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Conference on Retroviruses and Opportunistic Infections

Recently, the Conference on Retroviruses and Opportunistic Infections, sponsored by the International Antiviral Society-USA, provided researchers with an opportunity to translate their clinical findings into progress against the HIV epidemic, according to the organization. That mission includes treating those patients with coinfection with hepatitis C.

The conference is an international meeting that brings together nearly 4,000 scientists, researchers, clinicians and students, with almost half of attendees traveling from countries outside the United States. Representing a part of that international audience is Jürgen K. Rockstroh, MD, professor of medicine, University of Bonn, Germany, who served on the program committee. Here, Rockstroh gives HCV Next insight into what came out of CROI for HCV treatment.

Jürgen K. Rockstroh, MD

The study that got the most attention and has been most widely discussed was clearly the presentation from the Dutch group on expanded DAA uptake in the Netherlands. They showed that, since November 2015 when they implemented an allowance of DAA therapy for all patients regardless of fibrosis stage, there was a dramatic increase in uptake of therapy with 1,171 out of 1,420 patients initiating DAA based therapy since DAAs became available and an overall SVR rate of 70% in their patient population through January 2017.

Only 30% of patients are left untreated, which includes those who have never received treatment because of either low fibrosis stage or they were not ready to start and a smaller group of patients who have failed previous DAA plus pegylated interferon-ribavirin-based therapies and are waiting for retreatment.

Of note, 76% of all men who have sex with men with HCV/HIV coinfection have been successfully cured of HCV by now. The second presentation focused on this group and looked at how the overall incidence of acute HCV in the Netherlands is changing in light of the expanded DAA roll-out.

The researchers monitored this change with two large studies that included more than half of all acute HCV patients in the Netherlands. They saw 50% less patients in 2016 and if you divide 2016 into two half-years, it’s even less in the second half of 2016.

They’re showing that this dramatic increase in uptake of DAA therapy — particularly in the MSM population — led to a decline in new cases of HCV. That’s obviously one of the hopes we as practitioners have. If we can identify HCV easily in a given risk group, like in HIV-positive MSM, which will show up for CD4 count and viral load monitoring regularly, we then can start HCV therapy accordingly and prevent further HCV transmissions. Indeed, if we could treat everyone for HCV in that particular group we may be able to eliminate HCV in that group of patients.

This approach and the government funding of the DAA coverage does not protect against people coming in from other countries. It also does not impact transmission among HIV-negative individuals with HCV, but it clearly minimizes the pool of infected individuals and has a direct impact, which by now is in the range of 50% less infections.

That’s great news, showing if DAA therapies are rolled out more widely, we actually can have an impact on epidemiology.

Real-World Data

There was very little on treatment with new HCV agents, but there was some real-world data looking at outcome of DAA therapy in HIV/HCV coinfected individuals from Germany.

They showed that patients that had a lower CD4 count have a somewhat lower SVR rate than those with a higher CD4 count. This underlies the potential that having patients on ART and having good immune constitution prior to starting therapy could be useful, but of note, patients who are cirrhotic also had a lower SVR rate. Obviously, patients with a lower CD4 count usually also have more cirrhosis, so that overlaps.

Because of the higher risk for fibrosis progression in patients with lower CD4 counts, the lower overall cure rate is understandable. This reminds us all that just as you want to treat HIV early and not when CD4 counts have plummeted, you want to treat HCV early prior to developing cirrhosis because after cirrhosis the response rates become less favorable.

There was some interaction data on a new fixed-dose combination of glecaprevir/pibrentasvir (AbbVie) when administered with HIV medications. This is a new fixed-dose DAA combination that is pangenotypic; efficacy results of the HIV/HCV coinfection trial will likely be presented at the International Liver Congress in April.

At CROI, only the results of the interaction study between dolutegravir/abacavir/lamivudine (Triumeq, ViiV) or elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF; Genvoya, Gilead Sciences) and glecaprevir/pibrentasvir were presented. In particular, the E/C/F/TAF aspect was interesting because E/C/F/TAF contains cobicistat, so there’s a booster in there. And glecaprevir/pibrentasvir contains a protease inhibitor, so the question was whether there would be significant interaction through the cytochrome p450 system.

Interestingly, there was an increase in drug levels but not in a way needing dose adaptation. E/C/F/TAF will work and also the combination with dolutegravir/abacavir/lamivudine as another integrase-fixed-dose combination. There were also no significant changes in levels that would require dose adaptation.

Now, for two very commonly prescribed first-line integrase-inhibitor-based regimens, we have good interaction data. This new glecaprevir/pibrentasvir compound will be interesting because it has very good genotype 3 activity and also there’s good data on retreatment in prior DAA failure. So this could be a good option for this kind of patients.

