Impact of sustained virologic response on risk of type 2 diabetes among hepatitis C patients in the United States.

Data regarding the impact of hepatitis C (HCV) therapy on incidence of type 2 diabetes mellitus are limited. We used the data from the longitudinal Chronic Hepatitis Cohort Study-drawn from four large US health systems-to investigate how response to HCV treatment impacts the risk of subsequent diabetes. Among HCV patients without a history of type 2 diabetes mellitus or hepatitis B, we investigated the incidence of type 2 diabetes from 12 weeks post-HCV treatment through December 2015. Cox proportional hazards models were used to test the effect of treatment status (sustained virologic response [SVR] or treatment failure) and baseline risk factors on the development of diabetes, considering any possible risk factor-by-SVR interactions, and death as a competing risk. Among 5127 patients with an average follow-up of 3.7 years, diabetes incidence was significantly lower among patients who achieved SVR (231/3748; 6.2%) than among patients with treatment failure (299/1379; 21.7%; adjusted hazard ratio [aHR] = 0.79; 95% CI: 0.65-0.96). Risk of diabetes was higher among African American and Asian American patients than White patients (aHR = 1.82 and 1.75, respectively; P < .05), and among Hispanic patients than non-Hispanics (aHR = 1.86). Patients with BMI ≥ 30 and 25-30 (demonstrated higher risk of diabetes aHR = 3.62 and 1.72, respectively; P < .05) than those with BMI < 25; patients with cirrhosis at baseline had higher risk than those without cirrhosis (aHR = 1.47). Among a large US cohort of patients treated for HCV, patients who achieved SVR demonstrated a substantially lower risk for the development of type 2 diabetes mellitus than patients with treatment failure.

APRI and FIB-4 are good predictors of the stage of liver fibrosis in chronic hepatitis B: the Chronic Hepatitis Cohort Study (CHeCS).

We aim to determine the predictive ability of APRI, FIB-4 and AST/ALT ratio for staging of liver fibrosis and to differentiate significant fibrosis (F2-F4) from none to minimal fibrosis (F0-F1) in chronic hepatitis B (CHB). Liver biopsy results were mapped to an F0-4 equivalent fibrosis stage. Mean APRI and FIB-4 scores were significantly higher for each successive fibrosis level from F1 to F4 (P < 0.05). Based on optimized cut-offs, the AUROCs in distinguishing F2-F4 from F0 to F1 were 0.81 (0.76-0.87) for APRI, 0.81 (0.75-0.86) for FIB-4 and 0.56 (0.49-0.64) for AST/ALT ratio. APRI and FIB-4 distinguished F2-F4 from F0 to F1 with good sensitivity and specificity and can be useful for treatment decisions and monitoring progression of fibrosis.

Prevalence of chronic hepatitis B virus infection among patients in the HIV Outpatient Study, 1996-2007.

Coinfection with hepatitis B virus (HBV) is an important and preventable cause of chronic liver disease among HIV-infected patients. We calculated the prevalence of chronic HBV infection annually from 1996 to 2007 by age, gender, race/ethnicity, and HIV transmission risk in a multisite observational cohort study of HIV-infected patients. Prevalence of chronic HBV infection was calculated as the number of patients with a positive HBsAg or detectable HBV DNA divided by the number of patients tested using either one of these assays. Among 4467 (59%) patients tested for chronic HBV infection from a total of 7618 patients active during 1996-2007, median age was 38.5 years, 77% were men, 49% were white, 35% were black, 13% were Hispanic, and 53% were men who had sex with men (MSM). Overall, 8.4% tested positive for HBsAg or detectable HBV DNA. Annual chronic HBV prevalence during 1996-2007 ranged from 7.8% to 8.6% without a statistically significant trend. Overall, prevalence was greater among men compared with women; among whites, blacks, and persons of other race compared with Hispanics; among MSM compared with injection drug users and high-risk heterosexuals; and among patients aged 35-44 years compared with younger or older patients. MSM constituted the greatest fraction (63-72%) of all HBV-infected patients in the HIV Outpatient Study (HOPS) over the period. Of eligible patients, 5.8%, 23.4%, and 31.6% had received at least one dose of HBV vaccine by years 1996, 2002, and 2007, respectively. Despite the availability of an effective HBV vaccine for over two decades and long-standing recommendations for immunization of persons (with or without HIV infection) at risk for HBV, the prevalence of chronic HBV infection in this study has been largely unchanged over the past decade among patients in all groups, and overall was 20 times as high as the national population prevalence.

Distribution of disease phase, treatment prescription and severe liver disease among 1598 patients with chronic hepatitis B in the Chronic Hepatitis Cohort Study, 2006-2013.

