FDA Panel Recommends First Drug for HIV Prevention

Truvada (emtricitabine/tenofovir disoproxil fumarate)

From Medscape Medical News

Janis C. Kelly

May 11, 2012 — The US Food and Drug Administration's (FDA's) Antiviral Drugs Advisory Committee has strongly backed approval of the first-ever drug for the prevention of sexually acquired HIV-1 infection.

In a marathon 12-hour session, the panel recommended approval of a supplemental indication for Truvada (emtricitabine/tenofovir disoproxil fumarate) for preexposure prophylaxis (PrEP) in:

• HIV-uninfected men who have sex with men,
• HIV-uninfected partners in serodiscordant couples, and
• other individuals (such as sex workers) who are at risk of acquiring HIV through sexual activity.

The panel also urged the agency to "put some teeth into" Gilead's proposed risk evaluation and mitigation strategy (REMS) because of concerns that healthy people taking Truvada for HIV prevention will be harmed if they become infected with HIV and do not change from single-drug PrEP prophylaxis to a 3-drug combination antiretroviral treatment regimen, that continuing single-drug Truvada after HIV infection will lead to development of Truvada-resistant viral strains, and that taking the PrEP regimen increases the risk for adverse effects, particularly kidney damage.

The hearing occurred against the background of growing concern that the number of new HIV infections in the United States has remained at about 50,000 per year for the past decade. Most (75%) new HIV infections are in men. Black men have the highest incidence of new HIV overall: Incidence is 8 times higher in blacks and 3 times higher in Hispanics/Latinos than in whites.

The main driver of HIV transmission in the United States is unprotected anal sex between men who have sex with men (MSM), who represent about 2% of the population older than 13 years but account for from 56% to 61% of new HIV infections annually. The number of new HIV infections among 13- to 29-year-old MSM increased 38% from 2006 to 2009, largely because of a 48% increase among young black MSM, according to the FDA background document. Proponents of the Truvada PrEP approach hope that the daily pill will be "another tool in the toolbox" for reducing the continuing spread of HIV.

In support of the requested new indication, Gilead Science presented data from the Preexposure Prophylaxis Initiative (iPrEx) trial, which found that MSM participants who took Truvada daily had a 44% reduction in HIV incidence over the course of 1.2 years of follow-up compared with placebo. The study participants also received monthly HIV testing, free condoms, treatment for other sexually transmitted diseases, and routine counseling and were paid for participation in the study. Even with this supportive structure, nearly half of the study participants had no detectable level of Truvada when tested, suggesting that they were not taking the drug regularly.

Results of the iPrEx study were published online November 23, 2010, in the New England Journal of Medicine. Several speakers during the public comments part of the committee meeting reported that Truvada is already being seen as a "medical condom" (in the words of AIDS Healthcare Foundation's Whitney Engeran-Cordova) and might be taken intermittently or as a "party drug," leading to rapid development of Truvada-resistant HIV.

The resistance problem is one reason the FDA took the unusual step of asking that Gilead design a REMS, something that typically happens only when there are concerns about drug toxicity. The proposed REMS includes mailings to about 200,000 healthcare providers; a medication guide for uninfected individuals; voluntary training for primary care prescribers, infectious disease specialists, emergency medicine physicians, obstetrician-gynecologists, and addiction specialists on the importance of strict adherence to daily dosing and of regular monitoring of HIV serostatus; a prescriber safety brochure; an individual safety brochure; and a "TRUVADA for PrEP" wallet card for the patient. The REMS does not require participation by either physician or patient in the education program before making Truvada available.

The REMS plan also does not require a negative HIV test ("documentation of safe use condition") for a patient to receive each 30-day supply of Truvada, which sparked considerable criticism from the panel.

The possibility of "behavioral compensation" (reduced condom use by a patient who assumes protection from the pill) was dismissed by Gilead speakers but remained a concern for several panelists, who noted that condoms, used correctly, are more than 90% effective at preventing HIV infection.

Panelist and speakers also questioned whether the 44% protection seen in the clinical trial would also occur in "real-world" settings, as it requires daily use by a healthy person of a drug that costs $13,000 per year and carries some risk for adverse effects.

The committee voted 19 to 3 in favor of Truvada PrEP for HIV-uninfected MSM, 19 to 2 (1 abstention) in favor of Truvada PrEP for HIV-uninfected partners of those with HIV, and 12 to 8 (2 abstentions) in favor of Truvada PrEP for others at risk of acquiring HIV through sexual activity. The panel also favored monthly HIV testing and regular monitoring of renal function for those taking Truvada PrEP.

The panel ran out of time before full consideration of the proposed REMS, of postmarketing studies that should be required, and on whether current evidence makes the conduct of placebo-controlled trials of primary HIV prevention unethical.

The FDA is expected to make a final decision on the Truvada prophylaxis indication by June 15. It is already approved as part of combination therapy for treatment of HIV infection.

FDA Antiviral Drugs Advisory Committee Meeting. Silver Spring, Maryland. May 10, 2012.

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Guest Commentary: Baby boomers and hepatitis C in Colorado

Posted: 05/11/2012 01:00:00 AM MDT

By Nancy Steinfurth denverpost.com

Colorado's "baby boom" generation faces a ticking health care time bomb — and employers have the opportunity this year to help protect the health of their workers and potentially cut their company's health care costs at the same time.

The challenge that employers and baby boom employees alike face is that many Americans born between 1946 and 1964 have the hepatitis C virus (HCV) and don't know it. A quick blood test and a fast diagnosis results in a far more rapid and less expensive course of treatment. These proactive steps not only save lives but in turn help reduce costs and throw a lasso on soaring insurance premiums.

If it were as simple as all that, we know companies would be clamoring to raise workers' awareness. Unfortunately, myth and misinformation about HCV have left millions of Americans blissfully unaware that a serious and life-threatening disease may be brewing inside them — and by the time symptoms are noticeable, it can often be too late.

That's why exploding the myths surrounding HCV are so critical and having the imprimatur of company leaders in businesses large and small in this fight can make a massive difference.

Let's tackle the biggest myth head on. A number of baby boomers go untested because they assume that the only way to have contracted hep C is through intravenous drug use. Wrong. Many Americans — including many veterans — who had transfusions or blood products prior to 1992 were infected with HCV before donated blood was accurately and adequately screened for the disease. Other risk factors include tattooing in unsafe settings and having been on long-term dialysis.

These myths have consequences. Statistics show that more two-thirds of Americans with HCV are baby boomers and 75 percent of those with the disease are living their lives unaware.

Ignorance is not bliss.

Hepatitis C is a contagious liver disease prevalent — and widely undiagnosed — among baby boomers, with experts estimating that two-thirds of those with hep c were born in the baby boom years of 1946 to 1964. In raw numbers, of the 102 million Americans age48 to 66, an estimated 1.3 million are infected with hepatitis C virus but remain undiagnosed. Hepatitis C ranges in severity from a mild illness lasting a few weeks to a serious, lifelong illness that attacks the liver. It results from infection with the hepatitis C virus, which is spread through contact with the blood of an infected person.

The facts are that symptoms of hep C may not appear for 20 years or more and the later that the disease is diagnosed, the more difficult — and expensive — it is to treat.

That's why a federal strategy released in recent days recommends placing a priority on screening Americans by age, moving beyond the less effective method of screening by so-called "risk group." A new national study showed that screening all American baby boomers could save 48,000 lives.

Instead of allowing this status quo to continue, common-sense tells us to focus on the age group that faces the most dire challenges. That's the message we at Hep C Connection, a statewide organization that educates the general public about hepatitis C and provides resources and support for those affected by the virus, are sharing with employers throughout Colorado.

By focusing on this critical age group in every workplace, employers could literally save lives. Studies show that by raising awareness, employers could help ten times more baby boomers to get tested and three times as many men and women being diagnosed and getting early treatment.

At Hep C Connection, we provide free testing in the metro-Denver area and we connect patients with testing locations in other parts of Colorado which, in most cases, provide the screening free of charge.

The prevention of serious, life-threatening conditions as a result of the early screening is huge with, for example, an estimated 28,000 prevented cases of liver cancer and 6,000 liver transplants being avoided.

