Jean Marie Arduino

Phase IIB Multicenter Trial of Vorinostat in Patients With Persistent, Progressive, or Treatment Refractory Cutaneous T-Cell Lymphoma

PURPOSE To evaluate the activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in persistent, progressive, or recurrent mycosis fungoides or Sézary syndrome (MF/SS) cutaneous t-cell lymphoma (CTCL) subtypes. PATIENTS AND METHODS Patients with stage IB-IVA MF/SS were treated with 400 mg of oral vorinostat daily until disease progression or intolerable toxicity in this open-label phase IIb trial (NCT00091559). Patients must have received at least two prior systemic therapies at least one of which included bexarotene unless intolerable. The primary end point was the objective response rate (ORR) measured by the modified severity weighted assessment tool and secondary end points were time to response (TTR), time to progression (TTP), duration of response (DOR), and pruritus relief ( > or = 3-point improvement on a 10-point visual analog scale). Safety and tolerability were also evaluated. RESULTS Seventy-four patients were enrolled, including 61 with at least stage IIB disease. The ORR was 29.7% overall; 29.5% in stage IIB or higher patients. Median TTR in stage IIB or higher patients was 56 days. Median DOR was not reached but estimated to be >or = 185 days (34+ to 441+). Median TTP was 4.9 months overall, and 9.8 months for stage IIB or higher responders. Overall, 32% of patients had pruritus relief. The most common drug-related adverse experiences (AE) were diarrhea (49%), fatigue (46%), nausea (43%), and anorexia (26%); most were grade 2 or lower but those grade 3 or higher included fatigue (5%), pulmonary embolism (5%), thrombocytopenia (5%), and nausea (4%). Eleven patients required dose modification and nine discontinued due to AE. CONCLUSION Oral vorinostat was effective in treatment refractory MF/SS with an acceptable safety profile.

Combination and Monotherapy with Zidovudine and Zalcitabine in Patients with Advanced HIV Disease

