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December 2008 HCV Advocate

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AASLD 2008 Drugs in Development: Part 1
Alan Franciscus, Editor-in-Chief


HealthWise: Deciphering Food Labels
Lucinda Porter, RN


HIV/HCV Coinfection at ICAAC and AASLD: Epidemiology and Hepatitis C Treatment
Liz Highleyman


HCV Advocate Eblast
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AASLD 2008 – Drugs in Development: Part 1
—Alan Franciscus, Editor-in-Chief

This year’s American Association for the Study of Liver Disease (AASLD) conference included information on many new drugs under development to treat hepatitis C, so much in fact that it is difficult to include all the new drugs that were presented at AASLD – the result being that I will not report on the pre-clinical data presented at AASLD.  Even excluding the pre-clinical trials, there is so much information to include that the report will be divided into two parts that will appear in the December 2008 and the January 2009 HCV Advocate newsletter. 

It’s amazing how far HCV drug development for treating hepatitis C has advanced over the years.  Just 5 years ago at the November 2003 AASLD conference I reported on the first HCV protease inhibitor that entered into human trials – BILN 2061.  I also reported on the pre-clinical data on VX-950 (telaprevir), early data on a long acting type of interferon (Albuferon) and a prodrug of ribavirin called viramidine.   

Since 2003, the clinical development of BILN 2061 has been halted due to safety concerns, and so far viramidine has not been shown to be as effective as ribavirin.  However, the good news is that telaprevir is still going strong, is now in Phase III clinical trials and has been shown to be safe, well-tolerated, and more effective than current treatments.  Albuferon is also in Phase III studies, but, unfortunately, the once a month dosing arms of the clinical trials had to be discontinued due to pulmonary (lung) problems.  It looks like the once every 2 weeks dosing is still a viable option although the effectiveness of albuferon does not seem to be any better than pegylated interferon.   But all in all the data presented at this year’s conference on HCV drugs in development are very encouraging.     

Telaprevir
The final and interim results from various studies of Vertex’s telaprevir, an HCV protease inhibitor, were released at this year’s conference.

PROVE 3: interim data on 453 patients who did not achieve a sustained virological response (SVR) with a previous course of pegylated interferon plus ribavirin – non-responders, relapsers and viral breakthroughs – was presented.  This included the interim results from the arms that received 12 weeks of telaprevir in combination with pegylated interferon plus ribavirin followed by 12 weeks of pegylated interferon plus ribavirin (without telaprevir).  HCV RNA negative was defined as  less than 10 IU/mL).

Note: the results given are SVR12 (12 weeks after treatment ends) and SVR24 (24 weeks after treatment ends) and the totals are combined:

Overall SVR results

52% (60 out of 115 patients-total)

Non-responders

41% (27 out of 66 patients)

Relapsers

73% (29 of 40 patients)

Breakthroughs

44% (4 of 9 patients)

Results for the control arm group (48 weeks of pegylated interferon plus ribavirin) are still pending. 

The side effect profile is consistent with pegylated interferon except there were higher incidences of pruritus (itching) and rashes, including severe rashes.  Sixteen percent of patients in the telaprevir-based arms discontinued treatment due to adverse events (side effects) compared to 4% in the group that received pegylated interferon plus ribavirin (without telaprevir).    

Study 107
Study 107 is another clinical trial that is evaluating the use of telaprevir in HCV prior non-responders, partial responders, relapsers and viral breakthroughs.  The patients in this study were people who were enrolled in the control arm (pegylated interferon/ribavirin without telaprevir) of a previous telaprevir study.   

The interim results at week 24 are listed below by type of prior response.  HCV RNA negative is defined as <10 IU/mL:

Null-reponders

43% (18 of 42 pts)

Partial responders

82% (18 of 22 pts)

Relapsers 

83% (5 of 6 pts)

Breakthroughs

0% (0 of 1 pt)

The safety profile is consistent with other studies of telaprevir, pegylated interferon and ribavirin.  

