Coinfection with hepatitis C virus (HCV) in human immunodeficiency virus (HIV) type 1-infected patients may decrease the effectiveness of highly active antiretroviral therapy. We determined the impact of HCV infection on response to highly active antiretroviral therapy and outcome among Danish patients with HIV-1 infection.
This prospective cohort study included all adult Danish HIV-1-infected patients who started highly active antiretroviral therapy from 1 January 1995 to 1 January 2004. Patients were classified as HCV positive (positive HCV serological test and/or HCV PCR results [443 patients [16%]]), HCV negative (consistent negative HCV serological test results [2183 patients [80%]]) and HCV-U (never tested for HCV [108 patients [4%]]). The study end points were viral load, CD4+ cell count, and mortality.
Compared with the HCV-negative group, overall mortality was significantly higher in the HCV-positive group (mortality rate ratio, 2.4; 95% confidence interval [CI], 1.9-3.0), as was liver disease-related mortality (mortality rate ratio, 16; 95% CI, 7.2-33). Furthermore, patients in the HCV-positive group had a higher risk of dying with a prothrombin time <0.3, from acquired immunodeficiency syndrome-related disease, and if they had a history of alcohol abuse. Although we observed no difference in viral load between the HCV-positive and HCV-negative groups, the HCV-positive group had a marginally lower absolute CD4+ cell count.
HIV-HCV-coinfected patients are compromised in their response to highly active antiretroviral therapy. Overall mortality, as well as mortality from liver-related and acquired immunodeficiency syndrome-related causes, is significantly increased in this patient group.
"CBP2 (also known as HSP47) is an ER resident protein involved in collagen synthesis. The observed up-regulation of CBP2 correlates with previous studies demonstrating significant increases in collagen deposition in HIV-1-infected tissue samples
[34,35]. GST constitutes the major intracellular antioxidant defense against reactive substances (RS) and oxidative stress. "
[Show abstract][Hide abstract] ABSTRACT: Background
Pathogenesis of liver damage in patients with HIV and HCV co-infection is complex and multifactorial. Although global awareness regarding HIV-1/HCV co-infection is increasing little is known about the pathophysiology that mediates the rapid progression to hepatic disease in the co-infected individuals.
In this study, we investigated the proteome profiles of peripheral blood mononuclear cells from HIV-1 mono-, HCV mono-, and HIV-1/HCV co-infected patients. The results of high-resolution 2D gel electrophoresis and PD quest software quantitative analysis revealed that several proteins were differentially expressed in HIV-1, HCV, and HIV-1/HCV co-infection. Liquid chromatography-mass spectrometry and Mascot database matching (LC-MS/MS analysis) successfully identified 29 unique and differentially expressed proteins. These included cytoskeletal proteins (tropomyosin, gelsolin, DYPLSL3, DYPLSL4 and profilin-1), chaperones and co-chaperones (HSP90-beta and stress-induced phosphoprotein), metabolic and pre-apoptotic proteins (guanosine triphosphate [GTP]-binding nuclear protein Ran, the detoxifying enzyme glutathione S-transferase (GST) and Rho GDP-dissociation inhibitor (Rho-GDI), proteins involved in cell prosurvival mechanism, and those involved in matrix synthesis (collagen binding protein 2 [CBP2]). The six most significant and relevant proteins were further validated in a group of mono- and co-infected patients (n = 20) at the transcriptional levels.
The specific pro- and anti- apoptotic protein signatures revealed in this study could facilitate the understanding of apoptotic and protective immune-mediated mechanisms underlying HIV-1 and HCV co-infection and their implications on liver disease progression in co-infected patients.
"Several studies reported a reduced CD4+ T-cell count recovery in patients with HIV and HCV co-infection with respect to patients with HIV alone [6-13]. This conclusion was further supported by a meta-analysis , but was not confirmed by other results [15-17]. "
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to explore the effects of HCV co-infection on virological effectiveness and on CD4+ T-cell recovery in patients with an early and sustained virological response after HAART.
We performed a longitudinal analysis of 3,262 patients from the MASTER cohort, who started HAART from 2000 to 2008. Patients were stratified into 6 groups by HCV status and type of anchor class. The early virological outcome was the achievement of HIV RNA <500 copies/ml 4-8 months after HAART initiation. Time to virological response was also evaluated by Kaplan-Meier analysis. The main outcome measure of early immunological response was the achievement of CD4+ T-cell increase by ≥100/mm3 from baseline to month 4-8 in virological responder patients. Late immunological outcome was absolute variation of CD4+ T-cell count with respect to baseline up to month 24. Multivariable analysis (ANCOVA) investigated predictors for this outcome.
