During June and July 2002, I was fortunate to attend two conferencesÑthe NIH Consensus Development Conference and the International AIDS Conference in Barcelona. Both of these meetings could have a great impact on the treatment of hepatitis C (HCV) and HIV and on those co-infected with HIV and hepatitis C virus. Following a brief introduction to HCV and HIV/HCV co-infection, I will review each conference from the point of view of co-infection issues.

Hepatitis C Virus Infection

HCV infection is increasing in the United States and around the world today. It is estimated that HCV has infected 170 to 240 million people worldwide. HCV infection is the most common chronic blood-borne infection in the United States.

Most people are chronically infected and might not be aware of their status because they may not display any symptoms. HCV-Infected people may transmit the virus to others and are at risk for chronic liver disease.

HCV/HIV Coinfection

Approximately 34.3 million people, worldwide, are living with HIV/AIDS. Forty percent (40%) or more of all those infected with HIV are already co-infected with HCV. For those with a history of injection drug use, the incidence rate for co-infection with HIV and HCV is between 60% to 96%.1,2 There is every reason to believe that the co-infection rate will only increase over the next decade.

Due to their similar transmission modes, an increasing number of people with either HIV or HCV or hepatitis B (HBV) are becoming infected with the other viruses. Because the widespread use in developed countries of highly active antiretroviral therapy (HAART) has improved survival rates for people with HIV, those co-infected with HIV and HCV are dying in increasing numbers as a result of their HCV infection, not their HIV infection.

People with co-infection of HIV/HCV have at least double the risk of developing severe liver damage, and there is some evidence that the course of liver disease development is more progressive in these patients.3

NIH Consensus Development Conference: Management of Hepatitis C

On June 10-12, 2002, a National Institutes of Health (NIH) Consensus Development Conference was held at the NIH campus in Bethesda, Maryland. The only other previous NIH conference on HCV was held in 1997, and that conference was held prior to current treatment advances, and improved technologies for treating HCV in people with HIV/AIDS in the US. Therefore, the 2002 conference was a very important development for all who are infected and affected by HCV. A preliminary draft statement was released by NIH on the last day of the conference and the Final Statement was released by NIH on August 27, 2002.

During the first day and a half of the conference, experts presented the latest HCV findings to an independent non-federal panel. After weighing all of the scientific evidence, the panel drafted a statement that addressed the following key questions4:

"     What is the natural history of HCV?

"     What is the most appropriate approach

to diagnose and monitor patients?

"     What is the most effective

therapy for HCV?

"     Which patients with HCV

should be treated?

"     What recommendations can be made to patients to prevent transmission of HCV?

"     What are the most important areas

for future research?

On the final day of the conference, the panel chairperson Dr. James L. Boyer read the draft statement to the conference attendees. At the end, advocates, physicians, and people with HCV had an opportunity to make comments and suggestions for the panel's consideration.

A press conference followed so that the media could ask questions of the panel and chairperson, James L. Boyer, MD, Ensign Professor

of Medicine, Departments of Internal Medicine and Digestive Diseases Director, Liver Center, Yale University School of Medicine, New Haven, Connecticut

The NIH Consensus Statement (see sidebar) presented guidelines for diagnosis and treatment and identified areas for future research. Many of the HCV activists, clinicians and caregivers were pleased with the Preliminary Draft Consensus Statement.

Data presented by international experts during the conference included the following:

"     2.7 million Americans have chronic

HCV infection (other estimates,

including CDC, are higher)1

"     Genotype 1a is the most common

genotype in the United States; 1b is

the most common worldwide.

"     The highest incidence of HCV occurs in people between 30 and 49 years of age.

"     68% of acute infections are due to injection drug use (IDU).

"     HCV RNA testing can identify virus in the blood within 7 to 14 days of infection.

"     Liver biopsy yields information on level of fibrosis and histology assessment that is not obtainable by other means.

"     Radiologic imaging (ultrasound, MRI, etc) is not reliable in diagnosing cirrhosis. Research is needed to develop noninvasive diagnostics.

"     15% to 45% of non-immune compromised healthy individuals who become infected with HCV will recover spontaneously.

"     Rates of sexual transmission vary

from 4% to 6%. In monogamous

couples, the risk is 2% to 4%.

"     Prospective studies identify the risk of progressive liver disease after 20 years

as approximately 2% to 4%

"     Liver-disease progression is influenced by age, gender, alcohol use, steatosis/fatty liver, HIV status, metabolic disorders (such as diabetes), and being overweight.

"     Little evidence was shown that the risk of liver-disease progression is associated with viral load, genotype, or quasispecies diversity.