In addition to the benefit to lives saved and diseases prevented, the cost of treating these and other serious conditions is very high. For employers, this means the savings of billions of dollars in employee health care costs — and health insurance premiums — going forward.

That is perhaps the most important, common-sense reason for business owners and executives to raise awareness among their baby boomer employees. But there is a bottom-line, dollars-and-sense reason as well. National studies show that age-based testing would save billions of dollars, including more than $4 billion in savings from the prevention of advanced live disease.

Coloradans living longer lives and employers lowering health care costs. By sounding the hep C alarm to baby boomers across our state, businesses can do well by doing good.

Nancy Steinfurth is excutive director of Hep C Connection, a statewide organization that educates the general public about hepatitis C and provides resources and support for those affected by the virus. (www.hepc-connection.org).

EDITOR'S NOTE: This is an online-only column and has not been edited

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Fatty Acids in Fish May Lower Liver Cancer Risk

^{© Suprijono Suharjoto/Fotolia.com}

Researchers found that fish that are rich in n-3 polyunsaturated fatty acids help lower risk of hepatocellular carcinoma.

By: MARY ANN MOON, Family Practice News Digital Network

The consumption of fish rich in n-3 polyunsaturated fatty acids was inversely related to the risk of developing hepatocellular carcinoma in a population-based study of Japanese adults, Dr. Norie Sawada and colleagues reported in the June issue of Gastroenterology.

In addition, higher intake of several individual n-3 polyunsaturated fatty acids (PUFAs) – particularly eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid – also correlated with lower hepatocellular carcinoma (HCC) risk.

The associations were dose dependent for intake of n-3 PUFA-rich fish and for intake of individual fatty acids, said Dr. Sawada of the National Cancer Center, Tokyo, and associates.

Dietary n-3 PUFAs, also called omega-3 PUFAs, have long been thought to lower the risk of developing several cancers, but few studies have examined a potential protective effect against liver cancer in particular. One recent prospective study in the United States showed an inverse association between consumption of "white meat," including fish, and liver cancer, but other studies have found no such correlation.

Dr. Sawada and colleagues examined the issue by analyzing data from a large cohort study launched in the 1990s and supervised by the Japanese department of public health. The investigators analyzed detailed dietary data from 90,296 adults who were aged 40-69 years at baseline and were followed for an average of 11 years.

The study subjects completed questionnaires regarding their usual intake of 138 food items during the previous year, using standard portions or units of consumption. Nineteen items on the questionnaire asked about dietary fish and shellfish, which in Japan includes salted fish; dried fish; canned tuna, salmon, or trout; and bonito, tuna, cod, sea bream, mackerel, sardine, mackerel pike, roe, eel, squid, octopus, prawn, clam, crab, vivipara, as well as various fish pastes.

The investigators used the subjects’ responses to calculate daily fish consumption. They also calculated daily intake of all n-3 PUFAS combined, and intake of four individual fatty acids. They separately calculated the consumption of fish rich in n-3 PUFAs, namely salmon, trout, sea bream, mackerel, sardine, mackerel pike, and eel.

Blood samples that had been taken during general health check-ups were screened for hepatitis C antibodies and hepatitis B surface antigen to determine whether the subjects were carrying hepatitis C or B.

A total of 398 cases of incident HCC developed during follow-up (Gastroenterology 2012 Feb. 20 [doi:10.1053/j.gastro.2012.02.018]).

Total fish consumption showed a weak inverse association with risk of HCC, with a multivariable hazard ratio of .64 for highest vs. lowest quintile (95% confidence interval, 0.41 to 1.02, P for trend = .07). The association reached statistical significance when the analysis was confined to fish rich in n-3 PUFAs with a HR of 0.64 (95% CI, .42 to .96, P for trend = .04).

Strong, dose-dependent inverse associations also were found between HCC risk and dietary intake of eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid.

These results did not change substantially when the data were adjusted to account for subject age, sex, smoking status, and body mass index. The findings also persisted across several subgroups of patients such as alcohol drinkers and coffee drinkers.

The inverse association between consumption of fish high in n-3 PUFAs and HCC risk also was strong in the subgroups of patients positive for hepatitis B or hepatitis C.

The reasons underlying this protective effect against liver cancer are not yet known. It is likely that the anti-inflammatory properties of polyunsaturated fatty acids play a role, "given that HCC is an inflammation-related cancer which has a background of chronic inflammation triggered by exposure to hepatitis virus infection or toxic compounds such as ethanol," Dr. Sawada and associates said.

This study was somewhat limited in that it was necessary to estimate the consumption of fish and individual fatty acids rather than measuring these amounts directly. Also, the dietary data were based on subjects’ self-report at only a single time point.

The study was supported by the National Cancer Center Research and Development Fund and the Ministry of Health, Labor, and Welfare of Japan, both in Tokyo. The authors reported no financial conflicts of interest.

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OraSure HIV Test Has Risks of False Results, FDA Says

By Anna Edney - May 11, 2012 3:30 PM ET

People who use what could be the first completely at-home HIV test under development by OraSure Technologies Inc. (OSUR) risk receiving false results, U.S. regulators said in a report.

Outside advisers to the Food and Drug Administration should weigh whether the benefits of the kit are greater than the potential risk of false negative and false positive results, agency staff said in the report today ahead of a May 15 advisory panel meeting. Regulators are considering approval of the OraQuick In-Home HIV Test, which would be sold without a prescription and provide users with their HIV status at home in a similar fashion to pregnancy tests.

“There is considerable personal and public health value in informing infected, but otherwise untested, persons of their true positive HIV status,” FDA staff wrote. “However, this benefit is offset in some measure by HIV-positive individuals who receive an incorrect message that they are not infected.”

OraSure fell 14 percent to $9.65 at 3:15 p.m. New Yorktime, the largest intraday decline in two years.

About 1.2 million people in the U.S. have HIV, the virus that causes AIDS, and 20 percent of those people are unaware they are infected, according to the Centers for Disease Control and Prevention. The test made by Bethlehem, Pennsylvania-based OraSure would be the first of its kind. Other kits, such as Home Access Health Corp.’s Express HIV Test System, require users to anonymously send blood samples to a laboratory for testing.

Clinical Trial Findings

A clinical trial of OraSure’s test identified 100 previously undiagnosed people infected with HIV of 5,800 patients who used the product, according to the company. OraSure markets the only FDA-approved rapid HIV test that detects HIV antibodies in oral fluid and provides results in a clinic or doctor’s office within 20 minutes.

OraQuick would produce one false negative result for every 13 true positive tests, FDA staff said. That would total an estimated 3,800 people with HIV who falsely test negative each year, according to the report. In addition, the test would produce one false positive result for every 3,750 true negative tests resulting in 1,100 people a year who aren’t infected believing they are, the report said.

The false negatives reported were higher than what the FDA considers a “minimum acceptable performance” while the false positives were lower.

‘Confident’ in Test

“We are very confident in the efficacy, safety and performance of the OraQuick In-Home HIV Test, which has been proven to have a calculated accuracy of 99 percent in extensive self-test clinical studies,” Ron Ticho, a spokesman, said in an e-mail.

OraQuick would identify 9,087 previously undiagnosed HIV-positive individuals for each 1 million who use the test, Ticho said.

OraSure doesn’t have an estimate for when the FDA may decide on the home-results test, said Susan Brophy, of Golin Harris, who is a spokeswoman for the company.

The FDA cleared the Home Access test in 1996. Results can be obtained the day a sample arrives at a laboratory and retrieved anonymously using a pin number, according to theHoffman Estates, Illinois-based company. The FDA stresses the benefit of having medical professionals help users interpret the results and understand treatment options on its website.

The FDA staff expressed concern that people who may have gotten tested professionally would turn to the “less sensitive, but more private,” alternative. No studies have been done to test the potential impact, according to the report.

“Counseling, which uses both printed material and telephone interaction, provides the user with an interpretation of the test result,” the FDA said on its website about the Home Access test system.

Counseling also can provide information on preventing transmission of the disease for people who are infected and on treatment options and doctor referrals, the FDA said.

More than 16,000 people with AIDS were estimated to have died in 2008, the CDC said.

To contact the reporter on this story: Anna Edney in Washington at aedney@bloomberg.net.

