Long-term kidney function, proteinuria, and associated risks among HIV-infected and uninfected men.

BACKGROUND: Factors affecting kidney function and proteinuria among HIV-positive (HIV+) and HIV-negative (HIV-) persons need better characterization. METHODS: We evaluated estimated glomerular filtration rate (eGFR, ml/min per 1.73 m) changes, proteinuria prevalence (a urine protein-to-creatinine ratio of ≥0.2 at two consecutive visits) and associated factors among HIV+ and HIV- men. RESULTS: There were 917 HIV+ men receiving HAART, 159 HIV+ men not receiving HAART, and 1305 HIV- men seen from October 2003 to September 2014. Median annual eGFR change was -0.5, -0.8% for HIV+ and -0.3% for HIV- men (P < 0.001). Factors significantly (P < 0.05) associated with more than 3% annual eGFR decline were HAART receipt (but no specific antiretroviral drug), age more than 50, hypertension, diabetes, current smoking. Proteinuria existed in 14.9% of visit-pairs among HAART recipients, 5.8% among non-HAART recipients, and 1.9% among HIV- men, and was associated with subsequent annual more than 3% eGFR decline (odds ratio 1.80, P < 0.001). Proteinuria-associated factors also included HAART use (vs. HIV-), age at least 50 (vs. <40), diabetes, hypertension, current smoking, hepatitis C virus-infection (all P < 0.05) and, among HIV+ men, lower CD4 cell count, didanosine, saquinavir, or nelfinavir use (all P < 0.05). After adjusting for proteinuria, among HAART users, having a detectable HIV RNA, cumulative use of tenofovir disoproxil fumarate, emtricitabine, ritonavir, atazanavir, any protease inhibitor, or fluconazole were associated with more than 3% annual eGFR decline. CONCLUSION: Longitudinal kidney function decline was associated with HAART use but no individual antiretroviral drug, and traditional kidney disease risks. Proteinuria was nearly seven times more common in HAART-treated men than HIV- men, reflected recent eGFR decline and predicted subsequent eGFR decline.

Frailty and Circulating Markers of Inflammation in HIV+ and HIV- Men in the Multicenter AIDS Cohort Study.

BACKGROUND: Frailty is associated with immune activation and inflammation in the elderly general population, but whether this is true in the younger HIV-infected (HIV+) population is not known. METHODS: We analyzed 24 serologic biomarkers of monocyte, T-cell, or B-cell activation in HIV- (n = 207) and HIV+ (n = 714; 75% virologically suppressed) men who have sex with men in the Multicenter AIDS Cohort Study (MACS) and were classified as frail or nonfrail according to expression or nonexpression of the frailty phenotype at 2 consecutive study visits. RESULTS: After correction for multiple comparisons and adjustment for age, race, study site, and education, frailty in HIV+ men was significantly (P < 0.002) associated with higher levels of sCD14, sIL2Rα, sTNF-R2, IL-6, and TNF-α; the association with higher levels of C-reactive protein (CRP) approached significance (P = 0.003). After further adjustment for body mass index (BMI), smoking, and comorbidities, only the association with C-reactive protein was significant at P < 0.002, with levels approximately 50% higher in frail compared with nonfrail men. These conclusions were not altered by restricting the analysis to HIV+ men who were virologically suppressed. Among HIV- men, none of these markers differed significantly by frailty. CONCLUSIONS: These data suggest that frailty in virologically suppressed HIV+ men was associated with immune activation beyond that due to treated HIV infection. The inflammatory markers associated with frailty were primarily products of activated monocytes/macrophages. Much, but not all, activation was accounted for by harmful behaviors and comorbidities. However, C-reactive protein, which is regulated by IL-6, was elevated in HIV+ frail men independent of these factors.

Data on serologic inflammatory biomarkers assessed using multiplex assays and host characteristics in the Multicenter AIDS Cohort Study (MACS).

This article contains data on the associations between fixed and modifiable host characteristics and twenty-three biomarkers of inflammation and immune activation measured longitudinally in a cohort of 250 HIV-uninfected men from the Multicenter AIDS Cohort Study (1984-2009) after adjusting for age, study site, and blood draw time of day using generalized gamma regression. This article also presents associations between each biomarker and each host characteristic in a sample restricted to 2001-2009. These data are supplemental to our original research article entitled "Host factors associated with serologic inflammatory markers assessed using multiplex assays" (McKay, S. Heather, Bream, H. Jay, Margolick, B. Joseph, Martínez-Maza, Otoniel, Phair, P. John, Rinaldo, R. Charles, Abraham, G. Alison, L.P. Jacobson, 2016) [1].