Several nucleoside analogs, including zidovudine, zalcitabine, and didanosine, inhibit the replication of human immunodeficiency virus type 1 (HIV) in vitro and improve CD4 cell counts and suppress HIV p24 antigenemia in patients with HIV disease [1-8]. Zidovudine therapy delays HIV disease progression [1-3] and improves survival in patients with advanced HIV disease [1, 9]. Didanosine therapy delays HIV disease progression in patients with advanced HIV disease who had previously received zidovudine, suggesting that switching antiretroviral therapy may be an important strategy in treating HIV disease [10, 11]. The combination of the nucleoside analogs zidovudine and zalcitabine has additive to synergistic inhibitory activity against HIV in vitro, and viral isolates resistant to zidovudine remain susceptible to zalcitabine in vitro [12-14]. Combination therapy with zidovudine and zalcitabine causes a greater and more sustained increase in CD4 cell counts and suppression of HIV p24 antigenemia than does either drug used alone in patients with advanced HIV disease who have not previously received therapy with zidovudine or zalcitabine [15]. The clinical correlation of these findings is unknown. These observations prompted us to try to determine whether zalcitabine monotherapy or combination therapy with zidovudine and zalcitabine would improve clinical outcome in patients with advanced HIV disease who had previously received zidovudine. Methods Study Sample The study sample consisted of patients with symptomatic HIV disease who had a CD4 cell count of 300 cells/mm3 or less or patients with asymptomatic HIV disease who had a CD4 cell count of 200 cells/mm3 or less. Participants had previously received and tolerated at least 6 months of zidovudine treatment. The eligibility criteria also included a hemoglobin concentration of 92 g/L or more, a neutrophil count of 1.0 109/L or more, a platelet count of 75 109/L or more, serum alanine aminotransferase and aspartate aminotransferase levels no higher than five times the upper range of normal, Karnofsky performance status of 60 or more, and positive results of serum tests for HIV antibody. We excluded patients with a history of intolerance to zidovudine at a dose of 600 mg/d or less, previous zalcitabine therapy, mild or more severe peripheral neuropathy, or Kaposi sarcoma requiring systemic therapy; women of childbearing age who were pregnant or breast-feeding were also excluded. We accepted patients receiving chemoprophylaxis for Pneumocystis carinii pneumonia, candidiasis and herpes simplex virus infection, and those receiving erythropoietin and granulocyte colony-stimulating factor. We excluded persons taking other antiretroviral drugs, biological response modifiers, cytotoxic chemotherapy, drugs other than isoniazid that cause peripheral neuropathy, or investigational drugs. We recruited patients from 35 AIDS Clinical Trials Units and 16 National Hemophilia Foundation sites between December 1990 and August 1991. The study was approved by the institutional review board at each institution, and patients gave written informed consent. Study Design and Treatment Regimen The study was a multicenter, randomized, double-blind clinical trial that compared the safety and efficacy of zidovudine, zalcitabine, and the combination of zidovudine and zalcitabine. Randomization was weighted at 2:2:3, favoring the combination group. Patients were stratified by HIV disease status (symptomatic or asymptomatic), by duration of previous zidovudine therapy ( 1 year or >1 year), and by P. carinii pneumonia chemoprophylaxis regimen (systemic therapy, nonsystemic therapy, both, or neither). Zalcitabine (Hivid; Hoffmann-La Roche, Inc., Nutley, New Jersey) was given in two 0.375-mg tablets every 8 hours. Zidovudine (Retrovir; Burroughs Wellcome Co., Research Triangle Park, North Carolina) was given in two 100-mg capsules every 8 hours. The primary end point for the study was time to an acquired immunodeficiency syndrome (AIDS)-defining event or death, whichever occurred first. All end points were reviewed in a blinded manner by the study chairpersons. Patients continued to receive blinded study medication after the development of a primary study end point. The protocol was modified on 20 March 1992 to allow patients who had reached a primary study end point the option to cross over to open-label combination therapy. Secondary end points included survival, CD4 cell count changes, and decreased HIV p24 antigenemia. Management of Toxic Effects All study medications were interrupted, regardless of whether the toxicity was believed to be associated with either zidovudine or zalcitabine, in patients in whom a moderate or severe peripheral neuropathy or another severe or worse toxic effect developed. Once the toxicity grade returned to pretreatment values or a lower grade, study medications were restarted at one half the initial dose. Study medications were permanently discontinued in patients who had a recurrent moderate or severe peripheral neuropathy or another severe or worse toxic effect within a 30-day period. Patients who had recurrent toxic effects after more than 30 days, except for those with peripheral neuropathy, continued to receive study medications once the toxicity grade returned to a lower grade or to pretreatment values. Patient Evaluation Patients were evaluated at weeks 0, 4, 8, and 12, and every 8 weeks thereafter. The CD4 cell counts were measured within 60 days before study enrollment, at weeks 0, 2, and 4, every 4 weeks until week 52, and every 8 weeks thereafter. Blood for HIV p24 antigen determinations was collected at weeks 0, 2, 4, 8, 12, 24, 36, 48, and 60 and every 16 weeks thereafter. Determinations of HIV p24 antigen were done simultaneously on stored serum aliquots by an enzyme-linked immunosorbent assay (Abbott Laboratories, North Chicago, Illinois). A positive assay result was one that detected an antigen level of 25 pg/mL or more. Laboratories measuring CD4 cell counts and serum p24 antigen levels had to meet the performance-monitored standards of the AIDS Clinical Trials Group. Statistical Analysis We assessed differences in proportions using the Fisher exact test. Time-to-event distributions were estimated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional-hazards model [16], with stratification for HIV disease status, duration of previous zidovudine therapy, and P. carinii pneumonia prophylaxis [17]. Analyses were based on an intention-to-treat approach [18]. We censored data on toxic effects 30 days after crossover or discontinuation of study medications. We used the hazard ratios, expressed as relative risk, and 95% two-sided confidence intervals. All P values were two-sided and were not adjusted for multiple comparisons. A test of trend evaluating the interaction between pretreatment CD4 cell counts and treatment effect on the primary end point was based on Cox models and included the study stratification factors as covariates and pretreatment CD4 cell counts as a continuous variable. For completeness, two additional tests of trend used stratified Cox models in which pretreatment CD4 cell counts were modeled as a categorical variable. In one analysis, pretreatment CD4 cell count was modeled as a binary variable, above and below the median CD4 cell count (119 cells/mm3). In a second analysis, pretreatment CD4 cell count was modeled as a discrete variable with three levels ( 1,0, 1) corresponding to the three planned CD4 cell subgroups. Changes in CD4 cell counts and serum HIV p24 antigen levels were expressed as the percentage change from pretreatment values for each patient. Trends in CD4 cell counts over time were evaluated by estimating the slopes from pretreatment to the time of aggregate peak (week 2) and separately estimating the slopes for subsequent time points. We compared the slopes using nonparametric tests [19]. We also analyzed treatment differences for patients with pretreatment CD4 cell counts of less than 50 cells/mm3, 50 to 150 cells/mm3, and 150 cells/mm3 or greater. The three CD4 cell count subgroups were specified by the study chairpersons in June 1992, which was before any interim review of the primary end-point data and unblinding to the study results by the study chairpersons (March 1993). The three CD4 cell count subgroups were chosen based on documented associations between CD4 cell counts and survival and development of zidovudine resistance. Results Study Sample We enrolled 1001 patients in the study between December 1990 and August 1991. No patients were ineligible for the study, except for those granted an exemption by the study chairpersons. We excluded 10 patients from the analyses: 7 who never received study medications and were not followed and 3 who were lost to follow-up within the first 2 weeks of treatment. The patients included 888 (90%) men and 103 (10%) women; their median age was 37 years. Overall, 809 patients (82%) were white, 152 (15%) were black, and 3% were neither; 117 (12%) were Hispanic and 884 (88%) were non-Hispanic. Eight hundred nineteen (83%) patients had symptomatic HIV disease. The median duration of previous zidovudine therapy was 18 months. The median pretreatment CD4 cell count was 119 cells/mm3, and 254 of 925 patients had detectable levels of serum HIV p24 antigen ( 25 pg/mL) before treatment. The treatment groups were well balanced with regard to pretreatment characteristics (Table 1). Table 1. Patient Characteristics by Treatment Group* We randomly assigned 283 patients to the zidovudine group, 285 to the zalcitabine group, and 423 to the combination group. Three hundred eighty-six patients had 150 or more CD4 cells/mm3, 336 had 50 to 150 CD4 cells/mm3, and 269 had fewer than 50 CD4 cells/mm3. Overall, the treatment groups within each CD4 cell subgroup were well balanced with regard to pretreatment characteristics (data not shown). The median duration of foll