Prove 2
The final PROVE 2 study results of 323 HCV genotype 1 treatment-naïve patients (never been treated) were also released at this year’s AASLD conference.  HCV RNA negative was defined as < 10 IU/mL.  The results showed that the 24-week arm (12 weeks of telaprevir plus pegylated interferon plus ribavirin followed by 12 weeks of pegylated interferon plus ribavirin without telaprevir) had the highest SVR rate, 69%, (56 out of 81 patients) compared to 46% (38 out of 82 patients) in the arm that received 48 weeks of pegylated interferon plus ribavirin (control arm).  The side effect profile was consistent with the side effects reported above.  Fourteen percent of patients discontinued treatment due to adverse events compared to 7% in the control group who received pegylated interferon plus ribavirin (without telaprevir). 

Study C208
Study C208 is a newer study that is evaluating different doses of telaprevir – 750 mg every 8 hours (q8h or three times a day) compared to a 1125 mg dose every 12 hours (q12h or twice a day) in HCV genotype 1 treatment-naïve patients.  In addition, the two different brands of pegylated interferon – alfa-2a (Pegasys) and alfa-2b (PegIntron) – were used.  The previous studies of telaprevir only included Pegasys.

The very preliminary results of patients who were undetectable (less than 10 IU/mL) at week 12 are listed below by dose and pegylated product:

q8h alfa-2a

93% (37 out of 40 pts)

q8h alfa-2b

93% (39 out of 42 pts)

q12h alfa-2a

83% (33 out of 40 pts)

q12h alfa-2b

85% (33 out of 39 pts

To date 13 patients have discontinued therapy due to adverse events – 6 patients in the q8h and 7 patients in the q12h arms.  A total of 9 patients had viral breakthrough – 4 patients in the q8h and 5 patients in the q12h. 

If the results between the different dosing schedules can be carried through to the end of the trial and the results of this trial can be replicated in a larger study, a twice-a-day dose of telaprevir may be a future option.

The results from these studies are very encouraging, showing higher treatment response rates in a variety of populations with HCV genotype 1 including treatment-naïve patients and patients who have not achieved an SVR with a prior course of pegylated interferon and ribavirin therapy.  Telaprevir began Phase III studies in March 2008 and it is believed that Vertex will apply to the Food and Drug Administration for approval to market telaprevir for the treatment of chronic hepatitis C in 2010-2011.   

New Study – 3 Antivirals, No Interferon:
Roche, InterMune, Inc, and Pharmasset jointly announced on November 10 a new study called INFORM-1 to evaluate the safety and antiviral activity of three antivirals – R7227 (ITMN-191) an HCV protease inhibitor, R7128 an HCV polymerase inhibitor and ribavirin. 

This will be the first clinical trial combining three antiviral medications without the use of interferon as a possible treatment of hepatitis C.    

The study will evaluate the three antiviral medications in HCV genotype 1 treatment-naïve patients.  The clinical study will be conducted in Australia and New Zealand.  Hopefully, this first of its kind study for treating hepatitis C will usher in a new era that will include many combinations of antivirals to treat hepatitis C, and which may ultimately lead to therapies that do not contain interferon or ribavirin.

Boceprevir
Interim results from Schering’s HCV protease inhibitor, boceprevir, were also presented at AASLD.  The SPRINT-1 study was a very complex study that included 5 treatment arms.  The study population consisted of HCV genotype 1 treatment-naïve patients.  The results below are listed by treatment arm.

Sustained Virological Response (SVR12 & SVR24)

Treatment Arm

All patients

a)  No lead-in, 28 weeks

55% SVR 24 (59 out of 107 pts)

b)  Lead-in, 28 weeks

56% SVR 24 (58 out of 103 pts)

c)  No lead-in, 48 weeks

66% SVR 12 (68 out of 103 pts)

d) Lead-in, 48 weeks

74% SVR 12 (76 out of 103 pts)

e) P/R control, 48 weeks

38% SVR 12 (39 out of 104 pts)

a) Boceprevir, PegIntron, ribavirin (no lead-in phase) – total treatment duration = 28 weeks.

b) PegIntron, ribavirin for 4 week lead-in followed by boceprevir, PegIntron, ribavirin for 24 weeks – total treatment duration = 28 weeks

c) Boceprevir, Pegintron, ribavirin (no lead-in phase) – total treatment duration = 48 weeks.

d) PegIntron, ribavirin for 4 weeks followed by boceprevir, PegIntron, ribavirin for 44 weeks – total treatment duration = 48 weeks.

e) Control group that received only PegIntron, ribavirin – total treatment duration = 48 weeks. 