Associations between antiretroviral use and subclinical coronary atherosclerosis.

OBJECTIVES: HIV infection is associated with increased prevalence of subclinical coronary plaque. The extent to which such plaque reflects effects of HIV infection or effects of long-term antiretroviral therapy (ART) use remains unclear and was the goal of this analysis. DESIGN AND METHODS: We compared the prevalence and extent of coronary plaque and stenosis between users of specific ART drugs or drug classes using coronary computed tomography (CT) among HIV-infected men in the Multicenter AIDS Cohort Study. To account for time-dependent confounders, including cardiovascular disease risk factors and time-varying reasons for using specific treatments, we conducted fully adjusted logistic and linear models with inverse probability of treatment weighting. RESULTS: There were 618 men who underwent noncontrast coronary CT; 450 also underwent coronary CT angiography. At the time of scanning, 81% had undetectable plasma HIV RNA. In fully adjusted models, cumulative use of zidovudine, abacavir, darunavir, and protease inhibitors as a drug class were inconsistently associated with specific forms of plaque presence or extent. CONCLUSION: Among virally suppressed HIV-infected men with extensive ART exposure, no consistent associations between use of specific ART drugs and both subclinical coronary plaque presence and extent were apparent. Our findings support the hypothesis that, among virally suppressed persons, type of ART used is not in general a major determinant of subclinical coronary plaque risk.

Host factors associated with serologic inflammatory markers assessed using multiplex assays.

Chronic systemic inflammation contributes to the development of adverse health conditions, yet the influence of fixed and modifiable risk factors on many serologic biomarkers of inflammation remains largely unknown. Serum concentrations of twenty-three biomarkers, including C-reactive protein (CRP), cytokines (CXCL11, CXCL8, CXCL10, CCL2, CCL13, CCL4, CCL17, CXCL13, IL-10, IL-12p70, IL-6, TNF-α, IL-2, IFN-γ, IL-1ß, GM-CSF, BAFF), and soluble immune receptors (sCD14, sIL-2Rα, sCD27, sgp130, sTNF-R2) were measured longitudinally using multiplexed immunometric assays in 250 HIV-uninfected men followed in the Multicenter AIDS Cohort Study (1984-2009). Generalized gamma regression was used to determine the statistical significance of factors associated with each biomarker. After accounting for age, race, and education, and for analysis of multiple biomarkers, higher concentrations of specific individual biomarkers were significantly (P<0.002) associated with hypertension, obesity, hepatitis C infection, stimulant use, and diabetes and lower concentrations with hypercholesterolemia. These associations should be taken into account in epidemiological studies of these biomarkers, and may provide potential targets for disease prevention and treatment.

Brief Report: Highly Active Antiretroviral Therapy Mitigates Liver Disease in HIV Infection.

To determine the impact of highly active antiretroviral therapy (HAART) on liver disease, we analyzed changes in the aspartate aminotransferase to platelet ratio index (APRI) pre- and post-HAART initiation among 441 HIV-monoinfected and 53 HIV-viral hepatitis-coinfected men. Before HAART, APRI increased 17% and 34% among the HIV-monoinfected and coinfected men, respectively. With HAART initiation, APRI decreased significantly in men who achieved HIV RNA of <500 copies per milliliter: 16% for HIV-monoinfected and 22% for coinfected men. Decreases in APRI were dependent on HIV suppression. This protective effect of HAART decreased after 2 years, particularly in the HIV-monoinfected men.

Spontaneous Clearance of the Hepatitis C Virus Among Men Who Have Sex With Men.

