FDA Advisory Committee Favors Truvada for PrEP

At a meeting of the Food and Drug Administration (FDA) Antiviral Drugs Advisory Committee on May 10, analysts presented a largely favorable review recommending that Truvada (tenofovir/emtricitabine) be approved for pre-exposure prophylaxis (PrEP).

Although a favorable Advisory Committee recommendation does not guarantee FDA approval, it carries some weight. Nothing in the FDA summary, presented by Peter Miele, suggested serious reservations about Gilead Sciences' application for a Truvada PrEP indication “for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults.”

Gilead proposed that Truvada PrEP efficacy rests on results of two large, placebo-controlled trials—iPrEx in men who have sex with men and Partners PrEP in HIV-discordant (one partner is HIV-positive, the other is not) heterosexual African couples. Both trials randomized HIV-negative participants to Truvada or placebo; Partners PrEP also tested Viread (tenofovir) alone to prevent HIV acquisition by HIV-negative partners. 

In their primary analyses, iPrEx documented a 42% lower HIV acquisition risk with Truvada, while Partners PrEP found a 75% lower risk with Truvada and a 67% lower risk with tenofovir alone.

Partners PrEP and iPrEx participants who were given Truvada had higher rates of certain kidney and bone toxicity markers than did people taking placebo, but overall Truvada did not appear to pose a short-term risk of kidney damage or fractures. 

On the basis of these findings, the Advisory Committee concluded that "safety and efficacy of [Truvada] for the prevention of HIV-1 infection in high-risk individuals is supported by two large clinical trials." 

The committee advised that “regular HIV testing, adherence, and behavioral counseling on safer sex practices, including condom use, are essential components of healthcare delivery around PrEP.”

The Advisory Committee offered this final conclusion in its briefing document: “If physicians prescribe and individuals utilize [Truvada] in the manner described for PrEP, in combination with other strategies to prevent HIV infection, the individual at risk may be spared infection with a serious and life-threatening illness that requires lifelong treatment with a three-drug antiretroviral regimen. That regimen, in line with current treatment guidelines for HIV-infected treatment-naive patients, will almost certainly contain [Truvada].”

A final decision on FDA approval is expected June 15.

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AVAC to Host Teleconference on Truvada for PrEP

AVAC, a global network of HIV prevention advocates, hailed the recommendation by  the FDA’s Advisory Committee that Truvada be approved for use as PrEP among sexually active adult men and women. According to a May 11 press release, “Citing the urgent need for new HIV prevention options to stem HIV infections, AVAC urges the FDA to issue an approval for all men and women at risk, and is calling on public health agencies, governments, advocates and funders to take action to ensure access to [Truvada] as PrEP.”

“This brings us closer to a watershed for global HIV prevention efforts,” said Mitchell Warren, executive director of AVAC. “PrEP, while not a panacea, will be an essential additional part to the world’s success in ending AIDS. For the millions of men and women who remain at risk for HIV worldwide, each new HIV prevention option offers additional hope that we will achieve the end of the epidemic.”

Join AVAC and its partners for an advocates’ teleconference on Tuesday, May 15 at 10am ET. The call will include a review of the committee recommendation and discussion of critical next steps, with a focus on the time between now and the FDA decision in June. It will explore the outcomes of the meeting in terms of the committee’s recommendations on labeling, patient education, follow-up research, and demonstration projects. It will also discuss the implications of this recommendation, and a potential FDA approval, for other countries, particularly in sub-Saharan Africa.

Register for the call at avac.org.

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The “Quad” Gains FDA Advisory Committee Backing

In more Advisory Committee news, on May 11, Gilead Sciences’ experimental HIV pill known as the “Quad,” received the committee’s 13-1 vote in favor of approving the drug.

The Quad, a combination of four drugs, would be the newest single tablet regimen (STR) that would enable HIV-positive people to control the virus by taking just one pill a day.

The medicine is designed to have fewer side effects than the current STRs Atripla and Complera. The Quad contains elvitegravir (an experimental integrase inhibitor), emtricitabine (brand name Emtriva), tenofovir (brand name Viread), and the experimental boosting agent cobiscistat.