"     HCV accounts for an estimated one-third of liver carcinoma in the United States.

"     HCV accounts for 37% of liver transplants

"     HCV accounts for approximately 4,000 deaths each year. (Although the official estimate by CDC states that in the US alone there are 8,000 to 10,000 deaths annually.)  

"     Even in the absence of severe liver disease, people with HCV may experience a number of extrahepatic manifestations including arthritic symptoms, keratoconjunctivitis sicca, lichen planus, glomerulonephritis, porphyria cutanea tarda, and essential mixed cryoglobulinemia.

"     Treatment response rates between 33% and 41% have been achieved with combination pegylated interferon and Ribavirin.

"     Treatment is recommended for patients who are at increased risk for progression to cirrhosis.

"     In certain situations, combination therapy may be stopped at week 12 if there is inadequate viral response.

"     Treatment-response rates depend on genotype and viral load.

 

"     The HALT-C trials are looking at the effects of long-term therapy.

"     In HCV-infected people with persistent elevated ALT levels with no fibrosis and little inflammation, progression to cirrhosis is likely to be slow or unlikely depending partially on the amount of time since initial exposure. Periodic monitoring was suggested.

"     All HIV-infected people should be screened for HCV.

"     Co-infection with HIV can accelerate the course of HCV and liver disease.

"     Little data is available on pharmaceutical treatment of injection drug users.

"     People infected with HCV should be vaccinated against hepatitis A and B.

"     HCV antibodies provide no protective immunity. This means re-infection after spontaneous recovery or pharmaceutical treatment is possible.

"     Campaigns to educate the general population about risk behaviors and to promote prevention and encourage organ donation are needed.

"     Additional funding is needed to increase research in the areas of prevention, diagnosis, and treatment.

Report from the 14th International AIDS Conference, Barcelona 2002: Focus on HIV/Hepatitis Co-Infection

The 14th International AIDS Conference was held in Barcelona, Spain, for seven intense days in July 2002. More than 14,000 people from every continent attended this important event. One of my main goals during the conference was to focus intensively on co-infection with HIV and hepatitis viruses. This year there were many more sessions on HIV/hepatitis co-infection than at previous conferences. Out of a total of 8,824 conference abstracts, there were 303 that included references to HCV and 52 that included references to HBV.5

The not-so-good news was that the abstracts and sessions pointed to a vast increase in co-infection rates in HIV and hepatitis B and C. Also, the abstracts revealed very little on the horizon regarding improvements in traditional treatment strategies.

During the conference it was reported that the significant hepatitis co-infection issues are the same in all countries. The main issues are making available testing for HCV and HBV; reducing transmission of viral hepatitis through education about transmission; preventing progression of disease through education around lifestyle changes; and making treatment decisions about to when to treat for each virus and disease process. However, in areas where HAART and/or hepatitis treatments are not readily available, the priority for medical treatment lands at the bottom of the list.

The range of topics reported in oral and poster sessions included epidemiology of HIV, HBV, and HCV; risk factors, including intravenous drug use, sexual transmission, and vertical (mother-to-infant) transmission; prevention of infection; progression of liver disease in those with co-infection; risk

of fibrosis in co-infection; side-effects of antiretroviral treatment in people co-infected with HCV; epatotoxicity with the use of HAART; and integrating hepatitis C into HIV/AIDS programs.6

Several key issues dominated the co-infection reports at this conference. They are summarized below.

More rapid progression to liver fibrosis and cirrhosis occurs in HIV/HCV co-infected patients

The conference added to previous knowledge with additional reports from larger studies in Spain,7 the United States,8 the United Kingdom,9 and Germany10 that confirmed earlier indications that there is more rapid progression to fibrosis and cirrhosis in those co-infected with hepatitis C and HIV than those infected with hepatitis C alone. There were also indications from some of the studies that the more rapid progression to fibrosis occurred in those with higher HCV viral load and lower CD4 (helper T-cell) counts.

Increased sexual transmission of HIV and HBV, but not HCV, was found in non-injecting drug users.

New injecting drug users (IDUs) are at substantial risk for sexually transmitted HIV. In particular, women who recently initiated drug injecting and new IDUs who share syringes are more likely to engage in unprotected sex and to have high-risk sex networks. Sex risk, especially among female recently initiated IDUs, as well syringe sharing, need to be equally targeted to prevent HIV, as well as HBV and HCV transmission among new IDUs.11 Non-injecting drug users (NIUs) who engage in unsafe sex and have high-risk sex networks are at risk of becoming infected with HBV and HIV. However, HCV seroconversion was not associated with sex risk.12

Antiviral treatments for hepatitis have moderate effects

Not much new was revealed in the area of treatment of co-infection. As noted in previous settings, combination therapy with pegylated interferon/ribavirin has about the same range of efficacy in HIV/HCV co-infected people as in HCV alone. Adefovir dipovoxil was shown to be useful in lamivudine-resistant HBV.13

 

Antiretroviral treatments for HIV may increase HCV emergence and liver toxicity in co-infected people

Abstracts from several countries, including from Cote d'Ivoire,14 Italy,15 Canada,16 and Australia,17 suggested that HIV-positive people might suffer increased liver toxicity and HCV emergence from HIV anti-retroviral medications.

