The Take Home

Infectious Disease Week 2016

The presence of many symposia regarding hepatitis C infection at Infectious Disease Week 2016 showed the continued and growing interest of ID physicians in treating and managing patients with HCV. Though new data were less prominent than you may see in our counterpart’s Take Home (page 21) from The Liver Meeting, there were important clinical management pieces discussed.

Michael S. Saag

The biggest study I saw was the Gilead study of sofosbuvir/vealpatasvir (Epclusa, Gilead Sciences) and their new protease inhibitor, voxilaprevir (GS-9857, Gilead Sciences). This is a three-drug combination that the company is developing into one pill inclusive of a NS5A, NS5B plus a protease inhibitor.

The three-drug combination was administered for 6, 8 and 12 weeks in all genotypes. The 6-week duration didn’t work well enough to be viable, but and the 8-week appeared to worked in non-cirrhotic patients who were treatment-naivenaïve; however an updated presentation at AASLD revealed that the 8 week duration was not non-inferior. Still,Therefore, for most patients, including those with cirrhosis — especially with certain genotypes — should get 12 weeks.

Finally, the researchers showed results for patients previously treated with direct-acting antiviral therapy and had NS5A treatment failures and it worked pretty well (details described below). I presume we will hear a lot about this new combination in the future.

There was also a study looking at the cost effectiveness of screening strategies among adolescents and young adults. This study showed that it is cost effective to test younger people for HCV at least once. Of course, it depends on the risk factors for the population tested, due to positive predictor value, but one-time testing was estimated at approximately $13,000 per QALY gained, which is cost-effective in the United States. The recommendation is to start considering this younger age of screening as a more routine procedure as opposed to just checking baby boomers.

Another study looked at NHANES evaluation of testing and linkage to care from 2001 to 2014. Collectively, we are getting better linking those with a positive HCV antibody test since the advent of DAAs.

Another study showed that people who are HCV-infected have a higher risk for acute myocardial infarctions despite normal lipid levels. While this may not be new information, the study provides additional data to back up the hypothesis. The real story, in my opinion, involves chronic inflammation in HCV-positive individuals and the subsequent complications we are seeing.

HCV Next also spoke with Ravi Jhaveri, MD, FIDSA, FPIDS, associate professor of pediatrics at the University of North Carolina, and Kristen Marks, MD, assistant professor at Weill Cornell Medical College, about their views from ID Week.

Michael S. Saag, MD

Co-Chief Medical Editor

HCV Next

Ravi Jhaveri, MD, FIDSA, FPIDS

Going into ID Week, I was very pleased that the committee included a session for treating children with hepatitis C. There is a growing idea among physicians that children are becoming recognized as a population in need of thoughtful treatment decisions. That’s often not reflected in the other meetings and should be noted.

In my session, Ronald Nahass, MD, FIDSA, FSHEA, presented the results of the phase 2 studies looking at sofosbuvir/valpatasvir plus GS-9857.

The results on the whole are in line with what you’d expect from these combination therapies. The key nugget from this study and its results was that in the subgroup of patients treated for 6 weeks with genotype 3, which has become a harder to treat genotype, 100% of those patients — 21 out of 21 — responded to that short regimen. The other genotypes responded at a very high rate, but that group doing so well with such a short duration of therapy is particularly promising.

The second presentation was from a group at Boston University, led by Sabrina Assoumou, MD, MPH, looking at strategies for screening for hepatitis C. Anticipating the increased drug use we are seeing today, this group modeled how we should strategize and change screening. Can we use regular blood screening? Can we use a rapid finger prick? Should screening be conducted by a counselor or MD?

They found that once you reach a certain prevalence of drug use in a community, you rapidly meet the criteria for cost effective screening. That could take place in any form and it was actually better if a trained counselor was doing it as opposed to just a physician.

Ravi Jhaveri

One of the limitations to their analysis was that it largely focused on more urban environments. One of the questions was how does this apply in a more rural, resource-limited setting where population density is not as high and there is not a trained counselor, yet certainly where the opioid epidemic has really taken off. That’s the down side to it.

Clearly, though, the issue that they shed light on was that we need to change our strategy for screening and it needs to be more broadly thought of than the Baby Boomer screening and asking if there is a drug history. Even this somewhat limited attempt to look at communities where this is a problem highlights that we need to change strategy from the current standard approach.

