Viral co-factors affecting disease progression

Co-infection with HIV and other viruses can affect disease progression. Co-infection with human T-lymphocyte virus type 1 (HTLV-1), a retrovirus commonly found in Africa, the Caribbean, and in people who inject drugs, is associated with an increased risk of developing AIDS. Co-infection with HTLV-2 may conversely be protective against disease progression.1

Being infected with various members of the herpes virus family may also increase one's risk of developing AIDS. These include cytomegalovirus (CMV) and human herpes virus type 6 (HHV-6). Herpes viruses produce proteins that may increase HIV replication in CD4 T-cells, while HHV-6 infects CD4 T-cells and seems to increase the number of CD4 receptor molecules on the cell surface. However, one study suggests that HHV-6, HHV-7, and HHV-8 are not co-factors in HIV progression.2

Those infected with both HIV and CMV may develop symptoms significantly faster than those who do not have CMV, and may have an increased likelihood of death.3  

Some studies of high doses of the anti-herpes drug aciclovir (Zovirax) have suggested that this treatment may prolong survival, at least in people with relatively advanced disease. This apparent benefit may be due to the inhibition of herpes co-factors, although other controlled studies did not find a survival benefit associated with aciclovir treatment (see Cytomegalovirus in the A to Z of illnesses).

Hepatitis C virus interacts with HIV, leading to more rapid progression of both HIV and hepatitis C-related diseases. Hepatitis C is mainly transmitted by contaminated blood and infrequently through sexual intercourse. Hepatitis C is often found in haemophiliacs and injecting drug users with HIV infection. People co-infected with HIV and hepatitis C have an increased risk of death, even in the era of antiretroviral therapy. (See Hepatitis C in the A to Z of illnesses.)4,5 

Research that is more recent suggests that the impact of hepatitis C on HIV progression differs by hepatitis C genotype and that HIV progression is faster in individuals infected with multiple hepatitis C genotypes. However, antiretroviral therapy may diminish the effect of hepatitis C genotype on HIV disease progression.6

Viruses that could have an attenuating effect on HIV include measles, influenza, HTLV-1 and 2, and HHV-6.7 More research is needed to explore mechanisms of interaction between these viruses and HIV.

GB virus C (GBV-C)

For years, researchers have been looking at the effect of the GB virus on HIV activity. In the beginning, this virus was termed hepatitis G, but it is now recognised that the virus does not cause hepatitis. Many studies indicated that the presence of GBV-C inhibited HIV replication. It is found in roughly 2% of healthy people and up to 35% of HIV-positive individuals. It has not been associated with any form of pathology or detrimental effect on quality of life.8

To date, studies have showed either a beneficial or a neutral effect of GBV-C on HIV replication.9 The question was looked at in two large cohort studies. In 2004, the Multicenter AIDS Cohort GBV-C substudy of 271 men concluded that the loss of GBV-C RNA five years after seroconversion raised nearly threefold the odds of death.10 A year later, the Amsterdam Cohort Study, looking at this question in over 300 patients, found that men who lost GBV-C over a course of 8 years had a nearly threefold increase in risk of death than did those who never had GBV-C, but hypothesise that the loss of GBV-C was a consequence, and not a cause, of CD4 cell loss.11 

In a South African study, five distinct GBV-C genotypes were identified. In vitro cultures showed an inhibition by genotype 1 and 5 of X4 and R5 HIV-1 isolates and an inducement of RANTES and stromal-derived factor-1 chemokines.12 Effect of GBV-C on HIV may depend on the strain present in viral RNA.

GBV-C's effect on HIV replication still needs to be elucidated, as does its effect in those triply infected with HIV, GBV-C, and hepatitis C virus. The question of the effect that hepatitis C treatment has, if any, in clearance of GBV-C also remains open.13 14

References

  1. Turci M et al. Coinfection with HIV-1 and human T-cell lymphotropic virus type II in intravenous drug users is associated with delayed progression to AIDS. J Acquir Immune Defic Syndr 41: 100-106, 2005
  2. Agut H et al. Infection with human herpes viruses 6, 7 and 8 in long-term non-progressors. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 452, 2003
  3. Deayton J et al. CMV viraemia is an independent predictor of disease progression and death in the era of HAART. Ninth Conference on Retroviruses and Opportunistic Infections, abstract 39, Seattle, 2002
  4. Braitstein P et al. Hepatitis C is an independent predictor of mortality among a population-based cohort of antiretroviral naive individuals initiating triple-combination therapy. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 1150, 2003
  5. Rosenthal E et al. Mortality due to hepatitis C-related liver disease in HIV-infected patients France in 2001 (MORTAVIC 2001 Study). Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 87, 2003
  6. Van Asten et al. Infection with concurrent multiple hepatitis C virus genotypes is associated with faster HIV disease progression. AIDS 18: 2313-2318, 2004
  7. Kannangara S et al. Attenuation of HIV-1 infection by other microbial agents. J Inf Dis 192: 1003-1009, 2005
  8. Tillmann HL et al. GB virus C infection and quality of life in HIV-positive patients. AIDS Care 16: 736-743, 2004
  9. Kaiser T, Tillmann HL GB virus C infection: is there a clinical relevance for patients infected with human immunodeficiency virus? AID Rev 7 (1): 2-12, 2005
  10. Williams CF et al. Persistent GH virus C infection and survival in HIV-infected men. N Engl J Med 350 (10): 981-990, 2004
  11. van der Bij A et al. GB virus C coinfection and HIV-1 disease progression: The Amsterdam Cohort Study. J Infect Dis 191 (5): 678-685, 2005
  12. Xiang J et al. South African GB virus C isolates: interactions between genotypes 1 and 5 isolates and HIV. J Inf Dis 192 (2): 2147-2151, 2005
  13. Schwarze-Zander C et al. GB Virus C (GBV-C) infection in Hepatitis C Virus (HCV)/HIV-coinfected patients receiving HCV treatment: importance of the GBV-C genotype. J Inf Dis 194 : 410-419, 2006
  14. Berzsenyi M and Roberts SK. What is the role of GB virus C infection in hepatitis C virus/HIV coinfection? J Inf Dis 194: 407-409, 2006
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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