Hepatitis C Virus Coinfection Increases Mortality in HIV-Infected Patients in the Highly Active Antiretroviral Therapy Era: Data from the HIV Atlanta VA Cohort Study

Rollins School of Public Health at Emory University, Emory University, Atlanta, Georgia, USA.
Clinical Infectious Diseases (Impact Factor: 8.89). 12/2004; 39(10):1507-13. DOI: 10.1086/425360
Source: PubMed


We compared survival among patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) with that among patients infected solely with HIV.
Descriptive, bivariate, and survival analyses were conducted using data for all HIV-positive patients who were seen during the period of January 1997 through May 2001 in the HIV Atlanta VA Cohort Study (HAVACS) and who had been tested for HCV antibody since 1992 (n=970).
The prevalence of HCV coinfection was 31.6%, and coinfected patients were significantly more likely to be older, black, and injection drug users. In multivariate analysis, the duration of survival from the time of diagnosis of acquired immunodeficiency syndrome (AIDS) was significantly shortened for HIV-HCV-coinfected patients (hazard ratio [HR], 1.84; 95% confidence interval [CI], 1.09-3.10), as was time from HIV diagnosis to death (HR, 2.47; 95% CI, 1.26-4.82). Recovery of CD4+ cell count from the time of initiation of HAART did not differ significantly by coinfection status.
HCV coinfection is common in this HIV-infected population and negatively affects survival from the time of both HIV and AIDS diagnoses, although this is apparently not associated with a difference in CD4+ cell recovery while receiving HAART. These findings differ from those of a previous study that was conducted in this cohort in the pre-HAART era, which found no association between HIV-HCV coinfection and HIV disease progression.

