HIV and Hepatitis C CoInfection

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HIV and Hepatitis C Co-Infection A very present
and growing health challenge
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Topics

• Comparison of HCV and HIV
• Epidemiology of HIV-HCV co-infection in the U.S.
• Impact of HIV upon the natural history of HCV
• Impact of HCV upon the natural history of HIV
• Impact of HAART therapy upon HCV

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Human Immunodeficiency Virus(HIV)

• ssRNA -Retrovirus
• Produce 1010 to 1011 virions/d
• High diversity (11 clades)
• Lymphocyte factory
• Receptors CD4, CCR5

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Hepatitis C Virion(HCV)

• ssRNA Flavivirus
• Virions produced per day 1012
• Diversity 6 genotypes
• Hepatocyte factory
• Receptors LDL, CD81
• Adapted from Robert Murphy, MD

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• Epidemiology of HIV-HCV Infection in the United
  States

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HIV-HCV Coinfection in the United States
X100,000
Adapted from David Thomas, M.D.
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HIV-HCV Coinfection Prevalence in a Southeast DC
Clinic
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HIV-HCV Coinfection Prevalence Johns Hopkins HIV
Clinic
Preva l ence
IDU Hetero MSM Total
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Impact of HCV upon HIV Impact of HIV upon HCV
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Increased Deaths from ESLD in Patients with HIV
and HCV
1/3 of 1998 cohort stopped HAART due to liver
toxicity More than ½ died with NDVL or CD4 gt200
mm3 prior.
ESLD Dea t h s
1991 1996 1998
Bica et al. Clin Infect Dis. 200132492-497
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HIV and HCV Natural History

• HIV co-infection accelerates HCV fibrosis
  progression (Benhamou, Hepatology 1999301054
  and DiMartino 2001.)
• Increased rate of ESLD (Bica, CID 2001)
• Of those that died in the Bica study, 55 had HIV
  viral loads that were undetectable or CD4gt500

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HCV may blunt CD4 response to HAART
Swiss Cohort Study
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Does HCV Accelerate HIV Disease Progression

• Swiss Cohort Study- Prospective Study of 3111
  patients
• 1954 HCV and 1157 HCV
• End points
• New OI or death
• Increased CD4 gt50, decreased VL
• Hepatitis C independently associated with
  decreased survival and HIV progression at 2 years

Greub et al. Lancet 2000 3561800 1805
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Effect of HCV on HIV disease progression

• Data are still preliminary
• Evidence for HCV replication in PBMC
• Early studies show no influence of HCV on HIV
  progression, BUT..
• These studies were not controlled for duration of
  HIV disease
• AND HCV may adversely affect the ability to
  tolerate HAART due to liver toxicity

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Morbidity and Mortality in HIV-HCV

• Retrospective study of 80 HIV-HCV co-infected
  patients compared to a matched population with
  HCV alone
• Multivariate analysis demonstrated these
  predictors of progression to cirrhosis
• Age at HCV infection RR 1.18
• CD4 count lt200 mm3 RR 4.06
• IFN therapy appears to be protective RR 0.21

DiMartino et al. Hepatology 2001341193-1199.
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Treatment Benefits

• Viral eradication
• Delay fibrosis progression
• Prevent adverse clinical outcomes
• Hepatic decompensation
• Hepatocellular carcinoma
• Death
• Improve tolerability and ? Effectiveness of HAART

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"You must be the change you wish to see in the
world." -Mahatma Gandhi

• Hundreds will become infected every day until we
  have effective, sustainable interventions for
  prevention, treatment and care.