The role of genetic variants in CRP in radiographic severity in African Americans with early and established rheumatoid arthritis.

This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.

Hepatitis C virus coinfection and the risk of cardiovascular disease among HIV-infected patients.

BACKGROUND: Among HIV-infected patients, hepatitis C virus (HCV) coinfection is associated with lower cholesterol levels, but it remains unclear how it affects cardiovascular outcomes. METHODS: We performed logistic regression to evaluate acute myocardial infarction (AMI) and cerebrovascular disease (CVD) events by HCV status among HIV-infected US veterans in the highly active antiretroviral therapy (HAART) era (1996-2004). We then performed survival analyses to evaluate incident AMI and CVD, exploring antiretroviral therapy (ART) as a time-dependent variable. RESULTS: A total of 19 424 HIV-infected patients [31.6% of whom were HCV-coinfected (HIV/HCV)] contributed 76 376 patient-years of follow-up. HCV coinfection was associated with lower rates of hypercholesterolaemia (18.0% in HIV/HCV vs. 30.7% in HIV-only patients; P<0.001), but higher rates of hypertension (43.8%vs. 35.6%; P<0.0001), type 2 diabetes mellitus (16.2%vs. 11.1%; P<0.0001) and smoking (36.7%vs. 24.7%; P=0.009). Rates of AMI and CVD were significantly higher among HIV/HCV than HIV-only patients: 4.19 vs. 3.36 events/1000 patient-years, respectively (P<0.001), for AMI; and 12.47 vs. 11.12 events/1000 patient-years, respectively (P<0.001), for CVD. When analyses were controlled for diabetes mellitus, hypertension, age and duration of ART, hazard ratios (HRs) among those with HIV/HCV (vs. HIV only) were 1.25 [95% confidence interval (CI) 0.98-1.61; P=0.072] for AMI and 1.20 (CI 1.04-1.38; P=0.013) for CVD. Hypertension (HR 2.05; P<0.001), greater age (HR 1.79; P<0.001) and longer duration (cumulative years) of antiretroviral use (HR 1.12; P=0.0411) were also associated with increased risk of AMI in the adjusted model. CONCLUSIONS: In the HAART era, HCV coinfection was associated with a significantly increased risk of CVD and a trend towards an increased risk of AMI among HIV-infected patients.

RisedronatE and ALendronate Intervention over Three Years (REALITY): minimal differences in fracture risk reduction.

SUMMARY: The comparative effectiveness of alendronate and risedronate has received limited evaluation. Among 19,063 new users of bisphosphonates, risedronate users had a higher relative rate of hip fracture compared to alendronate users, but the difference in absolute fracture rate was small. We conclude that the agents have comparable efficacy. INTRODUCTION: Bisphosphonates differ in their in vitro potency, avidity for bone, and rapidity of onset in clinical trials. To address potential differences between bisphosphonates in comparative effectiveness, we compared new users of alendronate and risedronate to determine if there were differences in the risk of clinical fractures at 1 year and beyond. METHODS: Using claims data from a U.S. health care organization, we identified new, adherent users of weekly alendronate or risedronate and assessed subsequent fractures. We calculated fracture incidence rate differences and ratios between the two agents. RESULTS: There were no significant differences in fracture rates between alendronate users (n = 12,956) and risedronate users (n = 6,107) at 1 year. Using all available data, the rate of hip fracture was higher among risedronate users compared to alendronate users (absolute rate difference approximately five per 1,000 person-years). Risedronate users had a higher relative rate (RR) of hip fracture (RR = 1.77, 95% CI 1.15-2.74) and similar rates of clinical vertebral and nonvertebral fractures compared to alendronate users. CONCLUSIONS: The absolute rate of clinical fractures among alendronate and risedronate users was similar both at 1 year and beyond, suggesting comparable effectiveness between agents.

Do physicians within the same practice setting manage osteoporosis patients similarly? Implications for implementation research.