The next study of note was an analysis of NHANES data from the CDC’s Center for Viral Hepatitis. They looked at people who tested positive and how often were they actually informed of results and how their follow-up progressed.

The bottom line is after people got tested for HCV, only a minority of patients got the appropriate follow-up testing, got RNA testing, were informed of their diagnosis, were appropriately referred and received appropriate specialty testing.

It really highlighted the idea that, similar to patients with HIV, we really need to work on the linkage to specialty care. Just knowing your diagnosis is not good enough. Patients need to be ushered through the system to get the appropriate follow-up.

They identified patients who received their letter notifying them of their results, but beyond that, there is so much room for improvement.

The limitation is that NHANES is a very small subset of patients every year that are sampled. You’re only selectively sampling people, but this showed the idea that the deficiencies are so great across the board for every question that they looked at that. There’s definitely room for us to do better.

The next two presentations delivered by Adeel Butt, MD, MS, analyzed an administrative database from the Veterans Administration, which is a limitation.

The researchers first looked at patients that had hepatic decompensation during treatment of HCV. We now have a black box warning for the combination of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak, AbbVie) due to reports of compensated cirrhosis that decompensated when they started treatment.

What this analysis did was look broadly at everyone who was treated with hepatitis C in the VA, including all regimens. What they showed was there was certainly a risk for hepatic decompensation in patients who received the four-part regimen, but also what they showed was that patients treated with other regimens where there is no black box warning also had an increased risk for decompensation compared with controls

It’s probably not so much the specific drug combination as it is in patients that are compensated but barely compensated that there is a broader risk for decompensation

The next presentation from Butt addressed lipid levels in patients that are infected and not infected with HCV and looked at the risk for myocardial infarction and other events. They showed that with hepatitis C, patients had lower overall lipid levels, but across the board, the risk for MI events is higher than their age-matched controls. Particularly in patients in their 40s and 50s where the risk should be low, the patients with HCV have an excess risk for cardiovascular events.

It’s notable that the researchers went out of the way to control for other factors, excluding anyone with identified heart disease or diabetes and those who smoke. In essence, you’re talking about the healthiest of the healthy and they still had an increased risk. So even in a very carefully manipulated environment, that risk stood out.

You can imagine in the real world where all those other factors come back into play, the risk would be even higher. That’s in line with other data that’s out there about cardiovascular mortality in patients with HCV, but it highlights why — when we’re thinking about reasons to treat somebody — there are reasons beyond just liver disease.

Another group from Oregon looked at the outcomes of liver disease by creating a registry to look at patients who ultimately progressed to HCC.

They found that patients of Asian ethnicity had the highest risk for developing HCC. One of the things that was interesting is that you might expect these patients might also have HBV and that to have been the driving risk factor but that was not the case. There were so few coinfected patients that they could not make that connection.

They concluded that Asian/Pacific Islander descent and age were the highest risk factors for progression to HCC. Once you look at these risk factors, the idea is you can then perhaps make different decisions about who to prioritize for treatment.

Overall, ID Week showed that the ID community is becoming more interested and involved in hepatitis C treatment and that is appropriate given where treatment is headed.

In this meeting, there’s now a separate category for hepatitis research so there was a robust poster representation for people doing work on hepatitis C, especially related to the married problem of HCV and injection and intravenous drug use.

The ID community is interested in treatment but also interested in epidemiology and the socioeconomic problems that are intrinsically related to this new wave of HCV infection. That’s where a lot of their interest is, which makes sense as the ID orientation is more epidemiology and public health. That’s appropriate.

There is attention being given to this problem and people are trying to figure out how to identify ways to intervene.

Kristen M. Marks, MD

HCV research was well represented at ID Week 2016, with posters on everything from screening and linkage to treatment and post-treatment monitoring.

One of the studies that stood out to me was the triple-drug regimen, sofosbuvir/velpatasvir/voxilaprevir discussed earlier, that examined 6-, 8-, and 12-week arms.

This and other data suggest 8 week regimens might be appropriate for certain patients. It will be a shorter treatment, but for patients I treat, having an additional drug confers additional concern about drug–drug interactions, so there’s a tradeoff there. So, to me, the most exciting use of this will be in treatment-experienced patients.

