FDA approves 1st pill to help prevent HIV

MATTHEW PERRONE  |  AP Health Writer

WASHINGTON — The Food and Drug Administration on Monday approved the first drug shown to reduce the risk of HIV infection, a milestone in the 30-year battle against the virus that causes AIDS.

The agency approved Gilead Sciences’ pill Truvada as a preventive measure for people who are at high risk of acquiring HIV through sexual activity, such as those who have HIV-infected partners.

Public health advocates say the approval could help slow the spread of HIV, which has held steady at about 50,000 new infections per year for the last 15 years. An estimated 1.2 million Americans have HIV, which develops into AIDS unless treated with antiviral drugs. With an estimated 240,000 HIV carriers unaware of their status, doctors and patients say new methods are needed to fight the spread of the virus.

Gilead Sciences Inc. has marketed Truvada since 2004 as a treatment for people who are already infected with the virus.

But starting in 2010, studies showed that the drug could actually prevent people from contracting HIV when used as a precautionary measure. A three-year study found that daily doses cut the risk of infection in healthy gay and bisexual men by 42 percent, when accompanied by condoms and counseling.

Last year another study found that Truvada reduced infection by 75 percent in heterosexual couples in which one partner was infected with HIV and the other was not.

Because Truvada is on the market to manage HIV, some doctors already prescribe it as a preventive measure. FDA approval will allow Gilead Sciences to formally market the drug for that use, which could dramatically increase prescribing.

Truvada’s groundbreaking preventive ability has exposed disagreements about managing the disease among those in the HIV community. Groups including the AIDS Healthcare Foundation asked the FDA to reject the new indication, saying it could give patients a false sense of security and reduce the use of condoms, the most reliable preventive measure against HIV.

But FDA scientists said Monday said there was no indication from clinical trials that Truvada users were more likely to engage in risky sexual behavior.

“What we found was that condom use increased over time and sexually transmitted infections either remained at baseline levels or decreased,” said Dr. Debra Birnkrant, FDA’s director of antiviral products. “So in essence, we don’t have any strong evidence that condoms were not used or there was a decrease in condom use.”

—  John Wright

AIDS at 30: Truvada study shows an increase in protection for HIV-negative men

Pre-exposure prophylaxis may be a way to help control the HIV epidemic, but many say the drug will promote unsafe sex, is too expensive and may have side effects

DAVID TAFFET | Staff Writer
taffet@dallasvoice.com

In November 2010, researchers released a study that found that HIV-negative men who took the anti-retroviral drug Truvada consistently and dramatically lowered their chances of contracting HIV.

But soon after, the AIDS Healthcare Foundation in Los Angeles published an ad in several newspapers — including Dallas Voice — disputing the results.

Among other concerns mentioned, they are afraid that men will stop using condoms if the drug is approved as pre-exposure prophylaxis, or PrEP.

A letter supporting the research was circulated and signed by 170 AIDS organizations. None of those was from Dallas, but several from Houston are on the list of supporters.

Dr. Robert Grant is the lead investigator of the Truvada study. The research was done independently of the drug manufacturer Gilead.

Although the company contributed the medication used in the study at no charge, Gilead had no other input.

Both those taking a placebo and those taking Truvada increased their condom use during the study. But the group that used Truvada consistently showed 72 to 95 percent more protection than those who only practiced safe sex.

Those who skipped a daily dosage were as unprotected as those who were on placebo.

In response to critics, Grant said that with counseling, condom usage should actually increase.

The AIDS Healthcare Foundation charged that condom usage would decrease with PrEP. They believe that many men would take the daily pill thinking that they would be protected from contracting HIV.

There is also concern that for those who use Truvada as a preventive medicine and then contract HIV, fewer treatment options would be available to control HIV. Representatives of the foundation questioned whether those who contract HIV after using Truvada as a prophylaxis might develop resistance to the drug.

Dr. Nick Bellos of Dallas, who has treated people with HIV since early in the epidemic, said he is pleased to see the PrEP study results.

“I think it’s promising. It does look like it could be beneficial,” Bellos said.

Although he said his long-term preference is for a vaccine, Bellos considers the PrEP treatment to be a step in the right direction.