*Dosing: PegIntron 1.5 ug/kg once a week, ribavirin 800-1400 mg/day & boceprevir 800 mg/3 times a day.

Results for the boceprevir arm and control arm that included low-dose ribavirin are still pending.  

The side effects reported were similar in the d) group (lead-in, 48 weeks) compared to the e) control group except for higher prevalences of fatigue (71% vs. 55%), Anemia (56% vs. 34%), neutropenia (low white blood cells, 30% vs. 12%), taste changes (27% vs. 9%) and muscle pain (26% vs. 16%). 

The increase in the SVR rates in group d (boceprevir lead-in phase,48 weeks treatment duration) is very impressive.  Schering began their Phase III studies in May 2008 and they are expected to apply to the FDA for marketing approval sometime in 2010 or 2011. 

Nitazoxanide
At last year’s AASLD nitazoxanide (brand name Alinia) burst upon the HCV treatment scene with impressive results as an add-on to Pegasys and ribavirin therapy.  Nitazoxanide is approved to treat diarrhea that is caused by Cryptosporidium parvum and Giardia lamblia, and has been found to have only mild side effects.  A last year’s conference, a 12 week lead-in phase of nitazoxanide followed by 36 weeks of nitazoxanide, Pegasys and ribavirin in genotype 4 treatment-naïve patients produced a 79% SVR  (in the triple combo arm) for treatment-naïve patients and 25% SVR in the treatment-experienced patients.  Since this time, Romark has launched a study on HCV genotype 1 patients. 

At this year’s conference, information about a small study of 44 patients to evaluate effectiveness of a 4 week lead-in phase of nitazoxanide dosed at 500 mg twice a day (taken with food) followed by the combination of nitazoxanide and pegylated interferon (no ribavirin used) for 36 weeks was released.  The SVR results are listed below:

100% SVR

3 of 3 HCV genotype 1 patients

100% SVR

1 of 1 HCV genotype 2 patient

78% SVR

31 of 40 HCV genotype 4 patients

The authors commented that a 12-week nitazoxanide lead-in phase can be reduced to 4 weeks without compromising SVR rates.  It was also concluded that more studies are needed to compare the effectiveness of nitazoxanide in combination with pegylated interferon with and without ribavirin in treatment-naïve and treatment-experienced patients.  Imagine that – a possibility of eliminating ribavirin from combination treatment.  Of course, much larger studies are needed to confirm these findings.  

Drugs in Early Clinical Development

R7128 is an HCV polymerase inhibitor that is being developed by Pharmasset and Roche.  Preliminary results from studies on HCV genotype 1 treatment-naïve and treatment-experienced patients have resulted in impressive HCV RNA (viral load) reductions.  Based on various studies, Pharmasset will further develop the 1000 mg dose BID (twice a day) in HCV genotype 1 treatment-naïve patients and the 1500 mg dose TID in HCV genotype 1 treatment-experienced patients – both doses in combination with Pegasys plus ribavirin. 

What about HCV genotypes 2 or 3?  At this year’s conference a study of R7128 in people with HCV genotype 2 or 3 who either were prior treatment non-responders or relapsers was released at AASLD.   Patients were given R7128 (1500 mg twice a day) in combination with Pegasys plus ribavirin for 28 days or placebo/Pegasys/ribavirin.  At the end of the treatment period there was a mean decrease in HCV RNA of 5.0 log10 in the R7128 arm compared to a 3.7 log10 in the placebo arm.  No serious adverse events were reported and the side effects reported in the R7128 group were similar to the group that did not receive R7128.   More studies are being planned. 

