# Presentation: 031498

## HIV and Hepatitis C Co-Infection

**A very present and growing health challenge**

## 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**

## Human Immunodeficiency Virus(HIV)

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

## Hepatitis C Virion(HCV)

- +ssRNA – Flavivirus
- Virions produced per day: 1012
- Diversity: 6 genotypes
- Hepatocyte factory
- Receptors: LDL, CD81
***Adapted from Robert Murphy, MD***

**Epidemiology of HIV-HCV Infection in the United States**

## HIV-HCV Coinfection in the United States

**Adapted from David Thomas, M.D.**

- X100,000

## HIV-HCV Coinfection Prevalence in a Southeast DC Clinic 

## HIV-HCV Coinfection Prevalence Johns Hopkins HIV Clinic

- Preva l ence

**IDU  ****     ****Hetero****        ****MSM****   ****Total**

## Impact of HCV upon HIV

**Impact of HCV upon HIV**
**Impact of HIV upon HCV**

## Increased Deaths from ESLD in Patients with HIV and HCV

- ESLD
- Dea t h s

**1991 ****    ****1996  ****      ****1998**

***Bica et al.  Clin Infect Dis. 2001;32:492-497***

**1/3 of 1998 cohort stopped HAART due to liver toxicity**
**More than 1⁄2 died with NDVL or CD4 >200 mm****3**** prior.**

## HIV and HCV Natural History

- HIV co-infection accelerates HCV fibrosis progression (Benhamou, Hepatology 1999;30:1054 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 CD4>500

## HCV may blunt CD4 response to HAART

**Swiss Cohort Study**

## 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 >50, decreased VL**
- Hepatitis C independently associated with decreased survival and HIV progression at 2 years

***Greub et al.  Lancet 2000; 356:1800 – 1805***

## 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

## 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**
**CD****4**** count <200 mm3  RR = 4.06**
- IFN therapy ‘appears’ to be protective RR= 0.21

***DiMartino et al.  Hepatology 2001;34:1193-1199.***

## Treatment  Benefits

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

## "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.