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CATIE - www.catie.ca

Study stimulates researchers to call for intensified HIV and HBV prevention and treatment efforts

15 December 2011- In Canada and other high-income countries, co-infection with the hepatitis B virus (HBV) is relatively common among some HIV-positive people, particularly gay and bisexual men and people who share equipment for injecting substances. Unprotected sex and exposure to unsterilized needles are the two most common routes of transmission.

Researchers with the U.S. military have been collecting health-related information on thousands of military personnel who are HIV positive and some of whom were also co-infected with HBV. In their most recent analysis of their data set, the researchers sought to understand the impact of HBV co-infection on the health of 2,352 HIV-positive people. They found that HBV co-infection had a significant impact-nearly doubling the risk of having severe infections or dying-compared to people with HIV infection alone. The results of this analysis underscore the dangers that HBV poses and have stimulated researchers at the U.S. Centers for Disease Control and Prevention (CDC) to call for accelerated efforts to prevent and treat both HIV and HBV. Before discussing the study further, here is some background information on HBV.

About HBV

HBV infects and damages the liver. Although some people can successfully fight off this infection, that is not always the case, particularly among HIV-positive people. Chronic HBV infection damages the liver and can lead to liver cancer.

HBV is found in bodily fluids, including semen and vaginal fluid. In high-income countries, HBV is most commonly spread in the following ways:

  • sharing equipment for substance use (such as needles, straws and cookers) with an infected person
  • intimate sexual contact with an infected person (such as unprotected intercourse)
  • sharing personal care items (such as razors, toothbrushes, nail clippers and scissors) with an infected person
  • vertical transmission-from an infected mother to baby during birth

Symptoms of initial HBV infection can include the following:

  • yellowing of the whites of the eyes and skin (jaundice)
  • nausea
  • dark urine
  • pale stools
  • abdominal pain

Many people with acute HBV infection may not get these symptoms and may not be aware that they are infected.

A vaccine for HBV is available and so is treatment. If you think that you may have been exposed to HBV, consult a healthcare provider about getting tested for HBV and other sexually transmitted infections (STIs).

Study details

The research team analysed health-related data collected between June 1986 and January 2010.

The average profile of participants when they entered the study was as follows:

  • age - 27 years
  • gender - 95% men, 5% women
  • 22% had previously been vaccinated for HBV
  • 36% had a history of STIs
  • 96% did not have HCV co-infection
  • CD4+ count - 500 cells
  • HIV viral load (when available) - 25,000 copies/ml

The researchers divided participants into the following groups:

  • Chronic HBV infection: These people repeatedly tested positive for a protein called hepatitis B surface antigen (HBsAg).
  • Isolated HBV infection: These people tested positive for antibodies to hepatitis B core antigen (HBcAg) on at least two occasions without other markers of HBV infection.
  • Resolved HBV: People in this group cleared HBV and repeatedly tested positive for both HBcAb and HBsAb.
  • No HBV infection: People in this group tested negative for both HBsAg and HBcAb.

Results

Participants who had both HBV and HIV infections were at heightened risk (almost two-fold) for developing AIDS or dying compared to people with HIV infection alone. This difference was statistically significant.

Surprisingly, even well into the era of antiretroviral therapy (ART), HBV co-infection was still associated with a significantly increased risk of death despite the use of at least one active anti-HBV drug.

Interestingly, participants who were HIV positive and subsequently exposed to HBV but who did not develop chronic HBV infection also had an elevated risk for developing AIDS or death, though this increase in risk did not become statistically significant.

These and other findings from the study suggest the following possibilities:

  • Exposure to HBV is a marker or signifier of something else-such as a behaviour, risk factor or perhaps other germ-that is harmful.
  • HBV infection, even if it resolves, has a profound impact on the health of HIV-positive people.