According to Gilead’s studies, patients taking these drugs were less likely to have abnormal dreams, trouble sleeping, dizziness, or rash compared to Atripla, also manufactured by Gilead.

An FDA review of studies funded by Gilead found a higher number of kidney complications reported in people taking Quad compared with other HIV treatments. Those side effects included four cases of kidney failure and one case of a rare syndrome where substances aren’t absorbed into the blood stream by the kidneys. Still, there were fewer patients who stopped taking the Quad early because of side effects and the incidence of side effects was similar to other drugs, the FDA said.

“Quad has a potential to fulfill an unmet medical need with patients with HIV infection,” Andrew Cheng, Gilead’s senior vice president for clinical research and development operations, told the panel.

“A once-a-day pill, depending on people’s lifestyle, that doesn’t have neuropsychiatric side effects could be very appealing,” said Demetre Daskalakis, an assistant professor at New York University School of Medicine’s infectious disease division. “I feel like people would pick the Quad as a first-line treatment.”

The FDA is scheduled to decide by August 27 whether to approve the Quad for U.S. sale.

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Obama Endorses Gay Marriage

President Obama endorsed gay marriage on May 9, becoming the first U.S. president to voice support for same sex-couples to legally marry, according to at report in The Hill.

"At a certain point, I’ve just concluded that for me personally it is important for me to go ahead and affirm that I think same-sex couples should be able to get married," Obama said in an interview with ABC's Robin Roberts. He said he had come to that conclusion after years of conversations with friends, family, and neighbors, as well as with members of his staff who are in same-sex relationships.

The announcement is a landmark for the gay rights movement, which has battled for decades to win legal recognition for same-sex marriages. But the sudden shift by Obama in an election year could prove to be not just a boon to the Left, but also courageous in its risk of alienating socially conservative, independent voters who do not support same-sex marriage.

“The timing on this isn’t exactly ideal,” a former senior White House official said, acknowledging that, “this probably isn’t the timing that we needed.” The former official said Obama’s admission is risky because it has the potential to further activating social conservatives.

The acknowledgment comes on the heels of an overwhelming vote in swing state North Carolina, which defines marriage as legal only between a man and a woman, and comes just days after Obama held his first official campaign rallies.

Obama acknowledged the shift could hurt him politically, saying it could "put us at odds with the views of others." But he cited his religion as another reason for his decision. 

"When we think about our faith, the thing at root that we think about is, not only Christ sacrificing himself on our behalf, but it’s also the Golden Rule, you know, treat others the way you would want to be treated," Obama said. "And I think that’s what we try to impart to our kids and that’s what motivates me as president and I figure the most consistent I can be in being true to those precepts, the better I’ll be as a dad and a husband and, hopefully, the better I’ll be as president.”

Gay rights advocates were quick to praise Obama's shift on the issue. "Today President Obama made history by boldly stating that gay and lesbian Americans should be fully and equally part of the fabric of American society and that our families deserve nothing less than the equal respect and recognition that comes through marriage," said Joe Solmonese, the president of the Human Rights Campaign. 

White House press secretary Jay Carney told reporters Obama has a solid record of supporting LGBT rights. “There are those who want to bring ‘Don’t ask, don’t tell’ back,” he said. “He very robustly fights against efforts to restrict or deny…rights to LGBT citizens and discriminate against them, and he’ll continue to do so.”

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TPAN’s Leslie Henderson Named “Hero with a Heart”

The CTK Foundation announced on May 10 the 2012 Heroes with a Heart grant award winners. Volunteers were nominated by their communities to receive awards in three categories: health and human services, animal welfare and environmental protection, and arts and literacy. Qualified applicants were chosen by vote on Facebook, and because of the high level of engagement, three second place prizes were added during the voting period (one for each of the categories) by Community TechKnowledge, Inc., sponsor of the CTK Foundation.

