U.S. health officials urge use of HIV pill for at-risk individuals

CHICAGO Wed May 14, 2014 7:11pm EDT

(Reuters) - U.S. health officials on Wednesday issued new recommendations urging healthcare workers to consider offering an HIV prevention pill to healthy individuals who are at substantial risk for HIV infection.

The guidelines, issued by the U.S. Centers for Disease Control and Prevention and the U.S. Public Health Service, involve the use of pre-exposure prophylaxis or PrEP, a strategy in which at-risk individuals take a daily dose of an antiretroviral drug to reduce their risk of HIV infection.

The strategy builds on a landmark 2010 study that found Gilead Sciences Inc's Truvada - a pill already widely used to treat the human immunodeficiency virus - was more than 90 percent effective at preventing HIV infections among test subjects who took the drug as prescribed.

According to the new guidelines, healthcare providers should consider PrEP for anyone who meets specific risk criteria, such as being in a relationship with an HIV-infected partner or having sex without condoms with partners known to be at risk for HIV, such as injecting drug users.

The guidelines offer the first comprehensive guidance from the CDC, replacing interim guidance that emerged after studies showed PrEP to be effective in different patient populations.

The CDC now estimates as many as 275,000 uninfected gay men and 140,000 heterosexual couples, in which one partner is HIV-infected, could benefit from PrEP.

Some 1.2 million people in the United States live with HIV, and new infections are estimated at 50,000 each year.

(Reporting by Julie Steenhuysen; Editing by Tom Brown)

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Experts address ethical issues raised by FDA's approval of Truvada for HIV prevention

Published on August 1, 2013 at 2:36 AM

The Food and Drug Administration's approval last year of the drug Truvada for prevention of HIV infection was a milestone in the fight against HIV/AIDS, but experts are cautioning that it is only the beginning of new ethical concerns for health care professionals, policy makers, researchers and those taking Truvada to prevent HIV infection.

"For the first time, we will have a large number of individuals who are not infected with HIV taking medication for HIV, which introduces ethical concerns of well-being and justice," says Jeremy Sugarman, Deputy Director for Medicine at the Johns Hopkins Berman Institute of Bioethics. He and Kenneth Mayer, the director of HIV prevention research at Beth Israel Deaconess Medical Center, advocate for ethical issues to be considered along with medical data in the Journal of Acquired Immune Deficiency Syndromes.

Sugarman and Mayer argue it is ethically critical to ensure that use of an antiretroviral drug like Truvada for "pre-exposure prophylaxis"(PrEP) does not have the ironic consequence of making individuals and communities less safe and healthy. Inconsistent, rather than daily, use of PrEP could result in HIV transmission and the evolution of drug-resistant strain of HIV, the authors warn. Likewise, misunderstanding of PrEP's prevention capacity could lead to the spread of other sexually transmitted infections.

"Communication and careful monitoring by health care professionals is essential for PrEP to be successful," says Sugarman. "Reinforcing the importance of daily dosing, incorporating safer sex counseling and frequent HIV testing will help meet the moral imperative that HIV be prevented and not exacerbated by PrEP," he says. He and Mayer recommend training programs for health care professionals that include explicit consideration of PrEP's ethical issues and their management.

Additionally, Sugarman and Mayer highlight what they say are 'critical, unanswered questions' of access and allocation. When limited antiretroviral drugs are available, should prevention be prioritized over treatment for those already infected with HIV, or vice-versa? Is a clinic environment the best setting to provide necessary counseling as part of PrEP? These questions, as well as how much PrEP should cost and who should pay for it, need to be answered as PrEP continues to be used and evaluated, the authors say.

"The fundamental moral claim for using PrEP, or any other HIV prevention strategy, is decreasing the burden of new HIV infections," Sugarman says. "For PrEP's full promise and medicine's moral obligations to be fulfilled, these complex ethical issues must be monitored along with the performance of PrEP."

