EASL 2012: New HCV Drug Induces Rapid, Durable Drops in Viral Load

From Medscape Medical News

Daniel M. Keller, PhD

April 30, 2012 (Barcelona, Spain) — In 3 phase 2 trials of GS-7977, there was a concordance between the sustained virologic response (SVR) 4 weeks after the end of therapy (SVR4) and SVRs at 12 and 24 weeks after therapy (SVR12 and SVR24) in treatment-naive patients infected with hepatitis C virus (HCV) genotypes 1, 2, or 3.

No patient relapsed after posttreatment week 12, and 99% of patients with SVR4 for whom posttreatment week 12 data were available achieved SVR12, Eric Lawitz, MD, from Alamo Medical Research in San Antonio, Texas, reported here at the International Liver Congress 2012.

GS-7977 (formerly PSI-7977) is a specific nucleotide analogue inhibitor of HCV NS5B RNA polymerase and is taken orally once daily. Previous reports have shown that it has broad antiviral activity against HCV genotypes 1, 2, and 3, with or without interferon, in treatment-naive patients, and has a high barrier to the development of viral resistance.

The aim of the study was to evaluate concordance between SVR4 and SVR12 or SVR24 among treatment-naive patients taking GS-7977 400 mg daily in the PROTON (n = 144), ELECTRON (n = 120), and ATOMIC (n = 332) phase 2 clinical trials. The trial protocols differed somewhat, but in general were various combinations and durations of GS-7977, pegylated interferon (Peg-IFN), and ribavirin.

In the PROTON and ATOMIC trials, depending on viral genotype, patients received GS-7977 plus Peg-IFN/ribavirin for 12 weeks followed by Peg-IFN for 12 weeks, Peg-IFN/ribavirin alone for 48 weeks, GS-7977 plus Peg-IFN/ribavirin for 12 or 24 weeks, GS-7977 plus PegIFN/ribavirin for 12 weeks followed by 12 weeks of GS-7977 alone or by GS-7977 plus ribavirin.

In the ELECTRON trial, some patients with genotypes 2 or 3 virus received similar combinations but only out to 12 weeks. Other patients with genotypes 1, 2, or 3 received GS-7977 plus ribavirin for 12 weeks.

The analysis involved only patients treated with GS-7977 400 mg in combination with interferon, ribavirin, or both for at least 4 weeks who had SVR4 plus SVR12 or SVR4 plus SVR24 data available. Of the 596 patients in the 3 studies, 259 (43%) were eligible for analysis.

At baseline in all treatment groups, mean age ranged from 43 to 52 years, and most patients were white, male, had similar body mass indices (mean, 26 to 28 kg/m²), and had interleukin-28B genotype non-CC. Mean baseline HCV RNA levels were mainly in the range of 6.3 to 6.7 log₁₀ IU/mL.

Dr. Lawitz presented results for virologic response at the end of therapy and for SVR4, SVR12, and SVR24.

"If we look at all regimens and look at the concordance between SVR4 and SVR12, we can see that 249 of the 251 [patients] were concordant between SVR4 and SVR12 — a concordance rate of 99%," he said. "If we look at concordance between SVR4 and SVR24, we can see that although the numbers are smaller, there is complete concordance — all 107 patients who had an SVR4 achieved an SVR24.... The concordance held, irrespective of the presence or absence of interferon. However, the dataset is fairly small in the noninterferon arm, limiting conclusions."

Dr. Lawitz concluded that "much of the concordance is due to the high response rates observed across all treatment groups. To date, relapse after week 4 is infrequent and was only observed in patients who received a peg-interferon-containing regimen."

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital, in Athens, Greece, and a member of the European Association for the Study of the Liver Governing Board Scientific Committee, told Medscape Medical News that GS-7977 "is a very interesting, very promising molecule. It seems to be rather safe and very effective, even in combination with ribavirin." Dr. Papatheodoridis was not involved in any of the studies.

In terms of new drugs to treat HCV, he said, "some of the new molecules are very genotype-specific.... Most of the protease inhibitors are developed to work only for genotype 1; some of them work for genotype 2, but not 3 and 4. The nucleoside polymerase inhibitors seem to work better across almost all genotypes, so this is the only class [of drug] that is not that genotype-specific."

Dr. Papatheodoridis wondered about the use of SVR4 as a standard efficacy measure. "I don't think that SVR4 will and should be the standard for SVR," he told Medscape Medical News. "Of course, we know that the FDA and most of the physicians have now accepted SVR12. So probably...SVR12 is going to be the standard for reporting trials in the near future. Still, with all these combinations, patients should have at least 1 examination, maybe 6 months or 12 months after SVR12, so we can be sure that this SVR remains over time. I think that SVR12 is going to be the standard from now on, but the patients treated with the new regimens should be followed for a bit longer."

He admitted that SVR4 looks predictive of later sustained responses. "You expect most of the patients to relapse soon after stopping treatment [if they are going relapse]. Of course, SVR4 is reasonable; we know and we expect that it is going to be associated with SVR12 and SVR24. There is no rush to decide the SVR just 4 weeks after treatment.... We should be sure that we eradicated the virus," he cautioned.

Dr. Lawitz reports financial relationships with Abbott, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, sanofi-aventis, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics. Dr. Papatheodoridis has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 7. Presented April 19, 2012.

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A baby is born addicted to drugs about once an hour, study says

By Karen Kaplan, Los Angeles Times / For the Booster Shots blog

April 30, 2012, 1:47 p.m.

Here’s some depressing news to kick off your week: The proportion of pregnant women who are addicted to opiates increased nearly fivefold between 2000 and 2009. Accordingly, the proportion of babies born addicted to the drugs who experience withdrawal after birth nearly tripled during the same period.

These calculations come courtesy of researchers from the University of Michigan and the University of Pittsburgh, who reported their findings in a study published online Monday by the Journal of the American Medical Assn. After combing through hospital data compiled by the federal Agency for Healthcare Research and Quality, the team found that 3.39 out of every 1,000 babies born in an American hospital in 2009 had neonatal abstinence syndrome, up from 1.2 out of every 1,000 hospital births in 2000. That translates to 13,539 newborns in 2009 – or roughly one born per hour that year.

Neonatal abstinence syndrome, or NAS, affects babies who become addicted to drugs in utero -- especially opiates -- and go through withdrawal once they are living outside the womb. Symptoms include seizures and tremors, respiratory distress, vomiting and an inability to eat without becoming sick.

Treatments haven’t improved much in the past decade, and some babies require morphine or methadone to get over their addictions. The typical baby born with NAS winds up staying in the hospital for about 16 days before he or she can be discharged, according to the JAMA report.

The immediate cause for this spike in babies with NAS is an even larger spike in pregnant women addicted to prescription painkillers, heroin and other opiates. According to the federal data, 5.63 out of every 1,000 mothers who gave birth in a hospital in 2009 were addicted to opiates, up from 1.20 per 1,000 in 2000, the study found. Experts estimate that 60% to 80% of babies exposed to heroin or methadone in utero wind up addicted themselves.

The average cost of caring for a baby with NAS has risen from $39,400 in 2000 to $53,400 in 2009 – an increase of 35%, despite the fact that the amount of time affected infants remained in the hospital didn’t change over the decade. Adjusting for inflation, the total money spent to care for babies with neonatal abstinance syndrome jumped from $190 million to $720 million over that period. The share of the total tab picked up by Medicaid rose from 69% in 2000 to 78% in 2009, according to the JAMA study.

In an editorial that accompanies the study, two experts from Maine (which has one of the highest rates of addiction to prescription opiates) bemoan the fact that treatment for infants with NAS and their addicted mothers has improved so little in recent years.

“Novel pharmacotherapy research is needed to improve maternal opiate maintenance strategies to protect the fetus from in utero withdrawal, and to reduce the incidence and severity of NAS,” they write. As one hopeful sign, they mention recent findings that link two particular genes with the severity of withdrawal symptoms in newborns. Someday, doctors may be able to tailor their treatments for these babies by checking to see what versions of these (and perhaps other) genes they have.

You can read the study here and the editorial here.

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May Is Hepatitis Awareness Month

April 30, 2012

By Ronald Valdiserri, M.D., M.P.H., Deputy Assistant Secretary for Health, Infectious Diseases, and Director, Office of HIV/AIDS and Infectious Disease Policy, U.S. Department of Health and Human Services; and John Ward, MD, Director, Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention

Every May, the Department of Health and Human Services (HHS), the Centers for Disease Control and Prevention (CDC), and our public health partners across the nation observe Hepatitis Awareness Month. This year, we are very pleased to be marking this observance during a time of increased awareness about and collaboration around viral hepatitis –due in large part to the work of our federal partners over the past year on the implementation of the Action Plan for the Prevention, Care and Treatment of Viral Hepatitis.

Developed by an inter-agency working group and announced last May by Dr. Howard Koh, Assistant Secretary for Health, the Action Plan details steps to increase viral hepatitis awareness and knowledge among healthcare providers and communities and strategies to improve access to quality prevention, care, and treatment services for persons living with viral hepatitis. For the past year, we have been collaborating with our colleagues across HHS, as well as from the Department of Veterans Affairs and Department of Justice’s Federal Bureau of Prisons, to pursue the strategies detailed in the Action Plan. Together, we are working to ensure that new cases of viral hepatitis are prevented and that persons who are already infected are tested, informed about their infection, and provided with counseling, care, and treatment.

