November 19, 2013

The new epidemic - hepatitis C and HIV coinfection

Positive Living 2013 September

Positive Living article • Graham Stocks

Hep C article

Photo: KNICKOHR

New cases of hepatitis C (HCV) are still being seen largely amongst people who inject drugs (PWID). However, in recent years it has become more recognised that HCV is also passed on sexually and that a disproportionate number of people living with HIV (PLHIV) are also living with HCV.

Between 2004 and 2008, the Australian Trial in Acute Hepatitis C (ATAHC) 1 found that around 30% of those who had recently acquired HCV were also HIV positive, and that 15% of those new HCV infections were attributed to male-to-male sexual activity 2.

In Australia, around 13% of PLHIV are also living with HCV. This estimate is similar in the USA 3, while in Europe up to 25% of PLHIV also have hepatitis C 4.

Globally, the figures vary widely across different geographic regions. Researchers taking a mobile medical clinic across the American urban northeast discovered this recently. Within this population, they found that 33% of those diagnosed with HIV between 2003 and 2011 also had hepatitis C 5 and that gay and other MSM were over three times more likely to have both infections compared to heterosexuals. In some areas of Eastern Europe and Central Asia (former states of the USSR) the rates of coinfection are higher still.

In her IAS 2013 plenary lecture, Karine Lacombe from the Université Pierre et Marie Curie in Paris, claimed that HIV/HCV coinfection constitutes a new epidemic, and provided an overview of the harmful and synergistic effects of having both.

Put simply, having both viruses complicates your clinical care considerably. The combination increases the chance of liver fibrosis and impairs Natural Killer (NK) cell anti-fibrotic activity. End-stage liver disease is the highest cause of death in people who are living bi-virally.

But it’s not all bad news. Treating HIV can restore your anti-HCV T-cell response (a good reason to initiate it early), and unlike HIV, HCV is a curable disease because it doesn't integrate into the host genome, so there are no archived mutations.

Plus, when you add the new first generation direct-acting antivirals, protease inhibitors boceprevir and telaprevir, to standard treatment peginterferon and ribavirin it can shorten treatment time and you’ve got a better chance of curing the HCV.

Results of trials with second generation protease inhibitors are also very encouraging. Both naive patients and relapsers showed an 80% sustained virological response with simeprevir and almost 90% early virological response with faldaprevir.

Treating people with HCV to reduce new transmissions is a real possibility in the near future, however this is a monumental task as globally around 185 million people are living with the virus.

A range of newer drugs are also in the pipeline, and hopefully some of these will be eventually licensed for use.

Treating and clearing HCV infection still results in a health burden, as there is an increased risk of liver cancer, specifically hepatocellular carcinoma. So, ongoing care and monitoring of liver health is essential 6.

Go to an excellent presentation for which both the webcast and presentation slides are available.

Another presentation on HCV and HIV coinfection amongst gay and MSM was delivered by Thomas Martin on behalf of a team from Chelsea and Westminster Hospital in London.

He began with a fairly gloomy overview. Having both infections reduces spontaneous clearance rates of HCV (PLHIV account for only 20% of all cases)7. HCV RNA set points tend to be higher which increases the chance of transmission8. Having both also increases the chance of progressing to cirrhosis faster. And while treatments are improving, there is still a reduced success rate among PLHIV.

Liver disease is a major non-AIDS cause of death among PLHIV, accounting for 9% of all deaths in the largely treated D:A:D Cohort (2009 to 2011) 9. Viral hepatitis infection (mainly HCV) was the main contributor to these deaths.

Sexual transmission of HCV in HIV positive gay men in Western Europe, North America and Australia has been occurring since the mid 1990s. But it has been increasing, rising steeply from 2005, and currently up to 5% of positive gay may become infected annually 10

The opposite is the case for PWID. A recent analysis of the needle and syringe program (NSP) in Australia revealed that between 1995 and 2010 the number of new cases of HCV in people using NSPs had halved 11.

Some risk factors which have been identified for HCV transmission include ulcerating genital infections, unprotected anal intercourse and activities such as use of sex toys, group sex, fisting and recreational drug use.

A major German study recently confirmed that blood (even in imperceptible amounts) is the critical medium of transmission, noting that HCV remains transmissible at room temperature for the order of 16 hours 12.

A UK study specifically addressed HCV reinfection rates in 191 coinfected gay men who had either been successfully treated for acute or chronic HCV or who had spontaneously cleared their HCV. Overall 23% of these gay men were reinfected within two years, and were treated a second time. Of the 24 who cleared their HCV a second time, 8 (33%) were reinfected again. This represents a very high risk of ongoing reinfection in gay men with HIV who are diagnosed with HCV infection.
Treatment was generally successful for those who were reinfected, with sustained virological response (SVR) of 73% for HCV genotype 1 and 4 and 100% for genotypes 2 and 3. Standard treatment (pegIFN/RBV) was used for all patients in these clinics.

Spontaneous clearance of HCV reinfection was 20% which is consistent with primary (first) HCV infection clearance. The study also demonstrated weak evidence for any protective immunity after spontaneous clearance.