Still, he said, he would like to see more research that shows the benefits of PrEP.

Dr. Louis Sloan of North Texas Infectious Disease Consultants at Baylor is less optimistic. He said he is concerned about the side effects associated with using Truvada, noting that even if only 3 percent of patients experienced kidney failure, that number was high when simple condom use is effective.

AIDS Arms Executive Director Raeline Nobles said that her agency will be doing some PrEP trials.

Nobles said that while she is also concerned about decreased condom usage, she thinks some situational PrEP usage might be extremely helpful in controlling the spread of the virus.

Grant suggested that some people who use Truvada as a prophylaxis will use it situationally. He said someone coming out of a long-term relationship might begin PrEP until they become more comfortable with safer-sex practices.

A couple who has recently begun a relationship may use PrEP until they feel enough time has passed for them to both be tested as negative. Or the negative member of a sero-discordant couple may use the preventive medication to maintain his negative status.

A heterosexual couple trying to get pregnant when one of the partners is positive is another short-term situational use of the medication.

Among other things, the AIDS Healthcare Foundation charges that the Truvada study shows that the drug is less effective than condom use. They wrote that the study did not replicate real world experience, pointing out that participants were counseled monthly, which doesn’t translate into the way most people would take the drug.

Another concern is cost. The current price of Truvada is $45 per pill, which is more than $16,000 annually. Insurance doesn’t cover the cost of a flu shot, an annual preventive vaccine that costs less than a single Truvada, and there are questions over whether insurance companies would cover the cost of a daily preventive medication.

They also question whether uninfected men are likely to take preventive pills daily for the rest of their lives. A quick, unscientific poll of 10 single gay men, some in the Dallas Voice office, showed that only three in 10 would.

As questions remain, however, PrEP studies continue, including one at Dallas’ AIDS Arms, that could answer some of them.

—  John Wright

Truvada breakthrough gets mixed reaction from local docs, advocates

Report that drug could protect HIV-negative men from infection is good news, but concerns remain over long-term effects, some say

David Taffet  |  Staff Writer taffet@dallasvoice.com

REMEMBERING THEIR NAMES | Two unidentified visitors console each other at the NAMES Project AIDS Memorial Quilt display in October 1989 in Washington, D.C. Panels from the Quilt will be on display in the International Peace Chapel at Cathedral of Hope on World AIDS Day 2010, Wednesday, Dec. 1. More coverage of World AIDS Day events in North Texas begins on Page 14. (Doug Mills/Associated Press)

An extensive study released this week indicates that use of the anti-retroviral drug Truvada by HIV-negative men can prevent infection. Use of the drug for prevention is called Pre-Exposure Prophylaxis or PrEP.

Dr. Nick Bellos, a local infectious disease specialist, called the results of the study a step in the right direction. But Bellos also warned that the study only showed 75 percent effectiveness in preventing infection among people who were most compliant. And he said he had concerns about patients developing resistance to the drug and not using other risk-reduction techniques.

Local AIDS activist Bret Camp, associate executive director for health and medical services at Resource Center Dallas, also warned that the side effects and long-term effects of using Truvada can be severe.

Global HIV Vaccine Enterprise executive director Dr. Alan Bernstein, referring to another recent study using a topical microbicide that appears to prevent HIV infection in women and another study that included the first demonstration of efficacy by an HIV vaccine regimen, said, “The announcement [about Truvada] … is a very important addition to what is the most promising 15 months in the field of HIV prevention research since the epidemic began 27 years ago.”

The Centers for Disease Control said the findings in the Truvada study are a major advance in prevention research and a new tool to reduce the risk of infection among gay men and bisexuals.

Dr. Brady Allen, a Dallas internist, was optimistic, but also had some concerns.

“I think we have a lot of issues to consider with PrEP,” he said. “We will certainly need recommendations from the CDC. In addition, I think it is promising work.”

AIDS Arms Executive Director Raeline Nobles was also optimistic.

“This study shows hope and a new way to battle the HIV epidemic,” Nobles said. “Usually we are a little apprehensive when there is a press release about new drugs or vaccines being tested, as we know there will be years of further study and validation — and often failure over time to come to fruition.”

But, she added, the Truvada study has her excited about the future.

