Is the increased risk of liver enzyme elevation in patients co-infected with HIV and hepatitis virus greater in those taking antiretroviral therapy?

OBJECTIVES: To investigate if the risk of liver enzyme elevation (LEE) in HIV/hepatitis B or C (HBV, HCV) co-infection is altered by HAART (two or more drugs). METHODS: Analysis comprised HIV-positive patients in the ICoNA study without acute hepatitis who had >or= 1 positive HCV antibody test and > 1 positive HBV surface antigen test. LEE was defined as > 5x baseline alanine aminotransferase (ALT) or > 3.5x baseline if the baseline was > 40 IU/l. Analysis used Poisson regression with generalized estimating equation correction to examine HBV or HCV co-infection, use of HAART, baseline ALT and demographics as LEE predictors. RESULTS: Of the 5272 patients, 47.6% were co-infected with HCV/HBV; 29.9% were female and 39% were intravenous drug users. There were 275 episodes of LEE during 18 259 person-years follow up. Taking HAART did not significantly increase risk of LEE [adjusted relative risk (RR), 1.19; 95% confidence interval (CI), 0.81-1.75; P = 0.37]. Co-infection increased the risk of LEE (adjusted RR, 5.07; 95% CI, 3.47-7.48; P < 0.001), with no significant differences if taking HAART (adjusted RR, 4.99; 95% CI, 3.38-7.37) or not (adjusted RR, 6.02; 95% CI, 2.02-17.98) (P = 0.74 for interaction). Females were at lower risk of LEE than males (adjusted RR, 0.59; 95% CI, 0.42-0.83; P = 0.02). CONCLUSIONS: HIV and HBV/HCV co-infection per se is associated with increased risk of LEE that is not modified by HAART. The recommendation for caution in HAART use in co-infected patients, simply based on a high rate of LEE in people on therapy, may be questionable.     

Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study

BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death. RESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02). CONCLUSIONS: Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.     

HIV and hepatitis C coinfection within the CAESAR study

The declining incidence of AIDS-related opportunistic diseases among people with HIV infection has shifted the focus of clinical management to prevention and treatment of comorbidities such as chronic liver disease. The increased risk of hepatitis C virus (HCV)-related advanced liver disease in people with HIV infection makes early HCV diagnosis a priority. To assess HCV prevalence and predictors of HIV/HCV coinfection, we have conducted a retrospective analysis of people enrolled in the CAESAR (Canada, Australia, Europe, South Africa) study, a multinational randomized placebo-controlled study of the addition of lamivudine to background antiretroviral therapy. The impact of HCV on HIV disease progression was also examined. Anti-HCV antibody testing on 1649 CAESAR study participants demonstrated a HIV/HCV coinfection prevalence of 16.1%, which varied from 1.9% in South Africa to 48.6% in Italy. The strongest predictor of HIV/HCV coinfection was HIV exposure category (P<0.0001), with odds ratios (ORs) compared to homosexual as follows: injecting drug use (IDU), 365 [95% confidence interval (CI): 179-742]; transfusion or blood products, 32.2 (95% CI: 15.2-67.6); homosexual and IDU, 22.9 (95% CI: 8.5-62.1). The prevalence of HIV/HCV was low (3.7%) among homosexual men without reported IDU. Other predictors of HIV/HCV coinfection were alanine aminotransferase (ALT), country of residence, ethnicity and stage of HIV disease. A history of IDU or ALT > or =40 U/L at baseline had a positive predictive value (PPV) of 35%, negative predictive value (NPV) of 96%, sensitivity of 82% and specificity of 71% for HIV/HCV coinfection. HIV disease progression was similar in HIV monoinfected and HIV/HCV coinfected patients. People with HIV and a history of IDU or elevated liver function tests should be targeted for HCV testing. The low prevalence of HIV/HCV coinfection among homosexual men without a history of IDU suggests low efficiency of sexual HCV transmission.     

