POSITIVELY AWARE May/June 2012
Victrelis ‘not recommended’ with some HIV meds
The new hepatitis C drug Victrelis (boceprevir) is “not recommended” to be taken with some HIV medications, according to a “Dear Doctor” letter issued in February by Merck & Co. Merck reported drug interaction data showing that Victrelis and some HIV medications reduce each other’s effectiveness when taken together. As a result, the company does not recommend that Victrelis be taken with any Norvir-boosted HIV protease inhibitor (Aptivus, Crixivan, Invirase, Kaletra, Lexiva, Prezista, or Reyataz).
The Food and Drug Administration (FDA) reported that patients already taking Victrelis along with a boosted HIV protease inhibitor should not stop any of their medications, but consult with their doctor. The FDA also suggested that providers closely monitor these patients for their antiviral response to both treatments.
Along with Victrelis, Incivek (telaprevir), the other new hepatitis C protease inhibitor medication that was FDA approved in May of last year, also interacts with some HIV medications. Of the HIV protease inhibitors, it can only be taken with boosted Reyataz. It can also be taken with Sustiva and Isentress, with an increased dose of Incivek if taken with Sustiva. But the company behind Incivek, Vertex Pharmaceuticals (with development originally by Tibotec Pharmaceuticals), made these interactions known at the time of FDA approval.
In his outstanding blog HIV and ID Observations, Dr. Paul Sax wrote, “For now, the bottom line is that there really is no optimal HCV protease inhibitor for HIV/HCV co-infected patients, especially for those on a boosted PI. And why careful assessment of those with HIV/HCV is critical [since] many patients are stable enough to wait for the next wave of HCV drugs.”
Merck was criticized by the advocacy group Hepatitis C Community Advisory Board (HCAB) for being so late in bringing these drug interactions to light. HCAB stated in a press release that, “Although we commend the sponsor, Merck, for opening one of the first co-infection trials with a [direct-acting antiviral], we were outraged that Merck chose not to conduct [drug-drug interaction, or DDI] studies with commonly used antiretroviral agents prior to launching the trial, and prior to gaining approval for boceprevir [Victrelis]. Vertex and Tibotec were able to bring telaprevir [Incivek] to market with a much fuller portfolio of DDI data, although both drugs were developed within the same timeframe.”
HCAB urged companies to conduct interaction studies with HIV medications along with studies in HIV/HCV co-infected people before applying for regulatory approval, as well as research with hormonal contraceptives, methadone, burprenorphine, lipid-lowering and immunosuppressive medications, herbal remedies, and commonly prescribed psychiatric drugs.
Note: Increase Incivek dose to 1,125 mg three times a day when taking it with a Sustiva regimen, or with Atripla or Complera.
Intelence now for kids ages six and older
The HIV medication Truvada (Viread plus Emtriva in one pill) has been accepted by the FDA for a six-month Priority Review for use in preventing HIV infection. Such use by HIV-negative individuals is called PrEP, for pre-exposure prophylaxis (prevention). Gilead Sciences’ supplemental New Drug Application (sNDA) for Truvada PrEP is set to go before the FDA on June 15.
FDA to consider Truvada for PrEP
The second edition of 100 Questions & Answers About HIV and AIDS by Dr. Joel Gallant is now available. Dr. Gallant is a frequent contributor to PA and the doctor for the Positively Aware HIV Drug Guide for the last two years. This handy book provides answers to the most common questions asked by people living with HIV and AIDS, their partners, and their families. Order your copy today from Amazon.com and jblearning.com.
New edition of HIV Q&A book available
The HIV drug Intelence (etravirine) received approval from the Food and Drug Administration (FDA) for use by children ages six to 18 weighing at least 35 pounds, who have previous anti-HIV treatment experience. This includes children whose virus has developed drug resistance to the same class of medications as Intelence (non-nucleoside reverse transcriptase inhibitors, or NNRTIs). Sustiva and Viramune are the NNRTIs previously available for pediatric use. A new scored 25 mg tablet of Intelence is now available for pediatrics
For more information about the drug, go to positivelyaware.com/intelence.
Dolutegravir aces SPRING-2 study, now available via EAP
Initial results of a large Phase 3 study of dolutegravir, an investigational second-generation integrase inhibitor, showed it to be non-inferior to Isentress. “Non-inferior” is a scientific designation applied to study results meaning that the drug studied is not less effective than the one it is compared to. If approved, dolutegravir may be at an advantage because it is given once a day, while Isentress is given twice daily.