Camp stressed that “The anti-retroviral prophylaxis approach is promising but only a piece of the solution.”

He said that the new drug therapy cannot replace traditional prevention methods, and he pointed out that new infections did occur among men who took the medication.

Among the 2,500 enrolled participants, 36 new infections occurred among individuals who received the drug. Among placebo recipients, there were 64 new infections. Researchers estimated that the use of the preventive medication cut new HIV infections by an estimated 44 percent overall when compared to placebo.

“Adherence to taking the pills is key to success,” Camp said.

The study did show that those who took Truvada daily had a much higher rate of protection than those who took the pills only half of the time.

Camp said that “two participants who seroconverted had resistance after” that would have been built by irregular use of the drug, causing it to be at a lower-than-therapeutic level in the blood at the time of infection.

Dr. Nick Bellos
Dr. Nick Bellos

Bellos said that those patients also may have contracted a strain of the virus that is resistant to Truvada.

But Bellos still called the results promising and said that prophylaxis is a good idea.

“In a perfect world, if we could get everyone treated, we could plateau the epidemic,” he said.

While the CDC called “developing guidance on the safe and effective use of PrEP and determining how to most effectively use PrEP in combination with other prevention strategies to reduce new infections in the U.S.” its most urgent priority, Camp warned of the risks.
While he said that compared to some of the other anti-retrovirals on the market, Truvada is fairly well tolerated, it can still cause headaches, nausea and diarrhea.

“It’s known to cause decreases in renal function,” he said. “We could be setting people up for renal issues and the long-term effects are just now coming to our attention. Cardio-vascular disease, diabetes — we don’t know what the next 10 to 20 years on those drugs will be.”

Bellos noted that metabolic bone disease could also be an issue.

He said that anyone taking the drug as a prophylactic measure would need to be medically monitored on a regular basis, just as someone who is HIV-positive.

Despite his concerns, Camp did say he believes the results are a breakthrough that proved a non-intended use or expected finding. Previous studies have shown a benefit of drugs for medical personnel accidentally exposed to the virus but this was the first time prevention was proven through sexual exposure.

“The value is more in post-exposure, when traditional HIV prevention mechanisms fail,” he said.

Camp said he is more excited about the research into anti-microbial topical gels that have recently also proven effective in preventing infection after exposure.

Bellos agreed.

“My preference is for a vaccine,” Bellos said.

“Then we don’t have to worry about it.”

He said that a study has been done in South Africa among couples where one is HIV-positive and the other is negative, showing that when the positive partner’s viral load is undetectable, the risk to the negative partner is about 6 percent.

“On therapy, 94 percent of the negative partners stayed negative,” he said.

Bellos also warned that the Truvada study showed that even for the most compliant participants in the study showed only 75 percent effectiveness in preventing infection.

He said he is concerned that people will ignore traditional prevention methods that have proven effective and instead rely on the less-effective prophylaxis.

Nobles said it has long been known that strict adherence to anti-retroviral treatment among HIV-positive people leads to less transmission of the virus to others.

But she wondered about some of the ethical implications that need to be studied, including the cost and availability of Truvada.

“If we can’t afford to treat all HIV positive people living with the disease today — which we cannot — how will we ever be able to afford paying for preventive medications, too?” Nobles said.

The drug costs about $45 per pill in the United States. Because the manufacturer gave away the patent for production by generic drug makers in other countries, it is available in some countries for under $1.

“One wonders if insurance companies are going to be willing to pay for this,” Allen said.

Bellos said that he has some patients with family members in places like Pakistan and Thailand and they are able to get the drug from overseas.

“We should have two other large PrEP trials reported on in 2011 in other high-risk groups, which will help confirm or refute these results,” said Allen.

President Barack Obama also weighed in on the importance of the study.

“I am encouraged by this announcement of groundbreaking research on HIV prevention,” the president said in a statement released Tuesday, Nov. 23.

“While more work is needed, these kinds of studies could mark the beginning of a new era in HIV prevention,” the president said.

“As this research continues, the importance of using proven HIV prevention methods cannot be overstated.”

……………………..