Tuberculosis risk varies with the duration of HIV infection: a prospective study of European drug users with known date of HIV seroconversion

BACKGROUND: It is not known whether the risk of active tuberculosis disease varies with the length of time that individuals are infected with HIV. OBJECTIVE: To study how, independently of CD4 T cell count, the risk of tuberculosis varies with the duration of HIV infection. METHODS: Using Poisson regression analysis, the incidence of and risk factors for tuberculosis were studied in 683 injecting drug users (IDU) with a documented date of HIV seroconversion followed in seven cohorts in six European countries until 1998. RESULTS: Overall incidence was 11.5/1000 person-years. Adjusted for CD4 T cell count and geographic region, the risk ratio (RR) for tuberculosis (both pulmonary and extrapulmonary), compared with the first 3 years of HIV infection, was 2.8 for years 4 to 6 of HIV infection [95% confidence interval (CI), 1.3-6.3], 1.2 for year 7 to 9 (95% CI, 0.3-4.2) and 4.6 after 9 years (95% CI, 1.4-15.0). The adjusted RR for geographic region was 13.1 (95% CI, 4.3-40.0) for Amsterdam and 15.8 (95% CI, 4.8-52.0) for the Valencian region of Spain compared with all other sites combined. CONCLUSION: The risk of tuberculosis is increased relatively early in HIV infection (year 4 to 6) and also later (after year 9) with possibly a relatively silent period between. As expected, IDU in Southern Europe have a substantially higher risk of tuberculosis than IDU in Northern and Central Europe. Amsterdam forms an exception for Northern Europe, with very high incidence rates.     

The shifting pattern of cause-specific mortality in a cohort of human immunodeficiency virus-infected and non-infected injecting drug users

AIMS: To monitor changes in cause-specific mortality before and after 1997 according to human immunodeficiency virus (HIV) serological status in a cohort of injecting drug users (IDUs) observed for a 17-year period (1987--2004). DESIGN: Community-based prospective cohort study of IDUs recruited in three acquired immunodeficiency virus (AIDS) prevention centres (1987--96) and followed-up until to 2004. METHODS: We obtained annual overall mortality rates and mortality rates by specific causes according to HIV status. Poisson regression models were adjusted to compare mortality rates between calendar periods. Significant changes in slope trends were evaluated by join-point regression. Disease-specific mortality rates were estimated using competing risk models. FINDINGS: From 7186 IDUs recruited (80677.218 person-years), 1589 deaths were observed with an overall mortality rate of 19.7 per 1000 person-years (95% CI, 18.8-20.7). This rate decreased from 22.9 per 1000 (95% CI, 21.4-24.7) before 1997 to 17.4 per 1000 (95% CI, 16.3-18.6) after 1997 [relative risk (RR) 0.83; 95% confidence interval (CI), 0.75-0.92]. Risk of death for HIV-positive was four times higher than for HIV-negative (RR 4.08; 95% CI, 3.63-4.58). Among HIV-positive individuals a significantly decreased change point in trend was found in 1997 for both total and AIDS mortality. HIV-negative individuals showed a similar pattern for drug overdose, suicide and accident mortality. Both groups showed an increase in proportional mortality by liver-related causes, cardiovascular diseases and cancer. Furthermore, a progressively increasing trend was observed for the three causes. However, there were no significant differences according to serological groups. CONCLUSIONS: Cardiovascular and cancer mortality are increasing among IDUs, but the increases are not related to HIV infection. We have not found a link between highly active antiretroviral therapy (HAART) introduction and increases in mortality for specific causes.     