UNLABELLED: Using data from long-term glucocorticoid users and long-term care residents, we evaluated osteoporosis prescribing patterns related to physician behavior and common practice settings. We found no significant clustering effect for common practice setting, suggesting that osteoporosis quality improvement (QI) efforts may be able to ignore this factor in designing QI interventions. INTRODUCTION: Patients' receipt of prescription therapies are significantly influenced by their physician's prescribing patterns. If physicians in the same practice setting influence one another's prescribing, evidence implementation interventions must consider targeting the practice as well as individual physicians to achieve maximal success. METHODS: We examined receipt of osteoporosis treatment (OP Rx) from two prior evidence implementation studies: long-term glucocorticoid (GC) users and nursing home (NH) residents with prior fracture or osteoporosis. Common practice setting was defined as doctors practicing at the same address or in the same nursing home. Alternating logistic regression evaluated the relationship between OP Rx, common practice setting, and individual physician treatment patterns. RESULTS: Among 6,281 GC users in 1,296 practices, the proportion receiving OP Rx in each practice was 6-100%. Among 779 NH residents in 66 nursing homes, the proportion in each NH receiving OP Rx was 0-100%. In both, there was no significant relationship between receipt of OP Rx and common practice setting after accounting for treatment pattern of individual physicians. CONCLUSION: Physicians practicing together were not more alike in prescribing osteoporosis medications than those in different practices. Osteoporosis quality improvement may be able to ignore common practice settings and maximize statistical power by targeting individual physicians.

Industry funding and the reporting quality of large long-term weight loss trials.

BACKGROUND: Quality of reporting (QR) in industry-funded research is a concern of the scientific community. Greater scrutiny of industry-sponsored research reporting has been suggested, although differences in QR by sponsorship type have not been evaluated in weight loss interventions. OBJECTIVE: To evaluate the association of funding source and QR of long-term obesity randomized clinical trials (RCT). METHODS: We analysed papers that reported long-term weight loss trials. Articles were obtained through searches of Medline, HealthStar, and the Cochrane Controlled Trials Register between the years 1966 and 2003. QR scores were determined for each study based upon expanded criteria from the Consolidated Standards for Reporting Trials (CONSORT) checklist for a maximum score of 44 points. Studies were coded by category of industry support (0=no industry support, 1=industry support, 2=in kind contribution from industry and 3=duality of interest reported). Individual CONSORT reporting criteria were tabulated by funding type. An independent samples t-test compared the differences in QR scores by funding source and the Wilcox-Mann-Whitney test and generalised estimating equations (GEE) were used for sensitivity analyses. RESULTS: Of the 63 RCTs evaluated, 67% were industry-supported trials. Industry funding was associated with higher QR score in long-term weight loss trials compared with nonindustry-funded studies (mean QR (s.d.): industry=27.9 (4.1), nonindustry=23.4 (4.1); P<0.0005). The Wilcox-Mann-Whitney test confirmed this result (P<0.0005). Controlling for the year of publication and whether the paper was published before the CONSORT statement was released in the GEE regression analysis, the direction and magnitude of effect were similar and statistically significant (P=0.035). Of the individual criteria that prior research has associated with biases, industry funding was associated with greater reporting of intent-to-treat analysis (P=0.0158), but was not different from nonindustry studies in reporting of treatment allocation and blinding. CONCLUSION: Our findings suggest that the efforts to improve reporting quality be directed to all obesity RCTs, irrespective of funding source.

Cigarette smoking, disease severity and autoantibody expression in African Americans with recent-onset rheumatoid arthritis.

OBJECTIVE: To examine the association of smoking with clinical and serological features in African Americans with recent-onset rheumatoid arthritis (RA) and to explore whether this association is dependent on the presence of the HLA-DRB1 shared epitope (SE). METHODS: In African Americans with recent-onset RA (n = 300), we examined the association of cigarette smoking (current versus past versus never and pack-years of exposure) with anti-cyclic citrullinated peptide antibody, rheumatoid factor (RF) (IgM and IgA), rheumatoid nodules and baseline radiographic erosions using logistic and cumulative logistic regression (adjusting for SE status). We also examined for evidence of interaction between smoking status and SE for all outcomes. RESULTS: Although there was no association with RF-IgA seropositivity, current smokers were approximately twice as likely as never smokers to have higher IgA-RF concentrations (based on tertiles; OR = 1.74; 95% CI 1.05 to 2.88) and nodules (OR = 2.43; 95% CI 1.13 to 5.22). These associations were most pronounced in those with more than 20 pack-years of exposure. There was no association of smoking status or cumulative tobacco exposure with anti-cyclic citrullinated peptide antibody, IgM-RF or radiographic erosions. There was also no evidence of a biological or statistical SE-smoking interaction for any of the outcomes examined. CONCLUSIONS: This is the first study to systematically examine the association of cigarette smoking with RA-related features in African Americans. Cigarette smoking is associated with both subcutaneous nodules and higher serum concentrations of IgA-RF in African Americans with RA, associations that may have important implications for long-term outcomes in this population.