Source: Johns Hopkins Medicine

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AHF Advocacy Against Gilead’s Truvada as HIV Prevention Yields Stronger FDA Drug Warning Label

October 11, 2012 09:52 PM Eastern Daylight Time

New warning label is welcomed by AIDS advocates who were astounded by recommendation by an FDA Advisory Panel earlier this year to allow Gilead to market use of its blockbuster AIDS treatment as a form of HIV prevention in uninfected individuals without any HIV testing requirement whatsoever

AHF and other advocates strenuously opposed use of the AIDS treatment as a form of HIV prevention pill, concerned about efficacy, medication adherence issues among uninfected high-risk populations; ‘Black box warning’ label on Truvada for prevention now recommends HIV testing every three months

WASHINGTON--(BUSINESS WIRE)--AIDS Healthcare Foundation (AHF), the nation’s largest HIV/AIDS nonprofit medical provider, welcomed the news today the boxed warning label (also called the ‘black box warning’) on Gilead Sciences’ blockbuster AIDS treatment Truvada for use as a form of an HIV prevention pill appears much stronger than proposed versions of the label earlier this year. The new warning label is being welcomed by AIDS advocates from AHF and other organizations who were astounded by a recommendation by a Food and Drug Administration (FDA) Advisory Panel to allow Gilead to market use of Truvada as a form of HIV prevention in uninfected individuals, particularly when the panel—comprised of 23 physicians, scientists and members of the general public—also recommended that the FDA allow Gilead to market the drug for such use without any requirement for HIV testing whatsoever.

“From the beginning, AHF and many other advocates strenuously opposed use of this well-established AIDS treatment as a form of an HIV prevention pill, concerned about both the efficacy of the treatment as well as medication adherence issues among uninfected high-risk populations,” said Michael Weinstein, President of AIDS Healthcare Foundation. “It is difficult for many of those who are already infected with HIV to properly comply with daily drug regimens. Expecting uninfected people to remember to take a drug every day for a disease that they don’t have is an even more daunting challenge. At least now the ‘black box warning’ label on Truvada for prevention recommends HIV testing every three months. It is good to see that the FDA and Gilead have finally come to this realization. I believe it was in part because of our advocacy over the past year opposing the drug for this use that this warning label is now stronger.”

The FDA Advisory Panel took place in May in Silver Spring, MD, at FDA headquarters. Nearly 30 advocates from AHF and other groups spoke against use of the drug for HIV prevention to the panel, which nevertheless indicated it would give preliminary approval to Gilead for use as HIV prevention.

Later in the summer, at the ‘Controlling the HIV Epidemic with ARVs’Summit, held in London June 11-12, a Gilead official publicly disclosed in a plenary session in which he was participating that use of its blockbuster AIDS treatment Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP) to prevent possible HIV infection would have labeling indicating that a negative HIV test will be required before a prescription.

Following is what the Truvada packaging and printed drug warning inserts now state regarding use of the drug for pre-exposure prophylaxis (PrEP) for HIV prevention:

For PrEP:

"When prescribing TRUVADA for pre-exposure prophylaxis, healthcare providers must:

• prescribe TRUVADA as part of a comprehensive prevention strategy because TRUVADA is not always effective in preventing the acquisition of HIV-1 infection [See Warnings and Precautions (5.9)];
• counsel all uninfected individuals to strictly adhere to the recommended TRUVADA dosing schedule because the effectiveness of TRUVADA in reducing the risk of acquiring HIV-1 was strongly correlated with adherence as demonstrated by measurable drug levels in clinical trials [See Warnings and Precautions (5.9)];
• confirm a negative HIV-1 test immediately prior to initiating TRUVADA for a PrEP indication. If clinical symptoms consistent with acute viral infection are present and recent (<1 month) exposures are suspected, delay starting PrEP for at least one month and reconfirm HIV-1 status or use a test approved by the FDA as an aid in the diagnosis of HIV-1 infection, including acute or primary HIV-1 infection. [See Warnings and Precautions (5.9)]; and
• screen for HIV-1 infection at least once every 3 months while taking TRUVADA for PrEP."

About AIDS Healthcare Foundation

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 176,000 individuals in 27 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. To learn more about AHF, please visit our website: www.aidshealth.org, find us on Facebook: www.facebook.com/aidshealth and follow us on Twitter: @aidshealthcare.

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Study Underscores Truvada’s Potency in Preventing the Transmission of HIV

Findings on Alternate Doses Illustrate Robust Power of FDA-Approved Drug

By Anne Holden on September 12, 2012

New research from an international team of HIV/AIDS experts has reaffirmed the effectiveness of Truvada — the first and only medication approved by the FDA for HIV prevention.

Led by UCSF-affiliated Gladstone Investigator Robert Grant, MD, MPH, and Peter Anderson, PharmD, at the University of Colorado, the research provides the first estimate of the drug concentration levels needed for Truvada to prevent the spread of HIV/AIDS — expanding our understanding of Truvada’s potency and opening the door to new dosing strategies.