ITMN-191 is an HCV protease inhibitor being developed by InterMune and Roche.  The results from a monotherapy study of HCV genotype 1 treatment-naïve and treatment-experienced patients were released.  In the study there were 50 patients who received doses up to 600mg (every 12 hours or every 8 hours) or placebo for 14 days.  The mean reduction in the 200 mg every 8 hours group by day 14 was 3.8 log10 in treatment-naïve.  In the treatment-experienced patients the median viral load reduction was 2.5 log10. The reduction in HCV RNA was dose dependent.  The doses were considered safe and were well-tolerated with only one serious adverse event reported – vertigo – that was not considered related to the study drug.


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HealthWise: Deciphering Food Labels
Lucinda Porter, RN

Every year, the American Association for the Study of Liver Diseases (AASLD) highlights the latest liver disease information. Referred to as the annual “liver meeting,” this event attracts people from all over the world. This year, as in the past, more data has emerged regarding the potential danger of weight-related problems. These problems include being overweight, obese, diabetic or having metabolic syndrome. 

We all know the importance of maintaining a healthy weight and diet, but those living with hepatitis C have extra incentive to do so. Last month’s Healthwise covered basic nutrition. This column focuses on food labels.

If you ever dieted, you probably read food labels. Calorie counting starts with studying food packaging information. When low-fat diets were vogue, then we looked at fat content. Later it was protein and carbohydrates.

Product labeling provides more than just diet information. Those eating organic or vegetarian-based diets use labels when choosing food. Those with allergies depend on the label’s ingredient list.  Food safety can be maintained by paying attention to packaging dates. Nutrition can be promoted by using labels to look for specific nutrients.

The Food and Drug Administration (FDA) regulates food labeling. Under the Federal Food Drug and Cosmetic Act, most packaged food must have a nutrition label. This is voluntary for raw fruits, vegetables, and fish. The FDA also regulates food claims. Products must meet certain guidelines in order to connect their food to a health benefit. Here is an example of a food claim:

Three grams of soluble fiber from oatmeal daily in a diet low in saturated fat and cholesterol may reduce the risk of heart disease. This cereal has 2 grams per serving.” (FDA’s Guidance for Industry: A Food Labeling Guide)

When looking at labels, start with portion size. For awhile, I was hooked on calzones. These savory Italian pies were packed with chicken and vegetables. At 320 calories, it filled me up on a winter day. Unfortunately, I did not pay attention to the label. If I had, I would have seen that one calzone is 2 servings. I was eating 640 calories for lunch. 

Fortunately, I did not eat one every day. Had I, I’d be writing this while recovering from a gastric-bypass. Let’s see how much weight the extra 320 calories would have added to my body. Assume that I was maintaining my weight prior to discovering calzones and that my regular calorie intake at lunch was 320 calories.

An additional 320 calories for 365 days equals 116,800 calories. One pound of body weight is equivalent to about 3500 calories (116,800 ÷ 3500 = 33.37).  In a year, I would gain a whopping 33 lbs. In five years, it would be close to 167 lbs—all because I didn’t read a food label.  By the way, if I hadn’t wanted to give up calzones and tried to exercise an additional 320 calories a day, I’d have to walk about 4.5 miles at a 3 mph clip.  That’s in addition to the 3 miles that I already walk—or try to walk.

Brand A

Brand B

The lesson I learned: look at the serving size on a food label and note how many servings are in a container.  Compare the two labels on the opposite page.  Both have the same serving size—½ cup.  However, if I ate the entire can of Brand A I would consume 840 calories and 3720 mg of sodium.  A can of Brand B will net me 315 calories and 805 mg of sodium.  Both provide lots of fiber, but I don’t want to think of what would happen if I ate all of Brand A.

Nutrients are listed under calories.  These include fat, cholesterol, sodium, carbohydrates, protein, vitamins and minerals.  Fat, cholesterol, and sodium are first because we need to strive for less of these. Current recommendations are to limit saturated fat and avoid trans fat.

