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Survival and HLA-B*57 in HIV/HCV Co-Infected Patients on Highly Active Antiretroviral Therapy (HAART).

Dold L, Ahlenstiel G, Althausen E, Luda C, Schwarze-Zander C, Boesecke C, Wasmuth JC, Rockstroh JK, Spengler U - PLoS ONE (2015)

Bottom Line: In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections.Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.

ABSTRACT

Background and aims: HLA class I alleles, in particular HLA-B*57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCV- and HIV/HCV- co-infection receiving HAART.

Methods: In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV- (n=120), HIV- (n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.

Results: At recruitment the proportion of patients carrying a HLA-B*57 allele differed between HIV- (12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.

Conclusion: Differences in the prevalence of HLA-B*57 at study entry between HIV- and HCV- infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B*57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLA-B*57 for survival in HIV/HCV infection depending on the circumstances.

No MeSH data available.


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Long-term follow up and patient disposition in the Bonn HIV and HCV cohort.
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pone.0134158.g001: Long-term follow up and patient disposition in the Bonn HIV and HCV cohort.

Mentions: The initial cohort comprised 639 HLA-typed patients who were stratified into the 3 study groups as summarized in Fig 1. Longitudinal follow-up data could not be obtained in 15.0–18.8 percent of patients in the study groups. Patients who did not have Caucasian descent (2% to 14.1% in each group) had to be excluded because their distribution of HLA alleles did not match the background population. To minimize recruitment bias, we excluded further 11 patients whose follow-up was less than 1 week. The remaining 468 patients (HLA-A n = 414, HLA-B n = 468) constitute the available study population, comprising 186 patients with HIV infection, 120 patients with chronic hepatitis C, and 162 patients with HIV/HCV co-infection. Demographic and clinical data are summarized in Table 1.


Survival and HLA-B*57 in HIV/HCV Co-Infected Patients on Highly Active Antiretroviral Therapy (HAART).

Dold L, Ahlenstiel G, Althausen E, Luda C, Schwarze-Zander C, Boesecke C, Wasmuth JC, Rockstroh JK, Spengler U - PLoS ONE (2015)

Long-term follow up and patient disposition in the Bonn HIV and HCV cohort.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524598&req=5

pone.0134158.g001: Long-term follow up and patient disposition in the Bonn HIV and HCV cohort.
Mentions: The initial cohort comprised 639 HLA-typed patients who were stratified into the 3 study groups as summarized in Fig 1. Longitudinal follow-up data could not be obtained in 15.0–18.8 percent of patients in the study groups. Patients who did not have Caucasian descent (2% to 14.1% in each group) had to be excluded because their distribution of HLA alleles did not match the background population. To minimize recruitment bias, we excluded further 11 patients whose follow-up was less than 1 week. The remaining 468 patients (HLA-A n = 414, HLA-B n = 468) constitute the available study population, comprising 186 patients with HIV infection, 120 patients with chronic hepatitis C, and 162 patients with HIV/HCV co-infection. Demographic and clinical data are summarized in Table 1.

Bottom Line: In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections.Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.

ABSTRACT

Background and aims: HLA class I alleles, in particular HLA-B*57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCV- and HIV/HCV- co-infection receiving HAART.

Methods: In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV- (n=120), HIV- (n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.

Results: At recruitment the proportion of patients carrying a HLA-B*57 allele differed between HIV- (12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.

Conclusion: Differences in the prevalence of HLA-B*57 at study entry between HIV- and HCV- infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B*57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLA-B*57 for survival in HIV/HCV infection depending on the circumstances.

No MeSH data available.


Related in: MedlinePlus