The Food and Drug Administration (FDA) in July approved Truvada as the first medication to help prevent HIV infection. As expected, the approval came with restrictions.
Truvada, a combination of tenofovir (Viread) and emtricitabine (Emtriva), is one of the most prescribed medications for HIV in this country. For HIV prevention, the use of Truvada is called “PrEP,” for “pre-exposure prophylaxis.”
“[We] commend the FDA’s approval of [Truvada] for the use of [PrEP] to prevent HIV transmission. This approach can prevent many new infections and could dramatically impact HIV transmission worldwide,” said Kenneth H. Mayer, MD, Medical Research Director and Co-chair of The Fenway Institute at Fenway Health. “My colleagues and I are delighted to have helped to demonstrate the utility of this promising approach for HIV prevention.”
David Ernesto Munar, President/CEO of the AIDS Foundation of Chicago, said, “Our challenge now is to implement PrEP as strategically as possible, and to ensure the people who need it most, those who are most at risk for HIV, have access.”
“This is an enormous turning point, a real game changer, in the fight against HIV,” said Jim Pickett, AFC’s Director of Prevention Advocacy and Gay Men’s Health. “The toolbox we have now has Truvada as PrEP. We can look forward to more sex acts being protected, especially among individuals who have already chosen, for whatever reason, to not use condoms consistently.”
According to a press release from the FDA, “Truvada is to be used for [PrEP] in combination with safer sex practices to prevent sexually-acquired HIV infection in adults at high risk.”
The FDA said Truvada for PrEP should be used as part of a comprehensive HIV prevention plan that includes risk reduction counseling, consistent and correct condom use, regular HIV testing, and screening for and treatment of other sexually-transmitted infections, stating that “Truvada is not a substitute for safer sex practices.”
Truvada now carries a Boxed Warning on its drug label alerting health care professionals and uninfected individuals that Truvada for PrEP must only be used by people confirmed to be HIV-negative before being prescribed the drug and tested at least every three months during use to reduce the risk of developing drug resistance. Both the antiviral and the PrEP dose is one pill taken once daily.
Truvada maker Gilead Sciences worked with the FDA to create a Risk Evaluation and Mitigation Strategy (REMS) for Truvada PrEP. The REMS focuses on a prescriber training and education program in counseling and managing individuals who are taking or considering Truvada for PrEP. The REMS looks at the elements of a comprehensive HIV prevention strategy, the importance of adhering to the recommended daily dosing regimen, and the serious risks of taking Truvada for PrEP if already infected with HIV or of becoming infected while taking it.
According to the press release, “Truvada’s safety and efficacy for PrEP were demonstrated in two large, randomized, double-blind, placebo-controlled clinical trials. The iPrEx trial evaluated Truvada in 2,499 HIV-negative men or transgender women who have sex with men and with evidence of high risk behavior for HIV infection... Results showed Truvada was effective in reducing the risk of HIV infection by 42% compared with placebo in this population. Efficacy was strongly correlated with drug adherence in this trial.”
It was also shown in iPrEX that there was a 92% reduction of risk for HIV in participants who took Truvada in the prescribed once-daily dose.
“The Partners PrEP trial was conducted in 4,758 heterosexual couples, where one partner was HIV-infected and the other was not (serodiscordant couples),” the press release continued. “The trial evaluated the efficacy and safety of [both] Truvada and [Viread] tenofovir versus placebo in preventing HIV infection in the uninfected male or female partner. Results showed Truvada reduced the risk of becoming infected by 75% compared with placebo.
“No new side effects were identified in the clinical trials evaluating Truvada for the PrEP indication. The most common side effects reported with Truvada include diarrhea, nausea, abdominal pain, headache, and weight loss. Serious adverse events in general, as well as those specifically related to kidney or bone toxicity, were uncommon.”
As a condition of approval, Gilead Sciences is required to collect and analyze samples from individuals who become infected with HIV while taking Truvada to see if they’ve developed drug resistance. The company is also required to collect data on women who become pregnant while taking Truvada for PrEP and to conduct other research.