Risk of hip fracture after bisphosphonate discontinuation: implications for a drug holiday.

UNLABELLED: Based upon interest in a bisphosphonate drug holiday, we evaluate the risk for hip fracture after bisphosphonate discontinuation. Among women compliant with bisphosphonates for > or = 2 years, the risk of hip fracture was increased after discontinuation, although with higher compliance and a longer duration of preceding bisphosphonate therapy, this risk was attenuated. INTRODUCTION: Recent data suggest that hip fracture risk was not significantly increased among women receiving 5 years of bisphosphonate therapy who were subsequently randomized to placebo. We studied older women compliant with bisphosphonates > or = 2 years to evaluate the risk of hip fracture after bisphosphonate discontinuation. METHODS: Using administrative databases from a large U.S. healthcare organization, we identified women initiating bisphosphonate therapy compliant (Medication Possession Ratio, MPR > or = 66%) for 2 years. We examined the rate of hip fracture among women who discontinued bisphosphonates versus those who remained on therapy. RESULTS: At 2 years, 9,063 women were eligible for analysis. Hip fracture incidence among women who discontinued bisphosphonates versus those who did not was 8.43 versus 4.67 per 1000 person years (p = 0.016). The adjusted hazard ratio of hip fracture per 90 days following discontinuation was 1.2 (1.1-1.3). For women with higher compliance at 2 years (MPR > or = 80%) or compliant for 3 years, there were no significant differences in risk associated with discontinuation. CONCLUSIONS: The rate of hip fracture was increased among women compliant with bisphosphonate therapy for 2 years who subsequently discontinued, suggesting that discontinuation is not advisable under these conditions. This association was attenuated with higher compliance and a longer duration of previous bisphosphonate therapy.

Assessing effects of behavioral intervention on treatment outcomes among patients initiating HIV care: Rationale and design of iENGAGE intervention trial.

During the initial year of HIV diagnosis, while patients are often overwhelmed adjusting to this life changing diagnosis, they must develop self-care behaviors for attending regular medical care visits and antiretroviral therapy (ART) adherence to achieve and sustain viral suppression (VS). Maintaining "HIV adherence" and integrating it into one's daily life is required to sustain VS over time. The HIV care continuum or "treatment cascade," an epidemiological snapshot of the national epidemic in the United States (US), indicates that a minority of persons living with HIV (PLWH) have achieved VS. Little evidence exists regarding the effects of interventions focusing on PLWH newly initiating outpatient HIV care. An intervention that focuses on both retention in care and ART adherence skills delivered during the pivotal first year of HIV care is lacking. To address this, we developed a theory-based intervention evaluated in the Integrating Engagement and Adherence Goals upon Entry (iENGAGE) study, a National Institute of Allergy and Infectious Diseases (NIAID) funded randomized behavioral intervention trial. Here we present the study objectives, design and rationale, as well as the intervention components, targeting rapid and sustained VS through retention in HIV care and ART adherence during participants' first year of HIV care. The primary outcome of the study is 48-week VS (<200 c/mL). The secondary outcomes are retention in care, including HIV visit adherence and visit constancy, as well as ART adherence.