BACKGROUND: The probability of spontaneous hepatitis C virus (HCV) clearance ranges from 11% to 49%. Our previous cross-sectional study suggests that mode of acquisition explains some of this heterogeneity. We performed this prospective study to determine factors associated with spontaneous HCV clearance among men who have sex with men (MSM). METHODS: A mixture-cure model was used to evaluate the probability of spontaneous HCV clearance among 101 MSM in the Multicenter AIDS Cohort Study with acute HCV infection between 1984 and 2012. RESULTS: Spontaneous HCV clearance occurred in 46% of MSM (49% in non-injection drug users [IDUs] and 23% in IDUs). In the multivariable analysis, age <30 years (clearance ratio [CR] = 2.43; 95% confidence interval [CI], 1.53-3.87) and being human immunodeficiency virus (HIV) uninfected (CR = 2.97; 95% CI, 1.98-4.46) were independently associated with spontaneous clearance. Among men aged ≥30 years, being HIV uninfected, not having unprotected anal intercourse, older age, and being on highly active antiretroviral therapy were independently associated with higher clearance. The interferon lambda rs12979860 single nucleotide polymorphism (SNP) was not associated with spontaneous clearance among the 88 MSM who were not active IDUs (CR = 0.74; 95% CI, .46-1.21 for CC vs CT/TT genotype). CONCLUSIONS: The high probability of spontaneous HCV clearance together with the lack of an association between the rs12979860 SNP and spontaneous clearance among MSM who do not use injection drugs suggests that the immune mechanisms involved with a successful response to acute HCV differ by mode of virus acquisition. Understanding potential mechanistic differences could be important for HCV vaccine development.

Age, comorbidities, and AIDS predict a frailty phenotype in men who have sex with men.

BACKGROUND: Adults aging with HIV infection are at risk for age-related comorbidities and syndromes, such as frailty. The objective of this study was to evaluate the expression and predictors of the frailty phenotype (FP) among HIV-infected (HIV+) and HIV-uninfected (HIV-) men who have sex with men. METHODS: A prospective, observational cohort study was nested in the Multicenter AIDS Cohort Study from October 2007-September 2011. FP conversion was defined as the onset of FP over two consecutive study visits. Adjusted odds ratios and 95% confidence intervals ([,]) for FP conversion were estimated using logistic regression models with generalized estimating equations. RESULTS: Of 10,571 completed study visits from 1,946 men who have sex with men, 12% and 9% were FP+ among HIV+ and HIV- men, respectively (p = .002). The proportion of FP+ visits increased with age regardless of HIV status, but was significantly greater in HIV+ compared to HIV- men aged 50-64 years. Of the 10,276 consecutive visit pairs contributed by participants, 5% (537) were classified as FP conversion, and 45% of the men with FP conversion had only one FP+ study visit. FP conversion was significantly associated with a history of AIDS (adjusted odds ratios = 2.26 [1.50, 3.39], but not with HIV+ alone (adjusted odds ratios = 1.26 [0.98, 1.64]). Among men who had one or more FP+ visits, 34% of HIV+ and 38% of HIV- men had less than two comorbidities. CONCLUSIONS: These findings suggest that expression of the FP can be measured in men who have sex with men with and without HIV infection and reflects multisystem dysfunction in this population; further investigations are needed to better understand clinical utility.

Long-term predictive value of the Framingham Risk Score for Stroke in HIV-positive vs HIV-negative men.

OBJECTIVE: To test the predictive accuracy of the Framingham Risk Score for Stroke (FRS-S) in HIV-infected (HIV+) vs HIV-uninfected (HIV-) men. METHODS: The Multicenter AIDS Cohort Study (MACS) is an ongoing prospective study of HIV+ and HIV- men who have sex with men (MSM) enrolled in 4 US cities. We ascertained all reported stroke events during a recent 15-year timeframe (July 1, 1996 to June 30, 2011) among 3,945 participants (1,776 HIV+ and 2,169 HIV-). For those with strokes, FRS-S were calculated 10 years before the stroke event and assessed according to HIV status. RESULTS: A total of 114 stroke events occurred, including 57 HIV+ and 37 HIV- participants with first-ever strokes and 19 fatal strokes. The incidence of first-ever stroke was 1.7/1,000 person-years among HIV- and 3.3/1,000 person-years among HIV+ participants. Among those with strokes, HIV+ participants were younger than HIV- participants (median age 51.3 vs 61.8 years, p < 0.0001). For these men with stroke, the average 10-year risk of stroke was higher for HIV- MSM (6.6% [range 3%-26%] vs 4.9% for HIV+ MSM [range 0%-15%], p < 0.04). Traditional risk factors for stroke were similar among the Framingham cohort and the MACS HIV+ and HIV- participants. CONCLUSIONS: FRS-S prediction was systematically different in HIV+ vs HIV- men with stroke events. The FRS-S underestimates the long-term risk of stroke in HIV+ men.