The association between hepatitis C virus and HIV-1 in preparatory cohorts for HIV vaccine trials in Thailand

OBJECTIVES: To study the association between hepatitis C virus (HCV) and HIV-1, and HCV seropositivity as an indicator of HIV-1 risk behavior for HIV vaccine preparatory cohorts in Thailand. DESIGN: Cross-sectional study of HIV-1-infected persons identified at screening for potential HIV vaccine trial cohort studies. METHODS: Sera from HIV-1-infected and uninfected volunteers was matched by age, sex, and community, and tested for HCV reactivity. Logistic regression methods were used to measure associations between HIV-1, HCV and other risk factors for HIV infection. RESULTS: The prevalence of HCV among HIV-negative controls was 8.3% (6/72) for men and 4.2% (5/118) for women. Co-infection with HIV and occurred in 50.7% (37/73) of men and 3.4% (4/118) of women. Among men who reported injection drug use (IDU), 96.4% (27/28) were HCV seropositive. No women reported IDU. HCV was associated with HIV infection [odds ratio (OR), 11.3; 95% confidence interval (CI), 4.4-29.3] and IDU (OR, 12.0; 95% CI, 3.4-41.9) among men, but not women (OR, 0.8; 95% CI, 0.2-3.0). After adjustment for potential confounding, HCV, but not IDU, remained strongly associated with HIV-1 infection among men (OR, 9.4; 95% CI, 2.7-32.6). CONCLUSIONS: The strong associations between HCV seropositivity, HIV-1 infection, and IDU history suggest that IDU was reported accurately in this study. The surprisingly high prevalence of HCV among HIV-1-infected young men may assist health policy makers in the choice of behavioral interventions for this important subgroup of the population.     

Mortality risk associated with rheumatoid arthritis in a prospective cohort of older women: results from the Iowa Women's Health Study

OBJECTIVE: To determine whether rheumatoid arthritis (RA) is associated with excess mortality among older women. METHODS: RA associated mortality was examined in a prospective cohort study that was started in 1986, and included 31 336 women aged 55-69 years without a history of RA at baseline. Up to 1997, 158 cases of RA were identified and validated against medical records. The relative risk (RR) and 95% confidence interval (CI) were calculated as measures of association between RA onset and subsequent mortality (overall and cause-specific) using Cox proportional hazards regression. RESULTS: Compared with non-cases, women developing RA during follow up had a significantly increased mortality risk (RR=1.52; 95% CI 1.05 to 2.20). Mortality was higher among rheumatoid factor (RF) positive cases (RR=1.90; 95% CI 1.24 to 2.92) than among RF negative cases (RR=1.00; 95% CI 0.45 to 1.99). There were trends towards increased proportions of RA related deaths from infection (RR=3.61; 95% CI 0.89-14.69) and circulatory disease (RR=1.46; 95% CI 0.76 to 2.81) but not malignancy (RR=0.97; 95% CI 0.46 to 2.04). CONCLUSIONS: RA was associated with significantly increased mortality in a cohort of older women, and the association appeared to be restricted to those with RF positive disease.     

Hepatitis C virus coinfection in a cohort of HIV-infected individuals from Santos, Brazil: seroprevalence and associated factors

Although HIV/hepatitis C virus (HCV) coinfection has been recognized worldwide in individuals exposed to blood-borne and sexually transmitted diseases (STD), limited data are available on the epidemiology of this coinfection in Brazil. A cross-sectional study was carried out to estimate the prevalence of HCV seropositivity in a cohort of people living with HIV/AIDS in Santos, Brazil, and to investigate potential risk factors for HCV infection. Anti-HCV antibodies were sought by using two immunoenzymatic assays. Overall HCV seroprevalence was 36.2% (95% confidence interval [CI] 31.9-40.4%). However, it was significantly higher (84.8%, 95% CI 78.2-91.3%) among intravenous drug users (IDU) as compared to non-IDU (20.9%, 95% CI 16.8-25.1%) (p < 0.001). Multiple logistic regression analysis revealed that HCV seropositivity among IDU was independently associated with needle sharing (adjusted odds ratio [adjOR] = 4.28, p = 0.07) and with serologic evidence of exposure to other bloodborne agents: HBV (adjOR = 4.39, p = 0.01) and HTLV-I/II (adjOR = 6.43, p = 0.02). In contrast, no association with lifetime number of sexual partners, history of STD, or of sex with commercial sex workers (CSW) could be demonstrated. Among non-IDU, HCV seropositivity was independently associated with sexual partnership with IDU (adjOR = 2.15, p = 0.08) and with HBV seropositivity (adjOR = 1.71, p = 0.05), but not with engaging in oral or anal receptive intercourse or having sex with CSW. Results indicate that exposure to blood and sexual partnership with IDU constitute the main risk factors for HCV acquisition among HIV-positive patients in Santos, Brazil. Prevention of HCV spread in this population should thus include harm reduction measures and information on safer sex practices for both IDU and their sexual partners.     