“Today’s decision is the culmination of almost 20 years of research involving investigators, academic and medical institutions, funding agencies, and nearly 20,000 trial participants around the world, and Gilead is proud to have been a partner in this effort,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences.
The following is from a statement from Moises Agosto, Director of Treatment Education, Adherence, and Mobilization for the National Minority AIDS Council (NMAC):
“While PrEP shows substantial promise as a supplement to current HIV prevention efforts, it is by no means a panacea and is only effective when used in conjunction with traditional prevention and risk reduction strategies, such as condom usage.
“Anti-retroviral medications, like Truvada, are extremely powerful drugs with the potential for serious side effects. As such, PrEP should only be used by individuals who are highly vulnerable to HIV infection, including those in sero-discordant couples, sex workers, and gay men. Its efficacy is also directly related to an individual’s adherence to a regimen, and should only be used by those who can commit to taking it regularly. Finally, use of PrEP by individuals who may already be HIV-positive could increase the risk of drug resistance.
“In recent years, there have been a number of promising developments in biomedical interventions—from treatment as prevention and pre-exposure prophylaxis to microbicides and vaccine research. These advances have resulted in the greatest expansion of HIV prevention tools than at any other time in the history of this epidemic. Coupled with the reforms included in the Patient Protection and Affordable Care Act, as well as the National HIV/AIDS Strategy, we are in a position for the first time in over three decades to finally end this epidemic. Today’s decision is another important step in realizing that goal.”
Shionogi-ViiV Healthcare LLC announced that initial results from its Phase 3 study SINGLE (ING114467) show superiority of its investigational HIV medication dolutegravir plus Epzicom over Atripla, one of the most widely prescribed antiviral medications in the country. At 48 weeks, 88% of study participants on the dolutegravir regimen achieved undetectable viral load (less than 50 copies/mL) vs. 81% of those on Atripla, a statistically significant difference. The company said the difference was primarily driven by a higher rate of discontinuation due to adverse events in the Atripla arm. All individuals in the study were taking antiviral therapy for the first time, a group that does the best in HIV treatment. There were 414 individuals put on dolutegravir and 419 put on Atripla. Overall, 2% of those on the dolutegravir-based regimen discontinued due to adverse events vs. 10% of those receiving the Atripla regimen. The most common adverse events while on Atripla were neurological (reported by 41% of Atripla recipients vs. 15% of participants receiving the dolutegravir), while the most common drug-related adverse events with dolutegravir were in the gastrointestinal system (reported by 22% of people on dolutegravir vs. 22% of those given Atripla).
Dolutegravir is an investigational integrase inhibitor (INSTI), the same class as Isentress, the only INSTI currently on the market.
In June, the Food and Drug Administration (FDA) approved the OraQuick In-Home HIV Test, an HIV self-test kit that does not require sending a sample to a laboratory for analysis. The kit, which tests a swab from your mouth, is approved for sale in stores and online to anyone age 17 and older. (Although HIV is not found in saliva, evidence of exposure to the virus—called HIV antibodies—is found in the mouth and indicates infection.) A positive result at home must then be followed up with a confirmatory blood test from a laboratory.
The FDA said the test can be falsely negative for reasons that include the occurrence of HIV infection within three months before testing. People who engage in behaviors that put them at increased risk of getting HIV—including having unprotected sex with new partners, or injecting illegal drugs—should be re-tested on a regular basis. They should not interpret a negative test to indicate that engaging in high risk behavior is safe.
HarborPath, a new non-profit organization, has been established to create a program that offers a single place where uninsured HIV-positive people who otherwise qualify for manufacturer-sponsored patient assistance programs (PAPs) can apply for and receive their medications. The “one stop shop” portal will provide a streamlined, online process to qualify individuals and deliver the donated medications through a mail-order pharmacy. HarborPath will pilot the program in states with high need, including Alabama, Texas, and Virginia.
To create the portal, HarborPath worked closely with the National Alliance of State and Territorial AIDS Directors (NASTAD) and the Clinton Health Access Initiative (CHAI), which provided the seed funding for the organization. On World AIDS Day 2011, President Bill Clinton noted the need to fight HIV/AIDS in the U.S.
