In theory, one way to possibly reduce the risk of exposure to HIV is for people to serosort—have sex with other people of the same HIV status.

For HIV-positive people, having sex only with other HIV-positive people may remove the burden of worry about infecting someone else. For HIV-negative people, serosorting may reduce the worry about getting HIV.

In reality, serosorting carries risks, particularly when condoms are not used for intercourse:

• For HIV-positive people, unprotected anal intercourse can transmit many germs— including hepatitis-causing viruses (hepatitis B and hepatitis C viruses), LGV (Lymphogranuloma venereum), syphilis and HPV (human papillomavirus), as well as new and as yet unknown emerging infections. It can also allow for the transmission of new, perhaps drug-resistant strains of HIV. In the setting of HIV co-infection, hepatitis B and C viruses can cause accelerated liver damage and hepatitis recovery rates are generally lower than in HIV-negative people.

• For HIV-negative people, unprotected intercourse also carries the risk of transmitting many of the same germs and also HIV. What’s more, HIV antibody testing may provide a false sense of security among people who regularly engage in unprotected intercourse. This is because the immune system takes several weeks to produce antibodies after infection. Testing done during this period may not find any antibodies even though infection has taken place.

An outbreak of HCV

In the high-income countries and regions of Australia, North America and Western Europe, an outbreak of hepatitis C virus (HCV) is occurring among gay and bisexual men, particularly among men who are co-infected with HIV. This outbreak of HCV appears to be spread through unprotected anal sex and other high-risk activities. Perhaps because HIV infection weakens the immune system, HIV-positive people are at increased risk for other sexually transmitted infections (STIs), including HCV.

Doctors in Lyon, France, recently reported details on two gay men who engaged in repeated bouts of unprotected anal sex with other men and contracted HCV or both HCV and HIV infections. What is disturbing about these cases is that after diagnosis the men were treated for HCV infection and recovered, but because of further episodes of unprotected anal sex, they became re-infected with HCV.

Case 1

The first man in his early 40s sought care in August 2003. He had been HIV positive for 16 years. His CD4+ count at that time was 570 cells and his HIV viral load was 1,100 copies. For the past two years he had been taking the following drugs:

• nevirapine (Viramune);
• AZT (zidovudine, Retrovir);
• 3TC (lamivudine);
• abacavir (Ziagen).

In the past he had been diagnosed and successfully treated for these infections:

• hepatitis A;
• syphilis.

He had also been exposed to hepatitis B virus (HBV) but treatment helped prevent this virus from taking hold.

At the time he sought care in August 2003 his liver enzyme levels were several times greater than normal:

• AST (aspartate aminotransferase) – 189 IU/l;
• ALT (alanine aminotransferase) – 534 IU/l.

These findings suggested inflammation of his liver, probably by a viral infection, so his doctors ordered more blood tests, which detected antibodies to HCV. On previous visits, technicians had stored and preserved some blood samples from this man. These stored samples were also checked for HCV antibodies but the results were negative, suggesting that HCV infection was a recent event. His HCV viral load was about 6 million IU/ml and his subtype (or genotype) of HCV was 1a. This genotype does not usually respond well to therapy, particularly in people co-infected with HIV.

Realizing that the man was probably in the early stages of HCV infection, his doctors prescribed a long-acting form of interferon called peg-interferon and the antiviral drug ribavirin. This latter drug was prescribed at a total daily dose of 1,000 mg, taken in two divided doses. Both drugs were taken for about six months.

The man responded well to this treatment, with his HCV quickly becoming undetectable and remaining this way for three years, suggesting that he had been cured.

Re-infection

In August 2006, blood tests once again detected higher-than-normal levels of liver enzymes (AST and ALT). What’s more, this time the man’s HCV viral load was more than 12 million IU/ml and the genotype was 4. The doctors concluded that the man had been re-infected with a new strain of HCV.

At this time, his CD4+ count was 1,158 cells and his HIV viral load was less than 50 copies. Several months later he began therapy for HCV, again a combination of peg-interferon and ribavirin, and his HCV quickly became undetectable. But after four months he had to stop this therapy because he experienced mania, a possible side effect of HCV therapy. The man was fortunate because HCV has continued to be suppressed despite no further therapy. The doctors noted that his only risk factors for HCV infection were “unprotected anal intercourse with multiple HIV-infected partners.”

Case 2

A second man in his late 30s sought care from the Lyon doctors in October 2006 because of symptoms of HIV infection. His past medical history included these infections:

• 2004 – hepatitis A virus;
• 2005 – rectal gonorrhea.