The new study, available online today in Science Translational Medicine, builds on the 2010 “iPrEx” clinical study in which Grant and his colleagues found that Truvada — which had been used for years to treat HIV-positive patients — could also prevent new infections in people likely to come in contact with the virus. But questions about the drug’s real-world effectiveness at preventing HIV transmission remained — particularly concerning the issue of adherence to a regimen of taking a pill every day.

“After the initial iPrEx study, there was concern that the protective effect of Truvada was fragile, and that individuals taking the drug would need to adhere perfectly to daily regimen for it to work,” said Grant, who is also a professor at the University of California, San Francisco (UCSF). “This new study suggests that Truvada can help block the virus even if the person on a daily regimen doesn’t always adhere perfectly.”

Perfect adherence to drug regimens is notoriously difficult for people to accomplish. But finding out whether patients are taking medications as prescribed is also challenging — they tend to over-report their adherence because they think that is what the clinicians want to hear. So the research team had to find a better way to calculate Truvada’s effectiveness while taking into account differing adherence levels.

The team developed a clinical trial in which they gave different amounts of the drug (two, four or seven doses per week) to a cohort of 24 people without HIV. This resulted in different drug concentrations in blood drawn from each participant, thereby mimicking different levels of adherence. They then used a model to compare the drug concentrations in the blood of these participants to the concentrations of original iPrEx study participants in order to determine how well iPrEx participants adhered to the daily regimen, and how well they were protected against HIV at different levels of adherence.

“Surprisingly, we found that the iPrEx participants didn’t have to adhere perfectly to the drug regimen to reap Truvada’s benefits,” said Grant. “Even in those patients who didn't adhere perfectly, their risk of contracting HIV still dropped by more than 90 percent — offering a high level of protection against the virus.”

Traditionally, adherence to preventative drugs such as Truvada has been measured in qualitative terms, such as “adequate” or “perfect.” But this study is the first to establish an objective, quantitative method that estimates drug concentration levels and then correlates those levels with the drug’s effectiveness at preventing transmission. These results could open the door to the exploration of ways to optimize dosing — which would make it less costly, more convenient and more adaptable to people’s habits.

“Our immediate next step, however, is to take the methods we’ve developed and create simple yet powerful tools that can measure drug adherence to help doctors monitor how well Truvada is working in their patients,” said Anderson. “Yet until these and other efficacy studies of alternative dosing strategies have been completed, the only regimen that that should be used in clinical practice is the FDA-approved one Truvada each day.”

“Patients should still take one pill a day to achieve the best results, and we encourage people to explore multiple methods to prevent HIV — such as regular condom use, early treatment of HIV infection in partners, good communication and male circumcision,” Grant said. “We hope that our findings lead to more effective use of prevention tools that finally squash the HIV/AIDS epidemic.”

Senior Research Associate Vanessa MacMahan also participated in this research at Gladstone. Other research participants include UCSF Professor David Glidden, PhD, and San Francisco Department of Public Health Investigator Albert Liu, MD. The research was funded by the US National Institutes of Health with co-funding from the Bill and Melinda Gates Foundation.

Truvada is manufactured by Gilead Sciences, which donated the drug for the studies but was not otherwise involved in the research. Truvada is one tablet that contains two medications (emtricitabine and tenofovir disoproxil fumarate). The medications are available in generic forms at cost in the poorest countries of the world.

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Analysis: Use of pill to prevent HIV may be limited in U.S

September 07, 2012|Deena Beasley | Reuters

LOS ANGELES (Reuters) - The first preventive pill for HIV has been hailed as a landmark in the fight against AIDS in the United States, but experts say only a small percentage of those at risk will benefit from it.

U.S. health regulators last month approved Gilead Sciences Inc's Truvada -- already used globally to treat the human immunodeficiency virus -- for preventing the infection in healthy people at high risk of contracting the virus that causes AIDS.

A number of factors will limit the drug's use for preventing HIV, including the fact that in the United States many people most at risk of infection, as well as their sexual partners, do not have consistent access to healthcare. Even for those with coverage, insurance reimbursement for a $14,000-a-year drug is expected to be tricky.

In addition, therapy with the drug would require otherwise healthy young people to take a pill each day, plus show up for HIV testing every three months.

"There are a number of rather significant implementation challenges," said Dr. Stephen Morin, director of the Center for AIDS Prevention Studies at the University of California at San Francisco. "Part of it has to do with the requirement to take a pill a day, which could be addressed by a more long-term administration of the drug."

Scientists are exploring a variety of tactics for using AIDS drug formulations to prevent HIV infection, including long-acting injections, gels and vaginal rings.