“I am proud that my foundation is partnering with NASTAD and other pharmaceutical manufacturers to make sure Americans living with HIV have access to the life-saving medications they need,” said President Clinton. “This is an important step forward in our fight against the disease.”
ViiV Healthcare is the first pharmaceutical company to support the program with HIV/AIDS medications and funding.
The goal of HarborPath is to get all HIV/AIDS medications into the program and serve uninsured individuals with:
Murray Penner, Deputy Executive Director at NASTAD, said, “Under the current PAP process, an individual or their case manager has to apply separately to each company’s program for these medications, which can be complex and time-consuming. Missing doses or failing to fill prescriptions because of complications sometimes associated with these processes may result in serious health consequences, or even death, in addition to increased transmission of the virus. HarborPath is designed to address this urgent need in the U.S.”
The findings of two large international randomized studies published in The Lancet medical journal indicate that the new once-daily pill combining three antiretrovirals and a booster molecule is a safe and effective alternative to two widely used drug regimens for newly diagnosed HIV-positive adults who have had no previous treatment. The study results also indicate that the new “Quad” pill is faster acting, doesn’t have the neuropsychiatric side effects associated with other combinations, and could improve compliance with treatment.
“Patient adherence to medication is vital, especially for patients with HIV, where missed doses can quickly lead to the virus becoming resistant to medication. Older HIV treatment regimens involve taking several pills multiple times a day,” explains Paul Sax from Brigham and Women’s Hospital, Harvard Medical School, lead author of the first study. “Our results provide an additional highly potent, well-tolerated treatment option, and highlight the simplicity of treatment resulting from combining several antiretrovirals in a single pill. Studies have shown that single pill treatments improve both adherence and patient satisfaction, and help prevent prescription errors, thereby reducing the likelihood of treatment failure and drug resistance.”
The first study randomly assigned 700 patients from centers across North America to start treatment with two different single tablet regimens—either the Quad, combining the new integrase inhibitor elvitegravir (EVG) boosted with cobicistat (a new pharmacoenhancer; COBI) plus emtricitabine/tenofovir (Emtriva/Viread), or Atripla (efavirenz/emtricitabine/tenofovir), the current gold standard regimen approved by the FDA in 2006.
After 48 weeks of treatment, 88% of patients given the Quad had suppressed viral loads (less than 50 copies/mL), compared with 84% in the Atripla group.
Adverse events that led to patients discontinuing treatment were infrequent and similar in both groups. Mild nausea was more common with the Quad, but patients were less likely to have dizziness, abnormal dreams, insomnia, and rash compared with the Atripla regimen.
The second trial included 708 treatment-naïve adults from 146 medical centers across Australia, Europe, North America, and Thailand. Patients were randomly assigned to receive a once-daily Quad or a popular and recommended twice-daily combination of Norvir-boosted Reyataz (atazanavir/ritonavir) plus Truvada (emtricitabine/tenofovir).
The primary endpoint, to achieve viral levels below 50 copies/mL by week 48, was reached by 90% of people in the Quad group compared with 87% in the atazanavir/ritonavir/emtricitabine/tenofovir group.
The safety of the two regimens was also similar.
POSITIVELY AWARE editor Jeff Berry has joined other AIDS activists and journalists such as The Body’s Kellee Turrell, the AIDS Foundation of Chicago’s David Ernesto Munar, and others in becoming a blogger published by The Huffington Post.
In advance of the upcoming AIDS 2012 World AIDS Conference, Berry wrote “Reflections from an Epidemic: Carrying the Torch to AIDS 2012.” In it, he talks about the significance of this being the first conference to be held in the U.S. since President Obama lifted the travel ban on HIV-positive people, his anticipation of such events as displays of the AIDS Memorial Quilt, a planned march and demonstration, the performance of the Tony Award-winning play The Normal Heart, as well as the many global leaders in AIDS policy, advocacy, and treatment advances that presented at the conference.