Impact of human immunodeficiency virus infection on progression to end-stage liver disease in individuals with hemophilia and hepatitis C virus infection

Hepatitis C virus (HCV) is the major cause of chronic liver disease in hemophiliacs. To determine the effect of human immunodeficiency virus (HIV) on the natural history of HCV infection, we evaluated end-stage liver disease (ESLD) in 157 hemophiliacs (85 HIV positive and 72 HIV negative) with HCV infection for an average of 24 years. After adjusting for age at HCV infection, past or current hepatitis B surface antigen positivity, and history of alcohol abuse, we determined that the rate of ESLD was significantly greater among HIV-positive than among HIV-negative hemophiliacs (relative risk [RR], 3.72; 95% confidence interval [CI], 1.25-11.09), as was the adjusted RR for death due to ESLD (RR, 3.81; 95% CI, 1.19-12.16). Among HIV-positive hemophiliacs, crude RR for ESLD was lower, but not significantly so, with antiretroviral treatment (RR, 0.19; 95% CI, 0.03-1.14; P=.069) and increased with each decade of HCV infection (RR, 2.26; 95% CI, 1.42-3.59; P=.0006) and HIV infection (RR, 2.18; 95% CI, 1.36-3.49; P=.0013). These findings suggest that HIV accelerates HCV disease progression.     

Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects

We determined incidence and risk factors for acute and chronic hepatitis B virus (HBV) infection and HBV vaccination rates among human immunodeficiency virus (HIV)-infected subjects from the Adult/Adolescent Spectrum of HIV Disease Project, during 1998-2001. Among 16,248 HIV-infected patients receiving care, the incidence of acute HBV was 12.2 cases/1000 person-years (316 cases), was higher among black subjects (rate ratio [RR], 1.4; 95% confidence interval [CI], 1.0-2.0), subjects with alcoholism (RR, 1.7; 95% CI, 1.2-2.3), subjects who had recently injected drugs (RR, 1.6; 95% CI, 1.1-2.4), and subjects with a history of AIDS-defining conditions (RR, 1.5; 95% CI, 1.2-1.9) and was lower in those taking either antiretroviral therapy (ART) with lamivudine (RR, 0.5; 95% CI, 0.4-0.6), ART without lamivudine (RR, 0.5; 95% CI, 0.3-0.7), or >/=1 dose of HBV vaccine (14% of subjects) (RR, 0.6; 95% CI, 0.4-0.9). Prevalence of chronic HBV was 7.6% among unvaccinated subjects. HBV rates in this population were much higher than those in the general population, and vaccination levels were low. HBV remains an important cause of comorbidity in HIV-infected persons, but ART and vaccination are associated with decreased disease.     