Prevalence and correlates of coronary calcification in black and white young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Whereas cardiovascular risk factor levels are substantially different in black and white Americans, the relative rates of cardiovascular disease in the 2 groups are not always consistent with these differences. To compare the prevalence of coronary calcification, an indicator of coronary atherosclerosis, in young adult blacks and whites, we performed electron-beam computed tomography of the heart in 443 men and women aged 28 to 40 years recruited from a population-based cohort. The presence of calcium, defined as at least 1 focus of at least 2.05 mm(2) in area and >130 Hounsfield units in density within the coronary arteries, was identified in 16.1% of black men, 11.8% of black women, 17.1% of white men, and 4.6% of white women (P=0.04 for comparison across groups). Coronary calcium was associated with age and male sex, and after adjustment for age, race, and sex, coronary calcium was positively associated with body mass index, weight, systolic blood pressure, total cholesterol, low density lipoprotein cholesterol, triglycerides, and fasting insulin and negatively associated with education (all P<0.05). Independent risk factors included male sex, body mass index, and low density lipoprotein cholesterol. Race was not significantly associated with coronary calcium in men or women, before or after adjustment for risk factors. Coronary calcification is associated with increased levels of cardiovascular risk factors in young adults, and its prevalence is not significantly different in blacks and whites.

A prospective evaluation of the timing of postoperative radiotherapy for preventing heterotopic ossification following traumatic acetabular fractures.

PURPOSE: Preoperative and immediate postoperative irradiation of traumatic acetabular fractures (TAF), although known to reduce heterotopic ossification (HO), can cause significant organizational and logistic difficulties. We sought to determine an acceptable time interval between surgery and radiation without compromising control, as well as to update our large experience and to further validate our treatment philosophy. METHODS AND MATERIALS: Beginning in June 1995, we began a prospective study, irradiating 152 patients on postoperative days 1, 2, or 3. There were also 17 patients delayed further secondary to medical difficulties. RESULTS: All patients treated since June 1995 received 700 cGy/1 fx. Fifty-eight patients received radiation within 24 hours of surgery, 41 within 2 days, 53 within 3 days, 13 within 4 days, and 4 were delayed further. Delaying irradiation for up to 4 days postoperatively caused no statistical increase in HO (p = 0.625). Of 263 patients in our retrospective cohort, HO occurred in 5.3% of patients who received irradiation versus 60% of patients who did not. CONCLUSION: In our prospective study, we noted no perceptible increase in HO with up to a 3-day interval between surgery and radiotherapy. This allows a more structured treatment schedule and allows the patient more time to heal and recover. Updated results from our overall series continue to demonstrate that adjuvant radiation decreases the incidence and severity of HO after TAF.

Predictors of arteriovenous graft patency after radiologic intervention in hemodialysis patients.

Arteriovenous grafts in hemodialysis patients are prone to recurrent stenosis and thrombosis, requiring frequent radiologic and surgical interventions to optimize their long-term patency. Little is known about the factors that determine graft outcome after a radiologic intervention. The present study examined the clinical and radiologic predictors of intervention-free graft survival after elective angioplasty or thrombectomy. A prospective computerized database was used to determine the outcomes subsequent to all graft angioplasties (n = 330) and thrombectomies (n = 326) performed at the University of Alabama at Birmingham between April 1, 1996, and June 30, 1999. Primary graft survival rates after angioplasty and thrombectomy were 86% versus 43% at 1 month, 71% versus 30% at 3 months, 51% versus 19% at 6 months, and 28% versus 8% at 12 months, respectively. The median intervention-free graft survival time was substantially longer after angioplasty than thrombectomy (6.7 versus 0.6 months; P < 0.001). The superior outcome of angioplasty over thrombectomy was observed even for the subset of procedures with no residual stenosis (median survival, 6.9 versus 2.5 months; P < 0.001). The median graft survival was inversely related to the magnitude of residual stenosis for both elective angioplasty and thrombectomy. Median intervention-free graft survival after angioplasty was inversely related to the postangioplasty intragraft to systemic systolic pressure ratio (7.6, 6.9, and 5.6 months for ratios <0.4, 0.4 to 0.6, and >0.6, respectively; P < 0.001). Intervention-free graft survival after angioplasty or thrombectomy was not affected by graft location (forearm versus upper arm), number of stenotic sites, or presence of diabetes. In conclusion, graft survival is substantially longer after elective angioplasty than thrombectomy, even when the radiologic appearance after the procedure suggests complete resolution of the stenotic lesion. Moreover, the risk for requiring a subsequent graft intervention can be predicted from two simple radiologic measurements: grade of stenosis and intragraft to systemic systolic blood pressure ratio. These parameters may help determine the frequency of monitoring for recurrent stenosis in a given graft.