$1,500 has been awarded to TPAN volunteer Leslie Henderson of Chicago, the winner of the Susan Lee Winter Grant Award for HIV education and prevention. Leslie has volunteered at the reception desk of TPAN for two years. HIV-positive since 2007, Leslie has met every challenge with courage and determination. In addition to his friendly, professional way of answering the phone, he greets all who enter TPAN’s door with a welcoming smile. Leslie was featured in the July/August 2011 issue of Positively Aware in “Finding the POWER Within,” telling of his experience with TPAN’s POWER (Positive Outcomes for Wellness, Education, and Recovery) program. In that article he said, “POWER taught me how to defeat HIV and live everyday life.” Today he is living proof that HIV-positive people can live a life of resiliency and accomplishment.

The CTK Foundation and all the participants have found the Heroes with Heart grant program experience to be inspiring. You can read their stories on the CTK Facebook Page.

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Johns Hopkins Establishes New Center for AIDS Research

Johns Hopkins University has been awarded $15 million over the next five years from the National Institutes of Health (NIH) to establish the new Center for AIDS Research (CFAR). CFAR will support more than 180 HIV investigators from the University’s Bloomberg School of Public Health, the School of Medicine, the School of Nursing, and other schools. A major priority for CFAR will be to address Baltimore’s HIV epidemic in addition to training new investigators and conducting international research.

“HIV/AIDS is a major threat to global health and urban America, particularly here in Baltimore,” said Richard Chaisson, MD, lead investigator of CFAR and professor with the Johns Hopkins School of Medicine and the Bloomberg School of Public Health. “While we’ve made great improvements in HIV treatment and prevention, much more needs to be done to control the pandemic. CFAR will mobilize the substantial scientific, clinical and public health resources at Johns Hopkins to generate the knowledge necessary to tackle the HIV pandemic.”

CFAR will be comprised of six core initiatives and three scientific working groups to promote collaboration and synergy across the Johns Hopkins HIV research community. These areas will include an administrative core, a developmental core to support pilot research grants, mentoring, and recruitment, a clinical core to focus on co-infections and co-morbidities, a prevention core targeting comprehensive approaches to prevention research, a biostatistics and epidemiology methods core, and a laboratory core to facilitate access to laboratory services. The three scientific working groups will promote new collaborations to address issues related to substance abuse, bioethics and human rights, and eradication of HIV.

“CFAR represents a major commitment toward promoting excellence, productivity and growth of HIV research and control efforts at Johns Hopkins, in Baltimore and globally,” said CFAR Co-director Chris Beyrer, MD, MPH, professor with the Bloomberg School of Public Health and associate director of the Johns Hopkins Center for Global Health.

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Genetically Modified T-Cell Therapy Appears to Be Safe and Lasting

HIV patients treated with genetically modified T-cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.

“We have 43 patients and they are all healthy," says senior author Carl June, MD, a professor of Pathology and Laboratory Medicine at Penn Medicine. "And out of those, 41 patients show long term persistence of the modified T-cells in their bodies."

Early gene therapy studies raised concern that gene transfer to cells via retroviruses might lead to leukemia in a substantial proportion of patients, due to mutations that may arise in genes when new DNA is inserted. The new long-term data, however, alleviate that concern.

"If you have a safe way to modify cells in patients with HIV, you can potentially develop curative approaches," June says. "Patients now have to take medicine for their whole lives to keep their virus under control, but there are a number of gene therapy approaches that might be curative." A lifetime of anti-HIV drug therapy, by contrast, is expensive and can be accompanied by significant side effects.

To demonstrate the long-term safety of genetically modified T-cells, June and colleagues have followed HIV-positive patients who enrolled in three trials between 1998 and 2002. Each patient received one or more infusions of their own T-cells that had been genetically modified in the laboratory using a retroviral vector. The vector encoded a chimeric antigen receptor that recognizes the HIV envelope protein and directs the modified T-cell to kill any HIV-infected cells it encounters.