Labels must list amounts for calcium, iron, vitamins A and C. The listing of other vitamins and minerals is voluntary unless the product carries a health claim about a specific nutrient. Brand B’s label provides more information than is required by law.

The % daily value is based on a 2000 calorie per day diet. Assuming I need 2000 calories daily, if I ate ½ can of Brand A beans, I’d get 78% of the maximum sodium recommendations. Note that there is no daily value for trans fat, as we are encouraged to avoid it.

Ingredients must be listed by weight in order—starting with the highest. Brand A’s ingredient list has a few items that I’d prefer not to consume, especially compared with those in Brand B. Note that Brand B did not have to add natural flavors because it started as a natural food.  Is adding natural flavor an oxymoron?

For those monitoring sugar intake, note that sugar has many names. High fructose corn syrup, fruit juice concentrate, glucose, maltose, dextrose, sucrose, honey and maple syrup are all sugars.  If corn syrup is the first listed ingredient, then that is what you are eating the most of in that salad dressing.

One guideline I live by is that if I can’t pronounce an ingredient, perhaps I shouldn’t eat it. Maltodextrin found in Brand A is a carbohydrate made from a starch that is absorbed rapidly like glucose. Do I really need that?

When it comes to nutrition, simplicity reigns.  Choose single-ingredient foods and you are likely to avoid additives.  What can be simpler than fresh fruit or vegetables? Dried beans, fish, eggs, nuts or dried fruit don’t have complicated food labels.  Not all single-ingredient food is healthy, such as cane sugar or lard, but you get the picture.

Labeling is a handy resource, but what about all that food facing us at the holidays? I’ve never gone to a party that passes out nutrition information with those bite-sized quiches.  Preparation and practice may help. Spend a little time looking at labels of food that you might find at a party. You can find this at the grocery store or on the Internet. Choose plant-based foods. Fish and poultry that haven’t been fried are usually good choices.

Knowing what is in food can help us make better choices. This is fundamental during the holidays. Weight gain is not an automatic consequence during winter holidays. Before we pop those hors d’oeuvres in our mouths, ask – what is in this food that I am about to eat? If you don’t know, then perhaps it’s best to eat something else.

It is possible to celebrate and stay healthy. We can indulge and delight in small pleasures. The twentieth bite doesn’t taste any better than the first. If a particular food is going to lead to overeating, avoid that food altogether.  I have never been able to eat just one malt ball at Easter time, so I skip them. However, I can eat a few jellybeans without wanting the entire basket.

Following a healthy diet is like training to be an athlete. It takes education, preparation, and practice. Spend some time educating yourself, develop a plan of action and make a commitment to yourself. Read food labels. You are worth it.

Further Resources
 • Center for Science in the Public Interest (CSPI) www.cspinet.org Nutrition Action Health Letter™ Although this organization has been called the “Food Police,” it is an incredible resource. Check out archived issues, May 2008 for a guide to food additives.

 • www.mayoclinic.com/health/nutrition-facts/NU00293 Mayo Clinic: Nutrition Facts: An interactive guide to food labels

 • www.traderjoes.com/Attachments/
how_to_read_nf.pdf


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HIV/HCV Coinfection at ICAAC and AASLD: Epidemiology and Hepatitis C Treatment
—Liz Highleyman

The joint Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and Annual Meeting of the Infectious Diseases Society of America in late October, and the 59th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) the following week, both featured several presentations on HIV/HCV coinfection. This article looks at epidemiology and hepatitis C treatment studies, while next month’s issue will cover liver disease progression and immune response.