BACKGROUND: Limited information exists regarding the distribution of disease phases, treatment prescription and severe liver disease among patients with chronic hepatitis B (CHB) in US general healthcare settings. AIM: To determine the distribution of disease phases, treatment prescription and severe liver disease among patients with CHB in general US healthcare settings. METHODS: We analysed demographic and clinical data collected during 2006-2013 from patients with confirmed CHB in the Chronic Hepatitis Cohort Study, an observational cohort study involving patients from healthcare organisations in Michigan, Pennsylvania, Oregon and Hawaii. CHB phases were classified according to American Association for the Study of Liver Disease guidelines. RESULTS: Of 1598 CHB patients with ≥12 months of follow-up (median 6.3 years), 457 (29%) were immune active during follow-up [11% hepatitis B e antigen (HBeAg)-positive, 16% HBeAg-negative, and 2% HBeAg status unknown], 10 (0.6%) were immune tolerant, 112 (7%) were inactive through the duration of follow-up and 886 (55%) were phase indeterminate. Patients with cirrhosis were identified within each group (among 21% of immune active, 3% of inactive and 9% of indeterminate phase patients) except among those with immune-tolerant CHB. Prescription of treatment was 59% among immune active patients and 84% among patients with cirrhosis and hepatitis B virus (HBV) DNA >2000 IU/mL. CONCLUSIONS: Approximately, one-third of the cohort had active disease during follow-up; 60% of eligible patients were prescribed treatment. Our findings underscore the importance of ascertainment of fibrosis status in addition to regular assessment of ALT and HBV DNA levels.

Factors associated with the successful modification of antiretroviral therapy. HIV Outpatient Study Investigators.

OBJECTIVES: To assess the characteristics of medication regimen modification and the influence of a commercial genotypic resistance assay on the short-term (3-12 weeks) viral load response (> or = 0.5 log reduction) in HIV-1-infected patients extensively treated with antiretroviral therapy (ART). METHODS: A nested cohort study was performed in two clinics from the HIV Outpatient Study of 96 persons with a HIV-1 viral load of 10(4) log copies/ml or greater taking at least two antiretroviral medications. RESULTS: Successful modification was associated with adding at least two new medications [relative risk (RR), 1.5; 95% confidence interval (CI), 1.1-2.2], adding a drug from a previously unused class of agents (RR, 2.0; CI, 1.4-2.9), the initiation of a non-nucleoside reverse transcriptase inhibitor (NNRTI) (RR, 1.7; CI, 1.2-2.4), but not substituting a protease inhibitor or the use of a commercial genotypic resistance assay. CONCLUSION: Incorporating a drug from a previously unused class or changing at least two new medications, but, within the confines of this study, not using a commercial genotypic resistance assay, was associated with the successful modification of ART as measured by a reduction in viral load.

Clinical assessment of HIV-associated lipodystrophy in an ambulatory population.

OBJECTIVE: To identify clinical factors associated with prevalence of fat atrophy (lipoatrophy) and fat accumulation (lipoaccumulation) in HIV-1 infected patients. DESIGN: Evaluation of HIV-1 infected patients seen for routine care between 1 October and 31 December 1998 in the eight HIV Outpatient Study (HOPS) clinics. SETTING: Eight clinics specializing in the care of HIV-1 infected patients. PATIENTS: A total of 1077 patients were evaluated for signs of fat maldistribution. INTERVENTIONS: A 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 MEASURES: Demographic, 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. RESULTS: Independent 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. CONCLUSIONS: HIV-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.

Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV outpatient study (HOPS).

PURPOSE: Most HIV-infected persons are now treated as ambulatory patients. Obtaining continually updated data about these patients' changing conditions, therapies, and reimbursement is essential to health care provision and planning. The systematic tracking of patient medical and laboratory information in an ongoing commercial data collection program (The Health Research Network) allows clinicians to better understand health outcomes, practice patterns, and epidemiologic trends for their patients. METHODS: To evaluate trends in conditions and therapies of ambulatory HIV-infected patients, we analyzed such data electronically and prospectively collected in the HIV Outpatient Study (HOPS) from 1992 through 1996 from 1876 patients seen in 11,755 clinic visits to ten HIV clinical practices. RESULTS: Patients were as likely to be diagnosed with Mycobacterium avium complex ([MAC] 5.4 cases per 100 person-years) or wasting syndrome (7.8 cases per 100 person-years), as Pneumocystis carinii pneumonia ([PCP]; 7.6 cases per 100 person-years) or Kaposi sarcoma ([KS]; 6.9 cases per 100 person-years). A nested analysis showed that HIV-infected cigarette smokers were at substantially greater risk of pneumonia (relative hazard [RH] = 2.3), bronchitis (RH = 1.7) and hairy leukoplakia (RH = 1.9) than nonsmokers. By 1996, 35 (56%) of 62 patients with PCP, 9 (30%) of 30 patients with other pneumonias, 28 (90%) of 31 patients with KS, 35 (73%) of 48 patients with MAC, and 24 (63%) of 38 patients with cytomegalovirus retinitis were treated without hospitalization. CONCLUSIONS: The HOPS provides continually updated information on the changing characteristics, conditions, and therapy of ambulatory HIV-infected patients.