Notes on the study

This study was an observational study and its conclusions could have been affected by factors that were not expected, adjusted for or taken into account by the study team. To try to minimize the impact of such possibilities, the researchers conducted sensitivity analyses, which confirmed their initial conclusions

Due to built-in limitations of observational studies, the research team is not certain precisely why HBV co-infection had the serious impact that it did. Presumably, HBV has such a harmful effect on survival because of the severe damage it can cause to the liver. However, data on liver-related causes of death were not available for the research team to analyse.

The importance of testing and education

The findings from this study are likely most applicable to men who have sex with men, as the proportion of women and people who injected street drugs was relatively small. Educational programs for people at high risk for HBV infection need to continue.

A vital vaccine

The HBV vaccine is highly effective among healthy HIV-negative people. However, HIV-positive people may need more vaccinations because their immune systems may need more stimulation to produce protective levels of antibodies against HBV.

Researchers from the CDC who reviewed the study encourage HIV-positive people to get vaccinated early-"before their CD4+ cell counts fall below 350 cells." In some people who have initiated ART late in the course of HIV disease, some doctors may decide to delay HBV vaccination until the CD4+ counts of their patients increase. However, the CDC researchers stated that in such cases "vaccination should not be delayed while awaiting an increase in the CD4+ cell count [while] on ART."

Limiting damage

To improve survival among co-infected people, measures to limit further damage to the liver are useful. These include reducing or ideally eliminating substance use, cutting back on alcohol use and taking steps to avoid other co-infections such as hepatitis C virus (HCV) and syphilis, both of which can affect the health of the liver.

Addressing the underlying mental health issues that drive some people to use street drugs and/or consume excessive amounts of alcohol is also necessary.

Treatment

Some commonly used anti-HIV drugs are also active against HBV:

  • 3TC (lamivudine and in Kivexa/Epzicom and Trizivir)
  • tenofovir (Viread and in Truvada, Atripla and Complera)
  • FTC (emtricitabine and in Truvada, Atripla and Complera)

The relatively early initiation of ART with these drugs helps to slow the spread of damage in the livers of HBV co-infected people. The CDC researchers recommend the use of two of the previously mentioned drugs in treatment regimens for co-infected people, as follows:

  • tenofovir + 3TC
  • tenofovir + FTC (Truvada)

Further research is needed to fully understand the long-term impact of HBV infection and how HBV interacts with the immune system, even under treatment with dual agents.

- Sean R. Hosein

REFERENCES:

  1. Bertoletti A, Maini MK, Ferrari C. The host-pathogen interaction during HBV infection: immunological controversies. Antiviral Therapy . 2010;15 Suppl 3:15-24.
  2. Boni C, Fisicaro P, Valdatta C, et al. Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection. Journal of Virology . 2007 Apr;81(8):4215-25.
  3. Matthews GV, Manzini P, Hu Z, et al. Impact of lamivudine on HIV and hepatitis B virus-related outcomes in HIV/hepatitis B virus individuals in a randomized clinical trial of antiretroviral therapy in southern Africa. AIDS . 2011 Sep 10;25(14):1727-35.
  4. Matthews GV, Seaberg E, Dore GJ, et al. Combination HBV therapy is linked to greater HBV DNA suppression in a cohort of lamivudine-experienced HIV/HBV coinfected individuals. AIDS . 2009 Aug 24;23(13):1707-15.
  5. Crum-Cianflone N, Weekes J, Bavaro M. Syphilitic hepatitis among HIV-infected patients. International Journal of STD and AIDS. 2009 Apr;20(4):278-84.
  6. Chun HM, Roediger MP, Hullsiek KH, et al. Hepatitis B virus coinfection negatively impacts HIV outcomes in HIV seroconverters. Journal of Infectious Diseases . 2011; in press.
  7. Peters PJ, Marston BJ. Preventing deaths in persons with HIV/hepatitis B virus coinfection: a call to accelerate prevention and treatment efforts. Journal of Infectious Diseases . 2011; in press .

From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at http://www.catie.ca

Source: CATIE: CANADIAN AIDS TREATMENT INFORMATION EXCHANGE


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