Kristen M. Marksi

In this study, 40% of patients were treatment-experienced, including 27% who had previous NS5A inhibitor experience. Of the group who was treatment-experienced, the cure rate was at 100% with previous NS5A experience and 99% in those without.

With the exception of genotype 3, the 6-week arm had poorer results. I look forward to finding out whether resistance-associated variants or baseline viral load were predictive of success. It remains to be seen whether there is a subset in which 6 weeks works.

Eight vs. 12 weeks for treatment-naive is progress and it’s exciting to have a shorter regimen, but for these people who are hard to treat and experienced patients, that’s where I see the most potential for this regimen. It worked so well in those treatment-experienced patients without ribavirin and it seemed to work equally as well with or without ribavirin in treatment-naive, so there appears to be no reason to use ribavirin with that regimen.

In terms of a real-world cohort, Debika Bhattacharya, MD, MSc, presented a large cohort of 996 genotype 1 HCV/HIV coinfected veterans and their SVR outcomes when treated with either ledipasvir/sofosbuvir (Harvoni, Gilead Sciences) with or without ribavirin and ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin.

Interestingly, they didn’t see any difference between outcomes in blacks and other races and there was also no effect of proton pump inhibitors. The take home point was that they had very good cure rates — overall 91% — and it didn’t seem to depend on regimen. Both regimens did well and patients with cirrhosis saw an 86% SVR.

They also examined renal function in those patients on tenofovir disoproxil fumarate (Viread, Gilead Sciences) vs. not coadministered with the sofosbuvir/ledipasvir regimen. They observed that renal function did not worsen during HCV treatment, but I believe they plan to analyze if further by level of baseline renal dysfunction. I look forward to hearing more on this. Of course, because they were veterans, the group was 99% men, limiting the generalizability somewhat.

There were several posters on using transient elastography or Fibroscan (Echosens) after treatment for post-treatment monitoring. These posters suggest that there is continued improvement in fibrosis. You see initial improvement from the treatment, but some of them showed continued improvement in measured liver fibrosis post-treatment.

Though, at this time, I wouldn’t do that as routine clinical management, those studies are important to determine if those improvements in fibrosis scores translate to a lower risk for HCC or complications of cirrhosis. Overall, they were encouraging, but we need to see if there is a clinical parallel of less liver-related complications.

In another study by Butt, his team used the ERCHIVES cohort to look at whether there was a benefit of adding ribavirin for genotype 1 treated with ledipasvir/sofosbuvir, paritaprevir/ritonavir/ombitasvir/dasabuvir (except genotype 1a) or sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen).

With these three regimens, the addition of ribavirin did not seem to make a difference. It should be noted that the groups that did not receive ribavirin differ from the groups that do receive it, so there’s an inherent bias based on the indication for ribavirin.

Still, it was reassuring that there wasn’t a benefit to adding ribavirin so if there’s not a clear indication, there’s certainly no reason to use it. There are still certain indications, of course, for adding in ribavirin, but as a routine practice, this is reassuring that it’s not necessary.

I had the opportunity to attend a pre-meeting symposium on treatment of HCV and it was very well attended by ID physicians. There’s a lot of enthusiasm for treating HCV and people want to learn more.

The providers who attended commented that they are still struggling with access in many states, presenting a huge barrier still, but I was very encouraged that people supported treating everyone with HCV. They were there to learn how to treat if they didn’t already know. Many providers who attended are already treating patients; they were very focused on making sure they were monitoring and managing liver disease correctly. That’s an important part of doing this as an ID provider and that’s where people wanted more guidance and information. We should continue to disseminate that information.

For example, there were questions on the hepatitis B reactivation, given the recent notice from the FDA. There were questions on whether you need to continue to monitor for HCC after treatment and how to do that.

Those are questions where we don’t have all the answers, but they are on the radar. Continued research in those areas is important, but I was impressed that providers honed in on these important questions.

Disclosures: Jhaveri reports financial relationships with AbbVie, Alios, GenMark, Gilead, MedImmune and Merck. Marks reports financial relationships with Gilead and Merck. Saag reports financial relationships with AbbVie, Bristol-Myers Squibb, Gilead, Merck, Teva and ViiV.