Influence of human immunodeficiency virus infection on pelvic inflammatory disease.

OBJECTIVE: To examine the influence of human immunodeficiency virus (HIV) infection on clinical and microbiologic characteristics of pelvic inflammatory disease (PID). METHODS: Forty-four HIV-infected women and 163 HIV noninfected women diagnosed with PID by standard case definition were evaluated by using clinical severity scores, transabdominal sonograms, and endometrial biopsies. After testing for bacterial infections, patients were prescribed antibiotics as recommended by the Centers for Disease Control and Prevention (CDC). RESULTS: Symptoms of PID and analgesic use before enrollment did not differ by HIV serostatus. More HIV-infected women had received antibiotics before enrollment (40.9% versus 27.2%, P =.08), a factor associated with milder signs regardless of serostatus. More HIV-infected women had sonographically diagnosed adnexal masses at enrollment (45.8% versus 27.1%, P =.08), a difference that yielded higher median severity scores (17.5 of 42 points versus 15 of 42 points, P =.07). However, those differences were not significant at the P <.05 level. Mycoplasma (50% versus 22%, P <.05) and streptococcus species (34% versus 17%, P <.05) were isolated more commonly from biopsies of HIV-infected women. Within 30 days after enrollment, HIV-infected women generally responded as well to therapy as HIV-noninfected women did, regardless of initial CD4 T-lymphocyte percentage. CONCLUSION: Among women with acute PID, HIV infection was associated with more sonographically diagnosed adnexal masses. Clinical response to CDC-recommended antibiotics did not differ appreciably by serostatus. Mycoplasmas and streptococci were isolated more commonly from HIV-infected women, but those organisms also might be associated with PID in immunocompetent women.

Evaluation of hypophosphataemia in tenofovir disoproxil fumarate (TDF)-exposed and TDF-unexposed HIV-infected out-patients receiving highly active antiretroviral therapy.

OBJECTIVES: Cases of hypophosphataemia (often coincident with renal dysfunction) have been reported in HIV-infected patients taking tenofovir disoproxil fumarate (TDF), but randomized placebo-controlled trials of HIV-infected persons with normal baseline renal function have found a comparable incidence of hypophosphataemia in the TDF and placebo groups. We assessed the incidence of grade 2 and higher hypophosphataemia in the HIV Outpatient Study (HOPS). METHODS: We analysed a prospective cohort of patients who initiated either a TDF-containing highly active antiretroviral therapy (HAART) regimen [TDF-exposed (TDF+) group; n = 165] or a TDF-sparing HAART regimen [TDF-unexposed (TDF-) group; n = 90], and who had normal baseline phosphate and creatinine values. RESULTS: The TDF+ and TDF- groups had comparable median follow-up times (10.9 vs 8.8 months, respectively; P = 0.18) and number of phosphate measurements (median = 3 for both) and were similar on most clinical and demographic factors. During follow up, 12.7% of TDF+vs 6.7% of TDF-patients developed grade 2 hypophosphataemia (2.0-2.4 mg/dL), and 2.4% of TDF+ patients vs 0% of TDF-patients developed grade 3 hypophosphataemia (1.0-1.9 mg/dL); none developed grade 4 hypophosphataemia (<1.0 mg/dL). The incidence of grade 2 or higher hypophosphataemia was 16.7 per 100 person-years among TDF+ patients vs 8.0 per 100 person-years among TDF-patients (P = 0.11). CONCLUSIONS: The incidence of hypophosphataemia was somewhat elevated in HOPS patients who took TDF-containing HAART compared with those who took TDF-sparing HAART during the first 1 to 2 years of observation, but the difference was not statistically significant. Longer follow-up of a larger population is needed to determine if this trend towards an association achieves statistical significance and to evaluate the clinical consequences of hypophosphataemia.

Protease inhibitor exposure and increased risk of cardiovascular disease in HIV-infected patients.