Impact of injecting drug use on mortality in Danish HIV‐infected patients: a nation‐wide population‐based cohort study

Objectives To estimate the impact of injecting drug use (IDU) on mortality in HIV‐infected patients in the highly active antiretroviral therapy (HAART) era. Design Population‐based, nation‐wide prospective cohort study in Denmark (the Danish HIV Cohort Study). Methods A total of 4578 HIV‐infected patients were followed from 1 January 1997 or date of HIV diagnosis. We calculated mortality rates stratified on IDU. One‐, 5‐ and 10‐year survival probabilities were estimated by Kaplan–Meier methods, and Cox regression analyses were used to estimate mortality rate ratios (MRR). Results Of the patients, 484 (10.6%) were categorized as IDUs and 4094 (89.4%) as non‐IDUs. IDUs were more likely to be women, Caucasian, hepatitis C virus (HCV) co‐infected and younger at baseline; 753 patients died during observation (206 IDUs and 547 non‐IDUs). The estimated 10‐year survival probabilities were 53.2% [95% confidence interval (CI): 48.1–58.3] in the IDU group and 82.1% (95% CI: 80.7–83.6) in the non‐IDU group. IDU as route of HIV infection more than tripled the mortality in HIV‐infected patients (MRR: 3.2; 95% CI: 2.7–3.8). Adjusting for potential confounders did not change this estimate substantially. The risk of HIV‐related death was not increased in IDUs compared to non‐IDUs (MRR 1.1; 95% CI 0.7–1.7). Conclusions Although Denmark's health care system is tax paid and antiretroviral therapy is provided free of charge, HIV‐infected IDUs still suffer from substantially increased mortality in the HAART era. The increased risk of death seems to be non‐HIV‐related and is due probably to the well‐known risk factors associated with intravenous drug abuse.     

Hepatitis B or hepatitis C coinfection in HIV-infected pregnant women in Europe

Objectives

The aim of the study was to investigate the prevalence of and risk factors for hepatitis C or B virus (HCV or HBV) coinfection among HIV‐infected pregnant women, and to investigate their immunological and virological characteristics and antiretroviral therapy use.

Methods

Information on HBV surface antigen (HBsAg) positivity and HCV antibody (anti‐HCV) was collected retrospectively from the antenatal records of HIV‐infected women enrolled in the European Collaborative Study and linked to prospectively collected data.

Results

Of 1050 women, 4.9% [95% confidence interval (CI) 3.6–6.3] were HBsAg positive and 12.3% (95% CI 10.4–14.4) had anti‐HCV antibody. Women with an injecting drug use(r) (IDU) history had the highest HCV‐seropositivity prevalence (28%; 95% CI 22.8–35.7). Risk factors for HCV seropositivity included IDU history [adjusted odds ratio (AOR) 2.92; 95% CI 1.86–4.58], age (for ≥35 years vs. <25 years, AOR 3.45; 95% CI 1.66–7.20) and HBsAg carriage (AOR 5.80; 95% CI 2.78–12.1). HBsAg positivity was associated with African origin (AOR 2.74; 95% CI 1.20–6.26) and HCV seropositivity (AOR 6.44; 95% CI 3.08–13.5). Highly active antiretroviral therapy (HAART) use was less likely in HIV/HCV‐seropositive than in HIV‐monoinfected women (AOR 0.34; 95% CI 0.20–0.58). HCV seropositivity was associated with a higher adjusted HIV RNA level (+0.28log₁₀ HIV‐1 RNA copies/mL vs. HIV‐monoinfected women; P=0.03). HIV/HCV‐seropositive women were twice as likely to have detectable HIV in the third trimester/delivery as HIV‐monoinfected women (AOR 1.95; P=0.049).

Conclusions

Although HCV serostatus impacted on HAART use, the association between HCV seropositivity and uncontrolled HIV viraemia in late pregnancy was independent of HAART.     