The presence of many symposia regarding hepatitis C infection at Infectious Disease Week 2016 showed the continued and growing interest of ID physicians in treating and managing patients with HCV. Though new data were less prominent than you may see in our counterpart’s Take Home (page 21) from The Liver Meeting, there were important clinical management pieces discussed.

Michael S. Saag

The biggest study I saw was the Gilead study of sofosbuvir/vealpatasvir (Epclusa, Gilead Sciences) and their new protease inhibitor, voxilaprevir (GS-9857, Gilead Sciences). This is a three-drug combination that the company is developing into one pill inclusive of a NS5A, NS5B plus a protease inhibitor.

The three-drug combination was administered for 6, 8 and 12 weeks in all genotypes. The 6-week duration didn’t work well enough to be viable, but and the 8-week appeared to worked in non-cirrhotic patients who were treatment-naivenaïve; however an updated presentation at AASLD revealed that the 8 week duration was not non-inferior. Still,Therefore, for most patients, including those with cirrhosis — especially with certain genotypes — should get 12 weeks.

Finally, the researchers showed results for patients previously treated with direct-acting antiviral therapy and had NS5A treatment failures and it worked pretty well (details described below). I presume we will hear a lot about this new combination in the future.

There was also a study looking at the cost effectiveness of screening strategies among adolescents and young adults. This study showed that it is cost effective to test younger people for HCV at least once. Of course, it depends on the risk factors for the population tested, due to positive predictor value, but one-time testing was estimated at approximately $13,000 per QALY gained, which is cost-effective in the United States. The recommendation is to start considering this younger age of screening as a more routine procedure as opposed to just checking baby boomers.

Another study looked at NHANES evaluation of testing and linkage to care from 2001 to 2014. Collectively, we are getting better linking those with a positive HCV antibody test since the advent of DAAs.

Another study showed that people who are HCV-infected have a higher risk for acute myocardial infarctions despite normal lipid levels. While this may not be new information, the study provides additional data to back up the hypothesis. The real story, in my opinion, involves chronic inflammation in HCV-positive individuals and the subsequent complications we are seeing.

HCV Next also spoke with Ravi Jhaveri, MD, FIDSA, FPIDS, associate professor of pediatrics at the University of North Carolina, and Kristen Marks, MD, assistant professor at Weill Cornell Medical College, about their views from ID Week.

Michael S. Saag, MD

Co-Chief Medical Editor

HCV Next

Ravi Jhaveri, MD, FIDSA, FPIDS

Going into ID Week, I was very pleased that the committee included a session for treating children with hepatitis C. There is a growing idea among physicians that children are becoming recognized as a population in need of thoughtful treatment decisions. That’s often not reflected in the other meetings and should be noted.

In my session, Ronald Nahass, MD, FIDSA, FSHEA, presented the results of the phase 2 studies looking at sofosbuvir/valpatasvir plus GS-9857.

The results on the whole are in line with what you’d expect from these combination therapies. The key nugget from this study and its results was that in the subgroup of patients treated for 6 weeks with genotype 3, which has become a harder to treat genotype, 100% of those patients — 21 out of 21 — responded to that short regimen. The other genotypes responded at a very high rate, but that group doing so well with such a short duration of therapy is particularly promising.

The second presentation was from a group at Boston University, led by Sabrina Assoumou, MD, MPH, looking at strategies for screening for hepatitis C. Anticipating the increased drug use we are seeing today, this group modeled how we should strategize and change screening. Can we use regular blood screening? Can we use a rapid finger prick? Should screening be conducted by a counselor or MD?

They found that once you reach a certain prevalence of drug use in a community, you rapidly meet the criteria for cost effective screening. That could take place in any form and it was actually better if a trained counselor was doing it as opposed to just a physician.

Ravi Jhaveri

One of the limitations to their analysis was that it largely focused on more urban environments. One of the questions was how does this apply in a more rural, resource-limited setting where population density is not as high and there is not a trained counselor, yet certainly where the opioid epidemic has really taken off. That’s the down side to it.

Clearly, though, the issue that they shed light on was that we need to change our strategy for screening and it needs to be more broadly thought of than the Baby Boomer screening and asking if there is a drug history. Even this somewhat limited attempt to look at communities where this is a problem highlights that we need to change strategy from the current standard approach.