The early virological response was higher in HCV Ab-negative than HCV Ab-positive patients prescribed PI/r (92.2% versus 88%; p = 0.01) or NNRTI (88.5% versus 84.7%; p = 0.06). HCV Ab-positive serostatus was a significant predictor of a delayed virological suppression independently from other variables, including types of anchor class. Reactivity for HCV antibodies was associated with a lower probability of obtaining ≥100/mm3 CD4+ increase within 8 months from HAART initiation in patients treated with PI/r (62.2% among HCV Ab-positive patients versus 70.9% among HCV Ab-negative patients; p = 0.003) and NNRTI (63.7% versus 74.7%; p < 0.001). Regarding late CD4+ increase, positive HCV Ab appeared to impair immune reconstitution in terms of absolute CD4+ T-cell count increase both in patients treated with PI/r (p = 0.013) and in those treated with NNRTI (p = 0.002). This was confirmed at a multivariable analysis up to 12 months of follow-up.
In this large cohort, HCV Ab reactivity was associated with an inferior virological outcome and an independent association between HCV Ab-positivity and smaller CD4+ increase was evident up to 12 months of follow-up. Although the difference in CD4+ T-cell count was modest, a stricter follow-up and optimization of HAART strategy appear to be important in HIV patients co-infected by HCV. Moreover, our data support anti-HCV treatment leading to HCV eradication as a means to facilitate the achievement of the viro-immunological goals of HAART.
AIDS Research and Therapy 06/2012; 9(1):18. DOI:10.1186/1742-6405-9-18 · 1.46 Impact Factor
" risk factor for acquiring ( HCV ) ( Antiretroviral Therapy Cohort Collaboration , 2007 ) were neither a predictor in our cohort , nor was hepatitis C co - infection . Advanced immunosuppres - sion translates into faster disease progression in patients co - infected with hepatitis C virus ( HCV ) ( Backus et al . , 2005 ; Dorrucci et al . , 2004 ; Weis et al . , 2006 ) . A quarter of our cohort population was HIVÁHCV co - infected ; however , co - infection was not associated with decreased survival . In our full cohort , both CAD and renal insufficiency had a significant negative impact on survival . Both CAD and renal insufficiency have been associated with increased mortality among HIV - infected"
[Show abstract][Hide abstract] ABSTRACT: Survival among HIV-infected patients markedly improved with the introduction of highly active antiretroviral therapy (HAART). Easier to take and more effective HAART options have improved the one-year virologic success rate among naive patients. Numerous studies have shown that initiating HAART and restoration of CD4 cells positively impact survival. There are only a few evaluations that have been carried out on the changes in survival among patients who are severely immunosuppressed. We evaluated survival among a cohort of veterans with CD4<100 cells/mm(3) (CD4 < 100) in three time periods reflecting early, mid, and recent HAART. Using the HIV clinic database, all patients with CD4 < 100 seen between 1996 and 2004 were identified (n=394). Patients entered Cohorts 1 (n=219), 2 (n=72), and 3 (n=103) in 1996-1998, 1999-2001, and 2002-2004, respectively. Data on demographics, AIDS-defining illnesses, co-morbidities, treatment, CD4, and viral load (VL) were abstracted. Survival analysis controlling for the above variables was performed and odds ratios with 95% confidence intervals were calculated. Rate of virologic suppression was higher for Cohort 2 when compared to Cohort 1 (63% vs. 46%, p<0.05), but lower for Cohort 3 when compared to Cohort 2 (49%, p<0.05). Survival at one year was high for Cohorts 1 and 2 (92-95%), but significantly lower in Cohort 3 (80%). On logistic regression analysis and for the whole cohort, HAART use, achieving a CD4 > 200 and VL<400 were independent predictors of survival. Older age at cohort entry and having a diagnosis of lymphoma, Mycobacterium avium complex infection, coronary artery disease, or renal insufficiency were negative predictors. In the most recent HAART period 2002-2004, one year survival after CD4 < 100 significantly decreased in spite of availability of specialized HIV clinical and support services and antiretrovirals. Our results suggest that more than better drugs are needed for improving survival among certain patient populations with advanced immunosuppression.
AIDS Care 07/2010; 22(7):886-94. DOI:10.1080/09540120903499162 · 1.60 Impact Factor
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