A frailty-related phenotype before HAART initiation as an independent risk factor for AIDS or death after HAART among HIV-infected men.

BACKGROUND: In the general population, frailty, a late stage of the aging process, predicts mortality. We investigated whether manifesting a previously defined frailty-related phenotype (FRP) before initiating highly active antiretroviral therapy (HAART) affects the likelihood of developing clinical AIDS or mortality after HAART initiation. METHODS: Among 596 HIV-infected men in the Multicenter AIDS Cohort Study whose date of HAART initiation was known within ±6 months and who had an assessable FRP status within 3 years before HAART, survival analyses were performed to assess the effect of FRP manifestation on clinical AIDS or death after HAART. RESULTS: In men free of AIDS before HAART, AIDS or death after HAART occurred in 13/36 (36%) men who exhibited the FRP before HAART but only in 69/436 (16%) men who did not (hazard ratio = 2.6; 95% confidence interval = 1.4-4.6; p < .01). After adjusting for age, ethnicity, education, nadir CD4+ T-cell count, peak HIV viral load, and hemoglobin in the 3 years before HAART, having the FRP at >25% of visits in the 3 years before HAART significantly predicted AIDS or death (adjusted hazard ratio = 3.8; 95% confidence interval = 1.9-7.9; p < .01). Results were unchanged when the analysis was restricted to the 335 AIDS-free men who were HAART responders, to the 124 men who had AIDS at HAART initiation, or to the subsets of men for whom indices of liver and kidney function could be taken into account. CONCLUSION: Having a persistent frailty-like phenotype before HAART initiation predicted a worse prognosis after HAART, independent of known risk factors.

CD4+ T-cell counts and plasma HIV-1 RNA levels beyond 5 years of highly active antiretroviral therapy.

BACKGROUND: The heterogeneity of CD4 T-cell counts and HIV-1 RNA at 5-12 years after the initiation of highly active antiretroviral therapy (HAART) remains largely uncharacterized. METHODS: In the Multicenter AIDS Cohort Study, 614 men who initiated HAART contributed data 5-12 years subsequently. Multivariate regression was used to evaluate the predictors of CD4 counts and HIV-1 RNA levels. RESULTS: At 5 to 12 years post-HAART, the median CD4 T-cell count was 586 (interquartile range, 421-791) cells per microliter and 78% of the HIV-1 RNA measurements were undetectable. Higher CD4 T-cell counts 5-12 years post HAART were predicted by higher CD4 T-cell counts and higher total lymphocyte count pre HAART, lack of hepatitis B or C virus coinfections, and greater CD4 T-cell change and suppressed HIV-1 RNA in the first 5 years after starting HAART. Men who were 50 years and older with 351-500 CD4 cells per microliter at HAART initiation had adjusted mean CD4 T-cell count of 643 cells per microliter at 10-12 years post HAART, which was similar to the adjusted mean CD4 T-cell count (670 cells/µL, P = 0.45) in this period for younger men starting HAART with lower CD4 T-cell counts. HIV-1 RNA suppression in the first 5 years post HAART predicted subsequent viral suppression. CONCLUSIONS: Immunological and virological responses in the first 5 years post HAART predicted subsequent CD4 T-cell counts and HIV-1 RNA levels. The association between age and subsequent CD4 T-cell count supports incorporating age in the guidelines for use of HAART.

Cardiovascular disease in HIV infection.

PURPOSE OF REVIEW: Highly active antiretroviral therapy (HAART) use has markedly reduced AIDS-related mortality and opportunistic illness. With improved survival, cardiovascular disease (CVD) has emerged as an important noninfectious chronic comorbidity among antiretroviral (ARV)-treated HIV-infected persons. RECENT FINDINGS: HIV infection can impact CVD and comorbidities known to increase CVD risk. Untreated HIV can cause proatherogenic elevations in serum lipids. Chronic HIV viremia results in increases in systemic inflammation, hypercoagulation, and reductions in endovascular reactivity, all of which are at least partially reversible with virally suppressive HAART. Chronic T-cell activation can also result in adverse vascular effects. Use of some ARV drugs can impact CVD risk by causing pro-atherogenic serum lipid elevations, induction of insulin resistance, increases in visceral adiposity or subcutaneous fat loss. Abacavir use may increase myocardial infarction risk by reducing vascular reactivity and/or increasing platelet activation. Traditional risk factors such as advancing age, smoking, hyperlipidemia, and hypertension remain important predictors of CVD among HAART-treated HIV-infected persons. SUMMARY: HIV in the HAART era is a chronic manageable condition. CVD is an important cause of morbidity among HIV-infected persons. Untreated HIV can increase CVD risk in several ways and these effects are at least partially reversible with successful treatment. Use of specific ARVs can adversely impact CVD risk but the multiple long-term benefits of chronic HIV suppression and immune reconstitution achievable with potent HAART outweigh the adverse impact upon CVD risks that they may have. Standard CVD screening and risk-reducing interventions should be routinely undertaken for HIV-infected persons.