The researchers carefully monitored patients for any serious adverse events immediately after infusion, but none were seen. Additionally, because of the earlier concerns about long-term side effects, the Food and Drug Administration (FDA) also asked the team to follow the patients for up to 15 years to ensure that the modified T-cells were not causing blood cancers or other effects. Therefore, each patient underwent an exam and provided blood samples during each of the subsequent years.

Now, with more than 500 years of combined patient safety data, June and colleagues are confident that the retroviral vector system is safe for modifying T-cells. By contrast, June notes, the earlier, worrying side effects were seen when viral vectors were used to modify blood stem cells. The new results show that the target cell for gene modification plays an important role in long-term safety for patients treated. "T-cells appear to be a safe haven for gene modification," June says.

The multi-year blood samples also show that the modified T-cell population persists in the patients' blood for more than a decade. In fact, models suggest that more than half of the T-cells or their progeny are still alive 16 years after infusion, which means one treatment might be able to kill off HIV-infected cells for decades.

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We Were Here to Be Released on DVD, Shown on PBS

We Were Here revisits the beginning of the AIDS crisis in America through the eyes of five individuals who lived in San Francisco prior to the epidemic. From their different vantage points, the interviewees share their stories as caregivers, activists, researchers, friends, lovers, and people with AIDS themselves. Intensely personal, the stories illuminate the much larger themes of that time: the political and sexual complexities, the terrible emotional toll, and the role of women—particularly lesbians—in caring and fighting for their gay brothers.

Award-winning director David Weissman weaves together archival footage that illustrates a community coming together in compassion and courage in response to suffering and loss due to the disease. As a filmmaker and political activist who arrived in San Francisco in 1976 and was deeply impacted by the epidemic, Weissman brings a unique personal understanding to this history and provides a compelling look at an era of which many young people today only have a vague impression.

Following its 2011 premiere at the Sundance Film Festival and a critically-acclaimed national theatrical release, the film was nominated for Best Documentary at the 2012 Independent Spirit Awards and was shortlisted for the 2012 Academy Award for Best Documentary. We Were Here releases on standard digital platforms and DVD on May 15 and will premiere on PBS’s Independent Lens on June 7.

The DVD includes an interview with director David Weissman, AIDS prevention PSAs Weissman produced in the 1990s, and the theatrical trailer.

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Legislation Watch

By Sue Saltmarsh

**LATE-BREAKING NEWS**

Senate Majority Leader Harry Reid said Thursday (May 10) that the party’s platform will soon include a plank calling for the legalization of gay marriage.

“The president’s in favor of it— I’m sure it will be [included],” said Reid.

Ironically, unless the Democrats decide to move it, their national convention will take place in Charlotte, North Carolina, the state that just passed a constitutional amendment banning same-sex marriage and civil unions. North Carolina is the last Southern state without such legislation and now joins 30 other states denying gays and lesbians the right to marry. Perhaps President Obama’s decision to finally express support for gay marriage will turn out to be more courageous than he thought, though Facebook and the Internet are buzzing with petitions through which we can thank him and through which we can let him know it wasn’t a mistake.

Also on May 10, House Republicans voted to make major cuts in Medicaid spending and let across-the-board Medicare cuts take effect as scheduled. In a party-line vote, the House passed a budget reconciliation measure that would cut healthcare programs in order to pay for defense spending.

The proposal would block automatic cuts to the Pentagon budget, which were imposed as part of last year’s debt-ceiling agreement. It would replace the defense cuts with new cuts to Medicaid and President Obama’s healthcare law.

The measure would kill the Prevention and Public Health fund in the healthcare law, which would fund community health centers, prevention and screening programs, among other things, and would enable the states to drop more people from Medicaid.

Congress has been in a frenzy in both chambers of “temporarily suspending the duty” on literally hundreds of things from chemicals to Yellow Dye 151 to women’s hiking boots. Granted, I’m not fully versed on what the impact of these suspensions might be, but it seems to me that at a time when we’re cutting Medicare and Medicaid programs that people rely on to live, every penny of revenue we can raise would be helpful. Maybe I’m wrong in assuming that suspension of duty means letting some other country off the hook to pay a duty on some product they export to us, but if I’m not wrong, WTF?

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