Hepatitis Highlights From CROI
Sexual Transmission of Hepatitis B, Hepatitis C Survival in Syringes and More
Table of Contents
Hepatitis C virus (HCV) is more easily transmitted than HIV via syringes; while needle exchange programs have dramatically reduced HIV incidence among injection drug users, they have had less effect on new HCV infections.
Elijah Paintsil and colleagues from Yale (abstract 168) conducted a laboratory study to determine how long HCV could live in syringes. They first loaded syringes with HCV-spiked blood and depressed the plunger to expel it -- similar to what happens when a user "boots," or draws blood up into a drug-filled syringe. They then flushed out the syringes and tried to grow the recovered virus in cell cultures, either immediately or after storing them for up to two months at different temperatures. They looked at both low-volume (2 microliters of blood) insulin syringes with permanently attached needles and high-volume (32 microliters) tuberculin syringe with detachable needles.
In the low-volume syringes, the likelihood of finding infectious HCV decreased rapidly, with no recovered viable virus after three days in syringes stored at room temperature (72° F) or after seven days at 40° F (average refrigerator temperature). But nearly all high-volume syringes stored at 40° F still contained viable HCV after seven days, half still did after 35 days, and 5% still did after 63 days. Even at higher temperatures (72° or 98° F), viable HCV could still be recovered from a small proportion of high-volume syringes after two months.
Dr. Paintsil said that while it may be "advisable" for needle exchange programs to offer smaller insulin syringes, the most important thing is to distribute enough needles so that people never have to share.
People co-infected with HIV and HCV typically experience more rapid liver disease progression; they may also have more rapid HIV disease progression, but research is conflicting.
It is well known that interferon-based treatment for hepatitis C can slow or stop worsening of liver disease. Juan Berenguer and colleagues from Spain (abstract 167) reported that successful hepatitis C treatment can also reduce illness and death due to AIDS and other non-liver-related causes.
This study included more than 1,400 HIV/HCV co-infected participants starting interferon; about 60% had hard-to-treat HCV genotypes 1 or 4. A majority were also on combination antiretroviral therapy (ART) and had undetectable HIV viral load. Overall, 36% achieved sustained virological response (SVR), or continued undetectable HCV viral load six months after completing treatment.
After four years of follow-up, people who were sustained responders were significantly less likely to develop liver disease complications, including liver cancer and liver-related death, than non-responders or relapsers. In addition, sustained responders were about three times less likely to experience new AIDS-defining conditions and had less than half the risk of death due to non-liver-related causes. Dr. Berenguer said there were also "some hints" that people who had an end-of-treatment response but then relapsed also had improved outcomes.
Research continues to produce conflicting evidence about how rapidly liver disease progresses in HIV/HCV co-infected people. Juan Macias and colleagues from Spain (abstract 659) used the FibroScan method, which uses ultrasound waves, to estimate liver fibrosis progression in 179 co-infected patients. Most were on ART with undetectable HIV viral load, but they were not on hepatitis C treatment.
After 18-24 months of follow-up, 16% of participants showed fibrosis regression or improvement, 54% showed no change, and 30% progressed by at least one liver fibrosis category (for example, from mild stage F1 fibrosis to moderate stage F2 fibrosis, or from advanced stage F3 fibrosis to stage F4 cirrhosis). People with undetectable HIV and higher CD4 counts were less likely to experience fibrosis progression. The researchers concluded that despite ART, "liver fibrosis progresses in a significant proportion of HIV/HCV co-infected patients over a short period of time."
In another FibroScan study, Martin Vogel and colleagues (abstract 642) looked at fibrosis progression among 30 participants in the European NEAT cohort; again, most were on ART and the average CD4 cell count was relatively high. These were mostly gay/bisexual men who acquired acute hepatitis C -- likely due to sexual transmission -- after they were already HIV-positive.
A majority of participants had elevated liver enzymes, an indication of liver inflammation, and about one-quarter showed symptoms of acute hepatitis. Over a short 4-5 month follow-up period, the calculated fibrosis progression rate was very high, 3.8 fibrosis stages per year. A statistical analysis showed that short observation times were strongly associated with high progression rates.
This led the researchers to conclude that the apparent large increase in calculated fibrosis scores did not accurately reflect actual fibrosis progression, and that liver inflammation during early HCV infection might cause FibroScan to falsely overestimate fibrosis. However, researchers in New York using liver biopsies have also seen unusually rapid fibrosis progression in HIV-positive men with acute hepatitis C, so more study is needed.