The SPRING-2 study looked at about 800 individuals taking HIV therapy for the first time, half of them on a regimen with 50 mg dolutegravir once daily and half on a regimen with Isentress (400 mg twice daily). ViiV Healthcare and Shionogi & Co. reported that through 48 weeks, both groups achieved undetectable viral load (less than 50 copies per mL): 88% of the study participants given dolutegravir vs. 85% of those given Isentress.
Dolutegravir is now available through an expanded access program (EAP), which allows for drugs not yet approved by the FDA to be provided free of charge to those in great need.
More SPRING-2 results will be presented later this year. SPRING-2 is one of four Phase 3 studies expected to be reported in 2012.
Both dolutegravir and Isentress are from the class of drugs called integrase inhibitors (INSTIs, for integrase strand transfer inhibitors).
In other news involving Isentress, the already known results from the SWITCHMRK 1 and 2 studies were added to its drug label, showing that fewer people maintained undetectable viral load (less than 50 copies per mL) when switching from Kaletra to Isentress than those who continued on Kaletra. These studies enrolled individuals with previous virologic (viral load) HIV treatment failure. Moreover, they were not limited by the number of HIV regimens they had previously taken. Both of these make future therapy more apt to fail. Nevertheless, the combined data from both studies showed that 82.3% of the people given Isentress had undetectable viral load vs. 90.3% of those kept on Kaletra as a comparison group. Results are from 24 weeks. Several mitigating aspects of SWITCHMRK should be considered, however. See the One-on-One interview with Dr. Joe Eron in the May/June 2009 issue of Positively Aware.
New guidelines recommend ART for all
Treatment guidelines from the U.S. Department of Health and Human Services now recommend that all people with HIV be put on antiviral therapy. According to the panel of experts (including advocates living with HIV) that updated the guidelines on March 27, this and other changes “are primarily based on increasing evidence showing the harmful impact of ongoing HIV replication on AIDS and non-AIDS disease progression. In addition, the updated recommendations reflect emerging data showing the benefit of effective ART [antiretroviral therapy] in preventing secondary transmission of HIV.”
The panel divides the strength of their recommendations into three categories. For people with less than 350 CD4+ T-cells, the recommendation is “strong” based on data from randomized controlled studies (the gold standard of research). For people with CD4 counts between 350 and 500, the recommendation is also “strong,” but based on data from “well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes.” And for people with CD4 counts greater than 500, the recommendation is “moderate” and based on expert opinion.
As always, there are certain groups of individuals for whom the panel recommends treatment no matter what their CD4 counts are:
• Pregnant women
• People over age 50
• Anyone with a history of an AIDS-defining illness
• People with HIV-associated nephropathy (HIVAN)—kidney damage or disease, and
• People who also have hepatitis B
Other changes to the guidelines include new sections on older patients with HIV, the use of hormonal contraception (there is conflicting data on whether they increase the possibility of transmission), hepatitis C and tuberculosis information, new drug interactions, and updates on transmission. See the guidelines at www.aidsinfo.nih.gov.
Viread and kidney risk
Despite new data from the Veterans’ Administration (VA), the Viread (tenofovir) story remains the same: patients taking Viread should be monitored for kidney toxicity, especially if they have risk factors such as hepatitis C, high blood pressure, or diabetes. The study was published in February’s issue of AIDS and is available at www.natap.org.
Dr. Joel Gallant of Johns Hopkins University explains that, “The VA study essentially confirms what we already know: that tenofovir can cause kidney damage in some people who take it. It isn’t surprising that the risk increases with longer time on the drug; that’s true of most drug toxicities. Tenofovir has been included in the vast majority of clinical trials involving initial antiretroviral regimens. These trials have universally shown excellent long-term safety, including minimal development of kidney toxicity.”
The risk of kidney damage may be higher when Viread is combined with protease inhibitors, used by older people or those with pre-existing kidney disease, or in people who are taking other kidney-toxic drugs, such as non-steroidal anti-inflammatory drugs (e.g., ibuprofen).
However, Dr. Gallant added, “We know how to monitor for kidney toxicity, which generally happens gradually. We can always change drugs if it occurs.”
The observational study conducted by the San Francisco VA Medical Center and the University of California, San Francisco looked at the electronic health records of nearly 11,000 VA patients with HIV (the majority of them male). The study looked at three types of renal problems and after controlling for other risk factors, they found that each year of tenofovir use was associated with a 34% increased risk of proteinuria, 11% increased risk of rapid decline in kidney function, and 11% increased risk of chronic kidney disease (CKD). These risks were found after weighing other risk factors such as older age, non-white race, and smoking.