Distribution of hepatitis C virus genotypes in a diverse US integrated health care population

Hepatitis C virus (HCV) genotypes influence response to therapy, and recently approved direct‐acting antivirals are genotype‐specific. Genotype distribution information can help to guide antiviral development and elucidate infection patterns. HCV genotype distributions were studied in a diverse cross‐section of patients in the Northern California Kaiser Permanente health plan. Associations between genotype and race/ethnicity, age, and sex were assessed with multivariate logistic regression models. The 10,256 patients studied were median age 56 years, 62% male, 55% White non‐Hispanic. Overall, 70% were genotype 1, 16% genotype 2, 12% genotype 3, 1% genotype 4, <1% genotype 5, and 1% genotype 6. Blacks (OR 4.5 [3.8–5.5]) and Asians (OR 1.2 [1.0–1.4]) were more likely to have genotype 1 than 2/3 versus non‐Hispanic Whites. Women less likely had genotype 1 versus 2/3 than did men (OR 0.86 [0.78–0.94]). Versus non‐Hispanic Whites, Asians (OR 0.38 [0.31–0.46]) and Blacks (OR 0.73 [0.63–0.84]) were less likely genotype1a than 1b; Hispanics (OR 1.3 [1.1–1.5]) and Native Americans (OR 1.9 [1.2–2.8]) more likely had genotype 1a than 1b. Patients age ≥65 years less likely had genotype 1a than 1b versus those age 45–64 (OR 0.34 [0.29–0.41]). The predominance of genotype 1 among all groups studied reinforces the need for new therapies targeting this genotype. Racial/ethnic variations in HCV genotype and subtype distribution must be considered in formulating new agents and novel strategies to successfully treat the diversity of hepatitis C patients. J. Med. Virol. 84:1744–1750, 2012.

Epidemiology and outcome of major postoperative infections following cardiac surgery: Risk factors and impact of pathogen type