Hepatitis B and C virus coinfection in The TREAT Asia HIV Observational Database

BACKGROUND AND AIM: Most studies of hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection with HIV have been conducted among Western patient populations. This study aims to assess rates of HBV and HCV coinfection, and their impact on response to antiretroviral therapy and mortality, using data from The TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of patients with HIV in the Asia-Pacific region. METHODS: Patients who had been tested either HBV surface antigen (HBsAg) or HCV antibody were included. Patients who ever tested positive for HBV or HCV were regarded as coinfected for the duration of the study. RESULTS: Results of hepatitis tests were available for 55% (HBV) and 49% (HCV) of 2979 TAHOD patients, with prevalence of HBV and HCV coinfection both at approximately 10%. Mean CD4 change at 180 days after antiretroviral treatment initiation was 118.8 cells/muL and patients with either HBV or HCV had a lower but non-significant CD4 increase compared with patients with HIV only. Median time to reach undetectable viral load (<400 copies/mL) was 148 days and was not independently associated with HBV or HCV. In univariate analysis, patients with HCV had increased mortality (unadjusted hazard ratio, HR 2.80, P = 0.007). However, neither HBV (adjusted HR 0.80, 95% confidence interval CI 0.24-2.64, P = 0.710) nor HCV (adjusted HR 1.06, 95% CI 0.40-2.79, P = 0.905) was associated with increased mortality after adjustment for other covariates. Both HBV and HCV remained independently associated with elevated alanine aminotransferase (ALT) in the multivariate model (HBV, adjusted HR 1.94, 95% CI 1.04-3.62, P = 0.037; HCV, adjusted HR 2.74, 95% CI 1.47-5.12, P = 0.002). CONCLUSION: The impact of hepatitis coinfection on immunological and virological responses to antiretroviral therapy and HIV disease progression among this Asian cohort are similar to that seen in Western countries. The longer-term impact of hepatitis coinfection on both HIV disease and liver disease morbidity and mortality needs to be monitored.     

Minimal transmission of HIV despite persistently high transmission of hepatitis C virus in a Swedish needle exchange program

The aim of this study was to examine the prevalence and incidence of HIV and hepatitis B and C (HBV and HCV) among injecting drug users in a Swedish needle exchange programme (NEP) and to identify risk factors for blood-borne transmission. A series of serum samples from NEP participants enrolled from 1997 to 2005 were tested for markers of HIV, HBV and HCV (including retrospective testing for HCV RNA in the last anti-HCV-negative sample from each anti-HCV seroconverter). Prevalence and incidence were correlated with self-reported baseline characteristics. Among 831 participants available for follow-up, one was HIV positive at baseline and two seroconverted to anti-HIV during the follow-up of 2433 HIV-negative person-years [incidence 0.08 per 100 person-years at risk (pyr); compared to 0.0 in a previous assessment of the same NEP covering 1990-1993]. The corresponding values for HBV were 3.4/100 pyr (1990-1993: 11.7) and for HCV 38.3/100 pyr (1990-1993: 27.3). HCV seroconversions occurred mostly during the first year after NEP enrolment. Of the 332 cases testing anti-HCV negative at enrolment, 37 were positive for HCV RNA in the same baseline sample (adjusted HCV incidence 31.5/100 pyr). HCV seroconversion during follow-up was significantly associated with mixed injection use of amphetamine and heroin, and a history of incarceration at baseline. In this NEP setting, HIV prevalence and incidence remained low and HBV incidence declined because of vaccination, but transmission of HCV was persistently high. HCV RNA testing in anti-HCV-negative NEP participants led to more accurate identification of timepoints for transmission.     

Profile of patients triply infected with HIV and the hepatitis B and C viruses in the HAART era