Channeling and adherence with alendronate and risedronate among chronic glucocorticoid users.

INTRODUCTION: Despite the efficacy of bisphosphonates to reduce fractures in high risk populations, bisphosphonate adherence among chronic glucocorticoid users has received limited attention. Moreover, perceived differences in GI tolerability may lead physicians to preferentially prescribe particular bisphosphonates. METHODS: Among chronic glucocorticoid users (>60 days of therapy) enrolled in managed care, we identified individuals initiating therapy with alendronate or risedronate during 2001-2004. Multivariable logistic regression and proportional hazards models were used to examine factors associated with channeling patients to risedronate (versus alendronate) and with discontinuation (>3-month gap without refill). The Medication Possession Ratio (MPR) was calculated as the filled days of medication divided by the interval of time between prescriptions. RESULTS: Of 1,158 glucocorticoid users initiating bisphosphonate therapy, demographic characteristics of alendronate users (n=754) and risedronate users (n=404) were similar for age (mean 53 years) and gender (approximately 80% female). Past history of a GI symptom or event was associated with risedronate receipt (OR=2.24, 95% CI 1.15-4.35). After multivariable adjustment, rates of discontinuation (mean time to discontinuation approximately 18 months) and adherence (mean MPR=73%) were similar between users of the two bisphosphonates. Younger age, greater medical comorbidity, and lack of BMD testing were significantly associated with discontinuation. CONCLUSIONS: Overall persistence rates were suboptimal for bisphosphonate use among chronic glucocorticoids users and did not differ significantly by drug. Newer strategies to promote long-term adherence are needed to improve osteoporosis therapeutic effectiveness.

Putative contributors to the secular increase in obesity: exploring the roads less traveled.

OBJECTIVE: To investigate plausible contributors to the obesity epidemic beyond the two most commonly suggested factors, reduced physical activity and food marketing practices. DESIGN: A narrative review of data and published materials that provide evidence of the role of additional putative factors in contributing to the increasing prevalence of obesity. DATA: Information was drawn from ecological and epidemiological studies of humans, animal studies and studies addressing physiological mechanisms, when available. RESULTS: For at least 10 putative additional explanations for the increased prevalence of obesity over the recent decades, we found supportive (although not conclusive) evidence that in many cases is as compelling as the evidence for more commonly discussed putative explanations. CONCLUSION: Undue attention has been devoted to reduced physical activity and food marketing practices as postulated causes for increases in the prevalence of obesity, leading to neglect of other plausible mechanisms and well-intentioned, but potentially ill-founded proposals for reducing obesity rates.

Bacteremia associated with tunneled dialysis catheters: comparison of two treatment strategies.

BACKGROUND: Tunneled dialysis catheters are often used for temporary vascular access in hemodialysis patients, but are complicated by frequent systemic infections. The treatment of bacteremia associated with infected tunneled catheters requires both antibiotic therapy and catheter replacement. We compared the outcomes of two treatment strategies for catheter-associated bacteremia: exchange of the existing catheter with a new one over a guidewire versus catheter removal with delayed replacement. METHODS: We retrospectively analyzed the outcomes of all cases of tunneled dialysis catheter-associated bacteremia during a two-year period. The infection-free survival time of the subsequent catheter was evaluated in two groups of patients: group A (31 catheters), exchange of the existing infected catheter with a new catheter over a guidewire, and group B (38 catheters), removal of the infected catheter followed by delayed catheter replacement 3 to 10 days later. Patients in both groups received three weeks of systemic antibiotic therapy. Cox proportional hazard models were used to evaluate the factors predictive of infection-free survival time of the replacement catheter. RESULTS: On univariate proportional hazard regression analysis, the infection-free survival time of the replacement catheter was similar for groups A and B (P = 0.72), whereas the hazard of infection was significantly greater for patients with hypoalbuminemia (serum albumin < 3.5 g/dL), as compared with patients with a normal serum albumin (hazard ratio 2.81, 95% CI, 1. 21, 6.53, P = 0.016). The infection-free survival time was not affected by patient age, sex, diabetic status, or type of organism (gram-positive coccus vs. gram-negative rod). CONCLUSIONS: The infection-free survival time associated with the subsequent catheter is similar for the two treatment strategies. However, exchanging the catheter for a new one over a guidewire minimizes the number of separate procedures required by the patient. Hypoalbuminemia is the major risk factor for recurrent bacteremia in the replacement catheter.