The researchers wrote that based on this data, “If you were to follow 1,000 HIV-infected patients for a year, you would expect to see 50 extra cases of significant protein in urine, 38 extra cases of rapid decline, and 11 extra cases of chronic kidney disease in users of tenofovir versus non-users.”
Said Dr. Gallant in an email message, “Remember that while an increased risk of ‘11% to 34%’ sounds scary, an 11% to 34% increase in a very low risk is still a very low risk. As an example, if your risk of developing kidney disease without tenofovir is 1% per year, and tenofovir increases your risk by 11% to 34%, then your risk of kidney disease on tenofovir becomes 1.11% to 1.34% per year.”
Dr. Daniel S. Berger of Northstar Medical Center in Chicago, also a member of the PA advisory board, wrote, “Tenofovir, as does HIV infection itself, was long known to be associated with kidney function risks, but more commonly occurs with other predisposing illnesses such as diabetes and hypertension. We monitor renal function routinely in our daily practice, as we do for other side effects.”
Added Dr. Berger, “What makes Viread and Truvada the most popular HIV treatment today is its excellent safety profile, tolerability, and the forgiveness provided by its long intracellular half-life (longevity in the blood and cells). These characteristics are responsible for many important strides in HIV therapy and to many reasons that we currently observe much less nucleoside resistance with higher durability and lasting success of many HIV regimens overall.”
The VA study is the largest to date looking at the relationship between tenofovir and risk of renal toxicity. The study group also reported that kidney toxicity was not immediately reversible, but remained after people stopped taking tenofovir, from out to six months to a year. Tenofovir is also found in Truvada, Atripla, and Complera.
Doing what Fred Says
Dr. Rob Garofalo is a physician who has treated HIV-positive children and adolescents for more than two decades. He was diagnosed with cancer in 2006 and at a particularly low point in his life, he searched the Internet for “puppy Chicago” and an image of Fred popped up. Although he had never previously had a pet, Garofalo credits the Yorkshire terrier with bringing both peace and joy to his life again.
Fred’s healing properties have now led to a creative project aimed at helping teens who are HIV-positive and uninsured. By selling “Fred Says” greeting cards online, Garofalo is raising money to help this vulnerable population. According to their website, doc and dog have four goals:
- to raise as much money as possible for HIV-positive teens without health insurance,
- to be as popular as ”Boo” on Facebook (he’s Fred’s idol),
- to have their efforts noticed by Ellen Degeneres, and to go on her show (Fred just loves her), and
- to sell enough cards that they can make a beneficial impact on teens with HIV.
Garofalo is an attending physician at Children’s Memorial Hospital in Chicago, and Director of both the hospital’s Adolescent/Young Adult HIV Program and the Gender, Sexuality, and HIV Prevention Center. Garofalo is a strong advocate for HIV-positive adolescents through primary patient care and innovative HIV prevention research projects. To help him and Fred reach their goals, go to www.fredsays.org. A $1 e-card can help teens living with HIV.
Video readies inmates for return to society
The video “Outside the Walls: Life Beyond HIV,” from the AIDS Foundation of Chicago (AFC), will be shown inside Illinois Department of Corrections (IDOC) facilities starting this year. The four-minute video features two former inmates who are living with HIV along with AFC Director of Correctional Health and Community Affairs Rev. Doris J. Green.
Angela McLaurin describes that moment in 1995 when she tested positive for HIV while in prison as “the wake-up call.” Upon her release, Angela used an HIV services directory to link herself to resources, but she knows that a booklet of information is no substitute for individual assistance. That’s why she and Tawon Dale, both members of the AFC Community Advisory Board, agreed to appear in the educational video, to encourage inmates to know their HIV status and connect to HIV/AIDS services upon release.
“I’m a testament to the fact that there is life beyond HIV,” says Angela, a motivational speaker and educator. “Early detection is key because what I’m seeing is that people don’t get tested until it’s way too late. And it’s sad because the help is out here.”
Rev. Green talks about the services available, including housing, and says, “When you return to the community, know people care.” Rev. Green has worked for years to bring HIV education into prisons and jails and it was through her work as liaison between AFC and IDOC that production of the video was possible.
The video is available as a free download at http://bit.ly/outsidethewalls and is also being distributed in Chicago neighborhoods as a DVD through Men & Women in Prison Ministries, a non-profit organization that provides support to incarcerated populations, their families, and the community at large. It can also be viewed at www.aidschicago.org/corrections.