Learn More About Viral Hepatitis Risks, Tests and Treatment
An estimated 3.5–5.3 million Americans are living with chronic (lifelong) hepatitis B or hepatitis C virus infection. Most of them do not know that they are infected, placing them at greater risk for severe, even fatal, complications from the disease and increasing the likelihood that they will spread the virus to others. We encourage you to use Hepatitis Awareness Month to learn more about this “silent epidemic.” One place to start learning more is CDC’s Hepatitis Awareness Month webpage. Check back over the course of the month as exciting new resources and tools are added to this page. The CDCNPIN webpage is another important resource, where federal partners working to implement the Action Plan have posted downloadable materials designed to educate the public, patients, and providers about viral hepatitis. Select “hepatitis” as your topic and add relevant keywords below, such as “testing,” “treatment,” or “Asian American,” and you will get a list of materials to read and share with others.

Inaugural Hepatitis Testing Day Coming on May 19
As called for in the Action Plan, May 19th has been designated as Hepatitis Testing Day in the United States. Coinciding with Hepatitis Awareness Month, this inaugural Hepatitis Testing Day offers an important opportunity to remind healthcare providers and educate the public about who should be tested for viral hepatitis. We’ll be sharing more about this observance in a blog post later this month. In the meantime, to learn more and start thinking about how you and your organization can participate in promoting viral hepatitis awareness and testing, visit CDC’s Hepatitis Testing Day webpage.

We hope you will join with us in promoting both important observances as a way to enhance public awareness of viral hepatitis prevention, testing, care and treatment across the United States. Won’t you please commit to learning more yourself and/or sharing information about viral hepatitis with at least two other people? They can be family, friends, co-workers or neighbors. Working together, we can end the silence around this epidemic and in so doing, make great strides in improving the health of persons who are at risk for or living with viral hepatitis.

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AHF: Protesters Target Hershey at May 1st Annual Meeting over Child Labor/Fair Trade Violations and AIDS Discrimination

PRESS RELEASE

April 30, 2012, 5:00 p.m. EDT

 

Groups including Global Exchange, Green America and the International Labor Rights Forum, all part of the 'Raise The Bar Campaign' to make Hershey fair trade, will join together with activists from the National Guestworker Alliance (NGA) as well as MCC Philadelphia, ACT UP Philadelphia & AHF, protesting Hershey over AIDS discrimination at the Milton Hershey School

HERSHEY, Pa., Apr 30, 2012 (BUSINESS WIRE) -- --Protest Tuesday, May 1st from 9:30am to 11:30am outside Hershey's AGM in Hershey, PA

While the Hershey Company hosts its Annual General Meeting Tuesday, May 1st, in Hershey, PA, as many as one hundred activists from Global Exchange, Green America, International Labor Rights Forum, all from the Raise The Bar Campaign to make Hershey fair trade, will join together with activists from the National Guestworker Alliance (NGA) as well as Metropolitan Community Church of Philadelphia (MCC-Philadelphia), ACT UP Philadelphia, AIDS Healthcare Foundation (AHF), protesting Hershey over an incident of AIDS discrimination at the Milton Hershey School, will descend on Hershey, PA to host a lively protest outside the company's AGM. The protest is set for Tuesday, May 1st from 9:30am to 11:30am (Eastern).

WHAT: HERSHEY PROTEST--Up to 100 protesters expected to picket Hershey's Annual General Meeting over child labor and fair trade violations as well as a the case of AIDS discrimination at the Milton Hershey School following its decision to deny admission to an HIV-positive teen

WHEN: Tuesday, May 1st 9:30am - 11:30am (EASTERN)

WHERE: The Hershey Company Hershey Park Blvd. and Park Blvd., Hershey, PA 17033 (outside of Chocolate World)

WHO: Global Exchange, Green America, International Labor Rights Forum, all from the Raise The Bar Campaign; the National Guestworker Alliance (NGA) as well as Metropolitan Community Church of Philadelphia, ACT UP Philadelphia, and AIDS Healthcare Foundation

CONTACT: Jessica Reinhart, Grassroots Community Manager, Cell: (323) 203-6146

"Hershey needs to take corporate responsibility for their practices and we are demanding Hershey executives and trustees to stop exploiting children, students and workers as well as that the Milton Hershey School--funded by Hershey--reverse its decision to deny admission to an HIV-positive teen," said Jessica Reinhart, Grassroots Community Manager for AIDS Healthcare Foundation and a leader of several protests against Hershey over its AIDS discrimination. "We are honored to join again with MCC and Act Up Philadelphia to protest Hershey's AIDS discrimination and with the groups running Raise The Bar campaign targeting Hershey over fair trade and child labor issues as well as with NGA in their quest to protect Hershey workers and create local living wage jobs at the company in dignified conditions."

Background on Hershey School AIDS Discrimination

The Milton Hershey School--a boarding school for low-income students funded by the Hershey Company--recently rejected the boy for admission citing his HIV-positive status as the reason, misguidedly calling him a "direct threat to the health and safety of others." AHF has also launched a website www.EndHIVStigma.org where the public can learn more about the case, learn the facts about HIV/AIDS and send e-letters to three Hershey Company board members who also sit on the board of the Milton Hershey School Trust, urging them to denounce the discrimination and facilitate the boy's admission into the school.

"The blatant discrimination and ignorance displayed by Hershey in this case is simply unacceptable. Ultimately, it is the Hershey Company itself, as the main funder of the school, that must answer for the decision not to admit the boy--a decision fueled by prejudice and fear," said Michael Weinstein, President of AIDS Healthcare Foundation. "If Hershey is truly a company that believes in its social responsibility creed of 'commitment to consumers, community and children,' it will denounce this illegal and repugnant discrimination and immediately facilitate the enrollment of the boy at the school."

"It's appalling that Hershey Company would sit by and let AIDS stigma dictate school policy at the Milton Hershey School," said Rev. Jeffrey Jordan, pastor of MCC-Philadelphia. "We want to see the Hershey Company use their leverage as Board members to change the policy at the school for good."

According to the Associated Press (claim:Hershey School Rejects HIV-Positive Pa. Boy)(claim:By Peter Jackson)(claim:12/1/11): "A private boarding school connected with the Hershey chocolate company says it was trying to protect other students when it denied admission to a Philadelphia-area teenager because he is HIV-positive. The AIDS Law Project of Pennsylvania filed a lawsuit on behalf of the unidentified boy in U.S. District Court in Philadelphia on Wednesday, claiming the Milton Hershey School for disadvantaged students violated the Americans with Disabilities Act. School officials acknowledged that the 13-year-old boy was denied admission because of his medical condition. They said they believed it was necessary to protect the health and safety of the 1,850 others enrolled in the residential institution, which serves children in pre-kindergarten to 12th grade and where students live in homes with 10 to 12 others."

"The ignorance displayed by the Hershey School's leadership is unacceptable and demonstrates just how much work there is still to be done to dismantle the fear and misinformation that still surrounds this disease more than 25 years after Ryan White," said Jessica Reinhart, Grassroots Community Manager for AIDS Healthcare Foundation.

Ryan White was an American teenager from Kokomo, Indiana who, in the mid-1980s, was expelled from middle school because he was HIV-positive. A lengthy legal battle with the school ensued and White became a galvanizing force in educating the country about HIV & AIDS at a time when misinformation about the disease was widespread. After his death in 1990, the U.S. Congress passed a major piece of legislation named in his honor, the Ryan White CARE Act, which provides funding for HIV/AIDS programs for low-income Americans.

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 166,000 individuals in 25 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. www.aidshealth.org

SOURCE: AIDS Healthcare Foundation

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Digital Arts: Virtually Stitching The AIDS Memorial Quilt

(Credit: Anne Balsamo, University of Southern California)

Lori Kozlowski, Contributor

4/13/2012 @ 10:36AM

The first time one sees the AIDS Memorial Quilt, it’s the sheer size of it that is most striking. Panel after creative panel — each square with a personality and a name.

In its 25-year history, more than 91,000 names have been added.

What began in 1987 as a simple folk art installation to remember those who had died from AIDS, grew into the largest public art display of its kind.

Now, the quilt is being digitized. Images of the quilt panels have been virtually stitched together and displayed on Microsoft Surface – a 60-inch wide interactive table. Viewers can scroll through the large touchscreen tablet and see the quilt in its entirety.

Anne Balsamo, Professor of Interactive Media and Communication and a senior research fellow at the University of Southern California’s Annenberg Innovation Lab, led the project.

“The idea is that you use the table not as a substitute for looking at the textile panels. You still look at the physical panels — they’re richer than any digital experience. But what our table will allow you to do is search for a particular one. And also get a sense of the scale,” she said.

The table browser will allow viewers to see the entire 1.3 million square feet of the quilt, or zoom in and get metadata about a single person’s panel. The effort will also offer the opportunity for the public to add their own reflections.

The first version of the table will be on display at the Smithsonian Folklife Festival, June 27 – July 8.

On July 20, sections of the physical quilt will be laid out on the National Mall. (At this point, the quilt is so large that the whole thing can not fit on the Mall). When the quilt is displayed, four interactive tables will be placed around the Mall for viewers to use.

Balsamo is also building a mobile application that will offer a map to locate any panel and digital memorial pages, so people can leave messages. “If you walk by a panel that really moves you, you can type in the panel number, go to the digital memorial page, and leave a remembrance,” she said.

“We want to give people a way to get into the stories of the quilt.”