Association between human immunodeficiency virus infection and stiffness of the common carotid artery.

BACKGROUND AND PURPOSE: Individuals with human immunodeficiency virus (HIV) who use highly active antiretroviral therapy (HAART) may have an increased risk for cardiovascular-related events, although the underlying mechanism remains unclear. We tested the hypothesis that carotid arterial stiffness was higher among persons using HAART compared to HAART-naïve and HIV-uninfected persons. METHODS: Between 2004 and 2006, we performed high-resolution B-mode ultrasound on 2789 HIV-infected and HIV-uninfected participants of the Women's Interagency HIV Study (1865 women) and the Multicenter AIDS Cohort Study (924 men) and determined carotid arterial distensibility, which is a direct measure of carotid arterial stiffness. We used generalized estimating equations to evaluate the association between distensibility and HIV infection, CD4(+) cell count, and exposure to HAART adjusted for demographic, behavioral, and clinical characteristics. RESULTS: In multivariable analysis, distensibility was 4.3% lower (95% confidence interval, -7.4% to -1.1%) among HIV-infected vs uninfected participants. Among HIV-infected participants with <200 CD4(+) cells, distensibility was 10.5% lower (95% confidence interval, -14.5% to -6.2%) than that among HIV-uninfected participants, and this effect did not differ significantly by cohort or race. Concurrent HAART use was independently associated with lower distensibility among Multicenter AIDS Cohort Study participants but not among Women's Interagency HIV Study participants. CONCLUSIONS: Our finding that advanced HIV-related immunosuppression was associated with increased carotid arterial stiffness independent from the effects of traditional atherosclerosis risk factors suggests that the etiologic mechanism underlying reports of an increased cardiovascular disease risk among HIV-infected individuals might involve HIV-related immunosuppression leading to vascular dysfunction and arterial stiffening.

Absence of xenotropic murine leukemia virus-related virus in blood cells of men at risk for and infected with HIV.

Xenotropic murine leukemia virus-related virus has been detected in blood cells of patients with chronic fatigue syndrome and in 3.7% of healthy controls from the same geographic region. We evaluated 996 men who were participants in the Multicenter AIDS Cohort Study for xenotropic murine leukemia virus-related virus sequences in blood cells by means of a real-time quantitative PCR assay. Xenotropic murine leukemia virus-related virus was detected in none of the men on the basis of the absence of xenotropic murine leukemia virus-related virus DNA, suggesting that infection may be population-specific.

Examination of disease-based selection, demographic history and population structure in European Y-chromosome haplogroup I.

We attempted to refine the understanding of an association of Y-chromosomal haplogroup I (hg-I) with enhanced AIDS progression that had been previously reported. First, we compared the progression phenotype between hg-I and its phylogenetically closest haplogroup J. Then, we took a candidate gene approach resequencing DDX3Y, a crucial autoimmunity gene, in hg-I and other common European Y-chromosome haplogroups looking for functional variants. We extended the genetic analyses to CD24L4 and compared and contrasted the roles of disease-based selection, demographic history and population structure shaping the contemporary genetic landscape of hg-I chromosomes. Our results confirmed and refined the AIDS progression signal to hg-I, though no gene variant was identified that can explain the disease association. Molecular evolutionary and genetic analyses of the examined loci suggested a unique evolutionary history in hg-I, probably shaped by complex interactions of selection, demographic history and high geographical differentiation leading to the formation of distinct hg-I subhaplogroups that today are associated with HIV/AIDS onset. Clearly, further studies on Y-chromosome candidate loci sequencing to discover functional variants and discern the roles of evolutionary factors are warranted.