HIV-HCV-HBV-coinfected patients were assessed to characterize the viral interactions in the setting of HIV coinfection and in the HAART era. All positive anti-HCV antibody and HBs antigen-positive HIV-infected patients were identified at five HIV clinics. Antihepatitis delta (HDV) antibody, serum HIV RNA, HCV RNA, and HBV DNA quantification and genotype determinations were performed. Out of 67 patients identified 47 (70%) were receiving anti-HBV therapy. HCV RNA and HBV DNA were detectable in 52.5% and 37% of patients, respectively. All possible patterns were found, regardless of anti-HBV therapy. HDV coinfection was associated with undetectable HCV RNA [RR 9.52 (95% CI 1.85-49.01); p = 0.007]. Independent factors predicting undetectable HBV DNA lacked HBeAg [RR 13.94 (95% CI 3.05-63.72); p = 0.001] and use of anti-HBV therapy [RR 11.42 (95% CI 2.43-53.54); p = 0.002]. Replication and genotypes of HCV or HBV had no impact on the replication of the other virus. In conclusion, in this cohort of triple infection (HBV/HCV/HIV) various viral patterns were identified. Spontaneous HCV clearance was frequent, and it was independently associated with HDV coinfection. In the absence of HBV therapy, HBV most often actively replicates. HBV/HCV replication or genotypes were not related to the replication of the other virus.     

Physical activity recommendations and decreased risk of mortality

BACKGROUND: Whether national physical activity recommendations are related to mortality benefit is incompletely understood. METHODS: We prospectively examined physical activity guidelines in relation to mortality among 252,925 women and men aged 50 to 71 years in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Physical activity was assessed using 2 self-administered baseline questionnaires. RESULTS: During 1,265,347 person-years of follow-up, 7,900 participants died. Compared with being inactive, achievement of activity levels that approximate the recommendations for moderate activity (at least 30 minutes on most days of the week) or vigorous exercise (at least 20 minutes 3 times per week) was associated with a 27% (relative risk [RR], 0.73; 95% confidence interval [CI], 0.68-0.78) and 32% (RR, 0.68; 95% CI, 0.64-0.73) decreased mortality risk, respectively. Physical activity reflective of meeting both recommendations was related to substantially decreased mortality risk overall (RR, 0.50; 95% CI, 0.46-0.54) and in subgroups, including smokers (RR, 0.48; 95% CI, 0.44-0.53) and nonsmokers (RR, 0.54; 95% CI, 0.45-0.64), normal weight (RR, 0.45; 95% CI, 0.39-0.52) and overweight or obese individuals (RR, 0.48; 95% CI, 0.44-0.54), and those with 2 h/d (RR, 0.53; 95% CI, 0.44-0.63) and more than 2 h/d of television or video watching (RR, 0.50; 95% CI, 0.45-0.55). Engaging in physical activity at less than recommended levels was also related to reduced mortality risk (RR, 0.81; 95% CI, 0.76-0.86). CONCLUSIONS: Following physical activity guidelines is associated with lower risk of death. Mortality benefit may also be achieved by engaging in less than recommended activity levels.     

Risk factors for hepatitis C virus infection in United States blood donors. NHLBI Retrovirus Epidemiology Donor Study (REDS)

Injection drug use (IDU) is a known risk factor for hepatitis C virus (HCV) infection, but the strength of other parenteral and sexual risk factors is unclear. In 1997, we performed a case-control study of 2,316 HCV-seropositive blood donors and 2,316 seronegative donors matched on age, sex, race/ethnicity, blood center, and first-time versus repeat-donor status. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Questionnaires were returned by 758 (33%) HCV(+) and 1,039 (45%) control subjects (P =.001). The final multivariate model included only the following independent HCV risk factors: IDU (OR = 49.6; 95% CI: 20.3-121.1), blood transfusion in non-IDU (OR = 10.9; 95% CI: 6.5-18.2), sex with an IDU (OR = 6.3; 95% CI: 3.3-12.0), having been in jail more than 3 days (OR = 2.9; 95% CI: 1.3-6.6), religious scarification (OR = 2.8; 95% CI: 1.2-7. 0), having been stuck or cut with a bloody object (OR = 2.1; 95% CI: 1.1-4.1), pierced ears or body parts (OR = 2.0; 95% CI: 1.1-3.7), and immunoglobulin injection (OR = 1.6; 95% CI: 1.0-2.6). Although drug inhalation and a high number of lifetime sex partners were significantly more common among HCV seropositives, they were not associated with HCV after controlling for IDU and other risk factors. IDU, blood transfusion among non-IDU, and sex with an IDU are strong risk factors for HCV among United States blood donors. Weaker associations with incarceration, religious scarification, being stuck or cut with a bloody object, pierced ears or body parts, and immunoglobulin injection must be interpreted with caution.     