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Management of Anemia in Patients Receiving Protease Inhibitors

Gastroenterology & Hepatology Volume 8, Issue 4 April 2012

Stephen A. Harrison, MD, LTC, MC
Chief of Hepatology
Brooke Army Medical Center
Clinical Associate Professor of Medicine
University of Texas Health Science Center at San Antonio
San Antonio, Texas

G&H How frequently does anemia occur in patients who are receiving protease inhibitor– based therapy?

SAH Anemia occurs frequently in these patients—certainly more frequently than it does in patients receiving only pegylated interferon and ribavirin. In a pooled analysis of the clinical safety data from trials of telaprevir (Incivek, Vertex), hemoglobin values less than 10 g/dL were found to occur in approximately 36% of patients receiving telaprevir-based triple therapy. More severe anemia, defined as hemoglobin values less than 8.5 g/dL, was observed in about 14% of patients. Among patients treated with pegylated interferon and ribavirin alone, only 17% had hemoglobin values less than 10 g/dL, and 5% had hemoglobin values less than 8.5 g/dL.

Similar rates of anemia were seen in trials of boceprevir (Victrelis, Merck). Pooled data from SPRINT-1 and SPRINT-2 showed that approximately 49% of patients had hemoglobin values less than 10 g/dL, and approximately 6% of patients had hemoglobin values less than 8.5 g/dL. Similar rates of anemia were observed in RESPOND-2, a trial that evaluated boceprevir-based triple therapy in interferon-experienced patients: Approximately 49% of these patients had hemoglobin values less than 10 g/dL, and approximately 10% of patients had hemoglobin values less than 8.5 g/dL. Among patients in the control group, who were treated with pegylated interferon and ribavirin alone, approximately 30% of patients showed a hemoglobin value less than 10 g/dL, and only approximately 3% of patients had a hemoglobin value less than 8.5 g/dL. Overall, there is a significantly higher rate of clinically significant anemia when therapy includes either boceprevir or telaprevir compared to treatment with pegylated interferon and ribavirin alone.

G&H Are rates of anemia similar between these 2 protease inhibitors?

SAH Yes, rates of anemia seem to be fairly similar with both telaprevir and boceprevir. While the pooled registration data suggest that telaprevir has higher rates of grade 3/4 anemia (hemoglobin levels <8.5 g/dL; 14% with telaprevir vs 6–10% with boceprevir), the boceprevir studies allowed the use of erythropoietin at the investigator’s discretion. While prospective, randomized, head-to-head trials assessing both frequency and severity of anemia are lacking, interim data from an ongoing French study (presented as an abstract at HepDART 2011) found on preliminary analysis that moderate, grade 2 anemia (hemoglobin level of 8–10 g/dL) occurred in 33% of telaprevir-treated patients and 31% of boceprevir-treated patients. Grade 3/4 anemia (hemoglobin level <8 g/dL) occurred in 13% of telaprevirtreated patients and 6% of boceprevir-treated patients. The transfusion rate was 18% for telaprevir-treated patients and 6% for boceprevir-treated patients. Overall, these findings correlate with clinicians’ anecdotal clinical experience, which shows significant anemia with both drugs.

G&H How frequently does anemia lead to either dose reduction or discontinuation of therapy?

SAH Dose reductions occur roughly twice as often when a protease inhibitor is added to the treatment regimen. According to the registration trial data, dose reductions occur in approximately 26% of patients treated with boceprevir.

Similarly, data from the telaprevir registration trials show that dose reductions occur in approximately 32% of patients. In terms of treatment discontinuation, data show that boceprevir-based therapy is discontinued in approximately 1% of patients, and telaprevir-based therapy is discontinued in 3–4% of patients. Again, both drugs show roughly similar rates of dose reductions and discontinuation.

G&H What are the clinical consequences of anemia?

SAH The presence of anemia does not negatively impact sustained virologic response (SVR) rates. However, it is well known that quality of life is certainly affected, which can lead to potential compliance or adherence issues. Recent data with the protease inhibitors suggest that clinicians can dose-reduce ribavirin fairly significantly in the setting of anemia and still achieve high SVR rates. Treatment discontinuation obviously has a more significant effect on clinical outcomes, but discontinuation is rare. Nonetheless, more data are needed to clearly show how quickly ribavirin dose reductions can occur (before virus negativity) and how long ribavirin can be stopped without affecting overall SVR rates. In the meantime, I advocate dose reduction instead of drug discontinuation for anemia, especially given that clinicians can probably get by with lower doses of ribavirin in the era of direct-acting antiviral drugs than they could when treating patients with pegylated interferon and ribavirin alone. If clinicians must discontinue ribavirin, they should do so for a short period of time (2–3 days) and then restart ribavirin at a lower dose.

In addition to necessitating dose reductions or discontinuations, anemia can significantly affect patients’ quality of life in terms of fatigue, inability to go to work and/or be productive at work, and difficulty in performing activities of daily living. As a result, compliance with therapy can become an issue. Thus, the effects of anemia extend beyond the possible impact on SVR rates to include compliance and quality-of-life issues as well.

G&H Have any studies compared SVR rates in patients with and without anemia?

SAH Yes. There are 2 large studies in genotype 1 hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin (IDEAL, n=3,070; CHARIOT, n=871) showing that patients who developed anemia (hemoglobin level <10 g/dL) were significantly more likely to obtain SVR than those without anemia. Post–hoc, retrospective studies with telaprevir and boceprevir have also been conducted, but to date, these results remain in abstract form. Data from the REALIZE trial and combined data from ADVANCE and ILLUMINATE (with telaprevir) demonstrate that anemia is not a significant predictor of SVR. However, a retrospective review of the SPRINT-2 and RESPOND-2 trials (with boceprevir) did find a positive association with anemia and SVR.

G&H Are there any factors that predict the likelihood of anemia in patients receiving protease inhibitor–based therapy?

SAH Patients who had significant anemia during prior treatment with pegylated interferon and ribavirin and are re-treated with boceprevir- or telaprevir-based triple therapy are likely to develop anemia again, and anemia may be more severe given the addition of the protease inhibitor. Retrospective data from the telaprevir registration trials show on multivariate analysis that older age, lower body mass index, lower baseline hemoglobin level, more advanced fibrosis, and genotype 1b HCV are all significantly associated with anemia. Retrospective data from the boceprevir registration trials show on multivariate analysis that baseline hemoglobin level, gender, age greater than 40 years, statin use, and race were associated with anemia.

G&H Can clinicians address some of these factors before starting treatment?

SAH Clinicians need to do due diligence and look at the patient’s past treatment. Was there significant anemia? Are patients starting out with lower hemoglobin levels? Are they cirrhotic? Are they older? Do they have any renal impairment issues? If any of these factors are identified ahead of time, then clinicians should be quicker to dose-reduce or add an agent like erythropoietin if hemoglobin levels begin to drop.

G&H How effective is erythropoietin for the management of anemia in patients who are receiving a protease inhibitor plus pegylated interferon and ribavirin?

SAH We lack good, clear-cut data regarding the effect of erythropoietin on SVR rates in patients treated with directacting antiviral drugs. Erythropoietin was not allowed in the telaprevir registration trials. In the boceprevir registration trials, erythropoietin was allowed at the discretion of the investigator, but these studies were not designed to evaluate the effect of erythropoietin on SVR rates. The results of a recently completed prospective trial assessing the benefits of concomitant erythropoietin use for anemia in boceprevir-based therapy are anxiously awaited.

Prior to the advent of direct-acting antiviral drugs, a prospective, randomized, placebo-controlled trial showed that the use of erythropoietin for anemia related to treatment with pegylated interferon and ribavirin resulted in maintenance of the ribavirin dose, stabilization of the hemoglobin decline, and improvement in quality of life compared to ribavirin dose reduction alone.

G&H When do you consider adding erythropoietin to a patient’s treatment regimen?

SAH This decision should be made at the discretion of the individual clinician, as there are no guidelines regarding the use of erythropoietin. If a patient experiences anemia, I personally prefer to try ribavirin dose reduction of 400–600 mg as a first-line measure, depending on the initial severity of the anemia. Then, if the hemoglobin level has not stabilized, I will add erythropoietin before further dose-reducing ribavirin or withholding ribavirin. While adding erythropoietin is not my first-line treatment for anemia, it is an option if a patient’s hemoglobin level is not stabilizing. Consideration can also be given to pegylated interferon dose reduction, as this may also help anemia. Data from the previously mentioned IDEAL trial show that with conventional pegylated interferon and ribavirin therapy, dose reductions from 1.5 mcg/kg/week to 1.0 mcg/kg/week did not adversely affect SVR.

G&H In which patients is erythropoietin contraindicated?

SAH The black box warning for erythropoietin states that this drug should not be used in patients with hemoglobin values greater than 12 g/dL. Thus, clinicians should not start erythropoietin until the patient’s hemoglobin level falls below 12 g/dL, and erythropoietin should be discontinued once the hemoglobin level rises back above 12 g/dL. Caution should be used when treating patients with endstage renal disease as well. Clinicians should also be aware of the relatively rare, but significant, complication of pure red cell aplasia that has been reported with the use of recombinant erythropoietin.

G&H What further research do you hope to see in this area over the next couple of years?

SAH Telaprevir and boceprevir, both of which are now approved by the US Food and Drug Administration, are the first direct-acting antiviral agents to come onto the market. Unfortunately, these drugs are associated with significant anemia; in general, patients who are receiving either of these drugs experience an additional hemoglobin decline of approximately 1 g/dL beyond the hemoglobin decline caused by pegylated interferon and ribavirin alone. The good news is that the second-generation direct-acting antiviral agents currently in development will probably cause less anemia than the 2 drugs that are currently available.