To contact the editor responsible for this story: Reg Gale at rgale5@bloomberg.net

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Thomas Jefferson University Hospital Creates Comprehensive Hepatitis C Center

New Center Tailored to Treat Rising Population for “Silent Killer”

Philadelphia, PA (PRWEB) May 11, 2012

Thomas Jefferson University Hospital recently opened its new Jefferson Hepatitis C Center, one of only a few comprehensive, multidisciplinary centers dedicated to the study of hepatitis C virus and hepatic disease in the Pennsylvania, New Jersey and Delaware tri-state area.

According to the Centers for Disease Control and Prevention (CDC), 3.2 million Americans are infected with chronic hepatitis C – a virus that affects the liver. It is spread primarily by exposure to blood that is infected with hepatitis C. Left untreated, hepatitis C can cause cirrhosis, liver cancer and liver failure, and is also the leading indication for liver transplant in the US. Baby boomers, anyone born between 1945 and 1965, are the largest patient population according to the CDC, accounting for as much as two-thirds of hepatitis C infections.

“The Jefferson Hepatitis C Center aims to offer a coordinated approach to treatment for patients with hepatitis C by some of the area’s most experienced hepatologists,” says Jonathan Fenkel, M.D., director of the Center.

If liver damage cannot be controlled, Jefferson is home to the longest continuously active liver transplantation program in the Philadelphia area.

While two million people in the US suffer from Hepatitis C, an additional 1-2 million are undiagnosed, putting them at risk for devastating long-term effects. The virus is often called the “silent killer” because it can produce no symptoms and can go undetected for decades.

The Jefferson Hepatitis C Center offers patients:

• A tailored program to meet individual needs
• A twice-weekly outpatient hepatitis C treatment clinic
• A multidisciplinary monthly HIV/hepatitis C coinfection clinic
• An active clinical trials program
• Expert consultations for referring physicians and patients including a detailed plan highlighting potential drug interactions and treatment considerations

In addition to Dr. Fenkel and Jefferson’s three experienced hepatologists, the Hepatitis C multidisciplinary team includes close collaboration with pathologists, infectious disease specialists, psychiatrists, radiologists, clinical pharmacists, and diagnostic laboratories; all of whom are highly experienced in the testing and evaluation of Hepatitis C and other liver conditions.

“At the Jefferson Hepatitis C Center, we are working to find effective treatment options for those chronically infected with hepatitis C,” says Dr. Fenkel. “Until recently, few medications were able to successfully treat this infection. But now, we are at the dawn of a new era. Patients have access to new, FDA-approved medications that make treatment successful for nearly four out of five patients. Also, even better medications are still being studied and patients will have access to these ongoing and future clinical trials.”

Thomas Jefferson University Hospitals (TJUH) are dedicated to excellence in patient care and education. It is consistently ranked by U.S. News & World Report among the nation's top hospitals. It has over 950 licensed acute care beds with major programs in a wide range of clinical specialties. TJUH is one of the few hospitals in the U.S. that is both a Level 1 Trauma Center and a federally-designated regional spinal cord injury center. TJUH patient care facilities include: Jefferson Hospital, Jefferson Hospital for Neuroscience, and Methodist Hospital in South Philadelphia. Additional out-patient sites are located throughout Pennsylvania and New Jersey. TJUH is a part of Jefferson Health System and a partner of Thomas Jefferson University.

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FDA Advisory Committee Supports Approval of Gilead’s Once-Daily Quad Single Tablet Regimen for HIV

– Final FDA Decision On The Quad Anticipated Late Summer –

FOSTER CITY, Calif.--(BUSINESS WIRE)--May. 11, 2012-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Antiviral Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has voted 13 to 1 in support of approval of the Quad, a complete single tablet regimen of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate, for the treatment of HIV-1 infection in treatment-naïve adults.

The recommendations of the Advisory Committee are not binding, but will be considered by FDA as the agency completes its review of Gilead’s New Drug Application (NDA) of the Quad. Gilead submitted the NDA on October 27, 2011 and FDA has set a target action date under the Prescription Drug User Fee Act (PDUFA) of August 27, 2012. Applications for marketing approval of the Quad are also pending in Australia, Canada and the European Union.

“With new government guidelines recommending that people diagnosed with HIV begin treatment early, it is important that we continue to simplify and improve HIV therapy,” said Andrew Cheng, MD, PhD, Senior Vice President, HIV Therapeutics and Development Operations, Gilead Sciences. “The Quad is the latest example of Gilead’s ongoing efforts to develop highly effective and well tolerated single tablet regimens for people living with HIV.”

The Quad NDA is supported by the positive results from two pivotal Phase 3 studies in which Quad met its primary objective of non-inferiority as compared to Atripla^® (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) (Study 102) and to a regimen containing ritonavir-boosted atazanavir plus Truvada^® (Study 103). The NDA is also supported by Chemistry, Manufacturing and Controls (CMC) information on the individual components of the Quad and the co-formulated single tablet regimen.

In all studies, the Quad was well tolerated and most adverse events were mild to moderate. The most common adverse events observed were nausea, diarrhea, upper respiratory track infection and headache. Overall, there have been nearly 9 million patient years of experience with tenofovir-containing regimens.

About the Quad

The Quad contains four Gilead compounds in a complete once-daily, single tablet regimen: elvitegravir 150 mg; cobicistat 150 mg, a “boosting” agent that enables elvitegravir once-daily dosing; and Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg).

Elvitegravir is a member of the integrase inhibitor class of antiretroviral compounds. Unlike other classes, integrase inhibitors interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells. Elvitegravir was licensed by Gilead from Japan Tobacco Inc. (JT) in March 2005. Under the terms of Gilead’s agreement with JT, Gilead has exclusive rights to develop and commercialize elvitegravir in all countries of the world, excluding Japan, where JT retains rights.

Cobicistat is Gilead’s proprietary potent mechanism-based inhibitor of cytochrome P450 3A (CYP3A), an enzyme that metabolizes drugs in the body. Cobicistat acts only as a pharmacoenhancer and has no antiviral activity. In addition to studying the agent as part of the Quad, Gilead is also examining cobicistat’s potential in boosting commercially available HIV protease inhibitors.

The Quad, elvitegravir and cobicistat are investigational products and their safety and efficacy have not yet been established.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that FDA and other regulatory agencies may not approve the Quad and that any marketing approvals, if granted, may have significant limitations on their use. Further, even if approved, Gilead may not be able to successfully commercialize the Quad, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2012, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. full prescribing information for Atripla is available at www.Atripla.com.
U.S. full prescribing information for Truvada is available at www.Truvada.com.

Truvada is a registered trademarks of Gilead Sciences, Inc.
Atripla is a registered trademark of Bristol-Myers Squibb & Gilead Sciences, LLC.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000 .

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
Erin Rau, 650-522-5635 (Media)

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F.D.A. Panel Weighs Preventive Use of H.I.V. Drug

By DENISE GRADY

Published: May 10, 2012

SILVER SPRING, Md. — An advisory panel to the Food and Drug Administration is expected to vote Thursday on whether a drug already used to treat H.I.V. infection should also be approved to prevent it. Such a recommendation, if made, would mark the first time that government advisers have advocated giving antiviral medicine to healthy people who might be exposed through sexual activity to the virus that causes AIDS.

Studies have shown that people who take the medicine, Truvada, every day have a greatly reduced risk of infection.

The F.D.A. usually accepts the advice of its advisory panels, which are made up of outside experts, mostly from medical schools.

On Thursday morning, the panel evaluated studies of the once-a-day pill and heard scientific presentations about whether Truvada should be prescribed for people at high risk of infection, like gay men who have multiple sex partners, especially those who do not always use condoms, and people in relationships with someone who is H.I.V.-positive. Young black men who have sex with other men are at highest risk.

The drug is meant not to replace condoms and other safe-sex measures, but to be used with them for added protection.

Experts say better methods of prevention are needed because there are 50,000 new H.I.V. infections a year in the United States. Several speakers emphasized on Thursday that that number had not budged in 15 to 20 years. Counseling and condoms are not doing the job, they said, and many of the newly infected are men whose sexual partners do not realize they are H.I.V.-positive.

Worldwide, there were 2.4 million to 2.9 million new cases in 2010.