Harm-reduction strategies reduce transmission and are needed more widely

Reports from Thailand, Argentina,18 the United States, Canada,19 Romania, Pakistan,20 Indonesia,21 China, Brazil,22 Spain,23 and France indicated both the success of and need for harm-reduction strategies for preventing transmission of HIV, HBV, and HCV. These strategies included needle-exchange programs, encouraging drug users to switch to non-injection drug practices, and use of condoms. While vaccination against hepatitis A (HAV) and HBV was mentioned in various abstracts, it was as an aside in most of them. One interesting finding was that US military members who seroconverted since 1994 have an extremely low rate of HCV co-infection compared to other HIV-infected populations; the authors attributed this low seroprevalence rate to the "no drug use" policy in the US military, where soldiers routinely undergo periodic, random drug screenings.24 On a different note, there was also a call for United States prisons, the world's second largest prison system, to adopt harm-reduction strategies such as needle exchange, methadone maintenance programs, and condom and dental dam distribution, to prevent the growing epidemic of HIV, HCV, and HBV within prisons.25

Barriers to treatment for co-infection must be overcome for treatment availability and success

Several studies showed that mental health and psychiatric issues were prevalent among people with co-infection, yet there was relative lack of treatment for both HIV and HCV in these populations.26,27 Also, current drug addiction was also found to be a treatment barrier.28,29 Pilot programs showed that it was important to review treatment options on a case by case basis instead of not offering treatment based on mental illness or current drug addiction.30

 

SUMMARY

The 2002 AIDS Conference confirmed much

of what we had surmised about hepatitis/HIV co-infection. New studies helped us to better understand risk, epidemiology, harm reduction and the serious consequences of co-infection.

We can make the following conclusions after this conference

"     Co-infection with hepatitis and HIV is a growing problem. People co-infected with hepatitis and HIV are at increased risk for rapid disease progression, especially advanced liver disease, including fibrosis and cirrhosis.

"     Little new was presented on pharmaceutical treatment for HCV, although adefovir was shown to be effective in treating HBV infection.

"     For people with co-infection, data relating to increased liver toxicity indicated that there may be an increased emergence of HCV when HIV drugs are given to people with co-infection.

"     Risk reduction is especially important for people with either hepatitis and/or HIV infection to avoid co-infection. Harm-reduction strategies need to be implemented more widely to reduce transmission and disease severity.

"     There is a need to improve and create more inclusive treatment for co-infected patients who are dually and triply diagnosed with psychiatric illness and addiction.

See Misha Cohen's bio on page 19.

 References

     1.   Perez-Hoyos S, Sanvisens A, Catala R, Fuster D, Del Amo J, Hernandez-Aguado I, Muga R. Epidemiology of HIV and hepatitis C coinfection among injecting drug users. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7489]

     2. Uzdaviniene V, Rakickiene J, Chaplinskas S, Griskevicius A. Prevalence of viral hepatitis B and C among HIV-infected people in Lithuania. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract C10978]

     3.   Cohen M and Gish. The Hepatitis C Help Book. St, Martin's Press, 2000; p. 68.

     4.   NIH Consensus Development Conference: Management of Hepatitis C: 2002 handout.

     5.   Knowledge and Commitment for Action. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. <www.aids2002.com>

     6.   Ibid.

     7.   Arizcorreta C, Martinez C, Diaz F, Roldan R, Martin-Herrera L, Perez-Guzman E. Natural history of chronic hepatitis C: Unusually rapid progression to liver fibrosis and cirrhosis in human immunodeficiency virus co-infected patients. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract WePeB6036]

     8.   Stellrecht KA, McKenna B, Graffunder E. Risk for the development of HCV-related fibrosis in HIV-positive patients. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract WePeB6020]

     9.   Mohsen AH, Taylor C, Portmann B, Norris S, Kulasegaram R, Murad S. Progression rate of liver fibrosis in human immunodeficiency virus and hepatitis C virus co-infected patients, UK experience. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract MoOrB1057]