BACKGROUND Major postoperative infections (MPIs) are poorly understood complications of cardiac surgery. We examined the epidemiology, microbiology, and outcome of MPIs occurring after cardiac surgery. METHODS The study cohort was drawn from the Society of Thoracic Surgeon National Cardiac Database and comprised adults who underwent cardiac surgery at 5 tertiary hospitals between 2000 and 2004. We studied the incidence, microbiology, and risk factors of MPI (bloodstream or chest wound infections within 30 days after surgery), as well as 30-day mortality. We used multivariate regression analyses to evaluate the risk of MPI and mortality. RESULTS MPI was identified in 341 of 10,522 patients (3.2%). Staphylococci were found in 52.5% of these patients, gram-negative bacilli (GNB) in 24.3%, and other pathogens in 23.2%. High body mass index, previous coronary bypass surgery, emergency surgery, renal impairment, immunosuppression, cardiac failure, and peripheral/cerebrovascular disease were associated with the development of MPI. Median postoperative duration of hospitalization (15 days vs 6 days) and mortality (8.5% vs 2.2%) were higher in patients with MPIs. Compared with uninfected individuals, odds of mortality were higher in patients with S aureus MPIs (adjusted odds ratio, 3.7) and GNB MPIs (adjusted odds ratio, 3.0). CONCLUSIONS Staphylococci accounted for the majority of MPIs after cardiac surgery. Mortality was higher in patients with Staphylococcus aureus- and GNB-related MPIs than in patients with MPIs caused by other pathogens and uninfected patients. Preventive strategies should target likely pathogens and high-risk patients undergoing cardiac surgery.

Incidence of and Preoperative Risk Factors for Staphylococcus aureus Bacteremia and Chest Wound Infection After Cardiac Surgery

OBJECTIVE Staphylococcus aureus infections after cardiac surgery result in significant morbidity and mortality. Identifying patients at elevated risk for these infections preoperatively could facilitate efforts to reduce infection rates. The objectives of this study were to estimate the incidence of postoperative S. aureus infections in cardiac surgery patients, to identify preoperative risk factors for these infections, and to establish a patient risk profile by means of data available to clinicians prior to surgery. DESIGN Cohort study. SETTING Eight medical centers that participate in the Society of Thoracic Surgeons National Cardiac Database. PATIENTS Patients who were undergoing elective cardiac surgery during the period January 1, 2000 through December 31, 2004. METHODS Clinical and microbiological data from 16,386 patients were combined. Multivariable stepwise logistic regression analysis was performed to predict S. aureus infection, which was defined by culture results. RESULTS Of the 16,386 patients, 205 (1.3%) developed S. aureus bloodstream or chest wound infection within 90 days after surgery. On multivariable analysis, bootstrap-validated preoperative risk factors for S. aureus bloodstream or chest wound infection included a body mass index greater than 40 (adjusted odds ratio [aOR], 1.9 [95% confidence interval {CI}, 1.1-3.2]), chronic renal failure (aOR, 1.8 [95% CI, 1.1-2.9]), and chronic lung disease (aOR, 1.4 [95% CI, 1.0-2.0]). Only 8 patients had all 3 risk factors. CONCLUSIONS Although preoperative risk factors can be easily identified, the majority of patients who developed S. aureus infections after cardiac surgery did not have any risk factors. Preventive measures should not be restricted to a select group of cardiac surgery patients and should rather address the entire patient population.

Naturally occurring IgG antibody levels to the Staphylococcus aureus protein IsdB in humans

Staphylococcus aureus is a well-recognized, clinically important cause of nosocomial infections, and as such, a vaccine to prevent S. aureus infections would be an important achievement. A Phase IIB/III study of V710, a vaccine containing iron-regulated surface determinant B (IsdB), demonstrated significant sero-conversion rates in cardiovascular surgery patients following a single pre-surgery immunization. However, the vaccine was not efficacious in preventing bacteremia or deep sternal wound infection post-surgery, thus raising the possibility that IsdB might not be available for immune recognition during infection. The purpose of the work described herein was to evaluate and quantify the naturally occurring anti-IsdB levels at baseline and over time during infection, to understand whether IsdB is expressed during a S. aureus infection in hospitalized non-vaccinated patients. We evaluated baseline and follow-up titers in 3 populations: (1) healthy subjects, (2) hospitalized patients with non-S. aureus infections, and (3) hospitalized patients with S. aureus infections. Baseline anti-IsdB levels generally overlapped between the 3 groups, but were highly variable within each group. In healthy subjects, baseline and follow-up levels were highly correlated (Spearmans rho = 0.93), and the geometric mean fold-rise (GMFR) in anti-IsdB levels between study entry and last value was 0.9-fold (95% confidence interval (CI): 0.8 to 1.0 ; p = 0.09), showing no trend over time. The convalescent GMFR in anti-IsdB levels from baseline was 1.7-fold (95% CI: 1.3 to 2.2, p = 0.0008) during S. aureus infection, significantly different from the 1.0-fold GMFR (95% CI: 0.9–1.2, p = 0.60) in non-S. aureus infection, p = 0.005. Additionally, S. aureus isolates (51) obtained from the hospitalized patient group expressed the IsdB protein in vitro. Collectively, these data suggest that IsdB expression levels rise substantially following infection with S. aureus, but not with other pathogens, and IsdB is likely well-conserved across S. aureus strains.

Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4–5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial

BACKGROUND In the C-SURFER study, therapy with the all-oral elbasvir plus grazoprevir regimen for 12 weeks in patients with chronic hepatitis C virus (HCV) infection and stage 4-5 chronic kidney disease resulted in a high rate of virological cure compared with placebo. Here, we report sustained virological response (SVR), safety data, health-related quality-of-life (HRQOL), and virological resistance analyses in patients in C-SURFER who received immediate antiviral therapy or who received placebo before therapy. METHODS In this phase 3, multicentre, randomised, placebo-controlled study, we randomly assigned adults with HCV genotype 1 infection and stage 4-5 chronic kidney disease enrolled at 68 centres worldwide to either elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks (immediate treatment group) or placebo for 12 weeks followed by elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks beginning at week 16 (deferred treatment group). The primary safety and efficacy endpoints for the immediate treatment group and placebo phase of the deferred treatment group have been reported previously. Here, we report safety and efficacy data for the treatment phase of the deferred treatment group, as well as HRQOL assessed using the 36-Item Short Form Health Survey for all groups, and baseline and treatment-emergent resistance-associated substitutions (RASs). SVR at 12 weeks (SVR12) was assessed in the modified full analysis set (FAS), defined as all patients excluding those who did not receive at least one dose of study drug, who died, or who discontinued the study before the end of treatment for reasons determined to be unrelated to HCV treatment. This trial is registered with ClinicalTrials.gov, Number NCT02092350. FINDINGS Between March 30 and Nov 28, 2014, 235 patients were enrolled and received at least one dose of study drug. The modified FAS included 116 patients assigned to immediate treatment and 99 assigned to deferred treatment. 115 (99·1%; 95% CI 95·3-100·0) of 116 assigned to immediate treatment achieved SVR12 compared with 97 (98·0%; 92·9-99·7) of 99 assigned to deferred treatment. In patients with genotype 1a infections, SVR12 was achieved by 11 (84·6%) of 13 patients with detectable baseline NS5A RASs and in 98 (100%) of 98 without. HRQOL did not differ at week 12 between immediate treatment and the placebo phase of deferred treatment. Safety was generally similar between patients receiving immediate treatment and those receiving placebo in the deferred treatment group. One serious adverse event during deferred treatment (interstitial nephritis) and one during the placebo phase of deferred treatment (raised lipase concentration) were deemed related to study drug. Four patients died, one who received immediate treatment (cardiac arrest) and three who received deferred treatment (aortic aneurysm, pneumonia, and unknown cause); all four deaths were considered unrelated to study drugs. Of the three deaths in the deferred treatment group, one occurred during placebo treatment and two occurred before starting active treatment. There were no notable differences in aminotransferase elevations in the deferred treatment group compared with the immediate treatment group, and no patients in the deferred treatment group had total bilirubin elevations. INTERPRETATION These data add to the growing body of clinical evidence for the fixed-dose combination regimen of elbasvir plus grazoprevir for 12 weeks and support use of this therapy in patients with HCV genotype 1 infection and stage 4-5 chronic kidney disease. FUNDING Merck Sharp & Dohme.

Variation in the type and frequency of postoperative invasive Staphylococcus aureus infections according to type of surgical procedure.

OBJECTIVE To determine the epidemiological characteristics of postoperative invasive Staphylococcus aureus infection following 4 types of major surgical procedures.design. Retrospective cohort study. SETTING Eleven hospitals (9 community hospitals and 2 tertiary care hospitals) in North Carolina and Virginia. PATIENTS Adults undergoing orthopedic, neurosurgical, cardiothoracic, and plastic surgical procedures. METHODS We used previously validated, prospectively collected surgical surveillance data for surgical site infection and microbiological data for bloodstream infection. The study period was 2003 through 2006. We defined invasive S. aureus infection as either nonsuperficial incisional surgical site infection or bloodstream infection. Nonparametric bootstrapping was used to generate 95% confidence intervals (CIs). P values were generated using the Pearson chi2 test, Student t test, or Wilcoxon rank-sum test, as appropriate. RESULTS In total, 81,267 patients underwent 96,455 procedures during the study period. The overall incidence of invasive S. aureus infection was 0.47 infections per 100 procedures (95% CI, 0.43-0.52); 227 (51%) of 446 infections were due to methicillin-resistant S.aureus. Invasive S. aureus infection was more common after cardiothoracic procedures (incidence, 0.79 infections per 100 procedures [95%CI, 0.62-0.97]) than after orthopedic procedures (0.37 infections per 100 procedures [95% CI, 0.32-0.42]), neurosurgical procedures (0.62 infections per 100 procedures [95% CI, 0.53-0.72]), or plastic surgical procedures (0.32 infections per 100 procedures [95% CI, 0.17-0.47]) (P < .001). Similarly, S. aureus bloodstream infection was most common after cardiothoracic procedures (incidence, 0.57 infections per 100 procedures [95% CI, 0.43-0.72]; P < .001, compared with other procedure types), comprising almost three-quarters of the invasive S. aureus infections after these procedures. The highest rate of surgical site infection was observed after neurosurgical procedures (incidence, 0.50 infections per 100 procedures [95% CI, 0.42-0.59]; P < .001, compared with other procedure types), comprising 80% of invasive S.aureus infections after these procedures. CONCLUSION The frequency and type of postoperative invasive S. aureus infection varied significantly across procedure types. The highest risk procedures, such as cardiothoracic procedures, should be targeted for ongoing preventative interventions.