After the scientific presentations on Thursday morning, many panelists voiced concern about the possibility that people who become infected while taking Truvada could develop dangerous drug-resistant strains of the virus. And they asked why resistance occurs in people taking the medicine, given that it is such a powerful drug.

Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, said that one likely reason is that if people take the pills inconsistently, they may wind up with levels of the drug that are too low to prevent infection, but just high enough to allow resistance to occur.

An F.D.A. analysis found that people who are older and more educated are more likely to take the drug faithfully. So are men who reported having receptive anal sex without condoms. There is no data to tell whether Truvada would prevent H.I.V. infection spread by needle sharing.

Nausea and abdominal pain are common side effects for the first few weeks people take Truvada; those symptoms then diminish.

Because Truvada has already been approved to treat H.I.V. infection, doctors have been free to prescribe it for prevention, and some have been doing so. Prescribing a drug for something other than its approved purpose, called off-label use, is allowed by the F.D.A, though drug companies are not permitted to market or promote drugs for such uses.

Advocates of Truvada’s use for prevention say F.D.A. approval would help ensure the drug was more safely and effectively used. The medicine would have to be labeled with specific instructions for taking it, including which lab tests patients need to get for safety reasons. For instance, patients should be tested periodically for H.I.V. infection, because if someone who is already infected takes Truvada alone, drug-resistant strains of the virus may quickly develop. Some patients may also need to have their kidney function monitored. And the drug can also cause slight decreases in bone density that may need monitoring in some people. F.D.A. approval may also make it more likely that insurers would cover preventive use, which costs about $14,000 a year.

Truvada, which contains two antiviral drugs, is sold by Gilead Sciences, based in Foster City, Calif. Though it will be used alone for prevention, it must be taken along with other antiviral to treat H.I.V. First approved in 2004, it quickly became one of the best-selling H.I.V. drugs. Gilead reported Truvada sales of $758.3 million in the first quarter of this year, which would translate into more than $3 billion a year.

A Gilead official, Dr. Andrew Cheng, told the panel on Thursday that if Truvada is approved for prevention, the company will conduct safety monitoring and provide educational materials that will emphasize the importance of using other prevention methods as well, like condoms, counseling and regular H.I.V. testing. He said Gilead would also provide other services, including free condoms and testing for H.I.V. and hepatitis B; subsidized tests for viral resistance for people who become infected; and an assistance program for people with no prescription coverage.

A number of prevention studies of Truvada have been conducted in the past few years, with somewhat mixed results. A study of 2,499 gay men in six countries, published in 2010, found an overall risk reduction of 44 percent in men for whom Truvada was prescribed. When researchers looked more closely and checked blood levels of the drug, they found that many of the men had not taken it every day. Among those who did take it correctly, the risk reduction was about 90 percent. But only about 10 percent of the men took the pills exactly as directed.

Some studies in Africa and Asia have also shown significant risk reduction among healthy people whose partners were infected. But other studies in Africa were halted because the drug was showing no benefit in women; subsequent analyses revealed that many of the women were not taking the pills, sometimes because they did not think they were at risk.

The failure of some people in the studies to take the pills every day has led the AIDS Healthcare Foundation, a medical and advocacy group based in Los Angeles, to contend that prescribing Truvada as prevention could backfire, leaving people vulnerable while lulling them into believing that sex without condoms is safe.

“You will definitely have a result that is far worse than what you had in any of the studies,” Michael Weinstein, the foundation’s president, said in an interview.

But a researcher who conducted the study in gay men, Dr. Robert M. Grant of the Gladstone Institute of Virology and Immunology, which is affiliated with the University of California, San Francisco, disagreed, likening Mr. Weinstein’s argument to that of people in the 1970s who warned that air bags in cars would lead people to stop using seat belts.

“Did that happen?” Dr. Grant asked in an interview. “No.”

He said the goal of prevention research was to provide many ways to avoid infection so that everyone was using at least two of them.

Existing methods include condoms, counseling, male circumcision and widespread use of antiviral medicines by people who are already have H.I.V., even in the early stages, because treatment has been shown to significantly reduce the odds that they will infect others.

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HIV–HBV Coinfection — A Global Challenge

Perspective

Athena P. Kourtis, M.D., Ph.D., M.P.H., Marc Bulterys, M.D., Ph.D., Dale J. Hu, M.D., M.P.H., and Denise J. Jamieson, M.D., M.P.H.

N Engl J Med 2012; 366:1749-1752 May 10, 2012

Human immunodeficiency virus type 1 (HIV-1) and hepatitis B virus (HBV) exact a high toll worldwide. Both can lead to chronic disease, cancer, and death, and neither can be eradicated with the use of current therapies. Antiviral drug resistance often develops after patients have received treatment for some time and is usually followed by the loss of clinical benefit. Coinfection with the two viruses exacerbates the negative effects.

Worldwide, HBV is the leading cause of chronic liver disease and a leading cause of death, accounting for up to half of all cases of cirrhosis and hepatocellular carcinoma.1 An estimated 400 million people are infected with HBV,1 with the majority of cases occurring in regions of Asia and Africa where the virus is endemic. There, up to 70% of adults show serologic evidence of current or prior infection, and 8 to 15% have chronic HBV infection.1

These staggering infection rates largely reflect a failure of maternal and child health programs. The majority of HBV infections in settings where the virus is highly endemic occur through perinatal transmission (predominant in East and Southeast Asia) or in young children, transmitted through close household contact or through medical or traditional scarification procedures (predominant in Africa).1 Perinatal HBV infection is associated with a 90% risk of chronic hepatitis B, as compared with a risk of less than 5% among adults with intact immunity.1 The risk of perinatal transmission is lower in Africa than in Asia, a disparity that could be due to a lower prevalence of hepatitis B e antigen (HBeAg) and other differences in the pathogenic characteristics of circulating HBV genotypes.1

According to the Joint United Nations Program on HIV/AIDS (UNAIDS), about 33 million people are infected with HIV worldwide, and the majority of them live in Asia and Africa. Approximately 10% of the HIV-infected population has concurrent chronic hepatitis B,2 with coinfection more common in areas of high prevalence for both viruses. In countries where the viruses are highly endemic, the rate can be as high as 25%.2

In areas where HBV is less endemic (North America, Europe, and Australia), HBV and HIV are most often acquired during adolescence or adulthood through sexual transmission or injection-drug use. The prevalence of HIV–HBV coinfection in these regions is generally less than 10% of the HIV-infected population.2 However, up to half of injection-drug users infected with HIV are coinfected with HBV. Worldwide, there may be 3 to 6 million HIV-infected people living with chronic HBV (see maps).

HIV–HBV coinfection increases the morbidity and mortality beyond those caused by either infection alone. People coinfected with HIV have higher levels of hepatitis B viremia, have progression to chronic hepatitis B that is approximately five times as fast as that among people infected with only HBV, and have a higher risk of cirrhosis and hepatocellular carcinoma.1 HIV immunosuppression can even cause the loss of hepatitis B surface antibodies and reactivation to chronic hepatitis B.1 As compared with healthy, uninfected persons, those infected with HIV — particularly the most immunocompromised — mount poorer antibody responses to HBV vaccination. Managing hepatitis B in HIV-coinfected patients is further complicated by the dual activity of several nucleoside analogues, the emergence of resistant HIV or HBV strains, the limitations of and decreased response to interferons, and the more rapid development of lamivudine-resistant HBV.2

Very few studies have addressed coinfection with HBV among HIV-infected pregnant women. Studies in Africa indicate that they are three times as likely as HIV-negative pregnant women to test positive for HBV DNA and twice as likely to test positive for HBeAg. Both higher HBV DNA levels and HBeAg expression are associated with an increased risk of an HIV-infected pregnant woman's transmitting HBV to her child.1

Vaccination of infants against hepatitis B is highly protective, reducing the risk of infection by more than 70% (the addition of hepatitis B immune globulin reduces the remaining risk by half. However, many countries with a high prevalence of HBV lack universal or timely vaccination coverage, and hepatitis B immune globulin is often unavailable or prohibitively expensive. In 2006, for example, the coverage rate for the vaccine dose at birth was only 36% in countries where the prevalence of chronic HBV infection exceeded 8%.