Go to this stimulating and informative presentation for which the abstract and selected presentation slides are available. (see also 13).

This study confirms findings from previous smaller studies in two large HIV clinics in Amsterdam which found that overall 33% of positive gay men who cleared their HCV became reinfected 14.

The authors recommend PLHIV who have previously cleared their HCV to ensure that subsequent reinfection is detected and treated early. The British HIV Association (BHIVA) guidelines for the management of hepatitis virus and HIV coinfections issued earlier this year recommend HCV antibody testing every 3-6 months for gay men who remain at risk following clearance of an initial HCV infection. The current (2010) In Australia, the Sexually Transmissible Infections In Gay Men Action Group STIGMA Guidelines recommend annual HCV testing for HIV positive MSM, recognising that HCV may be acquired during sex.

These presentations add further to growing evidence base that HCV may be acquired sexually and that for PLHIV the course of HCV disease and its treatment may be more complicated. A number of PLWH organisation have information about reducing the risk of acquiring HCV through sex for HIV+ve gay men, go to just one  recent resource.

1.Dore GJ et al. for Australian Trial In Acute Hepatitis C Study Group. Effective treatment of injecting drug users with recently acquired hepatitis C virus infection. Gastroenterology. 2010 Jan;138(1):123-35.e1-2. doi: 10.1053/j.gastro.2009.09.019.

2.Grebely J et al for ATAHC Study Group. Hepatitis C virus reinfection and superinfection among treated and untreated participants with recent infection. Hepatology. 2012 Apr;55(4):1058-69. doi: 10.1002/hep.24754.

3.Spradling PR et al for HIV Outpatient Study Investigators. Trends in hepatitis C virus infection among patients in the HIV Outpatient Study, 1996-2007. J Acquir Immune Defic Syndr. 2010 Mar;53(3):388-96.

4.Lacombe K, Rockstroh J. HIV and viral hepatitis coinfections: advances and challenges. Gut. 2012 May;61 Suppl 1:i47-58. doi: 10.1136/gutjnl-2012-302062.

5.Morano JP, Gibson BA, Altice FL. The burgeoning HIV/HCV syndemic in the urban Northeast: HCV, HIV, and HIV/HCV coinfection in an urban setting. PLoS One. 2013 May 14;8(5):e64321. doi: 10.1371/journal.pone.0064321.

6.Taylor LE, Swan T, Mayer KH. HIV coinfection with hepatitis C virus: evolving epidemiology and treatment paradigms. Clin Infect Dis. 2012 Jul;55 Suppl 1:S33-42. doi: 10.1093/cid/cis367 http://cid.oxfordjournals.org/content/55/suppl_1/S33.full.pdf+html

7.Webster DP, Wojcikiewicz T, Keller M, Castelnovo D, Mistry H, Gilleece Y, Tibble J, Fisher M. Spontaneous clearance and treatment of acute hepatitis C infection in HIV-positive men with 48 weeks of interferon-alpha and ribavirin. Int J STD AIDS. 2013 Mar 20. doi: 10.1177/0956462412472317

8.Sherman KE et al. Viral kinetics in hepatitis C or hepatitis C/human immunodeficiency virus-infected patients. Gastroenterology. 2005 Feb;128(2):313-27

9.Weber R, Smith C, D:A:D Study Group. Trends over time in underlying causes of death in the D:A:D study from 1999 to 2011. Program and abstracts of the XIX International AIDS Conference; July 22-27, 2012; Washington, DC. Abstract THAB0304

10.van der Helm JJ, Prins M, del Amo J, Bucher HC, Chêne G, Dorrucci M, Gill J, Hamouda O, Sannes M, Porter K, Geskus RB; CASCADE Collaboration. The hepatitis C epidemic among HIV-positive MSM: incidence estimates from 1990 to 2007. AIDS. 2011 May 15;25(8):1083-91. doi: 10.1097/QAD.0b013e3283471cce.

11.Iversen J, Wand H, Topp L, Kaldor J, Maher L. Reduction in HCV incidence among injection drug users attending needle and syringe programs in Australia: a linkage study. Am J Public Health. 2013 Aug;103(8):1436-44. doi: 10.2105/AJPH.2012.301206.

12.Schmidt AJ et al. Trouble with bleeding: risk factors for acute hepatitis C among HIV-positive gay men from Germany--a case-control study. PLoS One. 2011 Mar 8;6(3):e17781. doi: 10.1371/journal.pone.0017781.

13.Martin TC, Martin NK, Hickman M, Vickerman P, Page EE, Everett R, Gazzard BG, Nelson M. HCV reinfection incidence and treatment outcome among HIV-positive MSM in London. AIDS. 2013 Jun 3. doi: 10.1097/QAD.0b013e32836381cc.

14.Lambers FA et al for MOSAIC (MSM Observational Study of Acute Infection with hepatitis C) study group. Alarming incidence of hepatitis C virus re-infection after treatment of sexually acquired acute hepatitis C virus infection in HIV-infected MSM. AIDS. 2011 Nov 13;25(17):F21-7. doi: 10.1097/QAD.0b013e32834bac44.

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