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    • "Similarly, some ISRN Gastroenterology studies have shown that the incidence of AIDS defining illnesses are increased among HIV/HCV infected individuals compared to those with HIV monoinfection [11] [12] [13], while others have not confirmed this [7] [13]. Regardless of the specific outcomes, it is well established that individuals with HIV/HCV coinfection have significantly higher morbidity and mortality compared to individuals with HIV monoinfection [7] [12] [13]. However, specific predictors of mortality and how they differ in the HIV/HCV coinfected versus HIV monoinfected individuals in the era of HAART have not been well documented. "
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    ABSTRACT: Background. Understanding the predictors of mortality in individuals with human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfection can be useful in management of these patients. Methods. We used the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) for these analyses. Multivariate Cox-regression models were used to determine predictors of mortality. Results. Among 8,039 HIV infected veterans, 5251 (65.3%) had HCV coinfection. The all-cause mortality rate was 74.1 (70.4-77.9) per 1000 person-years (PY) among veterans with HIV/HCV coinfection and 39.8 (36.3-43.6) per 1000 PY for veterans with HIV monoinfection. The multivariable adjusted hazard ratio (95% confidence interval) of all-cause mortality for HCV infection was 1.58 (1.36-1.84). Positive predictors of mortality included decompensated liver disease (2.33 (1.98-2.74)), coronary artery disease (1.74 (1.32-2.28)), chronic kidney disease (1.62 (1.36-1.92)), and anemia (1.58 (1.31-1.89)). Factors associated with reduced mortality included HCV treatment (0.41 (0.27-0.63)) and higher CD4 count (0.90 (0.87-0.93) per 100 cells/ μ L higher count). Data were insufficient to make informative analyses of the role of HCV virologic response. Conclusion. HCV coinfection was associated with substantial increased risk of mortality among HIV infected veterans. HCV treatment was associated with significantly lower risk of mortality.
    Full-text · Article · Apr 2014
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    • "However, HCV may also impact HIV disease progression. For instance, HCV RNA levels are correlated with accelerated HIV disease progression [6]–[12], while HCV seropositivity is associated with an increased risk of death among treatment-experienced HIV-positive individuals [13]. Thus, additional investigation is warranted. "
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    ABSTRACT: Hepatitis C virus (HCV) co-infection occurs in ∼30-40% of the HIV-infected population in the US. While a significant body of research suggests an adverse effect of HIV on HCV replication and disease progression, the impact of HCV on HIV infection has not been well studied. Increasing data suggest that hepatocytes and other liver cell populations can serve as reservoirs for HIV replication. Therefore, to gain insight into the impact of HCV on HIV, the effects of the HCV Core protein and infectious hepatitis C virions were evaluated on basal and Tat-induced activation of the HIV long terminal repeat (LTR) in hepatocytes. The HIV LTR was highly induced by the HIV transactivator protein Tat in hepatocytes. Activation varied according to the number of NF-kB binding sites present in the LTRs from different HIV subtypes. Involvement of the NF-kB binding pathway in LTR activation was demonstrated using an NF-kB inhibitor and deletion of the NF-kB binding sites. TNFα, a pro-inflammatory cytokine that plays an important role in HIV pathogenesis, also induced LTR activity in hepatocytes. However, HIV LTR activity was suppressed in hepatocytes in the presence of HCV Core protein, and the suppressive effect persisted in the presence of TNFα. In contrast, infectious hepatitis C virions upregulated HIV LTR activation and gene transcription. Core-mediated suppression remained unaltered in the presence of HCV NS3/4A protein, suggesting the involvement of other viral/cellular factors. These findings have significant clinical implications as they imply that HCV could accelerate HIV disease progression in HIV/HCV co-infected patients. Such analyses are important to elucidate the mechanisms by which these viruses interact and could facilitate the development of more effective therapies to treat HIV/HCV co-infection.
    Preview · Article · Jun 2013 · PLoS ONE
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    • "A large cohort study of HIV-1-infected subjects has demonstrated that HCV co-infection with HIV-1 accelerated the progression to a new AIDS-defining clinical event or to death through altering the immunological but not virological responses to HAART [5]. Several small cohort studies observed that a faster disease progression was coincident with HCV coinfection with HIV-1 [17]–[20]. However, the association between HCV coinfection and AIDS-related disease progression was not defined in EuroSIDA cohort study and several other studies [21]–[23]. "
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    ABSTRACT: It remains controversial how HCV coinfection influences the disease progression during HIV-1 infection. This study aims to define the influence of HCV infection on the replication of HIV-1 and the disease progression in HIV-infected former plasma donors (FPDs) naïve to ART. 168 HIV-1-infected FPDs were enrolled into a cohort study from Anhui province in central China, and thereafter monitored at month 3, 9, 15, 21 and 33. Fresh whole blood samples were used for CD4+ T-cell counting. Their plasma samples were collected and stored for quantification of HIV-1 viral loads and for determination of HCV and Toxoplasma. Out of 168 HIV-infected FBDs, 11.9% (20 cases), 80.4% (135 cases) and 7.7% (13 cases) were infected with HIV-1 alone, HIV-1/HCV and HIV/HCV/Toxoplasma, respectively. During the 33-month follow-up, only 35% (7 out of 20 cases) HIV-1 mono-infected subjects remained their CD4+ T-cell counts above 200 cells/microl and retained on the cohort study, which was significantly lower than 56% (75 out of 135 cases) for HIV/HCV group and 69% (9 out of 13 cases) for HIV/HCV/Toxoplasma group (p<0.05). CD4+ T cells in HIV mono infection group were consistently lower than that in HIV/HCV group (p = 0.04, 0.18, 0.03 and 0.04 for baseline, month 9, month 21 and month 33 visit, respectively). In accordance with those observations, HIV viral loads in HIV mono-infection group were consistently higher than that in HIV/HCV group though statistical significances were only reached at baseline (p = 0.04). These data indicated HCV coinfection with HIV-1 is associated with the slower disease progression at the very late stage when comparing with HIV-1 mono-infection. The coinfection of Toxoplasma with HIV and HCV did not exert additional influence on the disease progression. It will be highly interesting to further explore the underlying mechanism for this observation in the future.
    Full-text · Article · Dec 2008 · PLoS ONE
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