Even with appropriate vaccination, 5 to 15% of infants born to mothers who test positive for hepatitis B surface antigen (HBsAg) become infected. The proportion is much higher among infants whose mothers have high serum HBV DNA levels; transmission rates of 39% or higher have been noted.3 High HBV DNA levels are often seen in women with concurrent HIV infection, particularly in Southeast Asia, where HBV is highly endemic and perinatal transmission of HBV is already common.

Additional approaches are needed to protect children of infected mothers. For example, the use of antiviral therapy in pregnant women with high HBV loads has been examined in a few small studies and has shown promise in decreasing perinatal transmission3; this strategy appears to be cost-effective and should be explored further.4 Women coinfected with HIV would be good candidates for this preventive approach.

Even in areas with historically low rates of HBV, challenges exist. In the United States, the number of HBV-infected pregnant women is probably underestimated, with current methods relying on the expectation that certain ethnic groups are at high risk. In Europe, there is no consistent policy of testing women for HBV infection during pregnancy; some countries rely on assessment of “risk factors” alone. Immigration patterns in Europe and North America suggest that HBV prevalence will vary by region.

There are a number of unanswered questions about disease pathogenesis in coinfected persons and the management of HIV–HBV coinfection, especially in pregnant women. Pregnancy itself can trigger elevations of liver enzymes. The administration, during pregnancy, of antiretroviral prophylaxis containing one agent with anti-HBV activity may be associated with later development of HBV resistance. For pregnant women who, to prevent perinatal HIV transmission, take antiretroviral prophylaxis containing one or two agents with anti-HBV activity, the safety of stopping treatment after delivery is unknown. The administration of antiretrovirals without HBV activity in coinfected pregnant women may leave their infants unprotected against HBV. Finally, infection of the infant with HIV threatens the benefits of HBV immunization for perinatal prevention.

What will it take to address this crisis? First, we must acknowledge that HBV–HIV coinfection represents a major global public health threat. Because each virus affects the other's natural history and response to therapy, HIV–HBV coinfection requires dedicated research. A willingness to rapidly implement new scientific evidence is critical. Preventing transmission of both viruses to the next generation should be a priority for health policymakers.

Ideally, all pregnant women should receive early prenatal care with voluntary HIV and HBV testing to permit timely interventions aimed at preventing perinatal transmission.5 Use of antiretroviral agents with dual antiviral activity is a promising preventive approach — one limited, however, by a paucity of data on important agents (e.g., tenofovir) regarding safety during pregnancy, for both the fetus and the mother. As regimens including tenofovir become first-line therapy for many HIV-infected people (and are used as preexposure prophylaxis for the uninfected), determining the safety of these medications during pregnancy becomes a critical research need. Evaluating the HBV viral load in HIV-infected pregnant women should be an essential step of prenatal evaluation, so that the mother's health can be managed appropriately.

Continued improvements in the coverage and timeliness of HBV vaccination and the education of clinicians about its importance should be priorities everywhere. Making such improvements will require substantial advocacy and political and financial commitment. Now is the time to provide the best care we can for coinfected people and to protect a future generation of children from the largely hidden epidemic of HBV-related liver disease, which is being further fueled by the HIV epidemic.

The opinions expressed in this article are those of the authors and do not necessarily reflect the position of the Centers for Disease Control and Prevention.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Source Information

From the Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion (A.P.K., D.J.J.), the Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (D.J.H.), and the Division of Global HIV/AIDS, Center for Global Health (M.B.), Centers for Disease Control and Prevention, Atlanta; and the CDC Global AIDS Program, Beijing, China (M.B.).

Source

U.S. may speed approval of "breakthrough" drugs

Pills are seen on the production line of a pharmaceutical company in a file photo.

Credit: Reuters/Jacky Naegelen

By Anna Yukhananov

WASHINGTON | Wed May 9, 2012 2:26pm EDT

WASHINGTON (Reuters) - Experimental drugs that show a big effect early in development for treating serious or life-threatening diseases would get a faster and cheaper path to U.S. approval, under a proposal likely to become law this year.

U.S. drug regulators would be able to label such treatments "breakthrough" therapies, and work with companies to speed up clinical trials, for example by testing the drugs for a shorter time or enrolling fewer patients.

The U.S. Food and Drug Administration has said it supports the proposal, which is included in both versions of an FDA "must-pass" funding bill currently working its way through Congress and set to be passed by the end of the summer.

The plan fits with President Barack Obama's aim to foster innovation as a means of spurring job creation, and may pacify some critics who say the FDA lags European countries in approving new medicines or medical devices.

Dr. Janet Woodcock, head of the FDA's drugs center, has said the FDA needs more flexibility to bypass "business as usual" when it sees unexpected effects, or when a new medicine can greatly help patients.

"What happens when you have a breakthrough drug that shows an effect that's never been seen before?" she told reporters in March, discussing the proposal.

"If we'd done business as usual during the AIDS epidemic, we would have never controlled that epidemic," Woodcock said.

During a spike in new cases of AIDS in the early 1990s, the FDA created an "accelerated approval" process to get new AIDS drugs to the market more quickly by allowing companies to show indirect measures of how the drug helped people.

Jeff Allen, executive director of Friends of Cancer Research, said the time was right for another avenue to speed innovative treatments to patients.

Allen said new understanding of human biology and of diseases meant companies could create more effective drugs, but with fewer side effects, because they would be more targeted to specific patients or disease types.

He said a good example was Roche Holding AG's skin cancer drug Zelboraf, approved last year; people taking the pill were 63 percent less likely to die from melanoma than people on standard chemotherapy.

There was also Pfizer Inc's targeted lung cancer drug Xalkori, which could shrink or eliminate tumors in 10 to 12 months for people with a specific genetic mutation.

"The most promising drugs show an effect early," Allen said. "(But) there's a mentality among drug developers or FDA reviewers that you have to go through this multi-step approach" to get a drug to market.

"We're hoping to encourage getting away from that," he said.

Allen said the FDA would retain its power to require companies to do post-approval studies, or withdraw drugs from the market if initial evidence of benefit was not shown in follow-up trials.

(Reporting by Anna Yukhananov)

Source

Four Bad Actors Cause Most Infection-Related Cancer

From Medscape Medical News > Oncology

Nick Mulcahy

May 8, 2012 — Three types of viruses and 1 bacterium cause the vast majority of the new cases of cancer worldwide that are attributable to infections, according to a new study of global data.

The study found that in 2008 there were 12.7 million new cases of cancer worldwide, including 2 million that were related to infections. Helicobacter pylori, hepatitis B and C viruses (HBV and HCV), and human papillomaviruses (HPV) were responsible for 1.9 million of those infection-related cases.

Most of these new cases were gastric, liver, and cervix uteri cancers, according to study authors, who are from the International Agency for Research on Cancer in Lyon, France.

Their study is published online in the May 8 issue of LancetOncology.

The study authors, led by Catherine de Martel, MD, PhD, point out that the situation is largely remediable.

"Application of existing public-health methods for infection prevention, such as vaccination, safer injection practice, [and] antimicrobial treatments, could have a substantial effect on future burden of cancer worldwide," they write, referring to prevention measures for HBV and strains of HPV, HCV, and H pylori, respectively.

An expert not involved with the study emphasized the value of vaccination.

"Since effective and relatively low-cost vaccines for HPV and HBV are available, increasing vaccine coverage should be a priority for health systems in high-burden countries," writes Goodarz Danaei, MD, ScD, in an accompanying comment. He is from the Harvard School of Public Health in Boston, Massachusetts.

However, neither the study authors nor Dr. Danaei say where the funds will come from for this important prevention work.

The study indicates that less developed countries were 3 times as likely as more developed countries to have infection-related cancers.

The authors report that, in 2008, 1 in 6 (16%) new cases of cancer were related to infection. "This fraction was higher in less-developed countries (22.9%) than in more-developed countries (7.4%), and varied from 3.3% in Australia and New Zealand to 32.7% in sub-Saharan Africa," they note.

Dr. Danaei put the problem of infection-related cancers into a larger epidemiologic context.

"The estimated attributable fraction for all infections combined was 16.1% — by comparison, in 2004 WHO estimated the attributable fraction for the combined effect of 9 lifestyle and environmental risk factors as 35%," he writes, referring to smoking, drinking alcohol, excess weight, and other factors.