In addition to new drugs, we need further research regarding treatment of anemia in patients receiving telaprevir or boceprevir, including studies assessing how quickly we can dose-reduce ribavirin and by how much. The use of erythropoietin for anemia and its effect on SVR should be assessed. Finally, data suggest that polymorphisms in the inosine triphosphate pyrophosphatase (ITPA) gene may help to predict ribavirin-associated anemia during antiviral treatment, and further research is needed regarding the utility of this test. Should we be testing for this gene mutation in the same way that we now test for interleukin-28B (IL-28B) mutations prior to initiating antiviral therapy? More data are needed to determine whether this information would positively impact outcomes.

G&H How might such information help clinicians prevent treatment-induced anemia?

SAH If I had information suggesting that a patient was at increased risk for anemia, then I would probably check for anemia more frequently at the start of therapy. My preferred strategy—especially in patients who I feel are at risk for developing anemia—is to obtain complete blood counts at Week 1 and Week 2. If these tests show that the patient is doing well, then I may wait until Week 4 before performing follow-up testing. However, if testing at Week 1 and Week 2 shows that the patient’s hemoglobin level has dropped significantly, then I would adjust the ribavirin dose and obtain another complete blood count at Week 3. The key for treating anemia in the setting of HCV therapy is to address anemia very quickly, because it is much harder to bring hemoglobin levels back up after they have declined than it is to mitigate the rate of decline.

The opinion or assertions contained herein are the private views of the author and are not to be construed as official or reflecting the view of the US Department of the Army or the US Department of Defense.

Suggested Reading

Alavian SM, Tabatabaei SV, Behnava B. Impact of erythropoietin on sustained virological response to peginterferon and ribavirin therapy for HCV infection: a systematic review and meta-analysis. J Viral Hepat. 2012;19:88-93.

Mac Nicholas R, Norris S. Review article: optimizing SVR and management of the haematological side effects of peginterferon/ribavirin antiviral therapy for HCV—the role of epoetin, G-CSF and novel agents. Aliment Pharmacol Ther. 2010;31:929-937.

Nishimura T, Osaki R, Shioya M, et al. Polymorphism of the inosine triphosphate pyrophosphatase gene predicts ribavirin-induced anemia in chronic hepatitis C patients. Mol Med Report. 2012;5:517-520.

Jacobson IM, McHutchison JG, Dusheiko G, et al; ADVANCE Study Team. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416.

Zeuzem S, Andreone P, Pol S, et al; REALIZE Study Team. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417-2428.

Poordad F, McCone J Jr, Bacon BR, et al; SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206.

Bacon BR, Gordon SC, Lawitz E, et al; HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207-1217.

Source

Life expectancy for HIV patients improving

[Date: 2012-04-30]

Life expectancy for HIV patients treated with antiretroviral drugs, now considered common course in treating the virus, can expect to live considerably longer lives, new research from the United Kingdom shows. This study was funded in part by the EUROCOORD ('European network of HIV/AIDS cohort studies to coordinate at European and international level clinical research on HIV/AIDS') project, which is backed with EUR 12 million under the Health Theme of the EU's Seventh Framework Programme (FP7). EUROCOORD brings together a number of other networks, all of which have played a central role in developing our understanding, progression and treatment of HIV.

The efforts of healthcare professionals treating HIV patients are bearing fruit. In this latest study, a British team of researchers was able to discern that HIV patients aged 20, who started antiretroviral treatments 16 years ago, could expect to live to an average age of 50. Life expectancy, however, jumps to 66 for subjects in the same group who began their treatment just 4 years ago. The sample was made up of 17 661 adults aged 20 and over who had HIV and had started antiretroviral treatment in the United Kingdom between 1996 and 2008.

The study also discovered that HIV patients had a lower life expectancy when they began their antiretroviral treatment later in life. It should be noted that the average life expectancy of a person with HIV being treated with antiretrovirals was still shorter than that of a similarly aged person in the general population.

HIV is a pressing matter in Europe; it is currently estimated that more than 1.5 million Europeans are infected with HIV. In 2007, it was estimated that 100 000 people were newly infected with the disease, but the outcome for HIV patients has dramatically improved in countries where patients have access to combination antiretroviral therapy (cART). Healthcare professionals stress, however, that cART is not a cure for HIV and once a patient begins treatment, they must continue it for life.

The researchers stressed that the projected life expectancies will need to be confirmed by longer term follow-up. Their study they did not include other external factors that could influence results, such as lifestyle factors, which could lead to increased death from non-HIV causes. With those caveats in mind, the researchers said they feel confident in concluding that improvements in antiretroviral treatment are responsible for at least some of this improvement.

Overall, these results are encouraging and emphasise the improvements in treatments seen in recent years. However, the life expectancies among people with HIV are still projected to be lower than people among the general population. The researchers also excluded patients whose records were not 100% complete and were missing important information, including age, sex or ethnicity. Also excluded from the sample base were patients who, it was assumed, had contracted HIV through injecting drug use; the reason behind this exclusion is that they are reported to have a worse outlook than other groups.

For more information, please visit:
EUROCOORD:
http://www.eurocoord.net/

Related stories: 34095

Category: Project results
Data Source Provider: EUROCOORD
Document Reference: Based on information from the Queensferry Gazette.
Subject Index: Coordination, Cooperation; Life Sciences; Medicine, Health; Scientific Research

RCN: 34568

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Media Advisory - Interview Local Nurses Dedicated to the Hepatitis C Community: National Nursing Week - May 7 to 13, 2012

PRESS RELEASE

April 30, 2012, 7:00 a.m. EDT

TORONTO, April 30, 2012 /PRNewswire via COMTEX/ -- During National Nursing Week, Canadians will recognize and celebrate the important contributions nurses make daily to patient care in Canada. The role nurses play in the prevention and management of chronic hepatitis C, a potentially life-threatening virus, provides a powerful example of their impact as supporter, educator and counsellor.

Canadians living with chronic hepatitis C often fear the judgment of others because the virus infecting them is often associated with injection drug use. The reality is that people can contract the virus through a number of different ways including, body piercings, tattoos, blood transfusions or personal care items (razors).

Members of the Canadian Association of Hepatology Nurses (CAHN) build trusted relationships with patients by not focusing on how the hepatitis C virus was contracted, but rather on providing care and support that is beneficial, respectful and can lead to a cure.

The road to a cure is a difficult journey for patients living with chronic hepatitis C. While treatments can be very successful at getting rid of the virus, the stigma associated with the disease often requires patients to struggle through chemotherapy-like side effects in isolation.

CAHN wants to shatter the stigma for those people living with chronic hepatitis C by helping Canadians recognize that anyone, including someone they know and love, could be living with this virus. Stigma must not be a barrier to detection and treatment.

This National Nursing Week, celebrate the leadership provided by CAHN nurses in the prevention and management of chronic hepatitis C.

What: Interview opportunities with nurses and individuals living with chronic hepatitis C willing to share their stories Who: Cheryl Dale, President of the Canadian Association of Hepatology Nurses, CAHN members and individuals living with chronic hepatitis C Where: The following communities across Canada: Ontario (Toronto, Oakville, Mississauga, Guelph, Hamilton, Kitchener-Waterloo, Newmarket, Sutton, Sudbury, North Bay, and London), Quebec (Montreal), British Columbia (Vancouver, Kelowna, and Nanaimo), Alberta (Edmonton), Nova Scotia (Halifax), and Saskatchewan (Prince Albert) When: National Nursing Week (May 7-13, 2012)

SOURCE Canadian Association of Hepatology Nurses

Source

First full HCV infection model

doi:10.1038/nindia.2012.63; Published online 30 April 2012

Researchers have created what they claim to be the first mathematical model of the full course of infection of hepatitis C virus (HCV). This fully describes the impact of its viral and immune processes on the progression of hepatocellular carcinoma (HCC), the cancer it causes¹.

Most available mathematical models describe the short term dynamics of HCV after the antiviral therapy is given to patients. The new model, however, is based on the premise that long term conditions such as HCC are random and driven by cell-mediated immune response. The researchers have modelled the risk of cancer and the dynamics of HCV over the course of its infection.

The researchers have found approximately 9% prevalence of HCC in individuals after 40 years, a figure consistent with estimates in available literature. They also found that higher viral infection potential led to a greater likelihood of developing HCC but did not determine the speed with which it arose.

"This 'infectivity' drives the level of immune response, the amount of hepatocyte proliferation, and the risk of a mutational event," they say.

In their simulations, the probability of developing HCC increased with duration of infection at the rate of 2.4 incident cases per thousand HCV-infected person years. This indicated that the sooner viral replication can be suppressed through antiviral therapy, the greater the chance of forestalling HCC.

References

Chakrabarty, S. P.et al. Modelling hepatitis C virus infection and the development of hepatocellular carcinoma. J. Theor. Biol. 305, 24-29 (2012)

Source

Non-Interferon-Based Combination Therapy Offers High Response Rates for Hepatitis C Patients

By Chris Berrie

BARCELONA, Spain -- April 25, 2012 -- Combining ABT-450 with ritonavir
(ABT-450/r) plus ABT-333 plus ribavirin (RBV) is well tolerated, provides high
sustained virological response (SVR) in treatment-naïve patients infected with
hepatitis C virus (HCV) genotype 1, and shows relatively high SVR in previous
interferon-based nonresponders, researchers said here at the 47th Annual
Meeting of the European Association for the Study of the Liver (EASL).