Decreasing prevalence of HCV coinfection in all risk groups for HIV infection between 2004 and 2011 in Spain

While hepatitis C virus (HCV) infection seems to be expanding among HIV‐infected men who have sex with men (MSM), the rate of coinfection in intravenous drug users (IDU) is assumed to remain constant. We evaluated the serial prevalence of HIV/HCV coinfection across all risk groups for HIV infection in Spain. We used data from 7045 subjects included in the multicentre, prospective Spanish Cohort of Adult HIV‐infected Patients (CoRIS) between 2004 and 2011. We analysed risk factors for HIV/HCV coinfection by logistic regression analyses. The prevalence of HIV/HCV coinfection decreased from 25.3% (95% CI, 23.1–27.5) in 2004–2005 to 8.2% (95% CI, 6.9–9.5) in 2010–2011. This trend was consistently observed from 2004 to 2011 among all risk groups: IDU, 92.4% to 81.4%; MSM, 4.7% to 2.6%; heterosexual men, 13.0–8.9%; and heterosexual women, 14.5–4.0% (all P < 0.05). Strongest risk factors for HIV/HCV coinfection were IDU (OR, 54.9; 95% CI, 39.4–76.4), birth decade 1961–1970 (OR, 2.1; 95% CI, 1.1–3.7) and low educational level (OR, 2.4; 95% CI, 1.6–3.5). Hence, the prevalence of HIV/HCV coinfection decreased in Spain between 2004 and 2011. This decline was observed across all risk groups and is likely to be explained by a declining burden of HCV in the general population.     

HIV/HBV and HIV/HCV coinfection,and outcomes following highly active antiretroviral therapy

Objectives

To assess the prevalence and risk factors for HBV and HCV coinfection in the Australia HIV Observational Database (AHOD), and examine outcomes of HIV disease following initiation of highly active antiretroviral therapy (HAART).

Methods

Analyses were based on 2086 participants recruited to AHOD by September 2002. Of these, 1605 (77%) had been tested for HBV surface antigen, 1704 (82%) for anti‐HCV antibody and 1453 (70%) for both. Demographic and clinical predictors of HBV and HCV coinfection were examined. The impact of HBV and HCV coinfection on HIV disease progression was assessed by Kaplan‐Meier survival curves and Cox proportional hazard model of time to AIDS events and death.

Results

Among those tested, prevalence of HBV surface antigen and HCV antibody were 6.3% and 13.1%, respectively (4.8% and 10.7%, respectively, among the entire cohort). In multivariate analyses, the only independent risk factor for HIV/HBV coinfection was coinfection with HCV. Independent risk factors for HIV/HCV coinfection were HIV exposure category (with people who reported injecting drug use [MSM & IDU, IDU only] or receipt of blood or blood products at markedly increased risk) and HBV coinfection. HIV disease outcomes following first initiation of a HAART regimen were similar for HIV/HBV and HIV/HCV coinfected patients compared with HIV‐only patients in terms of AIDS‐free survival and detectable HIV virus during the first 12 months. However, patients coinfected with HIV/HCV appeared to have a poorer response to HAART in terms of CD4 count changes, with a CD4 count increase of 32 cells/μL (95% CI 1–67) less than HIV‐only patients.

Conclusions

Coinfection with HBV or HCV is relatively common among HIV‐infected participants in AHOD. HIV disease outcomes following HAART do not appear to be adversely affected by HBV/HCV coinfection, except for slightly poorer CD4 count responses in HIV/HCV coinfected patients.