The authors report that cervical cancer accounted for about 50% of the infection-related burden of cancer in women, and liver and gastric cancers accounted for about 80% of the burden in men.

Cancers and Infections

de Martel and her colleagues did a systemic analysis to estimate the proportion of cancers that could be tied to infection globally and in 8 regions by calculating the population-attributable fractions. This refers to the proportion of new cancer cases in a population that could have been prevented by an intervention on a specific exposure.

They used data from a number of sources, including GLOBOCAN statistics on incidence estimates for 27 cancers in 184 countries.

Cancers and Their Associated Infectious Agents Covered in the Study

Cancer	Associated Infectious Agents
Stomach	H pylori
Liver	HBV, HCV, Opisthorchis viverrini, Clonorchis sinensis
Cervix uteri	HPV with or without HIV
Anogenital (penile, vulva, vagina, anus)	HPV with or without HIV
Nasopharynx	Epstein-Barr virus (EBV)
Oropharynx	HPV with or without tobacco or alcohol use
Kaposi's sarcoma	Human herpes virus type 8 with or without HIV
Non-Hodgkin's lymphoma	H pylori, EBV with or without HIV, HCV, human T-cell lymphotropic virus type 1
Hodgkin's lymphoma	EBV with or without HIV
Bladder	Schistosoma haematobium

HIV was not listed as primary infectious agent because it causes cancer through immunosuppression, and is thus is considered a cofactor.

The study was supported by funding from the Fondation Innovations en Infectiologie and the Bill & Melinda Gates Foundation.

Lancet Oncol. Published online May 8, 2012. Abstract, Comment

Source

HIV, Other STD, and Pregnancy Prevention Education in Public Secondary Schools

From Morbidity & Mortality Weekly Report

45 States, 2008-2010

Laura Kann, PhD; Nancy Brener, PhD; Timothy McManus, MS; Howell Wechsler, EdD

Posted: 05/09/2012; Morbidity & Mortality Weekly Report. 2012;61(13):222-228. © 2012 Centers for Disease Control and Prevention (CDC)

Abstract and Introduction

Introduction

In the United States, 46% of high school students have had sexual intercourse and potentially are at risk for human immunodeficiency virus (HIV) infection, other sexually transmitted diseases (STDs), and pregnancy.^[1] The National HIV/AIDS Strategy for the United States recommends educating young persons about HIV before they begin engaging in behaviors that place them at risk for HIV infection.^[2] The Community Preventive Services Task Force (CPSTF) also recommends risk reduction interventions to prevent HIV, other STDs, and pregnancy among adolescents.^[3] To estimate changes in the percentage of secondary schools that teach specific HIV, other STD, and pregnancy risk reduction topics, a key intervention consistent with those supported by the National HIV/AIDS Strategy and CPSTF,^[2,3] CDC analyzed 2008 and 2010 School Health Profiles data for public secondary schools in 45 states. This report summarizes the results of those analyses, which indicated that in 2010, compared with 2008, the percentage of secondary schools teaching 11 topics on HIV, other STD, and pregnancy prevention in a required course in grades 6, 7, or 8 was significantly lower in 11 states and significantly higher in none; the percentage of secondary schools teaching eight topics in a required course in grades 9, 10, 11, or 12 was significantly lower in one state and significantly higher in two states; and the percentage of secondary schools teaching three condom-related topics in a required course in grades 9, 10, 11, or 12 was significantly lower in eight states and significantly higher in three states. Secondary schools can increase efforts to teach all age-appropriate HIV, other STD, and pregnancy prevention topics to help reduce risk behaviors among students.

School Health Profiles surveys have been conducted biennially since 1996 to assess school health practices in the United States.* States, territories, large urban school districts, and tribal governments participate in the surveys, either selecting systematic, equal-probability samples of their secondary schools (middle schools, junior high schools, and high schools with one or more of grades 6–12),^† or selecting all public secondary schools within their jurisdiction.^§ Self-administered questionnaires are sent to the principal and lead health education teacher at each selected school and returned to the agency conducting the survey. Lead health education teachers are asked questions regarding the content of required instruction related to HIV, other STD, and pregnancy prevention.^¶ Data are included in this report only if the state provided appropriate documentation of methods and had a school response rate ≥70% for both the 2008 and 2010 surveys. Across states included in this report, school response rates ranged from 70% to 93% (median: 73%) in 2008 and from 70% to 86% (median: 73%) in 2010. The number of lead health education teachers who participated, by state, ranged from 71 to 472 (median: 245) in 2008 and from 65 to 677 (median: 249) in 2010. Participation in School Health Profiles is confidential and voluntary. Follow-up telephone calls, e-mails, and written reminders are used to encourage participation. For states that use a sample-based method, results are weighted to reflect the likelihood of schools being selected and to adjust for differing patterns of nonresponse. For states that conduct a census, results are weighted to adjust for differing patterns of nonresponse.

This report includes data from 45 states that provided weighted School Health Profiles data in 2008 and 2010.** For each of these states, three composite measures were created to determine the percentage of schools that taught 1) all 11 topics listed in the questionnaire in a required course in grades 6, 7, or 8; 2) all eight topics listed in the questionnaire in a required course in grades 9, 10, 11, or 12; and 3) all three condom-related topics listed in the questionnaire in a required course in grades 9, 10, 11, or 12. These topics reflect the knowledge and skills that are the focus of interventions shown to be effective in reducing risk that CPSTF and others use as a basis for their recommendations about interventions for adolescents.^[3–6] For each state, the percentages of schools that taught individual topics and the composite measurements are reported. Significant (p<0.05) differences between results from 2008 and 2010 were determined by t-test. Statistical software was used to account for the sample design and unequal weights.

Compared with 2008, the percentage of schools in 2010 in which all 11 topics were taught in a required course in grades 6–8 was significantly lower in 11 states and significantly higher in no state (Table 1). The percentage of schools in which all eight topics were taught in a required course in grades 9–12 was significantly lower in one state and significantly higher in two states (Table 2). Additionally, the percentage of schools in which all three condom-related topics were taught in a required course in grades 9–12 was significantly lower in eight states and significantly higher in three states (Table 3). Among the 45 states in 2010, the percentage of schools that taught all 11 topics in grades 6, 7, or 8 ranged from 12.6% (Arizona) to 66.3% (New York) (median: 43.3%), the percentage of schools that taught all eight topics in grades 9–12 ranged from 45.3% (Alaska) to 96.4% (New Jersey) (median: 80.3%), and the percentage of schools that taught all three condom-related topics in grades 9–12 ranged from 11.3% (Utah) to 93.1% (Delaware) (median: 58.1%).

For five of the 11 topics (Table 1), the percentage of schools teaching the topic in a required course in grades 6–8 increased significantly in no state, and for the remaining six topics, the percentage increased significantly in one state. Conversely, the percentage of schools teaching any one topic decreased significantly in one to 10 states. The percentage of schools teaching how HIV and other STDs are diagnosed and treated decreased significantly in 10 states, as did the percentage teaching health consequences of HIV, other STDs, and pregnancy. The percentage of schools teaching how to prevent HIV, other STDs, and pregnancy decreased significantly in nine states.

For five of the eight topics (Table 2), the percentage of schools teaching the topic in a required course in grades 9–12 increased significantly in no state; for two topics, the percentage increased significantly in one state; and for the remaining two topics, the percentage increased significantly in two states. Conversely, the percentage of schools teaching any one topic decreased significantly in one to four states. The relationship among HIV, other STDs, and pregnancy was the one topic that showed significant decreases in the percentage of schools teaching it in four states. No state showed a significant increase, and one to seven states showed a significant decrease in the percentage of schools teaching any of the three condom-related topics in any of grades 9–12 (Table 3). The percentage of schools teaching how to obtain condoms decreased significantly in seven states.

