Antiretroviral treatment interruption leads to progression of liver fibrosis in HIV-hepatitis C virus co-infection
ABSTRACT Despite potential negative consequences, HIV/hepatitis C virus (HCV) co-infected patients may discontinue antiretroviral treatment (ART) for several reasons. We examined the impact of ART interruption on liver fibrosis progression in co-infected adults, using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate marker of liver fibrosis.
Data were analyzed from a multisite prospective cohort of 541 HIV-HCV co-infected adults. ART interruption was included as a time-updated variable and defined as the cessation of all antiretrovirals for at least 14 days. The primary endpoint was the development of an APRI score at least 1.5. Time-dependent Cox proportional hazards regression and inverse probability-of-treatment weighting (IPTW) in a marginal structural model were used to evaluate the association of baseline and time-varying covariates with developing significant fibrosis.
Patients were followed for a median of 1.02 years; 10% (n = 53) interrupted ART and 10% (n = 53) developed significant fibrosis. After accounting for potential confounders, including CD4 T-cell count, HIV viral load, baseline APRI score, age and gender, the hazard ratio for ART interruption was 2.52 (95% confidence interval 1.20-5.28). Use of IPTW resulted in a similar effect estimate, suggesting that mediation by time-varying confounders was negligible.
ART interruption was associated with an increased risk of fibrosis progression in HIV-HCV co-infection that was only partially accounted for by HIV viral load and CD4 T-cell counts. Our findings suggest that liver disease progression observed in ART-treated co-infected patients is partly due to the consequences of treatment interruptions.
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ABSTRACT: Highly active antiretroviral therapy has improved prognosis of HIV infection and substantially reduced the incidence of opportunistic diseases. However, hepatitis viruses and HIV share the same routes of transmission. Thus, chronic viral hepatitis is found frequently in HIV-infected patients. Antiretroviral drugs do not directly interact with the hepatitis C virus (HCV), so that end-stage liver disease (ESLD) in HCV/HIV co-infected patients has become a leading clinical problem in many co-infected patients. This review summarizes up-to-date guidelines in the management of ESLD and specifically addresses issues of cirrhosis in HCV/HIV co-infection. The most recent advances in the treatment of typical complication of ESLD such as esophageal varices (updated guidelines), variceal hemorrhage (early use of transjugular intrahepatic portosystemic shunt), ascites (updated guidelines), hepatorenal syndrome (vasopressor therapy, deleterious effects of beta-blockers), spontaneous bacterial peritonitis (primary prophylaxis) and hepatic encephalopathy (use of rifaximin) are discussed. This review also provides a basic outline on liver transplantation in HCV/HIV co-infected patients. Thus, physicians involved in the management of ESLD in HCV/HIV co-infected patients will find a comprehensive overview over current treatment strategies in ESLD of HIV-positive patients as well as a valuable collection of pivotal references on the most recent advances in the treatment of ESLD due to HCV/HIV co-infection.Current opinion in HIV and AIDS 09/2011; 6(6):527-33. DOI:10.1097/COH.0b013e32834bc691 · 4.39 Impact Factor
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ABSTRACT: Highly active antiretroviral therapy (HAART)-related hepatotoxicity, a relevant side effect in HIV/hepatitis C virus (HCV) co-infected patients, has evolved over time. Antiretroviral therapy might have a positive effect on the liver of HIV/HCV co-infected patients, but data are conflicting. HIV treatments have evolved and we have currently a drug armamentarium with a good liver safety profile. Most of the current first-line HAART regimens recommended by guidelines fit well to HIV/HCV co-infected patients. There are now multiple retrospective studies that suggest a possible benefit of HIV control and protection of CD4 cell counts to the liver of HIV/HCV co-infected patients. However, data are conflicting at times. This factor along with the methodological limitations of these studies prevent us from drawing definitive conclusions. Even assuming a positive effect, HAART does not appear to fully correct the adverse effect of HIV infection on HCV-related outcomes. In the era of HCV direct antiviral agents, the timing of HIV and HCV therapies has to be individualized in HIV/HCV co-infected patients given the variety of scenarios. With current HIV drug armamentarium it is possible to construct HAART regimens with optimal liver safety profile for HCV co-infected patients. The possible positive effect of HAART on the HCV-infected liver should not distract from the main intervention, which is HCV eradication with specific treatment.Current opinion in HIV and AIDS 11/2011; 6(6):546-52. DOI:10.1097/COH.0b013e32834bcbd9 · 4.39 Impact Factor
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ABSTRACT: OBJECTIVES: Hepatitis C virus (HCV) has emerged as an important health problem in the era of effective HIV treatment. However, very few data exist on the health status and disease burden of HIV/HCV-coinfected Canadians. METHODS: HIV/HCV-coinfected patients were enrolled prospectively in a multicentre cohort from 16 centres across Canada between 2003 and 2010 and followed every 6 months. We determined rates of a first liver fibrosis or endstage liver disease (ESLD) event and all-cause mortality since cohort enrolment and calculated standardized mortality ratios compared with the general Canadian population. RESULTS: A total of 955 participants were enrolled in the study and followed for a median of 1.4 (interquartile range 0.5-2.3) years. Most were male (73%) with a median age of 44.5 years; 13% self-identified as aboriginal. There were high levels of current injecting drug and alcohol use and poverty. Observed event rates [per 100 person-years; 95% confidence interval (CI)] were: significant fibrosis (10.21; 8.49, 12.19), ESLD (3.16; 2.32, 4.20) and death (3.72; 2.86, 4.77). The overall standardized mortality ratio was 17.08 (95% CI 12.83, 21.34); 12.80 (95% CI 9.10, 16.50) for male patients and 28.74 (95% CI 14.66, 42.83) for female patients. The primary causes of death were ESLD (29%) and overdose (24%). CONCLUSIONS: We observed excessive morbidity and mortality in this HIV/HCV-coinfected population in care. Over 50% of observed deaths may have been preventable. Interventions aimed at improving social circumstances, reducing harm from drug and alcohol use and increasing the delivery of HCV treatment in particular will be necessary to reduce adverse health outcomes among HIV/HCV-coinfected persons.HIV Medicine 05/2012; DOI:10.1111/j.1468-1293.2012.01028.x · 3.45 Impact Factor