Do HIV type 1 RNA levels provide additional prognostic value to CD4+ T lymphocyte counts in patients with advanced HIV type 1 infection?

Our objective was to assess whether HIV-1 RNA levels provide additional prognostic information beyond CD4(+) T lymphocyte counts in the prediction of subsequent HIV-1 disease progression among patients with advanced HIV-1 disease. In a nested case-control study conducted in patients with baseline CD4(+) T lymphocyte counts < 300 cells/mm(3) and receiving nucleoside reverse transcriptase inhibitors, 102 patients who progressed to an AIDS-defining event or death were matched within 10 CD4(+) T lymphocyte cells/mm(3) to patients who did not progress. The relationship between plasma HIV-1 RNA levels and HIV-1 disease progression was studied using conditional logistic regression analysis, which adjusts for the matching by baseline CD4(+) T lymphocytes. We observed a 0.10 log(10) copies/ml difference in baseline HIV-1 RNA levels between cases and their matched controls (p = 0.027). The relative risk for HIV-1 disease progression increased with increasing baseline HIV-1 RNA levels (odds ratio [OR] for a 3-fold higher HIV-1 RNA level, 1.42; 95% confidence interval [CI], 1.08--1.86), and remained important when also controlling for clinical status at baseline and CD4(+) T lymphocytes at 2 months (p = 0.038). Higher baseline HIV-1 RNA levels were associated with HIV-1 disease progression among patients with a baseline CD4(+) T lymphocyte count of 100 cells/mm(3) or greater (OR, 1.80; 95% CI, 1.15--2.81), but not among patients with a baseline CD4(+) T lymphocyte count < 100 cells/mm(3) (OR, 1.09; 95% CI, 0.73--1.63). We concluded that HIV-1 RNA levels predict subsequent HIV-1 disease progression independent of CD4(+) T lymphocyte counts. The magnitude and importance of the prognostic information contained in the HIV-1 RNA levels appear to depend on the CD4(+) T lymphocyte counts.

Impact of Renal Disease on Patients with Hepatitis C: A Retrospective Analysis of Disease Burden, Clinical Outcomes, and Health Care Utilization and Cost

Background/Aims: Few studies explore the magnitude of the disease burden and health care utilization imposed by renal disease among patients with hepatitis C virus (HCV). We aimed to describe the characteristics, outcomes, and health care utilization and costs of patients with HCV with and without renal impairment. Methods: This retrospective analysis used 2 administrative claims databases: the US commercially insured population in Truven Health MarketScan® data (aged 20-64 years), and the US Medicare fee-for-service population in the Medicare 20% sample (aged ≥65 years). Baseline characteristics and comorbid conditions were identified from claims during 2011; patients were followed for up to 1 year (beginning January 1, 2012) to identify health outcomes of interest and health care utilization and costs. Results: In the MarketScan and Medicare databases, 35,965 and 10,608 patients with HCV were identified, 8.5 and 26.5% with evidence of renal disease (chronic kidney disease [CKD] or end-stage renal disease [ESRD]). Most comorbid conditions and unadjusted outcome rates increased across groups from patients with no evidence of renal disease to non-ESRD CKD to ESRD. Health care utilization followed a similar pattern, as did the costs. Conclusions: Our findings suggest that HCV patients with concurrent renal disease have significantly more comorbidity, a higher likelihood of negative health outcomes, and higher health care utilization and costs.