* Additional information and questionnaires are available at http://www.cdc.gov/healthyyouth/profiles.
^† Alabama, Alaska, Arizona, Arkansas, California, Connecticut, Florida, Indiana, Iowa, Kansas, Kentucky, Maryland, Michigan, Minnesota, Mississippi, Missouri, Nebraska, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, South Dakota, Tennessee, Texas, Virginia, Washington, West Virginia, and Wisconsin.
^§ Delaware, Hawaii, Idaho, Maine, Massachusetts, Montana, Nevada, New Hampshire, Rhode Island, South Carolina, Utah, Vermont, and Wyoming.
^¶ In 2008, lead health education teachers were asked, "During this school year, did teachers in this school teach each of the following HIV, STD, or pregnancy prevention topics in a required course for students in any of grades 6, 7, or 8?" for a list of 11 topics (Table 1) (e.g., how HIV and other STDs are diagnosed and treated; how to prevent HIV, other STDs, and pregnancy; and the benefits of being sexually abstinent). Respondents were instructed to mark "yes" or "no" for each topic or "not applicable" if their school did not include grades 6, 7, or 8. Teachers also were asked the same question for grades 9–12 for a list of eight topics (Table 2) that repeated some of the 11 topics and added others (e.g., the relationship between alcohol and other drug use and risk for HIV, other STDs, and pregnancy), and three condom-related topics (Table 3). In 2010, lead health education teachers were asked, "During this school year, did teachers in your school teach each of the following HIV, STD, or pregnancy prevention topics in a required course for students in each of the grade spans below?" The topics, grade spans, and possible responses were the same as those specified in 2008.
** Alabama, Alaska, Arizona, Arkansas, California, Connecticut, Delaware, Florida, Hawaii, Idaho, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Vermont, Virginia, Washington, West Virginia, Wisconsin, and Wyoming.

Editorial Note

CPSTF recommends group-based comprehensive risk reduction interventions delivered to adolescents, in schools or communities, to promote behaviors that prevent or reduce the risk for HIV, other STDs, and pregnancy. This recommendation is based on evidence of effectiveness in reducing engagement in any sexual activity, frequency of sexual activity, number of partners, and frequency of unprotected sexual activity, and in increasing the self-reported use of protection against STDs and pregnancy.^[3]

Although a median of 90% of all public secondary schools across the 45 states in this report taught HIV prevention in a required course during 2010,^[7] the findings indicate that little progress was made in increasing the number of specific topics covered as part of HIV, other STD, and pregnancy prevention education during 2008–2010. The percentage of secondary schools that taught all HIV, other STD, and pregnancy prevention topics in a required course also varied widely across states. Further research is needed to understand determinants of the number of specific HIV, other STD, and pregnancy prevention topics taught in secondary schools.

HIV, other STD, and pregnancy prevention education in grades 6–8 is particularly important because most students in those grades are not yet sexually active.^[1,2] HIV, other STD, and pregnancy prevention education that is taught before most young persons engage in risk behaviors, and that includes information on the benefits of abstinence and delaying or limiting sexual activity, can prevent behaviors that might lead to HIV infection, other STDs, and pregnancy.^[2]

Because many students become sexually active during high school,^[1] HIV, other STD, and pregnancy prevention education in these grades also is critically important.^[2] HIV, other STD, and pregnancy prevention education that includes information on condom efficacy, the importance of using condoms consistently and correctly, and how to obtain condoms taught to those who might decide to be or are sexually active also can prevent behaviors that might lead to HIV infection, other STDs, and pregnancy.^[4–6]

HIV prevention education also can address misconceptions about how HIV is transmitted.^[2] A 2011 public opinion poll indicated that 20% of persons aged 18–29 years believe incorrectly that a person can become infected with HIV by sharing a drinking glass, or are unsure whether the statement is true or false.^[8]

The findings in this report are subject to at least three limitations. First, these data apply only to public secondary schools and, therefore, do not reflect practices at private schools or elementary schools. Second, these data were self-reported by lead health education teachers or their designees, and the accuracy of their description of the HIV, other STD, and pregnancy prevention topics taught in required courses was not verified by other sources. Finally, the effect of changes between 2008 and 2010 in the percentage of secondary schools in a state that taught HIV, other STD, and pregnancy prevention topics varies by the number of students attending public schools in the state during those years. States with fewer students would have less of a nationwide impact.

HIV prevention education supports strategies required to achieve the National HIV/AIDS Strategy goal of lowering the annual number of new HIV infections by 25% by 2015.^[2] Families, the media, and community organizations, including faith-based organizations, can play a role in providing HIV, other STD, and pregnancy prevention education. However, schools are in a unique position to provide HIV, other STD, and pregnancy prevention education to young persons because almost all school-aged youths in the United States attend school.^[9] School policies can provide critical support for implementation of comprehensive HIV, other STD, and pregnancy prevention education in secondary schools.^[10]

References

1. CDC. Youth risk behavior surveillance—United States, 2009. MMWR 2010;59(No. SS-5).
2. Office of National AIDS Policy. National HIV/AIDS Strategy for the United States. Washington, DC: The White House; 2010. Available at http://www.whitehouse.gov/sites/default/files/uploads/NHAS.pdf. Accessed December 9, 2011.
3. CDC. Guide to community preventive services. Prevention of HIV/AIDS, other STIs and pregnancy: interventions for adolescents. Atlanta, GA: US Department of Health and Human Services, CDC; 2010. Available at http://www.thecommunityguide.org/hiv/riskreduction.html. Accessed March 28, 2012.
4. CDC. Health Education Curriculum Analysis Tool (HECAT). Atlanta, GA: US Department of Health and Human Services, CDC; 2009. Available at http://www.cdc.gov/healthyyouth/hecat. Accessed December 13, 2011.
5. Kirby D, Laris BA, Rolleri L. Sex and HIV education programs for youth: their impact and important characteristics. Scotts Valley, CA: ETR Associates; 2006. Available at http://www.etr.org/recapp/documents/programs/sexhivedprogs.pdf. Accessed December 13, 2011.
6. Kirby D, Coyle K, Alton F, Rolleri L, Robin L. Reducing adolescent sexual risk: a theoretical guide for developing and adapting curriculum-based programs. Scotts Valley, CA: ETR Associates; 2011. Available at http://pub.etr.org/upfiles/reducing_adolescent_sexual_risk.pdf. Accessed December 13, 2011.
7. Brener ND, Demissie Z, Foti K, et al. School Health Profiles 2010: characteristics of health programs among secondary schools in selected U.S. sites. Atlanta, GA: US Department of Health and Human Services, CDC; 2011. Available at http://www.cdc.gov/healthyyouth/profiles/2010/profiles_report.pdf. Accessed December 9, 2011.
8. Kaiser Family Foundation. HIV/AIDS at 30: a public opinion perspective. Menlo Park, CA: Kaiser Family Foundation; 2011. Available at http://www.kff.org/kaiserpolls/upload/8186.pdf. Accessed December 9, 2011.
9. Snyder TD, Dillow SA. Table 7. Percentage of the population 3 to 34 years old enrolled in school, by age group: selected years, 1940 through 2009. In: Digest of education statistics 2010. Washington, DC: US Department of Education, National Center for Education Statistics, Institute of Education Sciences; 2011. Available at http://nces.ed.gov/programs/digest/d10/tables/dt10_007.asp?referrer=report. Accessed December 9, 2011.
10. National Association of State Boards of Education. Someone at school has AIDS: a complete guide to education policies concerning HIV infection. Alexandria, VA: National Association of State Boards of Education; 2001.

Sidebar

What is Already Known on this Topic?

Schools provide a unique setting for reaching most youths nationwide with information they can use to prevent human immunodeficiency virus (HIV) infection, other sexually transmitted diseases, and pregnancy.

What is Added by this Report?

In 2010, compared with 2008, the percentage of public secondary schools in 45 states teaching specific HIV, other sexually transmitted disease (STD), and pregnancy prevention topics in required courses generally did not increase, and percentages teaching all topics varied widely across these states.

What are the Implications for Public Health Practice?

To help reduce HIV-, other STD-, and pregnancy-related risk behaviors among students, secondary schools can increase efforts to teach all age-appropriate HIV, other STD, and pregnancy prevention topics.

Source

A Potential Game Changer in the Fight Against HIV/AIDS

Sean Cahill Director of Health Policy Research, The Fenway Institute

Posted: 05/09/2012 4:11 pm

Imagine what it would mean to have a medication that would make it harder for HIV to enter a person's body. Tomorrow, May 10, may lead to just such a turning point in the fight against HIV/AIDS. On this date the U.S. Food and Drug Administration will review a supplemental new drug application for emtricitabine/tenofovir disoproxil fumarate (FTC-TDF) to reduce the risk of acquiring HIV in men and women by pre-exposure prophylaxis (PrEP), offered as part of a comprehensive HIV-prevention package including risk reduction counseling.