At present, there are no treatment options for HCV-infected patients who are
ineligible or intolerant to the interferons.

“This is the first study combining ABT-450 with ABT-333 with ribavirin without
interferon in genotype 1 patients who were either treatment-naïve or previous
treatment failures,” stated Fred Poordad, MD, Chief of Hepatology and Liver
Transplantation at the Comprehensive Transplant Center of Cedars-Sinai Medical
Center, Los Angeles, California, presenting this open-label study here on April
21.

The study design included 3 arms, the first 2 of which treated naïve patients
with chronic HCV genotype 1 infection using ABT-333 400 mg twice daily plus RBV
1,000-1,200 mg once daily plus ABT-450/r either 250/100 mg once daily (arm 1; n
= 19) or 150/100 mg once daily (arm 2; n = 14). The third treatment arm was
similar to arm 2, but treated prior partial or null responders to previous
pegylated interferon plus RBV treatments (arm 3; n = 17).

The treatments were for 12 weeks, with 48 weeks follow-up.

These patients were mainly male, with a mean age of just over 50 years, and
were largely HCV genotype 1a. For IL28B genotype, 52.6% were CC in arm A and
35.7% in arm B, with no IL28B CC in arm 3.

The primary endpoint was extended rapid virological response (eRVR) based on
HCV RNA lower than the limit of detection from treatment weeks 4 to 12. As the
intent-to-treat analysis, these reached 90%, 79% and 59% in arms 1, 2, and 3,
respectively.

Similarly, for SVRs at weeks 4 (SVR4) and 12 (SVR12), high levels of response
were achieved for arms 1 (95%, 93%, respectively) and 2 (95%, 93%). These SVR4
and SVR12 responses were also relatively high for the previous nonresponding
patients in arm 3 (47%, 47%).

Comparisons across IL28B CT versus TT showed no differences in SVR12 either for
treatment-naïve patients, as arms 1 plus 2 (100% vs 100%) or for previous
nonresponders (50% vs 40%).

Based on clonal sequencing, Dr. Poordad highlighted the resistant variants at
baseline and at virologic failure in the previous nonresponders of arm 3. “It
is important to note that patients who had virologic failure developed
resistance variants to both the protease inhibitor as well as the polymerase
inhibitor,” he noted.

In the safety analysis, there were no deaths or serious adverse events
throughout, with only 1 adverse event leading to premature discontinuation, in
arm 1. Four patients showed adverse events assessed as severe, without
requiring study-drug interruption or discontinuation: hyperbilirubinaemia,
fatigue, pain, and vomiting.

The treatment-emergent adverse events and the laboratory abnormalities noted
were largely the same type and levels across the 3 treatment arms. Dr. Poordad
also noted that the transient asymptomatic elevation of indirect bilirubin that
was seen is consistent with the known effect of ABT-450 on the bilirubin
transporter OATO1B1.

“It does appear that ABT-450 with ritonavir, ABT-333 plus ribavirin for 12
weeks has the potential to achieve very high SVR in a high proportion of
patients without interferon,” he concluded.

Funding for this study was provided by Abbott.

[Presentation title: A 12-Week Interferon-Free Regimen of ABT-450/r +
ABT-333 + Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naïve HCV
Genotype-1 Infected Subjects and 47% of Previous Non-responders. Abstract 1399]

Source

Cerus, the University Hospitals of Geneva, and the Transfusion Service of the Swiss Red Cross Intend to Collaborate on Whole Blood Pathogen Inactivation for Africa

30th of April 2012 08:30 EST

Cerus Corporation (NASDAQ:CERS), the University Hospitals of Geneva (HUG) and their Blood Transfusion Center (CTS), and the Transfusion Service of the Swiss Red Cross (Transfusion CRS Suisse or Blutspende SRK Schwietz) announced today their intent to collaborate on adapting the Cerus INTERCEPT Blood System for red cells to enable inactivation of pathogens in whole blood, specifically for the African region. While patients in developed countries receive platelet, plasma or red cell transfusions, in many African countries whole blood transfusions remain common, and require development of pathogen inactivation methods optimized for use in local blood bank facilities.

The African blood supply is challenged by both transfusion-transmitted diseases and a shortage of available units for transfusion. Pathogen inactivation can provide protection from a broad range of transfusion-transmitted diseases without further restricting the scarce supply of blood donors. The collaboration is designed to draw on the distinctive strengths of each organization to seek the funding necessary to develop a whole blood PI system that can be evaluated in clinical use in Africa.

“We believe pathogen inactivation is critical to blood safety everywhere, and we currently use the INTERCEPT system to treat all platelet units produced in Switzerland,”

said Dr. Rudolf Schwabe, chief executive officer of the Transfusion CRS Suisse. “Africa’s blood supply is at risk from many transfusion-transmitted diseases that can be prevented by use of pathogen inactivation. We see a great need in ensuring the safety and availability of blood for those patients in Africa who need it most.” 

“In countries where whole blood transfusions are used to treat acute and chronic anemia as well as post-partum hemorrhage, the opportunity to reduce the risk of bloodborne diseases fits perfectly with the aim of our university hospital policy to develop international medical cooperation, training and humanitarian health actions to improve global health,”

commented Dr. Soraya Amar-El Dusouqui, project director, CTS-HUG (University Hospitals of Geneva).

Blood safety and supply are of major health concern in Africa. Only an estimated 40 percent of the demand for transfusions is currently being supplied (Bloch et al, Transfusion Medicine Reviews, 2012 Apr;26:164-80). Obstetric hemorrhage, sickle cell disease and childhood anemia, HIV, malaria and traffic accidents are among the many indications requiring transfusion as a critical life-saving intervention.

At the same time, local blood donors frequently have significant rates of well-known transfusion-transmitted agents like HIV, HTLV, hepatitis and bacteria, as well as infections endemic to the region including malaria, dengue, Chikungunya and yellow fever.

Unlike other blood safety techniques, pathogen inactivation is able to provide protection from a broad range of viruses, bacteria and parasites from a single added safety step. Cerus’ INTERCEPT systems for platelets and plasma are already used in Europe, the Commonwealth of Independent States (CIS) and the Middle East. The INTERCEPT red cell system is anticipated to begin phase III trials in Europe later this year. To treat whole blood in Africa, a treatment system must be designed to work within the limited infrastructure of local blood banks and hospitals, as well as effectively inactivating bloodborne pathogens.

“We are honored to join HUG, CTS, and SRK in the pursuit of a pathogen inactivation system to improve blood safety in Africa where the technology can have a great impact in improving human health,“ said William ‘Obi’ Greenman, Cerus’ president and chief executive officer.

"Pathogen inactivation is being increasingly used in Europe, CIS and the Middle East, and, like our collaborators in this project, we feel an obligation to bring this technology to regions like Africa where it has the potential to transform blood safety."

ABOUT CERUS

Cerus Corporation is a biomedical products company focused on commercializing the INTERCEPT Blood System to enhance blood safety. The INTERCEPT system is designed to reduce the risk of transfusion-transmitted diseases by inactivating a broad range of pathogens such as viruses, bacteria and parasites that may be present in donated blood. The nucleic acid targeting mechanism of action enables INTERCEPT treatment to inactivate established transfusion threats, such as hepatitis B and C, HIV, West Nile virus and bacteria, and is designed to inactivate emerging pathogens such as influenza, malaria and dengue. Cerus currently markets and sells the INTERCEPT Blood System for both platelets and plasma in Europe, the Commonwealth of Independent States, the Middle East and selected countries in other regions around the world. The INTERCEPT red blood cell system is in clinical development. See http://www.cerus.com for more information.

INTERCEPT and INTERCEPT Blood System are trademarks of Cerus Corporation.

This press release contains forward-looking statements. Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements, including, without limitation, statements relating to the intended collaborative activities of the parties, the potential efficacy, development and clinical evaluation of an INTERCEPT system adapted for use with whole blood and the anticipated timing of initiating Phase III INTERCEPT red blood cell studies in Europe. These forward-looking statements are based upon Cerus’ current expectations. Actual results could differ materially from these forward-looking statements as a result of certain factors, including, without limitation, risks associated with development and clinical evaluation of the INTERCEPT system for whole blood and for red blood cells, the risk that available funding may not be available to support whole blood-related activities under the proposed collaboration, risks associated with dependence on third-party potential collaborators to support whole blood-related development activities and other risks detailed in the Cerus' filings with, the Securities and Exchange Commission (SEC), including in Cerus' annual report on Form 10-K for the year ended December 31, 2011, filed with the SEC on March 5, 2012. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. Cerus does not undertake any obligation to update any forward-looking statements as a result of new information, future events, changed assumptions or otherwise.