The next study of note was an analysis of NHANES data from the CDC’s Center for Viral Hepatitis. They looked at people who tested positive and how often were they actually informed of results and how their follow-up progressed.

PAGE BREAK

The bottom line is after people got tested for HCV, only a minority of patients got the appropriate follow-up testing, got RNA testing, were informed of their diagnosis, were appropriately referred and received appropriate specialty testing.

It really highlighted the idea that, similar to patients with HIV, we really need to work on the linkage to specialty care. Just knowing your diagnosis is not good enough. Patients need to be ushered through the system to get the appropriate follow-up.

They identified patients who received their letter notifying them of their results, but beyond that, there is so much room for improvement.

The limitation is that NHANES is a very small subset of patients every year that are sampled. You’re only selectively sampling people, but this showed the idea that the deficiencies are so great across the board for every question that they looked at that. There’s definitely room for us to do better.

The next two presentations delivered by Adeel Butt, MD, MS, analyzed an administrative database from the Veterans Administration, which is a limitation.

The researchers first looked at patients that had hepatic decompensation during treatment of HCV. We now have a black box warning for the combination of ombitasvir, paritaprevir, ritonavir, and dasabuvir (Viekira Pak, AbbVie) due to reports of compensated cirrhosis that decompensated when they started treatment.

What this analysis did was look broadly at everyone who was treated with hepatitis C in the VA, including all regimens. What they showed was there was certainly a risk for hepatic decompensation in patients who received the four-part regimen, but also what they showed was that patients treated with other regimens where there is no black box warning also had an increased risk for decompensation compared with controls

It’s probably not so much the specific drug combination as it is in patients that are compensated but barely compensated that there is a broader risk for decompensation

The next presentation from Butt addressed lipid levels in patients that are infected and not infected with HCV and looked at the risk for myocardial infarction and other events. They showed that with hepatitis C, patients had lower overall lipid levels, but across the board, the risk for MI events is higher than their age-matched controls. Particularly in patients in their 40s and 50s where the risk should be low, the patients with HCV have an excess risk for cardiovascular events.

PAGE BREAK

It’s notable that the researchers went out of the way to control for other factors, excluding anyone with identified heart disease or diabetes and those who smoke. In essence, you’re talking about the healthiest of the healthy and they still had an increased risk. So even in a very carefully manipulated environment, that risk stood out.

You can imagine in the real world where all those other factors come back into play, the risk would be even higher. That’s in line with other data that’s out there about cardiovascular mortality in patients with HCV, but it highlights why — when we’re thinking about reasons to treat somebody — there are reasons beyond just liver disease.

Another group from Oregon looked at the outcomes of liver disease by creating a registry to look at patients who ultimately progressed to HCC.

They found that patients of Asian ethnicity had the highest risk for developing HCC. One of the things that was interesting is that you might expect these patients might also have HBV and that to have been the driving risk factor but that was not the case. There were so few coinfected patients that they could not make that connection.

They concluded that Asian/Pacific Islander descent and age were the highest risk factors for progression to HCC. Once you look at these risk factors, the idea is you can then perhaps make different decisions about who to prioritize for treatment.

Overall, ID Week showed that the ID community is becoming more interested and involved in hepatitis C treatment and that is appropriate given where treatment is headed.

In this meeting, there’s now a separate category for hepatitis research so there was a robust poster representation for people doing work on hepatitis C, especially related to the married problem of HCV and injection and intravenous drug use.

The ID community is interested in treatment but also interested in epidemiology and the socioeconomic problems that are intrinsically related to this new wave of HCV infection. That’s where a lot of their interest is, which makes sense as the ID orientation is more epidemiology and public health. That’s appropriate.

There is attention being given to this problem and people are trying to figure out how to identify ways to intervene.

Kristen M. Marks, MD

HCV research was well represented at ID Week 2016, with posters on everything from screening and linkage to treatment and post-treatment monitoring.

One of the studies that stood out to me was the triple-drug regimen, sofosbuvir/velpatasvir/voxilaprevir discussed earlier, that examined 6-, 8-, and 12-week arms.

This and other data suggest 8 week regimens might be appropriate for certain patients. It will be a shorter treatment, but for patients I treat, having an additional drug confers additional concern about drug–drug interactions, so there’s a tradeoff there. So, to me, the most exciting use of this will be in treatment-experienced patients.