Patient-perceived barriers to antiretroviral adherence: associations with race.

New antiretroviral (ARV) regimens require strict adherence if optimal suppression of HIV is to be maintained. This study is a theory-based examination of racial differences in patient-perceived barriers and reported ARV adherence. Participants (N=149) completed the Patient Medication Adherence Questionnaire (PMAQ), measuring adherence and perceived barriers to adherence. Adherence was defined as a self-report of 100% adherence in the past four weeks. Odds ratios were calculated to determine the relation of reported barriers to adherence for race and gender groups, and for the sample overall. For every ten-point increase in barrier score, there was an 86% increased risk of being non-adherent (OR=1.86; 95% CI: 1.19, 2.91). Adherence was not different between racial and gender groups, nor was total barrier score. However, individual barriers were differentially endorsed across groups. Rather than relying on demographic predictors, which may be only an indirect marker of adherence, evaluations of adherence should examine the psychological and social barriers to positive adherence outcomes in individual patients. Our findings support the use of theory-based behavioural interventions that address perceived barriers to adherence and other health promotion activities.

Health-related quality of life and virologic outcomes in an HIV clinic.

OBJECTIVE: The purpose of this study was to describe the relationship between viral load and health-related quality of life (HRQOL) in a cohort of persons with human immunodeficiency virus (HIV) infection. DESIGN: We evaluated HRQOL measurements in a clinical cohort of HIV-positive patients recruited from a university-associated HIV primary care clinic. HRQOL instruments included the medical outcomes survey-short form-36(MOS-SF-36) from which mental and physical component summary scores (MCS and PCS) and subscale scores were calculated. RESULTS: Significant negative associations were found between viral load and SF-36 PCS, physical functioning (PF), role-physical (RP), bodily pain (BP), general health (GH), role-emotional (RE), and vitality (VT). Similar negative associations were found between CD4 cell count and SF-36 summary and subscale scores, with the notable exception of bodily pain. Multivariate analyses controlling for the effects of CD4 cell count and other clinical variables indicated viral load as an independent predictor of SF-36 PCS, RP, BP and VT scores. CONCLUSIONS: The relationship between viral load, a measure of HIV disease activity, and several dimensions of the SF-36, a patient-focused measure of HRQOL, appears to be strong and independent of CD4 cell count. These findings suggest that having a lower viral load positively impacts the quality of life of HIV-positive patients.

Phenotypic drug susceptibility testing predicts long-term virologic suppression better than treatment history in patients with human immunodeficiency virus infection.

To assess the value of phenotypic drug susceptibility testing as a predictor of antiretroviral treatment response in human immunodeficiency virus (HIV)-infected people, drug susceptibility testing was performed retrospectively on plasma samples collected at baseline in a cohort of 86 antiretroviral-experienced, HIV-infected people experiencing treatment failure and initiating a new antiretroviral treatment regimen. Two separate criteria for reduced drug susceptibility were evaluated. In multivariate analyses, phenotypic susceptibility was an independent predictor of time to treatment failure (adjusted hazards ratio [HR], 0.70; 95% confidence interval [CI], 0.55-0.90; and adjusted HR, 0.76; 95% CI, 0.61-0.95, with reduced drug susceptibility cutoffs defined as 4.0-fold and 2.5-fold higher than reference virus IC(50) values, respectively). Previous protease inhibitor experience was also a significant independent predictor. Notably, drug susceptibility predicted on the basis of treatment history alone was not predictive of time to treatment failure. In this cohort, phenotypic testing results enhanced the ability to predict sustained long-term suppression of virus load.