The relationship between antibody to R7V and progression of HIV type 1 infection.

The presence of antibody to R7V (anti-R7VAb), a seven-amino acid sequence derived from beta(2)-microglobulin incorporated into HIV-1 virions from the surface of infected cells, has been proposed as an early marker of nonprogressive HIV-1 infection. The present study was undertaken because no prospective studies have tested this hypothesis. Stored samples collected prospectively from 361 HIV-1 seroconverting men in the Multicenter AIDS Cohort Study (0.44-1.53 years after seroconversion) were assayed for the presence or absence of anti-R7VAb, using a standardized ELISA. Using Cox proportional hazards models, crude and adjusted relative hazards (RH) were determined for the following outcomes: (a) clinically defined AIDS, (b) clinically defined AIDS or CD4 T cell count of <200 cells/microl, and (c) death. A total of 143 (39.6%) men had early anti-R7VAb and 218 (60.4%) did not; 192 (53.2%) developed AIDS. At the visit tested, men with anti-R7VAb had significantly lower CD4 T cell counts and higher plasma HIV-1 viral loads than those without antibody. After adjustment for CD4 T cell count, HIV-1 viral load, CCR5 polymorphism, and use of combined antiretroviral therapy, the presence of anti-R7VAb was associated with a higher risk of progression for all outcomes, but not significantly so. Absence of anti-R7VAb was significantly associated with expression of HLA-B*5701 and -B*2705, two alleles associated with slower progression of HIV-1 disease. The early presence of anti-R7VAb in HIV-1 seroconverters was not associated with slower progression of HIV-1 disease.

Fidelity of SNP array genotyping using Epstein Barr virus-transformed B-lymphocyte cell lines: implications for genome-wide association studies.

BACKGROUND: As availability of primary cells can be limited for genetic studies of human disease, lymphoblastoid cell lines (LCL) are common sources of genomic DNA. LCL are created in a transformation process that entails in vitro infection of human B-lymphocytes with the Epstein-Barr Virus (EBV). METHODOLOGY/PRINCIPAL FINDINGS: To test for genotypic errors potentially induced by the Epstein-Barr Virus transformation process, we compared single nucleotide polymorphism (SNP) genotype calls in peripheral blood mononuclear cells (PBMC) and LCL from the same individuals. The average mismatch rate across 19 comparisons was 0.12% for SNPs with a population call rate of at least 95%, and 0.03% at SNPs with a call rate of at least 99%. Mismatch rates were not correlated across genotype subarrays run on all sample pairs. CONCLUSIONS/SIGNIFICANCE: Genotypic discrepancies found in PBMC and LCL pairs were not significantly different than control pairs, and were not correlated across subarrays. These results suggest that mismatch rates are minimal with stringent quality control, and that most genotypic discrepancies are due to technical artifacts rather than the EBV transformation process. Thus, LCL likely constitute a reliable DNA source for host genotype analysis.

Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men.

CONTEXT: Immunological similarities have been noted between HIV-infected individuals and older HIV-negative adults. Immunologic alterations with aging have been noted in frailty in older adults, a clinical syndrome of high risk for mortality and other adverse outcomes. Using a frailty-related phenotype (FRP), we investigated in the Multicenter AIDS Cohort Study whether progressive deterioration of the immune system among HIV-positive individuals independently predicts onset of FRP. METHODS: FRP was evaluated semiannually in 1046 HIV-infected men from 1994 to 2005. CD4 T-cell count and plasma viral load were evaluated as predictors of FRP by logistic regression (generalized estimating equations), adjusting for age, ethnicity, educational level, AIDS status, and treatment era [pre-highly active antiretroviral therapy (HAART) (1994-1995) and HAART (1996-1999 and 2000-2005)]. RESULTS: Adjusted prevalences of FRP remained low for CD4 T-cell counts >400 cells per cubic millimeter and increased exponentially and significantly for lower counts. Results were unaffected by treatment era. After 1996, CD4 T-cell count, but not plasma viral load, was independently associated with FRP. CONCLUSIONS: CD4 T-cell count predicted the development of a FRP among HIV-infected men, independent of HAART use. This suggests that compromise of the immune system in HIV-infected individuals contributes to the systemic physiologic dysfunction of frailty.