Kristen M. Marksi

In this study, 40% of patients were treatment-experienced, including 27% who had previous NS5A inhibitor experience. Of the group who was treatment-experienced, the cure rate was at 100% with previous NS5A experience and 99% in those without.

With the exception of genotype 3, the 6-week arm had poorer results. I look forward to finding out whether resistance-associated variants or baseline viral load were predictive of success. It remains to be seen whether there is a subset in which 6 weeks works.

Eight vs. 12 weeks for treatment-naive is progress and it’s exciting to have a shorter regimen, but for these people who are hard to treat and experienced patients, that’s where I see the most potential for this regimen. It worked so well in those treatment-experienced patients without ribavirin and it seemed to work equally as well with or without ribavirin in treatment-naive, so there appears to be no reason to use ribavirin with that regimen.

PAGE BREAK

In terms of a real-world cohort, Debika Bhattacharya, MD, MSc, presented a large cohort of 996 genotype 1 HCV/HIV coinfected veterans and their SVR outcomes when treated with either ledipasvir/sofosbuvir (Harvoni, Gilead Sciences) with or without ribavirin and ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin.

Interestingly, they didn’t see any difference between outcomes in blacks and other races and there was also no effect of proton pump inhibitors. The take home point was that they had very good cure rates — overall 91% — and it didn’t seem to depend on regimen. Both regimens did well and patients with cirrhosis saw an 86% SVR.

They also examined renal function in those patients on tenofovir disoproxil fumarate (Viread, Gilead Sciences) vs. not coadministered with the sofosbuvir/ledipasvir regimen. They observed that renal function did not worsen during HCV treatment, but I believe they plan to analyze if further by level of baseline renal dysfunction. I look forward to hearing more on this. Of course, because they were veterans, the group was 99% men, limiting the generalizability somewhat.

There were several posters on using transient elastography or Fibroscan (Echosens) after treatment for post-treatment monitoring. These posters suggest that there is continued improvement in fibrosis. You see initial improvement from the treatment, but some of them showed continued improvement in measured liver fibrosis post-treatment.

Though, at this time, I wouldn’t do that as routine clinical management, those studies are important to determine if those improvements in fibrosis scores translate to a lower risk for HCC or complications of cirrhosis. Overall, they were encouraging, but we need to see if there is a clinical parallel of less liver-related complications.

In another study by Butt, his team used the ERCHIVES cohort to look at whether there was a benefit of adding ribavirin for genotype 1 treated with ledipasvir/sofosbuvir, paritaprevir/ritonavir/ombitasvir/dasabuvir (except genotype 1a) or sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen).

With these three regimens, the addition of ribavirin did not seem to make a difference. It should be noted that the groups that did not receive ribavirin differ from the groups that do receive it, so there’s an inherent bias based on the indication for ribavirin.

Still, it was reassuring that there wasn’t a benefit to adding ribavirin so if there’s not a clear indication, there’s certainly no reason to use it. There are still certain indications, of course, for adding in ribavirin, but as a routine practice, this is reassuring that it’s not necessary.

I had the opportunity to attend a pre-meeting symposium on treatment of HCV and it was very well attended by ID physicians. There’s a lot of enthusiasm for treating HCV and people want to learn more.

The providers who attended commented that they are still struggling with access in many states, presenting a huge barrier still, but I was very encouraged that people supported treating everyone with HCV. They were there to learn how to treat if they didn’t already know. Many providers who attended are already treating patients; they were very focused on making sure they were monitoring and managing liver disease correctly. That’s an important part of doing this as an ID provider and that’s where people wanted more guidance and information. We should continue to disseminate that information.

For example, there were questions on the hepatitis B reactivation, given the recent notice from the FDA. There were questions on whether you need to continue to monitor for HCC after treatment and how to do that.

Those are questions where we don’t have all the answers, but they are on the radar. Continued research in those areas is important, but I was impressed that providers honed in on these important questions.

Disclosures: Jhaveri reports financial relationships with AbbVie, Alios, GenMark, Gilead, MedImmune and Merck. Marks reports financial relationships with Gilead and Merck. Saag reports financial relationships with AbbVie, Bristol-Myers Squibb, Gilead, Merck, Teva and ViiV.