LifeGuide
[Treatment Horizons]
Approved as a Salvage Therapy, Tipranavir Is now Being Studied in Diverse Populations
by Chael Needle
Enrollment has started in the SPRING study, a clinical trial designed to look at tipranavir across gender and ethnic differences. [SPRING is short for “Safety, efficacy and Pharmacokinetics of tipRanavir boosted with low dose ritonavir (500 mg/200 mg) twice daily IN 400 racially and Gender diverse HIV positive treatment-experienced population.”]
Tipranavir, a second line of defense protease inhibitor, was FDA-approved for treatment-experienced patients relatively recently, but, as SPRING study lead investigator Dr. Kathleen Squires points out, the studies that led to its approval, such as RESIST 1 and 2, were overwhelmingly populated with white men. This distribution of study subjects is not unusual. Lower recruitment numbers in clinical trials for women of all ethnicities as well as all nonwhite individuals have persisted in HIV research since its inception. Safety and efficacy analyses based on sex/gender or ethnic/racial categories have been uncommon, if performed at all. A few studies have looked at viral load, T-cell counts and disease progression, drug metabolism, side effects, lipodystrophy, among other issues, as affected by gender and/or ethnic differences.
The research community and pharmaceutical companies are starting to recognize this blind spot, especially in an era when women are estimated to account for fifty percent of all infections and people of color globally have been disproportionately affected by HIV, reminds Dr. Squires, who serves as director of the Division of Infectious Diseases and Environmental Medicine at Thomas Jefferson University in Philadelphia.
The SPRING study was designed to account for patient populations who represent the “leading edge of the infection,” she explains. “It’s important that if you’re going to look at a drug, any specific drug, you want to study it in the population who are most affected by the condition you are trying to treat. I think [that] going forward, as new drugs are developed, it’s a challenge and I think something that needs to be prospectively addressed—how do we study these drugs in those populations?—rather than trying to look at it after the drug has been approved.”
In general, recruiting women and people of color has been limited by a number of issues. “For women, and I think this is also kind of true of people of color, the demographics would suggest that many of these patients have limited access to healthcare, by virtue of the jobs that they have or don’t have; that on average they are poor, quite frankly; that specifically many of these patients come from what I would call disenfranchised populations.” Transportation often becomes a hurdle, as do jobs that do not allow flexibility. She adds that, for women, the needs of others—especially family—often are placed ahead of their own needs. These barriers need to be addressed “proactively,” says Dr. Squires, “to really help patients access healthcare and stay in healthcare, or access clinical trials and stay in clinical trials.”
The SPRING study’s sponsor, Boehringer Ingelheim, makers of Aptivus, “has certainly paid attention to these issues in terms of trying to identify sites where patients who are women or of color are likely to be seen, and to work with those sites to help them work around these issues,” says Dr. Squires. The study will be conducted across seventy-two sites in the United States, Canada, Mexico, Germany, Italy, Spain, Argentina, and Brazil, and will recruit for diversity to include 200 men and 200 women across White, Black, Hispanic, Asian and American Indian ethnic backgrounds, among others. All participants will be highly treatment-experienced (having been on at least three classes of antiretrovirals and documented resistance to at least one PI).
SPRING is the largest randomized controlled trial to assess the use of therapeutic drug monitoring (TDM) in highly treatment-experienced HIV patients. TDM involves consecutive measurements of “levels of the drug in the patients’ system to see whether you need to change the levels of those drugs,” Dr. Squires says. A change in drug levels through a dosage change, she notes, may be needed to achieve a good therapeutic response, for example. Or drug levels higher than necessary for a good therapeutic response in those who are experiencing side effects may need to be lowered. Noting that there is some earlier evidence that suggests there may be differences in the way men and women metabolize drugs, and that on average women have higher drug levels than men do, she states that “therapeutic drug monitoring, or pharmacokinetic analysis of drugs, has been built into [the study design] to understand from every aspect how this particular drug may work, and its safety profile in different [ethnic/racial] populations and the two different sexes.”
Asked if HIV doctors appreciate gender or ethnicity when they’re trying to tailor regimens for individual patients, she responds that clinicians are increasingly realizing there may be differences, not in terms of efficacy, really, but in side effects and toxicity profiles, as some gender and racial background analyses have suggested. “I’m interested overall in HIV infection, but have been very interested in HIV infection in women and to be able to conduct trials where we can tease out these differences is very important and exciting.”
To learn more about criteria and SPRING study sites, log on to www.clinicaltrials.gov.
Chael Needle wrote about entry inhibitor candidate PRO 140 in the June issue.
July 2007 |
