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HCV/HIV Coinfection in Asia
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Recognition of Hepatitis C Virus Coinfection in HIV-Positive Injecting Drug Users in Asia
[Letters to the Editor]
JAIDS Journal of Acquired Immune Deficiency Syndromes:Volume 45(3)1 July 2007pp 363-365
Walsh, Nick MBBS, MPH, BSc(med)Hons*; Higgs, Peter BSW, MA; Crofts, Nick MBBS, MPH, FAFPHM*
*Turning Point Alcohol and Drug Centre Melbourne, Australia; Department of Epidemiology and Preventive Medicine Monash University Melbourne, Australia; Macfarlane Burnet Institute for Medical Research and Public Health Melbourne, Australia
To the Editor:
HIV and hepatitis C (HCV) are readily transmitted by the sharing of injecting equipment. It has been estimated that there are 2 to 9 million injecting drug users (IDUs) in the Asia Pacific region,1 of whom approximately 750,000 are living with HIV.2 Injecting drug use is a major mode of HIV transmission in many Asian countries, accounting for more than 30% of infections in Myanmar; 40% in China; and most infections in Vietnam, Indonesia, and Malaysia. This is superimposed on a geographically varied high population prevalence of HCV. Prevalence across Asia can be explained by unsterile medical injections,3,4 contaminated transfusions,5-7 traditional cultural practices,6 and, more recently, injecting drug use.1
There are few studies on the prevalence of HCV and HIV coinfection in Asia, although all demonstrate almost universal HCV infection in HIV-infected IDUs.8-10 Increasing coinfection as a proportion of HIV infections in some countries indicates that although sexual transmission of HIV may be reducing, transmission through sharing injecting equipment continues. A Thai study found that although the prevalence of HIV in military recruits (a marker of population HIV prevalence) decreased from 2.4% to 1.1% between 1995 and 2000, the proportion coinfected increased from 20.8% to 49.5% during the same period.11
Once an individual is coinfected with HCV and HIV, one infection influences the outcome of the other, although there are conflicting reports on the impact of HCV on HIV disease progression. HCV coinfection has been associated with lower baseline CD4 cell counts in untreated patients with similar viral loads, accelerated progression to an AIDS-defining condition, and a smaller degree of immune reconstitution after initiation of antiretroviral therapy (ART).12,13 In the latter HIV outpatient study, HCV infection did not statistically influence survival. Other longitudinal studies have agreed, showing that HCV does not influence HIV progression when adjusted for ART, although a more recent study showed that HCV was associated with lower CD4 cell counts, independent of other factors.14,15 In contrast to single genotype infection, multiple HCV genotype infection may accelerate the progression of HIV disease,16 disproportionally affecting those placed at continuous risk of acquiring HCV, such as IDUs. Injecting drug use is associated with multiple genotype infection,17 a high incidence of HCV infection,8 and reinfection with similar genotypes.18
HIV accelerates the progression of HCV, particularly in the absence of HIV treatment. The natural history of HCV is that of a self-limiting infection in approximately 15% to 25% of people, although retrospective cohort studies have shown higher clearance rates. Immunosuppression from HIV dramatically alters this. Only 5% to 8% of HIV-positive individuals are able to clear HCV, and this is dependent on the immune status of the person.19 In Asia, the almost universal prevalence of HCV in HIV-infected IDUs would suggest that these individuals have a high degree of immunosuppression. Infection with HIV has been shown to result in higher HCV viral loads,20 liver fibrosis,21 progression to cirrhosis,22 liver failure, and hepatocellular carcinoma. Despite this, adequate immune reconstitution with highly active antiretroviral therapy (HAART) has been shown to modify the course of HCV in HIV infection, including slowing the rate of progression of liver fibrosis23 and reducing complications.24
Recently, there has been a move toward the treatment of HIV with antiretroviral medications in Asia, driven by clinical trials and the 3 by 5 initiatives of the World Health Organization (WHO). This should continue as the Universal Access by 2010 paradigm driven by the WHO continues to grow. Because injecting drug use is a major risk factor for HIV transmission in Asia, a diagnosis of HIV in an IDU should indicate probable HIV-HCV coinfection. HCV is well established as an independent risk factor for hepatotoxicity with HAART.25 The mechanisms for this are believed to be hypersensitivity reactions and a direct effect of the medication on the liver.26 Protease inhibitors (particularly ritonavir) and nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with increased hepatoxicity in HCV-HIV coinfection,27 whereas nucleoside reverse transcriptase inhibitors (NRTIs) have been associated with higher rates of hepatitis steatosis in coinfection.28 Nevirapine is relatively inexpensive and is therefore widely used in resource-poor settings. A recent Asian study showed a high incidence of HAART hepatotoxicity particularly associated with the use of nevirapine (18.5 per 100 person-years) and nevirapine/efavirenz (44.4 per 100 person-years).29 Nevirapine has also been implicated in accelerated liver fibrosis in HIV-HCV-coinfected individuals.30 HAART regimens for initial therapy in resource-poor settings are commonly 2 NRTIs in combination with an NNRTI. Nevirapine is the most commonly used NNRTI because it is less expensive than efavirenz. In addition to nevirapine, low-cost first-line therapy is usually lamivudine (3TC) in combination with zidovudine (AZT) or stavudine (d4T) to complete the HAART regimen. Thus, the use of these 2 first-line regimens in the treatment of a coinfected individual poses the risk of hepatic complications.
The expense of hepatitis C treatment remains the major barrier to hepatitis C treatment in coinfected individuals across Asia. Combination pegylated interferon-ribavirin treatment is effective, with sustained virologic response (SVR) rates (no detectable virus in blood at 24 weeks after completion of treatment) between 27% and 40% overall and up to 73% in genotype non-1.31,32 The treatment of acute hepatitis C in the context of HIV coinfection may be more effective, with an SVR of just greater than 70% regardless of genotype.33 Although a number of studies have shown that it is possible to treat active IDUs for hepatitis C monoinfection and achieve good outcomes,34,35 few studies have looked at hepatitis C treatment in coinfected active IDUs. Hepatitis C treatment is most effective with adequate immune function31; thus, effective ART for IDUs in Asia should facilitate effective hepatitis C treatment when this becomes more widely available.
Without regard for this HCV-HIV-IDU triad, large numbers of individuals could be placed at risk of additional morbidity and potential mortality. HAART should be modified accordingly on a case by case basis to reduce antiretroviral-related hepatotoxicity, and liver function should be monitored at least during the initiation phase of therapy. Poorly managed ART increases the risk of liver-related mortality in HCV-HIV-coinfected individuals, indicating not only that the antiretroviral regimen should appropriate but that adherence should be maximized. In opiate-dependent IDUs, this should indicate treatment of the substance use disorder with opiate substitution therapy. In time, as treatment for HIV becomes more accessible in Asia, HCV-related morbidity and mortality are likely to rise, thus increasing the burden of liver-related diseases on health systems.
Nick Walsh, MBBS, MPH, BSc(med)hons*
Peter Higgs, BSW, MA
Nick Crofts, MBBS, MPH, FAFPHM*
*Turning Point Alcohol and Drug Centre Melbourne, Australia
Department of Epidemiology and Preventive Medicine Monash University Melbourne, Australia
Macfarlane Burnet Institute for Medical Research and Public Health Melbourne, Australia
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