What’s more, several times between 2000 and 2003 he sought anti-HIV medicines because he thought he might have been exposed to HIV thorough unprotected anal sex. The use of medicines in this way is called post-exposure prophylaxis (PEP).

At the time he sought care in 2006 his liver enzyme levels were normal. However, four weeks later he returned to the clinic because of symptoms of hepatitis. This time his liver enzyme levels and other test results were abnormal, as follows:

• AST – 233 IU/l;
• ALT – 468 IU/l;
• HCV viral load – nearly 600,000 IU/l.

His genotype of HCV was 4c/d. His CD4+ count was 543 cells and HIV viral load was 37,000 copies. Doctors prescribed a combination of peg-interferon and ribavirin 1,200 mg/day, both drugs for six months. As happened with the man in Case 1, this man’s HCV viral load fell during therapy and remained suppressed long after therapy ended, suggesting that he had been cured of HCV.

Counselling and therapy

Doctors gave this man safer-sex counselling and ensured that he received psychotherapy so that he would understand the dangers of unprotected intercourse and perhaps gain some insight into his behaviour. However, he later developed syphilis and several rectal infections, including gonorrhea and LGV, suggestive of unprotected anal sex. What’s more, in April 2008 routine blood tests detected highly elevated liver enzymes, as follows:

• AST – 1,438 IU/l;
• ALT – 2,315 IU/l.

His HCV viral load was also positive and had a reading of nearly 7,000 IU/ml but this time the genotype of HCV was 1a. This confirms that he was infected with a different strain of HCV. His CD4+ count was nearly 900 cells and his HIV viral load was 74,000 copies. Doctors treated him with another course of peg-interferon and ribavirin, resulting in his recovery from this second bout of HCV.

Bear in mind

The reports of these two cases underscore these points:

• HCV can be transmitted via unprotected anal sex.
• Prior infection with HCV does not confer immunity against future exposures to this virus.

The French doctors caution that in the context of HIV infection “serosorting and associated unprotected intercourse alone should be considered a major risk factor for the transmission of HCV and other sexually transmitted infections.”

It is not clear why the two men would put themselves at repeated risk for STIs and HCV infection and HCV treatment. At best, the combination of peg-interferon and ribavirin causes highly unpleasant side effects and some people would find that a deterrent from future HCV infection. The men were not addicted to any particular substances nor did they inject drugs. They told doctors that because they were HIV positive they felt that “nothing worse could happen to them.” They also disclosed that the combination of alcohol and recreational drugs together with group sex helped them feel more powerful (personal communication, Laurent Cotte, MD).

More research needs to be done to find out how common HCV reinfection is among gay and bisexual men. Hopefully, such research will reveal that this is an isolated problem.

According to German infectious disease specialists Martin Vogel and Jürgen Rockstroh, more than 1,000 HIV-positive gay and bisexual men have become infected with HCV in the ongoing HCV epidemic in high-income countries and regions. Unless anti-HCV education efforts are enhanced, the current epidemic will continue.

—Sean R. Hosein

REFERENCES:

1. Parsons JT, Schrimshaw EW, Bimbi DS, et al. Consistent, inconsistent, and non-disclosure to casual sexual partners among HIV-seropositive gay and bisexual men. AIDS. 2005 Apr;19 Suppl 1:S87-97.
2. Danta M, Brown D, Bhagani S, et al. Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with men linked to high-risk sexual behaviours. AIDS. 2007 May 11;21(8):983-91.
3. Schmidt AJ, Vogel M, Rockstroh J, et al. Risk factors for hepatitis C in HIV positive MSM. A preliminary evaluation of a case-control study. In: Program and abstracts of the 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007, Sydney, Australia. Abstract MOPEB037.
4. van de Laar T, Pybus O, Bruisten S, et al. Evidence of a large international network of HCV transmission in HIV-positive men who have sex with men. Gastroenterology. 2009 May;136(5):1609-17.
5. Legrand-Abravanel F, Colson P, Leguillou-Guillemette H, et al. Influence of the HCV subtype on the virological response to pegylated interferon and ribavirin therapy. Journal of Medical Virology. 2009 Dec;81(12):2029-35.
6. Vogel M, Rockstroh JK. Treatment of acute hepatitis C in HIV infection. Journal of Antimicrobial Chemotherapy. 2010; in press.
7. Cotte L, Chevallier Queyron P, Schlienger I, et al. Sexually transmitted HCV infection and reinfection in HIV-infected homosexual men. Gastroentérologie Clinique et Biologique. 2009 Oct-Nov;33(10-11):977-80.