There were two studies, one as an oral presentation and one as a poster, looking at the risk for developing hepatocellular carcinoma after achieving SVR under DAA therapy.

This is something that has been hypothesized as a concern in monoinfection patients where some groups have reported higher risk of developing HCC after achieving SVR with one of the available DAA therapies.

Of note, this is difficult to judge because patients who have been treated with DAAs are very different than the patients of the old days with interferon. In the old days, if you had advanced cirrhosis, you couldn’t be treated with interferon-based therapies. With DAAs being so well tolerated, the threshold for treating patients has been lowered considerably and everyone qualifies for therapy. That includes patients with very advanced liver disease who are obviously already at a higher risk for liver cancer.

The question is: are we treating different patients or are we really seeing more cancers? The Spanish study was well done and showed the data from different treatment periods: modified interferon, pegylated interferon plus ribavirin, first DAA generation plus pegylated interferon and then DAA-only era.

There were a higher number of cases of HCC in the DAA era, but when they looked at all the patients and followed them over time, the incidence did not increase at all. It’s really just that you’re treating more sick patients at a higher risk. You’re seeing more cases, maybe, but not necessarily as a consequence of SVR after DAA.

That was reassuring that, yes, you have to monitor someone who had cirrhosis even if they achieve SVR. That risk remains and you will have to monitor for HCC, but it’s not that the risk itself is increased.

Beyond HCV: Hepatitis B

There was also some data on hepatitis B. One, from my group with our colleagues from Cologne, looked at patients who had HIV and chronic HBV infection and were treated long-term with tenofovir disoproxil fumarate (TDF; Viread, Gilead Sciences). The median time on therapy was 7 years with a median follow-up of 104 months.

The overall HBsAg loss — something we desire as a goal of HBV therapy — was 16%, much higher than what you see in monoinfected patients. The story here is when you have HIV and then get HBV, your risk for developing chronic infection is six times higher because HBV clearance is immune-mediated so when you are immunodeficient due to HIV, you can’t do it as well.

When antiretroviral therapy kicks in and your immune system is restored, some of those patients who probably would have lost HBV in the first place, can clear the infection due to improved immune system. For the practitioner, you have to monitor your patients, because endpoints may be reached and your patient may seroconvert.

In a study from Thailand, they looked at vertical transmission of HBV in pregnant women with chronic HBV and they randomized the pregnant women to TDF or placebo and then the neonates were vaccinated five times plus received HBV immunoglobulin.

Only 2% of the children in the placebo arm were infected. That’s very low compared with other studies, suggesting that this intensive vaccination schedule of five vaccination shots plus HBV immunoglobulin was effective in preventing transmission.

Also, no one in the TDF group was infected, suggesting that if you indeed add TDF, that is something that will help to prevent perinatal HBV transmission. There are guidelines recommending the use of TDF in women who have more than 6 log HBV DNA because that’s where risk is highest. This is reinforcing some of the guidelines and papers in the literature with a very large trial and it continues to support the use of TDF for HBV transmission in the perinatal setting.

• References:
• Boesecke C, et al. Abstract 551. Presented at: The Conference on Retroviruses and Opportunistic Infections 2017; Feb. 13-16, 2017; Seattle.
• Boesecke C, et al. Abstract 580. Presented at: The Conference on Retroviruses and Opportunistic Infections 2017; Feb. 13-16, 2017; Seattle.
• Jourdain G, et al. Abstract 584LB. Presented at: The Conference on Retroviruses and Opportunistic Infections 2017; Feb. 13-16, 2017; Seattle.
• Kosloski MP, et al. Abstract 413. Presented at: The Conference on Retroviruses and Opportunistic Infections 2017; Feb. 13-16, 2017; Seattle.
• Merchante N, et al. Abstract 139. Presented at: The Conference on Retroviruses and Opportunistic Infections 2017; Feb. 13-16, 2017; Seattle.
• Rijnders B, et al. Abstract 137LB. Presented at: The Conference on Retroviruses and Opportunistic Infections 2017; Feb. 13-16, 2017; Seattle.
• Virlogeux V, et al. Abstract 135. Presented at: The Conference on Retroviruses and Opportunistic Infections 2017; Feb. 13-16, 2017; Seattle.

• For more information:
• Jürgen K. Rockstroh, MD, can be reached at Oberarzt an der Medizinischen Universitätsklinik, Innere-Rheuma-Tropen Ambulanz, Sigmund Freud Strasse 25, 53105 Bonn-Venusberg, Germany; email: Juergen.Rockstroh@ukbonn.de.

Disclosure: Rockstroh reports financial relationships with Abbott Laboratories, AbbVie, Boehringer Ingelheim Pharmaceuticals, Bristol-Myers Squibb Company, Cipla, Gilead Sciences Medical Affairs, Merck, Roche Laboratories, Tibotec and Viiv Healthcare.