OBJECTIVES: To study the relationship between exposure to protease inhibitor (PI) therapy and increased risk of cardiovascular events in HIV-infected patients. METHODS: We estimated the risk of cardiovascular disease (CVD) events with PI exposure in a cohort of HIV-infected patients using a time-dependent Cox proportional hazards model adjusting for the major CVD risk factors. Only the first CVD event for each subject was counted. RESULTS: Of a total of 7542 patients, 77% were exposed to PIs. CVD event rates were 9.8/1000 and 6.5/1000 person-years of follow-up (PYFU) in the PI-exposed and nonexposed groups, respectively (P=0.0008). PI exposure >/=60 days was associated with an increased risk of CVD event [adjusted hazards ratio (HR(adj)) 1.71; 95% confidence interval (CI) 1.08-2.74; P=0.03]. Results from a subgroup of patients aged between 35 and 65 years were similar (HR(adj) 1.90; 95% CI 1.13-3.20; P=0.02). Other significant risk factors included smoking status, age, hypertension, diabetes mellitus and pre-existing CVD. CONCLUSIONS: Patients exposed to PI therapy had an increased risk of CVD events. Clinicians should evaluate the risk of CVD when making treatment decisions for HIV-infected patients.

Discontinuation of chemoprophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection. HIV Outpatient Study (HOPS) Investigators.

BACKGROUND: HIV-infected patients with sustained immunologic improvement from antiretroviral therapy may be able to discontinue chemoprophylaxis against Pneumocystis carinii pneumonia (PCP). OBJECTIVE: To compare PCP incidence in HIV-infected patients who had sustained CD4+ lymphocyte counts greater than 200 cells/mm3 and who either discontinued or continued PCP prophylaxis. DESIGN: Nonrandomized prospective cohort study. SETTING: 10 HIV clinics in eight U.S. cities. PATIENTS: 146 patients had follow-up visits for a mean of 18.2 months after discontinuation of PCP prophylaxis, and 345 patients who continued PCP prophylaxis had follow-up visits for a mean of 14.0 months. MEASUREMENTS: Incidence of PCP. RESULTS: Patients who discontinued PCP prophylaxis had higher maximum and minimum CD4+ cell counts and lower vira loads than patients who continued PCP prophylaxis. Pneumocystis carinii pneumonia did not develop in either group (upper 95% exact binomial confidence limit of incidence for those who discontinued PCP prophylaxis, 2.3/100 person-years). CONCLUSIONS: Discontinuation of PCP chemoprophylaxis may be appropriate for some HIV-infected ambulatory patients.

Pneumocystis carinii pneumonia incidence and chemoprophylaxis failure in ambulatory HIV-infected patients. HIV Outpatient Study (HOPS) Investigators.

BACKGROUND: Pneumocystis carinii pneumonia (PCP) remains the most frequently reported serious opportunistic infection in AIDS patients and the second highest cause of mortality among persons with AIDS in the United States, despite the availability of effective chemoprophylaxis. METHODS: To evaluate incidence of PCP and determinants of PCP chemoprophylaxis failure, we analyzed data from 2842 patients visits to infectious diseases physicians at 10 HIV clinics (eight private and two public) in eight U.S. cities from January 1992 through June 1996 as part of the HIV Outpatient Study (HOPS). We performed a time-dependent regression analysis to examine potential determinants of PCP chemoprophylaxis failure. RESULTS: The incidence of chemoprophylaxis failure was 4.6 PCP cases/100 person-years on chemoprophylaxis; these cases represent 67% of all incident episodes of PCP. In a multivariate analysis, the only significant predictors of chemoprophylaxis failure were the use of agents other than trimethoprim-sulfamethoxazole (TMP-SMX), history of prior PCP, and a CD4+ T-lymphocyte cell count of <50 cells/microl. Dosing or frequency of TMP-SMX did not seem to influence risk of chemoprophylaxis failure. DISCUSSION: Chemoprophylaxis failure, especially among those with the most advanced immunosuppression or history of prior PCP, was the most significant source of new PCP cases in the HOPS cohort and thus represents one of the largest contributors to morbidity and mortality in this cohort.

Possible effectiveness of clarithromycin and rifabutin for cryptosporidiosis chemoprophylaxis in HIV disease. HIV Outpatient Study (HOPS) Investigators.

CONTEXT: Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent. OBJECTIVE: To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex. DESIGN: Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992. SETTING: Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities. PATIENTS: A total of 1019 HIV-infected patients with CD4+ cell counts less than 0.075 x 10(9)/L. MAIN OUTCOME MEASURES: Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin. RESULTS: Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard [RH], 0.25 [95% confidence interval (CI), 0.10-0.67]; P=.004). Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 [95% CI, 0.04-0.62]; P=.01). Prophylactic efficacy of either drug was 75% or greater. No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 [95% CI, 0.44-5.04]; P=.46). CONCLUSIONS: Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted.

Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.

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.