MORE ON TRUVADA

Truvada is a combination drug therapy known as a nucleoside analog reverse transcriptase inhibitor. Two anti-HIV medications, Emtriva® and Viread®, are combined into one pill that is taken once a day with or without food.

In the United States, the cost of the treatment is more than $1,000 per month.

Manufacturer Gilead has given away the patent for generic manufacturers to produce and sell it in third world countries. There, the cost of the drug averages 45 cents a day or about $15 per month.

Those generic medications are not available in the United States.

Dr. Nick Bellos said that patients of his who have access to the generic medication have family members in those countries that are filling the prescription and sending them the drug.

Truvada has been one of the more successful HIV medications. Fewer people seem to experience side effects on this drug than on some of the others.

Studies show that more people became and stayed undetectable over a three-year period on Truvada than on Combivir or Sustiva, two other popular HIV medications.

Those on Truvada showed a greater increase in the number of CD4 cells than on other medications.

Side effects include nausea, vomiting, unusual muscle pain and/or weakness.

Longterm use could lead to liver damage, renal failure, increased risk of diabetes and metabolic bone disease.

Changes in body fat have been seen in some people taking Truvada.

—David Taffet

This article appeared in the Dallas Voice print edition November 26, 2010.

—  Michael Stephens

Study: Pill helps gay men avoid HIV infection

Experts call Truvada research ‘a major milestone’ but warn that condoms remain the ‘first line of defense’

MARILYNN MARCHIONE  |  Associated Press

MILWAUKEE — Scientists have an exciting breakthrough in the fight against AIDS. A pill already used to treat HIV infection turns out to be a powerful weapon in protecting healthy gay men from catching the virus, a global study found.

Daily doses of Truvada cut the risk of infection by 44 percent when given with condoms, counseling and other prevention services. Men who took their pills most faithfully had even more protection, up to 73 percent.

Researchers had feared the pills might give a false sense of security and make men less likely to use condoms or to limit their partners, but the opposite happened — risky sex declined.

The results are “a major advance” that can help curb the epidemic in gay men, said Dr. Kevin Fenton, AIDS prevention chief at the U.S. Centers for Disease Control and Prevention. But he warned they may not apply to people exposed to HIV through male-female sex, drug use or other ways. Studies in those groups are under way now.

“This is a great day in the fight against AIDS … a major milestone,” said a statment from Mitchell Warren, head of the AIDS Vaccine Advocacy Coalition, a nonprofit group that works on HIV prevention.

Because Truvada is already on the market, the CDC is rushing to develop guidelines for doctors using it for HIV prevention, and urged people to wait until those are ready.

“It’s not time for gay and bisexual men to throw out their condoms,” Fenton said. The pill “should never be seen as a first line of defense against HIV.”

As a practical matter, price could limit use. The pills cost from $5,000 to $14,000 a year in the United States, but only 39 cents a day in some poor countries where they are sold in generic form.

Whether insurers or government health programs should pay for them is one of the tough issues to be sorted out, and cost-effectiveness analyses should help, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

“This is an exciting finding,” but it “is only one study in one specific study population,” so its impact on others is unknown, Fauci said.

His institute sponsored the study with the Bill & Melinda Gates Foundation. Results were reported at a news conference Tuesday and published online by the New England Journal of Medicine.

It is the third AIDS prevention victory in about a year. In September 2009, scientists announced that a vaccine they are now trying to improve had protected one in 3 people from getting HIV in a study in Thailand. In July, research in South Africa showed that a vaginal gel spiked with an AIDS drug could cut nearly in half a woman’s chances of getting HIV from an infected partner.

Gay and bisexual men account for nearly half of the more than 1 million Americans living with HIV. Worldwide, more than 40 million people have the virus, and 7,500 new infections occur each day. Unlike in the U.S., only 5 to 10 percent of global cases involve sex between men.

“The condom is still the first line of defense,” because it also prevents other sexually spread diseases and unwanted pregnancies, said the study leader, Dr. Robert M. Grant of the Gladstone Institutes, a private foundation affliated with the University of California, San Francisco.

But many men don’t or won’t use condoms all the time, so researchers have been testing other prevention tools.