Source

Advances in the Treatment of Hepatitis C Virus Infection

Advances in HCV Treatment Volume 20 Issue 1 April/May 2012

Top Antivir Med. 2012;20(1):5-10
©2012, IAS–USA

Perspective

Advances in HCV Treatment Volume 20 Issue 1 April/May 2012 Since 2007, the annual age-adjusted mortality rate in HIV disease in the United States has been surpassed by that of hepatitis C virus (HCV) disease, reflecting the continuing decline in HIV-related mortality and the continuing increase in HCV-related mortality.1 The prevalence of HCV-related cirrhosis is projected to continue to increase until it reaches a peak around 2020, reflecting what is commonly a 20- to 40-year period between HCV acquisition and the later-stage manifestations of cirrhosis, end-stage liver disease, and liver cancer. These projections assumed no changes in our ability to treat HCV infection. The rate of sustained virologic response (SVR; ie, absence of HCV RNA in blood for 6 months after the end of treatment) with what has been the standard treatment of peginterferon alfa plus ribavirin is approximately 40% in patients with HCV genotype 1 Dr Thomas is Professor of Medicine and Director of the Division of Infectious Diseases at The Johns Hopkins University in Baltimore, MD. Since 2007, the annual age-adjusted mortality rate in hepatitis C virus (HCV) infection in the United States has been greater than that in HIV disease, reflecting the continuing decline in HIV-related mortality and the continuing increase in HCV-related mortality. The approval of 2 new direct-acting antivirals within the past year, as well as the promise offered by numerous other direct-acting agents in development, provides hope that we will be able to markedly improve our ability to cure HCV disease. The addition of a protease inhibitor (PI) to what has been the standard HCV therapy of peginterferon alfa and ribavirin dramatically improves sustained virologic response rates in treatment-naive patients with genotype 1 infection. Similar results have been observed in some treatment-experienced patients in whom prior peginterferon alfa/ribavirin therapy has failed. The use of these new agents has also permitted response-guided therapy, wherein early sustained virologic response to treatment allows for a shortened treatment duration. However, these new PIs add cost and adverse effects to HCV therapy. Boceprevir is associated with increased risk of anemia and dysgeusia, and telaprevir is associated with increased risk of anemia and skin and gastrointestinal adverse effects. Early studies indicate that the addition of PIs results in high response rates in patients with HCV/HIV coinfection. Other studies suggest that combinations of PIs and other direct-acting antivirals may ultimately permit cure when used in interferon sparing regimens. This article summarizes a presentation by David L. Thomas, MD, MPH, at the IAS–USA live continuing medical education course held in New York City in October 2011.

Since 2007, the annual age-adjusted mortality rate in HIV disease in the United States has been surpassed by that of hepatitis C virus (HCV) disease, reflecting the continuing decline in HIV-related mortality and the continuing increase in HCV-related mortality.1 The prevalence of HCV-related cirrhosis is projected to continue to increase until it reaches a peak around 2020, reflecting what is commonly a 20- to 40-year period between HCV acquisition and the later-stage manifestations of cirrhosis, end-stage liver disease, and liver cancer. These projections assumed no changes in our ability to treat HCV infection.

The rate of sustained virologic response (SVR; ie, absence of HCV RNA in blood for 6 months after the end of treatment) with what has been the standard treatment of peginterferon alfa plus ribavirin is approximately 40% in patients with HCV genotype 1 infection, the predominant type of infection in the United States. The rate is less than 30% in HIV/HCV-coinfected patients with HCV genotype 1. However, the past year has brought the approval of 2 new drugs for treating HCV infection—the HCV protease inhibitors boceprevir and telaprevir— and numerous new drugs are in advanced stages of development. It is hoped that these new weapons will allow us to improve the projections for HCV disease outcomes.

Treatment Outcomes With Telaprevir and Boceprevir

Treatment-Naive Patients

In the trial supporting approval of telaprevir, more than 1000 treatment-naive patients with HCV genotype 1 infection were randomly assigned to receive telaprevir for 8 weeks or 12 weeks plus concurrent standard peginterferon alfa/ribavirin therapy for up to 48 weeks, or peginterferon alfa/ribavirin alone for 48 weeks.2 Patients receiving telaprevir who achieved a virologic response that was sustained between weeks 8 and 12 were further randomly assigned to stop peginterferon alfa/ribavirin after week 24 or continue for the full 48 weeks. Overall, cure (ie, SVR) was achieved in 69% of patients receiving 8 weeks of telaprevir and 75% of those receiving 12 weeks of telaprevir, compared with 44% of those receiving peginterferon alfa/ribavirin alone. In black patients, who are known to have lower rates of response to peginterferon alfa/ribavirin, SVR rates were 25% with standard therapy, versus 58% and 62% with 8 weeks and 12 weeks of telaprevir, respectively. Among nonblack patients, SVR rates were 48% with peginterferon alfa/ribavirin, compared with 73% and 79% with the addition of telaprevir for 8 weeks and 12 weeks, respectively.

Patients who stopped therapy at 24 weeks after an early response to telaprevir-containing therapy had outcomes similar to those who continued to receive peginterferon alfa/ribavirin for the full 48-week course. The 12-week course of telaprevir was approved in 2011 by the US Food and Drug Administration (FDA) for use in combination with peginterferon alfa/ ribavirin, as was the shortened treatment duration in patients with early sustained response to treatment.

With regard to the ability to abbreviate therapy based on early response to treatment, Sherman and colleagues performed a study in treatment-naive, genotype 1–infected patients.3 Patients who achieved early rapid virologic response (eRVR; defined as undetectable HCV RNA at week 4 and week 12) with telaprevir plus peginterferon alfa/ribavirin therapy were randomly assigned to continue receiving peginterferon alfa/ribavirin for the full 48 weeks or to stop treatment after a total of 24 weeks. The overall SVR rate was 72%, with 65% of the total of 540 patients achieving eRVR. SVR rates were 92% among those stopping treatment after 24 weeks and 88% among those receiving 48 weeks of treatment. Among those who did not achieve eRVR, the SVR rate was 64%.

In the pivotal boceprevir trial, approximately 1100 treatment-naive patients with genotype 1 infection received a lead-in of peginterferon alfa/ ribavirin for 4 weeks.4 This was followed by either continuation of peginterferon alfa/ribavirin treatment for 44 weeks (total of 48 weeks); addition of boceprevir for 44 weeks (fixed-duration group); or addition of boceprevir for 24 weeks followed by treatment discontinuation if virus was undetectable from 8 weeks to 24 weeks or treatment continuation with peginterferon alfa/ribavirin alone for 20 weeks if virus was detectable (responseguided therapy group). Overall, SVR rates were 63% in the response-guided therapy boceprevir group and 66% in the fixed-duration boceprevir group, compared with 38% in the peginterferon alfa/ribavirin treatment group. SVR rates were improved with the addition of boceprevir in black patients (42% in the response-guided therapy group and 53% in the fixed-duration group vs 23% in the standard treatment group) and nonblack patients (67% and 69% vs 41%, respectively). Boceprevir was approved by the FDA in 2011 for use in combination with peginterferon alfa/ribavirin, including a shortened response-guided course of therapy in treatment-naive patients.

Treatment-Experienced Patients

Telaprevir and boceprevir have each been shown to achieve cure in a substantial proportion of HCV-infected patients in whom prior peginterferon alfa/ribavirin therapy had failed. In a study of more than 600 treatmentexperienced patients, Zeuzem and colleagues found SVR rates of 64% with the combination of 12 weeks of telaprevir plus 48 weeks of peginterferon alfa/ribavirin; 66% with a 4-week lead-in regimen of peginterferon alfa/ ribavirin followed by 12 weeks of telaprevir and 44 weeks of peginterferon alfa/ribavirin; and 17% with retreatment with 48 weeks of peginterferon alfa/ribavirin.5 Among patients with relapse (ie, those who relapsed after having undetectable virus at the end of prior treatment) SVR rates were 83%, 88%, and 24%, respectively. Among those who had shown a partial virologic response to prior treatment, SVR rates were 59%, 54%, and 15%, respectively. For those with no virologic response to prior treatment (null responders), SVR rates were 29%, 33%, and 5%, respectively.

In a trial in approximately 400 treatment-experienced patients conducted by Bacon and colleagues, overall SVR rates were 66% in patients receiving boceprevir and 48 weeks of peginterferon alfa/ribavirin, 59% in those receiving boceprevir with response-guided therapy, and 21% in those receiving standard peginterferon alfa/ribavirin.6 SVR rates were 75%, 69%, and 29%, respectively, among patients who had relapsed after prior therapy and 52%, 40%, and 7%, respectively, among those who had partial response to prior treatment.

Increased Toxic Effects With Addition of Telaprevir or Boceprevir

Jacobson and colleagues reported that adverse events occurred more frequently in telaprevir-containing study arms than in the peginterferon alfa/ribavirin alone arm. Adverse effects included pruritus (45%-50% with telaprevir vs 36% with peginterferon alfa/ribavirin), nausea (40%-43% vs 31%), rash (35%-37% vs 24%), anemia (37%-39% vs 19%), and diarrhea (28%-32% vs 22%). In the boceprevir trial conducted by Poordad and colleagues, anemia (49% in the boceprevir group vs 29% in standard treatment group) and dysgeusia (37%-43% vs 18%, respectively) were more common in boceprevircontaining study arms.

Resistance to HCV Protease Inhibitors

Because neither interferon alfa nor ribavirin is a direct-acting antiviral agent, viral resistance is a new phenomenon in HCV treatment. Resistance to the protease inhibitors (PIs) telaprevir and boceprevir is detected in approximately 50% of patients in whom therapy containing these agents fails.7,8 To date, there is no evidence that resistant variants have greater replicative fitness or pathogenicity than wild-type virus. As has been observed with HIV, there is a return to predominance of wild-type virus generally within 18 months of stopping HCV PI treatment.9 However, unlike HIV, there is no biologic basis for archiving of PI-resistant variants in the body.