     10.  Klausen G, Kolberg J, Niedobitek F, Goelz J, Moll A, Schleehauf D, Prziwara D, Cordes C. Liver biopsy in HIV/HCV co-infected patients. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract WePeB6023]

     11.  Gyarmathy VA, Neaigus A, Miller M. Increased sexual risk among women who recently initiated drug injecting. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract MoPeC3398]

     12.  Neaigus A, Gyarmathy VA, Miller M, Friedman SR, Des Jarlais DC. Sexual risk and HIV, HBV and HCV seroconversions among non-injecting heroin users. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract MoPeC3528]

     13.  Benhamou Y, Bochet M, Thibault V, et al. Safety and efficacy of long-term adefovir dipivoxil (ADV) for lamivudine-resistant (Lam-R) HBV in HIV infected patients. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7528]

     14.  Dakoury C, Eholie S, Aka-Kakou R, Bissagnene E, Konan-Koko R, Kadio A. Role of viral infections HCV and HBV in liver toxicity among patients receiving antiretroviral treatment in HIV drugs access initiative in Cote d'Ivoire. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract MoPeB3280]

     15.  Dorrucci M, Valdarchi C, Castelli F, Zaccarelli M, Pezzotti P, Rezza G. The effect of HIV-HCV coinfection in a cohort of HIV-serconverters before and after the introduction of HAART. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7502]

     16.  Klein MB, Lalonde RG, Suissa S. Hepatitis C (HCV) co-infection is thwarting health improvements associated with highly active antiretroviral therapy (HAART). Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7515]

     17.  French MAH, Stone SF, Lee S, Keane NM, PPrice P. Hepatotoxicity after HAART in HIV/HCV

co-infected patients is associated with increased HCV core-specific IgG antibody and sCD26 (DDP IV) enzyme activity. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract B10538]

     18.  Lottero M, Lavarello D, Toledo A, et al. Harm reduction within public health systems: linking intravenous drug users, IDUs, with a primary care health center of Rosario, Argentina. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract TuPeF5276]

     19.  Miller CL, Spittal PM, Laliberte N, Li K, O'Shaughnessy MV, Schechter MT. Risk factors for HIV and HCV prevalence and incidence among young injection drug users in a city coping with an epidemic. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract MoPeC3401]

     20.  Ghauri AK, Rehman N, Azam S, Shah SA. Harm reduction program for injecting drug users (IDUs) in Karachi, Pakistan. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract TuPeF5272]

     21.  Nugraha SAM. Harm reduction in Indonesia. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeE7899]

     22.  Villarinho L, Gravato N, Barreto AS, Novaes E, Queija Santos T. Filters for crack users: a new harm reduction strategy in Santos, Brazil. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract TuPeF5258]

     23.  Bolao F, Sanvisens A, Egea JM, Shaw E, Navio M, Muga R. HIV-1 and hepatitis C virus infections among recent injecting drug users. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract MoPeC3380]

     24.  Crum NF, Brodine SK, Grillo M, Wallace MR. Absence of Hepatitis C Virus (HCV) infection amoung HIV-infected U.S. military members. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7504]

     25.  Reynolds A and the HIV and HCV in Prison Committee. The need for harm reduction in U.S. prisons: an activist's view. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract WeOrE1320]

     26.  Taylor LE, Tashima KT, Alt E, Feller ER, Costello T, Flanigan TP. Addiction and mental illness are barriers to Hepatitis C treatment among HIV/Hepatitis C virus co-infected individuals. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7513]

     27.  Marsh BJ, Rosenberg SD, Butterfield MI, Constantine NT, Essock SM, Goodman LA, Osher FC, Swartz MS, Wolford GL. Comorbidity of human immunodeficiency virus, hepatitis B virus and hepatitis C virus in people with severe mental illness. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract B10540]

     28.  Taylor LE, Tashima KT, Alt E, Feller ER, Costello T. Addiction and mental illness are barriers to Hepatitis C treatment among HIV/Hepatitis C virus co-infected individuals. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7513]

     29.  Calzavara L, Orekhovsky V, Yakovlev A, Nikitina T, Volkova G, Michalchenko M, Saldanha V. Fuelling HIV epidemic in Russia: the stigma of IDU and HIV and its impact on treatment access and testing. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPpE2153]

     30.  Schwartzapfel B, Taylor LE, MacLeod C, Feller ER, Rich JD, Tashima KT. A pilot program for treating hepatitis C in HIV/hepatitis C virus co-infected individuals with comorbid psychiatric illness and/or addiction. Abstracts of the 14th International Conference on AIDS, Barcelona, 2002. [Abstract ThPeC7512]