Some past studies indicate that HIV/HCV co-infected people experience slower and smaller CD4 cell gains after starting ART than those with HIV alone, but others have seen no difference. Martin Potter and colleagues (abstract 676) looked at the effect of hepatitis C treatment on CD4 count among 319 participants in the Canadian Co-infection Cohort Study; most were on ART and the median CD4 cell count was 376 cells/mm3.
Seventeen people spontaneously cleared HCV without treatment, 212 had continued detectable HCV viral load but were not treated for hepatitis C, 59 were treated but were non-responders, and 31 achieved sustained response. Sustained responders had a significantly higher average CD4 count at baseline (486 cells/mm3). Over two years of follow-up, spontaneous clearers had the steepest CD4 cell increase. Sustained responders also experienced good CD4 cell recovery, while people who were treated but failed to achieve SVR still had larger CD4 cell gains than untreated participants.
"Successful HCV treatment with clearance of HCV RNA improved the CD4 reconstitution, independent of ART," the researchers concluded. "Our findings suggest that active HCV RNA replication has a negative impact on HIV progression which may partially be restored through successful HCV treatment."
Andri Rauch from University Hospital Bern (abstract 162) presented an overview of the IL28B gene, the main topic of the CROI oral hepatitis session. Specific variations (genotypes) in the IL28B gene were linked to spontaneous HCV clearance and hepatitis C treatment response in HCV mono-infected people just last year. The gene encodes interleukin 28 -- also known as interferon lambda -- a chemical messenger with antiviral activity. Session moderator Ken Sherman said the discovery had "revolutionized the way we think about treatment and management issues."
Researchers identified the link by scanning the human genome for differences between people who responded well and those who did not respond to interferon. Among HCV mono-infected people, sustained responders were about half as likely as non-responders to have the high-risk IL28B genotype, and it was even less common among spontaneous clearers. Black people, who have the poorest response to interferon, were most likely to have the high-risk genotype.
After research groups in the U.S., Europe, Australia, and Japan confirmed this association in HCV mono-infected individuals, European investigators looked for the same link in HIV/HCV co-infected people. Jacob Nattermann and colleagues (abstract 164) found that co-infected individuals with the high-risk IL28B genotype were less likely to achieve SVR, but the effect was not as strong as for HCV mono-infected people.
Norma Rallon and colleagues (abstract 165) saw a strong association between IL28B genotype and both spontaneous HCV clearance and sustained response among co-infected people, but the latter was only statistically significant for HCV genotype 1. (HCV genotype and IL28B human genotype are two distinct factors, an unfortunate confusion of terminology.)
Although its exact mechanism is not yet known, the high-risk IL28 gene variant may produce interferon lambda with weaker antiviral activity against HCV. An IL28B genotypic test might help predict which patients are likely to respond to interferon-based therapy, but Rauch said it should not be the only factor influencing treatment decisions.
Hepatitis B virus (HBV) is a sexually transmitted infection, and men who have sex with men are at elevated risk. Ann Marie Liapakis and colleagues sought to determine whether HBV DNA (like HIV RNA) might remain detectable in semen from HIV-positive and HIV-negative men with chronic hepatitis B who achieved undetectable blood HBV viral load.
They looked at 10 men (seven HIV-negative and three HIV-positive) with undetectable blood HBV DNA on a treatment regimen containing the nucleotide analogs tenofovir (Viread, also in the Truvada and Atripla combination pills) or adefovir (Hepsera). These drugs are active against both HIV and HBV (though adefovir is only approved for hepatitis B) and can penetrate the genital "compartment," which is protected by a physiological barrier that keeps some drugs out. Ten other men had detectable blood HBV viral load; one was HIV-positive and taking tenofovir, while the rest were HIV-negative and not taking either drug.
Among men with undetectable serum HBV DNA, none had detectable semen HBV viral load. However, three of the 10 men with detectable blood HBV viral load (all quite high) also had detectable HBV in their semen -- including the sole HIV-positive man in this group.
"In this cross-sectional analysis, HBV DNA was not detected in the semen of patients with undetectable blood level as a result of nucleotide antiviral therapy," the investigators concluded, suggesting that such men are unlikely to transmit HBV via sex.
Liz Highleyman (email@example.com) is a freelance medical writer based in San Francisco.
Prevalence, Incidence and Risk Factors for Hepatitis C in Homosexual Men: Data From Two Cohorts of HIV-Negative and HIV-Positive Men in Sydney, Australia
This article was provided by Positively Aware. It is a part of the publication Positively Aware. Visit Positively Aware's website to find out more about the publication.
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