Table 1. Sustained Virologic Response Rates According to Patient and Disease Characteristics in Treatment-Naive Patients Receiving Telaprevir or Boceprevir plus Peginterferon Alfa/Ribavirin Compared with Peginterferon Alfa/Ribavirin Alone

TPV 12 indicates patients receiving telaprevir for 12 weeks; Peg/RBV 24-48, peginterferon alfa and ribavirin for 24 to 48 weeks; Peg/RBV 48, peginterferon alfa and ribavirin for 48 weeks; BOC 44, boceprevir for 44 weeks. Adapted from Jacobson et al2 and Poordad et al.4

The long-term consequences of selecting for HCV PI resistance are unclear at this time. Investigations are currently underway on whether emergence of resistance will result in poorer response to subsequent treatment containing a PI. There are no convincing data thus far that baseline resistance to HCV PIs affects response to treatment. Thus, although there is a commercially available assay for testing for HCV resistance, for now there is no indication for testing to guide immediate treatment decisions. However, it may be prudent to document resistant variants in case the information becomes useful in the future.

More Potent Therapy Reduces Predictive Value of Some Risk Factors for Poor Response

More potent anti-HCV therapy reduces the value of some of the traditional factors predictive of poor response to peginterferon alfa/ribavirin therapy. This is a good thing, however, because the loss of predictive value is the result of higher cure rates in subgroups of patients with traditionally greater risk of poor response. Most notable is the diminished effect of higher HCV viral load in predicting poorer treatment outcome with peginterferon alfa/ribavirin (see Table 1). For example, in the pivotal telaprevir trial, SVR rates were similar among telaprevir-receiving patients with baseline HCV RNA viral load 800,000 IU/mL or higher and those with viral load less than 800,000 IU/mL (74% and 78%, respectively).2 The SVR rate in those with elevated viral load receiving telaprevir represents a striking improvement over the response rate among patients with high viral load receiving peginterferon alfa/ ribavirin alone (36%). In the pivotal boceprevir trial, the SVR rate among boceprevir recipients with elevated baseline viral load was 63%, compared with 33% among patients with elevated baseline viral load receiving peginterferon alfa/ribavirin alone.4

As noted previously, black race is also a risk factor for poorer response to peginterferon alfa/ribavirin. The difference in the frequency of the unfavorable interleukin-28B genotype explains about half of the difference in treatment response between black and nonblack patients. Although there was still a difference in SVR rates between black patients and white patients receiving telaprevir (62% and 75%, respectively), the SVR rate in black patients represents a striking improvement over that achieved with peginterferon alfa/ribavirin alone (25%).2 Similarly, black patients receiving boceprevir had a lower SVR rate than white patients, but the high cure rate in black patients receiving boceprevir compared with those receiving peginterferon alfa/ribavirin alone is another striking improvement—53% versus 23%, respectively.4 Some of the differences observed between the telaprevir and boceprevir studies, with regard to response rates in patient subgroups, likely reflect the fact that the post hoc analyses were performed in different patient populations.

Comparison of Telaprevirand Boceprevir-Containing Regimens

Table 2 provides an overview of characteristics of HCV treatment with telaprevir- and boceprevir-containing regimens. A 4-week lead-in period with peginterferon alfa/ribavirin is recommended before adding boceprevir and no lead-in is recommended for patients receiving telaprevir,8,10 reflecting the way the drugs were developed in phase II and, especially, phase III studies. Boceprevir is administered for 24 weeks or 44 weeks in treatment-naive patients and for 32 weeks or 44 weeks in treatment-experienced patients, depending on early virologic response, whereas telaprevir is administered for 12 weeks in both treatment-naive and treatment–experienced patients.

Table 2. Selected Characteristics of Boceprevir and Telaprevir

*RGT indicates response-guided therapy; PI, protease inhibitor; eRVR, early rapid virologic response. RGT is not recommended in patients with cirrhosis or HIV coinfection.

Response-guided therapy is not recommended in patients with cirrhosis or in HIV-coinfected patients. Responseguided therapy in HIV-seronegative, noncirrhotic, treatment-naive patients is permitted based on an HCV RNAnegative response during weeks 8 to 24 with boceprevir treatment and at weeks 4 and 12 with telaprevir treatment. Based on clinical trial data, it is estimated that 44% of treatment-naive patients receiving boceprevir and 58% to 65% of treatment-naive patients receiving telaprevir are eligible for response-guided therapy. The total duration of anti-HCV treatment in treatment- naive patients, depending on presence or absence of early virologic response, is 28 weeks or 48 weeks for boceprevir, and 24 weeks or 48 weeks for telaprevir.

Response-guided therapy in treatment- experienced patients is not recommended for patients receiving boceprevir who were null responders to prior treatment or for patients receiving telaprevir who were partial or null responders. For treatment-experienced patients receiving boceprevir, total anti-HCV treatment duration is 36 weeks (for those with eRVR) or 48 weeks. Total treatment duration is 24 weeks or 48 weeks for patients receiving telaprevir. Anti-HCV therapy with boceprevir should be stopped due to futility if HCV RNA level is greater than 100 IU/mL at week 12 or if there is detectable HCV RNA at week 24. The recommended stopping rule for telaprevir- containing therapy is a viral load of greater than 1000 IU/mL at week 4 or 12, or detectable virus at week 24.

As noted previously, there are added adverse effects with the addition of either of the PIs to peginterferon alfa/ ribavirin. There is an increased risk of anemia with boceprevir compared with peginterferon alfa/ribavirin therapy alone, and telaprevir is associated with increased risk of anemia and skin and gastrointestinal side effects. Pill burdens differ between the two treatments, with boceprevir requiring four 200 mg pills every 8 hours and telaprevir requiring two 375 mg pills every 8 hours. There is also a difference in food requirements: boceprevir needs to be taken with some food, whereas each dose of telaprevir needs to be taken with a meal containing at least 20 g of fat.

The addition of a new agent to HCV treatment regimens increases cost as well as cure rates. A 48-week course of peginterferon alfa/ribavirin costs approximately $38,000. Full courses of telaprevir (12 weeks) and boceprevir (up to 44 weeks) cost approximately $50,000.

Ongoing Studies of HCV PIs

Patients with HCV infection in whom PI treatment has yet to be fully evaluated are those with more advanced disease (eg, patients with decompensated cirrhosis and transplant patients), those with HBV coinfection, and those with HIV coinfection. In addition, safety and efficacy of these drugs have not been established in patients with HCV genotype 2 or 3 infection. Genotype 2 infection is responsive to peginterferon alfa/ribavirin in most patients, and there is some indication that cure rates are improved with the addition of a PI. Genotype 3 infection is more difficult to treat in many cases, and there is some evidence indicating that response rates are not improved with the addition of a PI.

Studies in HIV Coinfection

In a small study by Sulkowski and colleagues, patients with HCV/HIV coinfection received a full 48-week course of anti-HCV therapy with telaprevir plus peginterferon alfa/ribavirin or peginterferon alfa/ribavirin alone with or without antiretroviral therapy.11 The group receiving peginterferon alfa/ribavirin without antiretroviral therapy included patients with high CD4+ cell counts who did not meet current guidelines for initiation of antiretroviral therapy. Patients who received antiretroviral therapy took efavirenz/tenofovir/emtricitabine, or ritonavir-boosted atazanavir with tenofovir/emtricitabine or tenofovir/lamivudine. Patients who received the efavirenz-containing regimen received an additional telaprevir pill with each dose to compensate for lowered blood levels due to pharmacokinetic interaction with efavirenz. As shown in Figure 1, the telaprevir-containing regimen markedly improved week 4 and week 12 virologic responses in patients receiving and not receiving antiretroviral therapy. These promising findings need to be confirmed in larger studies.

Figure 1. Hepatitis C virus (HCV) virologic responses to telaprevir-containing therapy at week 4 (left) and week 12 (right) in patients with HCV/HIV coinfection, according to antiretroviral regimen. Numerals in bars show total number of patients in treatment group. EFV indicates efavirenz/tenofovir/emtricitabine; ATV/r, ritonavir-boosted atazanavir with tenofovir/emtricitabine or tenofovir/lamivudine. Adapted from Sulkowski et al.11

A phase II trial of boceprevir with peginterferon alfa/ribavirin in HIV/ HCV-coinfected patients is ongoing. A total of 99 coinfected patients with stable HIV disease are being treated with a lead-in of 4 weeks of peginterferon alfa plus weight-based ribavirin, then randomly assigned to add boceprevir (800 mg every 7-9 hours) or placebo for an additional 44 weeks. Subjects were allowed into the study if they were on raltegravir or ritonavirboosted PIs. Baseline HCV RNA level was above 800,000 IU/mL for 88% of subjects; 82% were white, and 5% had cirrhosis.12

The proportion of patients with undetectable HCV RNA at week 8 was higher in the group receiving boceprevir (24 of 64 [37.5%] with undetectable HCV RNA) than in the group receiving placebo (5 of 34 [14.7%]). At week 24, HCV RNA was undetectable in 43 of 61 patients (70.5%) in the boceprevir arm and undetectable in 11 of 32 (34.4%) in the placebo arm. Treatment was discontinued in 3 (9%) and 9 (14%) of the patients in the placebo and boceprevir arms, respectively, because of adverse events.