Is HIV/HCV Coinfection Declining?
Spain has consistently had one of the highest HIV/HCV coinfection rates in Western Europe, particularly among injection drug users (IDUs), but the epidemiology appears to be changing. S. Perez Cachafeiro and colleagues (ICAAC abstract V-1629) collected data from more than 5,000 HIV positive antiretroviral therapy-naïve patients from two cohorts initiating care at Spanish institutions: a retrospective cohort from January 1997 through December 2003 (CoRIS-MD) and a prospective cohort from January 2004 through November 2006 (CoRIS). They found that the prevalence of HCV steadily decreased, from 71% among patients who entered the study in 1997 to 16% among those who started in 2006. During the same period, the proportion of IDUs in the cohorts decreased dramatically, from 67% to 15%. The investigators concluded that seroprevalence of hepatitis C coinfection in HIV positive antiretroviral therapy-naïve patients in Spain decreased from 1997 to 2006. “This decrease is driven by a change in HIV transmission patterns,” they added, notably a decrease in transmission via injection drug use.

Interferon-Based Therapy for Coinfected Patients
Researchers continue to explore alternatives to standard hepatitis C treatment for “hard-to-treat” patients who respond poorly to interferon-based therapy. A. Murphy and colleagues (ICAAC abstract V-4220) compared virological response in 19 genotype 1 HIV/HCV coinfected patients randomly assigned to receive either the standard-of-care regimen of 180 mcg once-weekly pegylated interferon alfa-2a (Pegasys) plus 1,000-1,200 mg/day weight-adjusted ribavirin for 48 weeks, or else 180 mcg twice-weekly pegylated interferon for four weeks followed by once-weekly for an additional 44 weeks with the same daily dose of ribavirin.

Participants receiving pegylated interferon more frequently had significantly lower HCV RNA on days 5 and 7, as well as a steeper slope of viral load decline through day 28. Among the African-American patients, the total HCV RNA decline was also greater. The study did not, however, have sufficient power to demonstrate a difference in sustained virological response (SVR) between the standard and double-frequency arms (40% vs 45%, respectively). The researchers concluded that twice weekly pegylated interferon “is associated with better early viral kinetics, particularly among African Americans, with similar safety profiles when compared with standard therapy.”

Partial Rapid Response
In another presentation on interferon-based therapy, investigators with the pivotal APRICOT study described data from a retrospective analysis of predictors of response. M. Rodriguez-Torres and colleagues (AASLD abstract 1855) looked at 176 HIV/HCV coinfected patients (out of 868 total trial participants) who had HCV genotype 1 and were randomized to receive 180 mcg/week pegylated interferon alfa-2a plus 800 mg/day ribavirin for 48 weeks (today, 1,000-1,200 mg/day ribavirin is considered standard therapy for this population).

It was previously shown that full rapid virological response (RVR) – or undetectable HCV viral load (< 50 copies/mL) at week 4 of therapy – was associated with a high rate of sustained response (82%). Here, the researchers looked at the effect of different levels of partial rapid response. They found that 79% of patients with unquantifiable HCV RNA (< 600 copies/mL) achieved SVR, compared with 43% who experienced at least a 3 log decline in HCV RNA at week 4, 32% who experienced at least a 2 log drop, 13% with at least a 1 log drop, and just 8% with less than a 1 log decrease. Based on these findings, they recommended that since patients in the first three rapid response strata had a high likelihood of SVR, “[a] response in one of these categories should be a strong incentive to continue planned treatment.”

Ribavirin Dose and Anemia
Looking at ribavirin-related adverse events, V. Soriano and colleagues (ICAAC abstract H-2321) assessed whether pre-emptive administration of erythropoietin (EPO; Procrit or Epogen) before the development of anemia could enable HIV/HCV coinfected patients to take higher doses of ribavirin, since adequate ribavirin has been shown to help prevent HCV relapse. The Spanish PERICO study included 175 participants (most with HCV genotypes 1 or 4) being treated for hepatitis C for the first time. They were randomly assigned to receive 180 mcg/week pegylated interferon alfa-2a plus either 1,000-1,200 mg/day ribavirin for the full duration, or else 2,000 mg/day ribavirin for four weeks, then dropping down to the standard dose. Those in the higher ribavirin dose arm also received 50,000 IU once-weekly EPO.

