegative men. Each additional year of exposure to nucleoside analogue reverse transcriptase inhibitors (NRTI) was associated with increased odds of hyperinsulinemia [odds ratio (OR), 1.08; 95% confidence interval (CI), 1.02–1.13) and a lower QUICKI (−0.04; 95% CI, −0.07 to −0.01). Cumulative exposure to non-nucleoside analogue reverse transcriptase inhibitors or PI drugs was not associated with either insulin resistance marker. Of individual medications examined, stavudine was associated with the highest risk of hyperinsulinemia (OR, 1.2; 95% CI, 1.2–1.3). Conclusions:Fasting surrogate markers suggest increased insulin resistance in HIV-infected men, which is related to cumulative NRTI exposure.

Durability and predictors of success of highly active antiretroviral therapy for ambulatory HIV-infected patients.

ObjectiveTo evaluate the durability and correlates of the effectiveness of highly active antiretroviral therapy (HAART) in terms of AIDS-related mortality and morbidity, HIV viremia, and CD4 cell count. Design and settingThe HIV Outpatient Study (HOPS), a prospective observational cohort from eight clinics in the USA that has been running since 1994. ParticipantsMortality and opportunistic infection (OI) rates were calculated for 1769 HOPS patients with CD4 cell count ever < 100 × 106/l. Data from 1022 HAART recipients with CD4 cell count ever < 500 × 106/l were analyzed. Main outcome measuresMortality and AIDS-related OI rates. Treatment success was defined as a reduction in plasma HIV RNA copies/ml of 1.0 log10 or more, or to an undetectable level, with a stable or rising CD4 cell count. Durable success was a successful response lasting at least 12 consecutive months. ResultsHAART use remained high; mortality and OIs low. Patients received a mean of 1.8 HAART regimens. Median time on first HAART (n = 1022) was 11.8 months; second HAART (n = 424) 7.4 months; and third HAART (n = 213) 7.2 months. Treatment success was most likely for pre-HAART treatment naive patients; durably successful first HAART most often contained one protease inhibitor, particularly indinavir or nelfinavir (P = 0.006, adjusted for prior antiretroviral therapy). Durable success was most likely with first (49.0%) than with second (29.6%, P = 0.013) or third or more HAART regimens (14.9%, P < 0.0001). Time to success with first HAART was shorter for durable than non-durable responders (3.6 versus 5.3 months, respectively; unadjusted P = 0.002). ConclusionsDurable response to HAART was associated with being pre-HAART therapy naive, prompt response to HAART, and single protease inhibitor-based initial HAART (indinavir or nelfinavir). Sequential HAART regimens were of progressively shorter duration, demonstrated less viral suppression and CD4 cell count benefit, yet low morbidity and mortality rates were sustained.

Changes in adherence to highly active antiretroviral therapy medications in the Multicenter AIDS Cohort Study.

Objectives: To characterize the determinants of changes in adherence to antiretroviral therapy and examine whether there are persistent lower adherers. Design: A cohort study with repeated measurements. Methods: Self-reported 100% adherence was defined as taking all doses and numbers of pills over a 4-day period as prescribed for current HIV medications. Independent predictors of changing adherence (< 100% to 100% and 100% to < 100%) were determined by logistic regression, correcting for correlated repeated measures for 597 HIV-positive men reporting the use of highly active antiretroviral therapy (HAART) between October 1998 and October 2000. Results: Of the 942 visit-pairs with initial 100% adherence, 106 (11.3%) reduced adherence to less than 100%, and 836 (88.7%) remained 100% adherent at the next 6-month visit. No recent outpatient visits, younger age, depression, less than college educated, and later in calendar time predicted decreasing adherence. Among 186 visit-pairs starting with less than 100% adherence, 133 (71.5%) improved adherence to 100% and 53 (28.5%) remained less than 100% adherent at the next visit. The determinants of improving adherence included not being African-American, not using recreational drugs, and having had more than three HAART regimens. Lower adherence was not a random event; it was significantly correlated across visits within the individual. Conclusion: Characteristics associated with improving and lowering adherence differed and should be considered in developing interventions to enhance adherence and optimize effective therapies.

Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants.

Objective:To evaluate the efficacy and safety of antiretroviral simplification from a ritonavir-boosted protease inhibitor-based regimen [protease inhibitor+RTV+two nucleos(t)ide reverse transcriptase inhibitors (NRTIs); ≥6 months of exposure prior to study entry with no prior treatment failure] to the single-tablet regimen (STR) rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) in virologically suppressed, HIV-1-infected participants. Design:Phase 3b, randomized, open-label, international, 48-week switch study. Methods:Participants were randomized 2 : 1 to switch to RPV/FTC/TDF immediately or stay on their baseline protease inhibitor+RTV+2NRTIs regimen with a delayed switch to RPV/FTC/TDF at week 24. The primary endpoint was noninferiority (12% margin) of RPV/FTC/TDF compared with protease inhibitor+RTV+ two NRTIs in maintaining plasma HIV-1 RNA less than 50 copies/ml at week 24 by Snapshot analysis. Results:A total of 476 participants were randomized and received at least one dose of study drug. Demographics and baseline characteristics were similar between arms. The primary objective of noninferiority at week 24 was met: HIV-1 RNA less than 50 copies/ml by Snapshot analysis, 93.7% of RPV/FTC/TDF versus 89.9% of protease inhibitor+RTV+ two NRTIs (difference 3.8%, 95% confidence interval −1.6 to 9.1%). Through week 48, 89.3% of participants in the immediate switch group maintained virologic suppression. High rates of suppression were maintained with RPV/FTC/TDF regardless of participants pre-antiretroviral HIV-1 RNA level. Overall development of resistance mutations after switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF recipients than those in the protease inhibitor+RTV+ two NRTIs group. Conclusion:Switching to the STR RPV/FTC/TDF from an RTV-boosted protease inhibitor regimen in virologically suppressed, HIV-1-infected participants maintained virologic suppression with a low risk of virologic failure, while improving total cholesterol, LDL, and triglycerides.

Elevated Levels of Monocyte Activation Markers Are Associated With Subclinical Atherosclerosis in Men With and Those Without HIV Infection

BACKGROUND Heightened 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. METHODS We 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. RESULTS Levels 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. CONCLUSIONS sCD163, 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.