About 50,000 new HIV infections are reported each year in the United States. The number of patients taking Truvada to prevent HIV will likely be "a lot less" than that, said Howard Jaffe, head of the Gilead Foundation and a member of the company's senior management since 1991.

Gilead declined to give its own sales estimate.

"We are not expecting a meaningful increase or uptick in Truvada use from it," Jaffe said, referring to the FDA prevention approval. "We do expect it to enter into the conversation with regard to certain high-risk populations."

He said use of Truvada to prevent HIV infection will likely be most important outside of the United States, as developing countries where AIDS remains an epidemic look for additional ways to curb transmission of the virus.

Gilead has deals, mainly with generic drugmakers in India, to produce low-cost versions of its drugs for use in sub-Saharan Africa and other developing regions.

Dr. Paul Volberding, director of the Center for AIDS Research at the University of California at San Francisco, says Truvada could become a valuable tool for "a small fraction of people" who understand they have a high risk of exposure -- mainly female sex workers whose clients won't use condoms and gay men who decide they are going to engage in riskier sex.

"There is an easy consensus now that somebody that is on treatment and fully suppressed has either zero, or close to it, risk of transmitting the virus," Volberding said.

He and others emphasized that wider testing for HIV -- and treatment of already infected patients -- are the keys to reducing HIV incidence.

Of the 1.2 million Americans estimated to be infected with human immunodeficiency virus, almost 20 percent of them do not know it, according to the U.S. Centers for Disease Control and Prevention .

A recent study by the CDC found that 41 percent of U.S. HIV patients are under continual care of a doctor and just 28 percent had the viral infection under control.

PREVENTION THROUGH PREP

The U.S. Food and Drug Administration in July approved Truvada for adults who do not have the virus but may engage in sexual activity with HIV-infected partners, a concept known as pre-exposure prophylaxis (PrEP). The approval was for use in combination with safer sex practices, such as condoms.

The drug, which combines two anti-HIV drugs in one pill, was already approved for use with other antiretroviral agents to treat patients 12 and older who are infected with the virus. Antiretrovirals are designed to block various steps in replication of the virus.

Critics, including the AIDS Healthcare Foundation, a non-profit provider of HIV/AIDS medical care, argue that Truvada was shown to be only partially effective in preventing HIV transmission, can cause side effects including kidney problems and may cause healthy people to become resistant to it.

No U.S. public money has been allocated for treating uninsured individuals who do not already have AIDS, and some doctors question the degree to which insured patients would be covered.

"I would find it very difficult for there to be a provision to support funding for such a program when we have (HIV-positive) patients on waiting lists," said Murray Penner, deputy executive director at the National Alliance of State and Territorial AIDS Directors, which represents public-health departments.

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FDA Decision Delayed for Truvada in HIV PrEP

From Medscape Medical News

Emma Hitt, PhD

June 11, 2012 — The US Food and Drug Administration (FDA) has delayed its decision on allowing the use of tenofovir disoproxil fumarate/emtricitabine (Truvada, Gilead) as preexposure prophylaxis (PrEP) so that the proposed risk evaluation and mitigation strategy (REMS) can be reviewed.

In early May, the FDA's Antiviral Drugs Advisory Committee strongly backed approval of the first-ever drug for the prevention of sexually acquired HIV-1 infection.

However, concerns by the panel at the time included that people may neglect condom use if they feel they are protected by PrEP. Panelists were also concerned that uninfected people taking PrEP who become infected with HIV may not switch to a 3-drug regimen as recommended.

According to the company, the FDA has postponed the target date to September 14 so it can review Gilead's REMS plan to help ensure that patients will not misuse the drug.

The committee's recommendation for supplemental approval of tenofovir/emtricitabine for PrEP is based on the findings of 3 large randomized controlled clinical trials in men who have sex with men and transgender women (iPrEx) and in heterosexual men and women (Partners PrEP and TDF2).

The drug's efficacy was highest in people who adhered to daily dosing (about 10% of participants), and overall, PrEP resulted in a 44% to nearly an 80% reduction in risk of contracting HIV, depending on the level of adherence and drug availability.

After the PrEP trial results came out, the US Centers for Disease Control and Prevention (CDC) developed interim guidance in January 2011 for physicians electing to provide PrEP for HIV prevention among men who have sex with men.

At this time, the CDC recommends that PrEP be used only men who have sex with men. In addition, to minimize the risk for drug resistance, PrEP should not be started in persons with signs or symptoms of acute viral infection unless HIV-negative status is confirmed by HIV RNA testing or a repeat antibody test is performed after the viral syndrome resolves.

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