The higher ribavirin dose did not lead to higher plasma trough concentrations or a significantly higher frequency of severe anemia. Furthermore, in a planned interim analysis, the proportion of patients achieving RVR at week 4 was the same (23%) in both ribavirin dose arms. “The use of greater ribavirin doses (2 g/day) along with pre-emptive EPO during the first 4 weeks of HCV therapy is safe,” the researchers concluded, “but fails to enhance ribavirin plasma exposure and rate of RVR.”

In a related retrospective analysis, J. Quioc and colleagues from France (AASLD abstract 1269) found that serum ribavirin concentrations were significantly lower on average in HIV/HCV coinfected patients on HAART than among HCV monoinfected individuals receiving the same doses, which the researcher attributed to a metabolic interaction between ribavirin and antiretroviral drugs; the difference was not apparent in coinfected patients not taking antiretroviral therapy. Here too, however, there was no association between ribavirin blood concentration and end-of-treatment or sustained response rates.

Telaprevir-Tenofovir Interaction
The latest approach to hepatitis C therapy using “STAT-C” agents targeting various steps of the HCV lifecycle have not yet been studied in HIV/HCV coinfected patients, but investigators are beginning to lay the groundwork. R. Van Heeswijk and colleagues from Tibotec (ICAAC abstract A-966) analyzed interactions between the experimental HCV protease inhibitor telaprevir (VX-950) and the nucleotide analog antiretroviral drug tenofovir (Viread, also in the Truvada and Atripla combination pills). During three 7-day periods, 18 healthy volunteers without HIV or HCV received tenofovir 300 mg once-daily monotherapy, telaprevir 750 mg every eight hours monotherapy, and both drugs combined; all treatments were taken with food. Co-administration of the two drugs did not influence telaprevir pharmacokinetics, but did increase tenofovir exposure by about 30%. The combination was generally well-tolerated, with no drug-related serious adverse events or discontinuations. The researchers recommended further interaction studies with telaprevir and other antiretroviral drugs prior to starting clinical trials in coinfected patients – advice that should also apply to other anti-HCV agents in the pipeline.

Who Gets Treated?
Finally, A. Butt and colleagues (ICAAC abstract V-1634) looked at treatment eligibility and access among veterans with hepatitis C receiving care between 1998 and 2003, using an “Electronically Retrieved Cohort of HCV-Infected Veterans” (ERCHIVES) assembled from the VA National Patient Care Database, Pharmacy Benefits Management database, and Decision Support Systems database. In total, 1225 of the 3636 coinfected patients (34%) and 27,452 of the 86,814 HCV-monoinfected patients (32%) in the cohort had adequate clinical and laboratory data available. Of these, 85% and 74%, respectively, had an indication for anti-HCV therapy.

However, 67% of the coinfected patients and 50% of the HCV-monoinfected patients had at least one contraindication to treatment according to current guidelines. The most common overall – with rankings differing somewhat for the two groups – were anemia, decompensated liver disease, chronic obstructive pulmonary disease, kidney failure, recent alcohol or illicit drug use, coronary artery disease, uncontrolled diabetes, and severe psychiatric disorders. Anemia (associated with some antiretroviral drugs, notably AZT) was a contraindication for 43% of coinfected patients compared with 18% of HCV monoinfected patients. Kidney failure (20% vs. 9%) and decompensated liver disease (29% vs. 16%) both were about twice as likely to be contraindications in coinfected veterans. After excluding individuals with contraindications, 33% of coinfected patients and 50% of HCV-monoinfected patients were considered eligible for treatment; of these, 14% and 22%, respectively, actually received any hepatitis C therapy. The investigators concluded that most veterans with HCV – both HIV positive and HIV negative – are not eligible for treatment according to current guidelines, but they added that several contraindications are modifiable (e.g., treatment of anemia or depression), and suggested that “aggressive management of those may improve treatment prescription rates.”

 • For complete conference coverage, see:
ICAAC: http://www.icaacidsa2008.org

 • AASLD: http://www.aasld.org/THELIVERMEETING


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