Before Westerners go to some African countries, they take malarial drugs as a preventive strategy. PrEP works much the same way: HIV treatment medications are taken to make it harder for HIV to enter the body.

PrEP has shown efficacy with men who have sex with men (MSM) and heterosexual women and men. Biomedical prevention interventions such as PrEP have great potential, especially if coupled with traditional prevention approaches such as condom use, expanded testing, and linkage to treatment and care. Modeling demonstrates the most effective deployment of PrEP will be in combination with scaled-up HIV treatment of people who are known to be HIV-positive, as this was shown to reduce infections.

The FDA's Antiviral Drugs Advisory Committee will consider and vote on whether to recommend approving FTC-TDF for PrEP with MSM, serodiscordant couples, and others at risk of HIV through sexual activity. The FDA is expected to issue a final decision in mid-June.

We are hopeful that the full dossier of submitted PrEP research, based on multiple clinical trials with a number of different populations vulnerable to HIV, can lead to a responsible regulatory and marketing plan that allows for safe use in the populations that may benefit most from this innovative development. If the FDA approves the additional indication of the use of tenofovir-emtricitabine for PrEP, health programs and individuals will have improved choices to address one of the administration's domestic health priorities, and save lives.

Some have raised concerns about PrEP related to potential side effects, risk compensation (the idea that people will stop using condoms if PrEP becomes available), and drug resistance. However, reviews of five major clinical trials involving about 6,000 participants by the Forum for Collaborative HIV Research found no greater risk of side effects, no risk compensation, and no clinically significant development of drug resistance in participants.

Recent press coverage has emphasized the cost of FTC-TDF. Last year the Centers for Disease Control and Prevention estimated the medications would cost $8,030 per person per year. While the cost of PrEP in the U.S. would be substantial, private insurers and state Medicaid departments are open to providing coverage. Low-cost generic medications could enable access in low-income countries. The prioritization of highly vulnerable populations could increase the cost-effectiveness of PrEP. Providing PrEP is also much less expensive than treating someone for HIV over the course of a lifetime. Recent modeling of PrEP implementation coupled with scaled-up treatment (focusing on MSM in San Francisco, the general adult population in Botswana, and serodiscordant couples in South Africa) predicts that PrEP could significantly reduce HIV incidence and prevalence, saving health care costs and lost economic productivity.

We therefore urge the FDA to approve the application of Gilead Sciences Inc.'s supplemental new drug application for emtricitabine/tenofovir disoproxil fumarate for reducing the risk of acquiring HIV by means of pre-exposure prophylaxis (PrEP) offered as part of a comprehensive prevention package including risk reduction counseling.

We believe that if the FDA looks closely at the science, it will see the merit of allowing PrEP to be added to our toolkit to prevent HIV infections. We must deploy new tools to prevent new infections, which are affecting 50,000 Americans each year and more than 2 million people worldwide, most in Africa. PrEP combined with sustained behavioral interventions and medical care to maintain adherence could help us finally begin to turn the tide with this virus.

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Study: 16% of cancers worldwide caused by preventable infections such as HPV

(Credit: istockphoto)

May 9, 2012 10:11 AM

By Ryan Jaslow

(CBS News) Treatable infections lead to two million cancer cases each year worldwide, a new study suggests. Out of 7.5 million people who died of cancer across the world in 2008, about 1.5 million were due to preventable and treatable infections such as human papillomavirus (HPV) and hepatitis C (HCV).

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"Infections with certain viruses, bacteria, and parasites are one of the biggest and preventable causes of cancer worldwide," study authors Dr. Catherine de Martel and Dr. Martyn Plummer, scientists from the International Agency for Research on Cancer, France, said in a written statement. "Application of existing public-health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on future burden of cancer worldwide."

For the study, researchers calculated the proportion of cancers caused by infections by reviewing statistics on 27 types of cancer from 184 countries. They found 16 percent of all cancers worldwide were infection-related, with rates about three times higher in developing countries. For example, 3.3 percent of cancers in Australia and New Zealand were infection related, while 32.7 percent in sub-Saharan Africa were due to infectious agents. The four main infections associated with cancer were HPV, hepatitis B and C, and Helicobacter pylori (which infects the stomach). Those four infections in particular are responsible for an estimated 1.9 million cancer cases each year, including gastric, liver and cervical cancers.

In women, cervical cancer accounted for 50 percent of the infection-related cancers; in men, liver and gastric cancers accounted for more than 80 percent of cancers caused by infections. The study is published in the May 9 issue of The Lancet Oncology.

"One thing that infection-associated cancers have in common is that a chronic infection is required," Plummer told Fox News. "It takes decades for an infection to progress to cancer."

In an accompanying editorial in the same journal, Dr. Goodarz Danaei, an assistant professor of global health at Harvard School of Public Medicine in Boston wrote, "Since effective and relatively low-cost vaccines for HPV and HBV are available, increasing coverage should be a priority for health systems in high-burden countries."

The HPV vaccine is recommended for all 11 or 12 year old girls, and women who did not receive it during that time can get it until they are 26. In February of this year, the CDC also recommended the shot for all males between the ages of 11 and 21, HealthPop reported.

Dr. Otis Brawley, chief medical officer of the American Cancer Society, who was not involved with the research, told CNN,"The more people you vaccinate, male and female, the more likely you are to get a population that doesn't have the disease."

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Achillion Advances Second Generation Pan-Genotypic NS5A Inhibitor, ACH-3102, Into Clinical Development

May 9, 2012

Structurally Distinct NS5A Inhibitor Displays Potent Preclinical Activity Against Commonly Observed Resistant Variants

NEW HAVEN, Conn., May 9, 2012 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced that it has begun dosing ACH-3102 in a Phase 1 clinical trial. ACH-3102 is Achillion's second generation pan-genotypic NS5A inhibitor being investigated for the treatment of chronic hepatitis C virus (HCV) infection.

ACH-3102 is a structurally distinct small molecule compound that has demonstrated potent inhibition of the NS5A protein across all genotypes of HCV in preclinical studies. Furthermore, the unique chemical structure of ACH-3102 has resulted in enhanced potency in vitro against resistant mutants that have emerged during clinical studies with first generation NS5A inhibitors.

The randomized, double-blind, placebo-controlled Phase 1 trial will enroll approximately 96 healthy volunteers in the U.S. to investigate the safety, tolerability and pharmacokinetic profile of ACH-3102. The trial will assess dosing in single and multiple ascending oral doses for up to 28 days.

"We believe that NS5A inhibitors, in combination with protease inhibitors, will play an integral role in achieving the goal of an all-oral interferon-free treatment regimen for all segments of the HCV infected patient population," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "With our continued focus on compounds with potentially best-in-class characteristics, including safety and efficacy, broad genotypic effect with once-daily dosing and enhanced resistance profiles, we hope to move ACH-3102 through Phase 1 for HCV-infected subjects and toward combination studies with ACH-1625, our Phase 2 protease inhibitor, during the third quarter of 2012."

About NS5A Inhibitors and ACH-3102

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. ACH-3102, Achillion's second generation NS5A inhibitor, has demonstrated potent activity against all HCV genotypes in vitro and in preclinical studies achieved additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin. In preclinical studies, ACH-3102 demonstrated excellent potency, in the pico-molar range, against wild type HCV RNA replication, as well as potency against resistant mutants that have been identified in clinical studies.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including more than 5 million people in the United States, more than twice as widespread as HIV. Three-fourths of the global HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000.

Forward-Looking Statements

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the potency, safety, tolerability, effectiveness and other characteristics of Achillion's ACH-1625 and ACH-3102; Achillion's expectations regarding timing for the commencement, completion and reporting of results of clinical trials of ACH-1625 and ACH-3102; and Achillion's ability to advance a potentially best-in-class all-oral, interferon-free combination of ACH-1625 and ACH-3102. Among the factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage preclinical studies and clinical trials of ACH-1625 and ACH-3102; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any obligation to update any forward-looking statement, except as required by applicable law.

Source Achillion Pharmaceuticals, Inc.

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