Does hepatitis C virus affect HIV disease?

Whether or not HCV infection leads to more rapid HIV disease progression has been a controversial issue. Until the late 1990s, most experts believed that HCV did not accelerate HIV disease. Although evidence has accumulated indicating that HCV may in fact lead to lower CD4 cell counts and an elevated risk of death, there is still not a clear consensus.

Several studies have found CD4 cell count changes and the rate of progression to new AIDS-defining illnesses to be similar in co-infected patients and those with HIV alone in many patient populations and settings.1 2 3 4 5 6

However, other studies have found that co-infected individuals are at greater risk of HIV disease progression, including higher rates of opportunistic infections (OIs), hospitalisation and mortality.7 8 9  For example, an Italian comparison of the incidence of AIDS-defining illnesses found that coinfected individuals were 2.6 times more likely to develop an AIDS-defining illness, while co-infection was associated with a three- to five-fold increased risk in the development of bacterial, fungal, and protozoal infections. The risk was most strongly elevated in co-infected individuals with cirrhosis.10

Other European and American data support the theory that HCV infection accelerates HIV disease progression, independent of antiretroviral therapy.11 

Several studies have suggested that CD4 cell counts may be chronically lower in people with liver disease, and that CD4 cell percentages may more accurately reflect immune status (and the need for HIV treatment) in people with HIV/HCV co-infection.12 The question of whether HIV therapy should be initiated earlier in co-infected individuals is being investigated.

In a recent study of United States veterans, for example, HIV/HCV co-infected individuals had a shorter average survival period than those with HIV alone, although they did not progress more rapidly to AIDS13 – suggesting that prognosis may be worse although not specifically AIDS-related. An analysis of a cohort of recent seroconverters in Italy found that since the advent of HAART, co-infected individuals were significantly more likely to progress to AIDS, a difference that may be partly attributable to shorter use of combination antiretroviral therapy.14

However the largest study to date, a meta-analysis of 30 studies involving in excess of 100,000 patients with HIV, has shown that hepatitis C co-infection does not increase the risk of progression to AIDS.15

Ten of the studies were conducted in the era before effective antiretroviral therapy became available. These included 4413 co-infected patients and 10,213 individuals who were only infected with HIV.

These studies showed that before HIV treatment became available, co-infected patients had a modestly reduced risk of HIV disease progression compared to individuals who were HIV-monoinfected.

The investigators then looked at the studies conducted after 1996 when effective antiretroviral therapy first became available. These studies included 25,319 co-infected patients and 61,697 individuals only infected with HIV.

When combined, these studies showed that co-infected patients had a 35% increase in their risk of death compared to mono-infected patients.

Co-infected patients who were older, or who were taking antiretroviral therapy had an especially elevated risk of death.

Moreover, the longer an individual was living with co-infection, then the greater was their risk of death.

However, the results of the seven studies that only assessed progression to AIDS showed that co-infected and mono-infected patients had an equal risk of this outcome.

Seven studies reported on the impact of HIV disease progression when this was defined as either diagnosis with AIDS or death. These studies showed that co-infected patients had a 49% increase in their risk of progression to these outcomes compared to mono-infected individuals.

HCV genotype appears to be a factor: infection with multiple HCV genotypes has been associated with more rapid HIV disease progression;16 and lower CD4 cell counts have been seen with HCV genotype 1.17 As a result, experts in the field such as Dr Vincent Soriano now suggest that hepatitis C can be considered a co-factor in HIV progression.18

Possible explanations for accelerated HIV disease progression in HCV-co-infected patients include failure to maintain effective anti-HIV CD8 T-cell responses.19

HIV/HCV co-infected people may be at higher risk for brain and psychological impairment20 21 and of certain lymphomas than people with HIV alone. However, co-infected people do not appear more likely to develop sensory neuropathy than HIV monoinfected people.22

Co-infection has definite effects on antiretroviral treatment: see Antiretroviral treatment in co-infected individuals.