AIDS drugs already are used to prevent infection in health care workers accidentally exposed to HIV, and in babies whose pregnant mothers are on the medication. Taking these drugs before exposure to the virus may keep it from taking hold, just as taking malaria pills in advance can prevent that disease when someone is bitten by an infected mosquito.

The strategy showed great promise in monkey studies using tenofovir (brand name Viread) and emtricitabine, or FTC (Emtriva), sold in combination as Truvada by California-based Gilead Sciences Inc.

The company donated Truvada for the study, which involved about 2,500 men at high risk of HIV infection in Peru, Ecuador, Brazil, South Africa, Thailand and the United States (San Francisco and Boston). The foreign sites were chosen because of high rates of HIV infection and diverse populations.

More than 40 percent of participants had taken money for sex at least once. At the start of the study, they had 18 partners on average; that dropped to around 6 by the end.

The men were given either Truvada or dummy pills. All had monthly visits to get HIV testing, more pills and counseling. Every six months, they were tested for other sexually spread diseases and treated as needed.

After a median followup of just over a year, there were 64 HIV infections among the 1,248 men on dummy pills, and only 36 among the 1,251 on Truvada.

Among men who took their pills at least half the time, determined through interviews and pill counts, the risk of infection fell by 50 percent. For those who took pills on 90 percent or more days, risk fell 73 percent. Tests of drug levels in the blood confirmed that more consistent pill-taking gave better protection.

The treatment was safe. Side effects were similar in both groups except for nausea, which was more common in the drug group for the first month but not after that. Unintended weight loss also was more common in the drug group, but it occurred in very few. Further study is needed on possible long-term risks.

What’s next?

All participants will get a chance to take Truvada in an 18-month extension of the study. Researchers want to see whether men will take the pill more faithfully if they know it helps, and whether that provides better protection. About 20,000 people are enrolled in other studies testing Truvada or its component drugs around the world.

The government also will review all ongoing prevention studies, such as those of vaccines or anti-AIDS gels, and consider whether any people currently assigned to get dummy medicines should now get Truvada since it has proved effective in gay men.

Gilead also will discuss with public health and regulatory agencies the possibility and wisdom of seeking approval to market Truvada for prevention. The company has made no decision on that, said Dr. Howard Jaffe, president of Gilead Foundation, the company’s philanthropic arm. Doctors can prescribe it for this purpose now if patients are willing to pay for it, and some already do.

Some people have speculated that could expose Gilead to new liability concerns, if someone took the pill and then sued if it did not protect against infection.

“The potential for having an intervention like this that has never been broadly available before raises new questions. It is something we would have to discuss internally and externally,” Jaffe said.

Until the CDC’s detailed advice is available, the agency said gay and bisexual men should:

• Use condoms consistently and correctly.

• Get tested to know their HIV status and that of their partners, and get tested and treated for syphilis, gonorrhea and other infections that raise the risk of HIV.

• Get counseling to reduce drug use and risky sex.

• Reduce their number of sexual partners.

—  John Wright

BREAKTHROUGH: Study shows anti-retroviral drugs reduce infection in HIV-negative men

A study published today in the New England Journal of Medicine found that the use of daily anti-retroviral medication reduces the risk of infection in HIV-negative gay men.

The study was done in six countries with 2,500 gay, bisexual and other men who have sex with men. Using the drug Truvada, they found that it can prevent men from acquiring HIV.

Among the enrolled participants, there were 36 infections among individuals who received the drug and 64 new infections among placebo recipients. Researchers estimated that the use of the preventive medication cut new HIV infections by an estimated 44 percent overall when compared to the placebo. This is the first evidence that a drug regimen can reduce the risk of HIV among HIV-negative men.

“Condoms are still the first line of defense, but we’re hopeful that [Pre-Exposure Prophylaxis Initiative] may be an important addition to a comprehensive prevention toolbox that will help prevent new infections among gay men,” said National Alliance of State and Territorial AIDS Directors executive director Julie Scofield.

Bret Camp from Resource Center Dallas’ Nelson-Tebedo Clinic called it a milestone but cautioned about the side effects and long-term damage of Truvada. He stressed that this therapy will not replace traditional prevention methods.

More on the breakthrough in this Friday’s World AIDS Day Edition of Dallas Voice.

—  David Taffet