Updates on the trials described above were presented at the 19th Conference on Retroviruses and Opportunistic Infections in March 2012. In the telaprevir trial in HIV/HCV-coinfected patients, 28 of 38 patients (74%) receiving telaprevir plus peginterferon alfa/ribavirin had undetectable levels of HCV RNA at week 24 (end of treatment), compared with 12 of 22 patients (55%) in the peginterferon alfa/ribavirin–only control group.13 Twelve weeks after stopping therapy, all 28 of the 38 (74%) who had undetectable levels of HCV RNA at the end of telaprevir treatment had sustained virologic response. In the control group, 10 of 22 patients (45%) had sustained virologic response.

In the boceprevir trial, 39 of 61 coinfected patients (63.9%) receiving boceprevir plus peginterferon alfa/ribavirin had undetectable HCV RNA at week 48 (end of treatment), compared with 10 of 34 (29.4%) receiving peginterferon/ alfa alone.14 Twelve weeks after stopping therapy, 37 of 61 patients (60.7%) who had received boceprevir had sustained virologic response, compared with 9 of 34 (26.5%) in the peginterferon alfa/ribavirin–only group.

These results in coinfected patients are notable because in both studies, virologic response was substantially better than with interferon alfa/ribavirin alone. Virologic response rates were also nearly as high as those in monoinfected patients.

Potential for Cure Without Interferon Alfa

Peginterferon alfa therapy is associated with considerable toxicity, and there is intense interest in developing treatments that would spare patients from the rigors of such therapy. An example of studies assessing this possibility was reported by Lok and colleagues.15 Patients who were prior null responders to peginterferon alfa/ribavirin therapy received a combination of an HCV PI and an HCV nonstructural protein 5A (NS5A) inhibitor (which is active at different steps of the viral replication process than PIs), with or without peginterferon alfa/ribavirin.

Four of 11 patients receiving the PI and NS5A inhibitors without peginterferon alfa/ribavirin had viral loads that fell below the limit of quantitation at week 12 and remained undetectable after stopping therapy, showing in principle that cure is achievable without interferon alfa therapy. Six of the 11 patients exhibited viral breakthrough. It is also noteworthy that all 10 patients receiving the 2 direct-acting antivirals in combination with peginterferon alfa/ribavirin had undetectable virus at week 12, a remarkable outcome of treatment in prior null responders. There is considerable excitement over what might be achieved with multidrug combinations of the numerous investigational direct-acting agents.

Although formal guidelines for treatment of HIV/HCV-coinfected persons are being planned, at this time treatment should be prioritized for those with advanced liver fibrosis (cirrhosis and bridging fibrosis). When possible, coinfected patients should be enrolled in clinical trials to expand the available information on optimal HCV treatments in that setting.

Summary

The current era in HCV treatment is reminiscent of the transformation of HIV treatment that occurred in the mid-1990s. With the new HCV treatments, cure and complications occur more frequently. We can make smart applications of the treatments available to us right now in some patients, and we await tomorrow’s treatments for other patients. As with the first wave of HIV medications in the potent antiretroviral era, the new HCV drugs offer huge advantages but also present substantial challenges.

Presented by Dr Thomas in October 2011. First draft prepared from transcripts by Matthew Stenger. Reviewed and edited by Dr Thomas in February 2012.

Dr Thomas has received grants and research support from Gilead Sciences, Inc, and Merck & Co, Inc. He has served as a consultant to Merck & Co, Inc.

References

1. Ly KN, Xing J, Klevens RM, Jiles RB, Ward JW, Holmberg SD. The increasing burden of mortality from viral hepatitis in the United States between 1999 and 2007. Ann Intern Med. 2012;156:271-278.

2. Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405-2416.

3. Sherman KE, Flamm SL, Afdhal NH, et al. Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med. 2011;365:1014-1024.

4. Poordad F, McCone J, Jr., Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1195-1206.

5. Zeuzem S, Andreone P, Pol S, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417-2428.

6. Bacon BR, Gordon SC, Lawitz E, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207-1217.

7. Vierling JM, Kwo PY, Lawitz E, et al. Frequencies of resistance-associated amino acid variants following combination treatment with boceprevir plus PEGINTRON (peginterferon alfa-2b)/ribavirin in patients with chronic hepatitis C (CHC), genotype 1 (G1). Hepatology. 2010;52(Suppl S1):702A-703A.

8. Telaprevir [package insert]. Cambridge, MA: Vertex Pharmaceuticals; 2011.

9. Zeuzem S, Sulkowski M, Zoulim F, et al. Long-term follow-up of patients with chronic hepatitis C treated with telaprevir in combination with peginterferon alfa- 2a and ribavirin: interim analysis of the Extend study. Hepatology. 2010;52(Suppl S1):436A.

10. Boceprevir [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2011.

11. Sulkowski M, Dieterich D, Sherman K, et al. Interim analysis of a phase 2a doubleblind study of TVR in combination with pegIFN-alfa2a and RBV in HIV/HCV coinfected patients. [Abstract 146LB.] 18th Conference on Retroviruses and Op- portunistic Infections (CROI). February 27-March 2, 2011; Boston, MA.

12. Sulkowski M, Pol S, Cooper C, et al. Boceprevir plus peginterferon/ribavirin for the treatment of HCV/HIV co-infected patients: interim on-treatment results. [Abstract LB-37.] 49th Annual Meeting of the Infectious Diseases Society of America (IDSA). October 20-23, 2011; Boston, MA.

13. Dieterich D, Soriano V, Sherman K, et al. Telaprevir in combination with pegylated ininterferon- a-2a+RBV in HCV/HIV-co-infected patients: a 24-week treatment interim analysis. [Abstract 46.] 19th Conference on Retroviruses and Opportunistic Infections (CROI). March 5-8, 2012; Seattle, WA.

14. Sulkowski M, Pol S, Cooper C, et al. Boceprevir + pegylated interferon + ribavirin for the treatment of HCV/HIV-co-infected patients: end of treatment (week-48) interim results. [Abstract 47.] Proceedings from the 19th Conference on Retroviruses and Opportunistic infections (CROI). March 5-8, 2012; Seattle, WA. 15. Lok AS, Gardiner DF, Lawitz E, et al. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012;366:216-224.

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Addressing Disparities, Promoting Health Equity and Ending HIV/AIDS

Jeffrey Levi

Executive Director, Trust for America's Health; Chair of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health

Posted: 04/27/2012 1:54 pm

While we have made incredible strides in addressing HIV/AIDS over the past 30 years, the disease remains devastatingly prevalent in America, especially among gay and bisexual men. This population accounts for 57 percent of new HIV infections and a gay man who is 18 years old faces a two in five chance of becoming infected with HIV by the time he is 40, as noted by a Trust for America's Health (TFAH) issue brief. In 2009, the estimated rates of new HIV infections among black men and Latino men were 6.5 times and 2.5 times as high, respectively, as that of their white counterparts. Disparities are most severe among young black gay and bisexual men.

The National HIV/AIDS Strategy (NHAS) provides a roadmap for national efforts to end the HIV/AIDS epidemic. The primary goals of the NHAS are to reduce HIV incidence, increase access to care, optimize health outcomes and reduce HIV-related health disparities. The NHAS describes priority areas in need of interventions, outlines steps for a coordinated national response to the HIV epidemic and identifies measurable outcomes. This strategy reinforces the importance of focusing efforts on those at greatest risk, and is paramount in addressing the prevalence of HIV/AIDS among gay and bisexual men, particularly among racial and ethnic minorities.

A critical step in achieving the goals of the National AIDS Strategy is increasing awareness of HIV status (or "serostatus") among gay and bisexual men. Almost 50 percent of HIV transmissions come from the 20 percent of HIV-positive individuals who are unaware of their status. Promoting HIV testing and early linkage to care helps suppress viral load, reinforces less risky behavior, and helps prevent the transmission of HIV.

Increasing knowledge of serostatus requires routine HIV testing in the clinical setting, which can be accomplished through changes to guidelines and reimbursements. This is incredibly important because most individuals who do not know their status have actually had a recent interaction with the health care system but, unfortunately, were not tested. In order to reach the highest-risk populations, including racial and ethnic minorities, there is a need to train providers on testing and creating culturally competent approaches to gay men's health in general.

Representative Maxine Waters recently introduced important legislation that would promote increased HIV testing by removing cost as an obstacle. The Waters bill, Routine HIV Screening Coverage Act of 2012 (HR4470), would require all individual, group and federal employee health insurance plans to reimburse for HIV testing. This bill would be a significant step toward encouraging those who are unaware of their status to get tested.

As noted by the NHAS, HIV testing is just one piece of a comprehensive set of services that are needed to end the HIV epidemic. Expanded knowledge of serostatus must be complemented by a supportive environment for the gay and bisexual community. HIV prevention and treatment efforts, especially for racial and ethnic minorities, can be compromised by stigma and the social determinants of health, including access to stable housing, education, health care, and other key resources. Resources must be provided to mobilize the gay and bisexual community and promote gay men's health at the national, state and local level.

We've come a long way in the battle against HIV/AIDS. However, we must remain vigilant: We cannot ignore the startling statistics of new HIV infections of gay and bisexual men, especially among black and Hispanic men. By pursuing the comprehensive approach to prevention and treatment outlined in the National HIV/AIDS Strategy, we can begin to end the HIV/AIDS epidemic.

Trust for America's Health is proudly taking part in the Health Equity Can't Wait! blog carnival celebrating National Minority Health Month. Participating bloggers are health, consumer, civil rights, and provider advocates committed to promoting health equity. You can find all the posts for the carnival here.

For more by Jeffrey Levi, click here.

For more on HIV/AIDS, click here.

Follow Jeffrey Levi on Twitter: www.twitter.com/HealthyAmerica1

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