A closely related question – how does HCV treatment affect HIV disease? – was investigated in a Spanish study of co-infected individuals beginning HCV treatment. Compared to non-responders, people with sustained response to HCV treatment not only had lower rates of death from liver disease as expected (0.10 vs 0.98 per 100 person-years [p-y]), but also developed fewer new AIDS-defining conditions (0.26 vs 0.94 per 100 p-y), and had fewer deaths from AIDS-defining conditions (0 vs 0.08 per 100 p-y) and overall mortality (0.31 vs 1.71 per 100 p-y).23

References

  1. Sulkowski M et al. Hepatitis C and progression of HIV disease. JAMA 288: 199-206, 2002
  2. Amin J et al. HIV and hepatitis C coinfection within the CAESAR study. HIV Med 5: 174-179, 2004
  3. Tedaldi EM et al. Hepatitis A and B vaccination practices for ambulatory patients infected with HIV. Clin Infect Dis 38: 1483-1489, 2004
  4. Sabin CA et al. Markers of HIV-1 disease progression in individuals with haemophilia coinfected with hepatitis C virus: a longitudinal study. Lancet 360: 1546-1551, 2002
  5. Hershow RC et al. Hepatitis C virus coinfection and HIv load, CD4+ cell percentage, and clinical progression to AIDS or death among HIV-infected women: Women and Infants Transmission Study. Clin Infec Dis 40 (6): 859-867, 2005
  6. Rockstroh J et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis: 192(6):992-1002, 2005
  7. Greub G et al. Clinical progression, survival, and immune recovery during antiretroviral therapy in patients with HIV-1 and hepatitis C virus coinfection: the Swiss HIV Cohort Study. Lancet 356: 1800-1805, 2000
  8. Klein MB et al. The impact of hepatitis C virus coinfection on HIV progression before and after highly active antiretroviral therapy. J Acquir Immune Defic Syndr 33: 365-372, 2003
  9. Stebbing J et al. Hepatitis C virus infection in HIV type 1-infected individuals does not accelerate a decrease in the CD4+ cell count but does increase the likelihood of AIDS-defining events. Clin Infect Dis: 41(6): 906-11, 2005
  10. d'Arminio Monforte A et al. Risk of developing specific AIDS-defining illnesses in patients coinfected with HIV and hepatitis C virus with and without liver cirrhosis. Clin Infect Dis 49: 612-622, 2009
  11. Soriano V et al. HIV-1 progression in hepatitis-C-infected drug users. Lancet 357: 1361-1362, 2001
  12. Gandhi T et al. Long-term immunologic and virologic responses in patients with highly resistant HIV infection who are treated with an incompletely suppressive antiretroviral regimen. Clin Infect Dis 45: 1085-1092, 2007
  13. Anderson KB et al. Hepatitis C virus coinfection increases mortality in HIV-infected patients in the highly active antiretroviral therapy era: data from the HIV Atlanta VA Cohort Study. Clin Infect Dis 39: 1507-1513, 2004
  14. Dorrucci M et al. The effect of hepatitis C on progression to AIDS before and after highly active antiretroviral therapy. AIDS 18: 2313-2318, 2004
  15. Chen T-Y et al. Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression. Clin Infect Dis 49 (10): 1605-1615, 2009
  16. Van Asten et al. Infection with concurrent multiple hepatitis C virus genotypes is associated with faster HIV disease progression. AIDS 18: 2313-2318, 2004
  17. Antonucci G et al. Effect of hepatitis C virus genotype on CD4+ T cell count in a cohort of antiretroviral-naive HIV-1-infected individuals. J Infect Dis 192: 703-704, 2005
  18. Soriano V et al. Editorial review: care of patients with chronic hepatitis C and HIV co-infection: recommendations from the HIV-HCV International Panel. AIDS 16: 813-828, 2002
  19. Harcourt GC et al. Longitudinal analysis of CD8 T-cell responses to HIV and heptatitis C virus in a cohort of co-infected haemophiliacs. AIDS 19: 1135-1143, 2005
  20. Cherner M et al. Hepatitis C augments cognitive deficits associated with HIV infection and methamphetamine. Neurology 64: 1343-1347, 2005
  21. Yang Y et al. Hepatitis C and neuropsychological function in treatment-naive HIV-1-infected subjects - A5097s baseline analysis. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 26, 2004
  22. McArthur J Risk factors and determinants for HIV-associated sensory neuropathies: is hepatitis C a modifier? Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 27, 2004
  23. Berenguer J et al. Sustained virological response to interferon plus ribavirin reduces HIV progression and non-liver-related mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Seventeenth Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 167, 2010

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