States to explore putting restrictions on AIDS drug Trizivir

AIDS Healthcare Foundation (AHF) has sent a letter dated October 20, 2004, to the heads of all state Medicaid programs asking them put in use treatment authorization request (TAR) procedures on GlaxoSmithKline's (GSK) fixed-dose combination AIDS drug, Trizivir, as a standalone regimen for treatment naïve patients.

The letter is the latest action by AHF in response to a 2003 National Institute of Health (NIH) study published in the New England Journal of Medicine that showed that the three-drugs-in-one-pill regimen performed poorly as a standalone when compared to two standard efavirenz (Sustiva) containing triple regimens. In fact, the Trizivir regimen has been removed from the DHHS guidelines for recommended antiretroviral therapy for naïve patients. AHF has received a number of positive responses in reply to the letter sent by the organization's officials advising the states of the regimen's deficiencies.

AHF's concern has been that physicians not expert in HIV medicine may continue to prescribe the fixed dose combination (FDC) Trizivir as a standalone regimen to treatment naive patients, therefore putting those patients at risk. The letter (text included below) intended to raise awareness about this important issue, and encouraged states to take action to protect the health of treatment naive HIV-positive individuals. "The recent daily headline news stories surrounding the FDA and the safety of drugs, should serve as just another example to the public for the need to be vigilant in protecting our own health," said Michael Weinstein, President of AIDS Healthcare Foundation. "Since most people do not regularly thumb through the New England Journal of Medicine and since months after the NIH study was released, GSK continued to run ads stating that "Trizivir treats HIV infection alone or in combination ... " we believe it is important to relay this message to health officials, so that they too can take steps to protect the health of treatment naive HIV-positive individuals."

AHF has received a positive response from at least six states that they are taking further action on the matter. The Florida state Medicaid program for example, replied that it is "considering all the options for a timely implementation of prior authorization to limit the use of Trizivir in antiretroviral treatment naive patients." Many states including Missouri, Colorado, North Carolina, and New York have referred the content of the letter onto the appropriate committee for further discussions. Idaho, as well, agreed that the information from the NIH study warrants restrictions of the FDC regimen Trizivir in naive patients.

"We are pleased with the positive responses that we have received from the health officials of many states," said Weinstein. "We will persist in our efforts to inform people of the dangers of this drug when it is used as a standalone regimen and look forward to working with others to encourage action on this issue, as we continue to be proactive in our efforts to protect the health of people living with HIV."

In mid-March, 2003 the NIH suspended part of a three-arm, two-year government sponsored AIDS CLINICAL TRIALS GROUP STUDY (ACTG 5095) comparing AZT+3TC+abacavir (the components of Trizivir) to other regimens (Trizivir+Sustiva and Combivir+Sustiva) when it quickly found that the Trizivir combination when used as a standalone does not protect patients as well as some other combinations of medicines. The Trizivir-only arm of the study was stopped after a percentage of patients experienced virologic failure -- their viral load increased to a dangerous level much sooner than that of the patients in the other two arms of the study.

The full text of AIDS Healthcare Foundation's letter to the states Medicaid directors follows:

This is to request that the (state) Medicaid program place treatment authorization request procedures ("TAR") on Trizivir, a product of GlaxoSmithKline ("GSK") used to treat HIV/AIDS.

Based on recent tests and studies, AIDS Healthcare Foundation ("AHF"), the nation's largest AIDS treatment organization believes that Trizivir, a fixed dose combination drug containing three separate medications used to treat HIV/AIDS, is not appropriate in most cases for treatment naive HIV patients. We are concerned that physicians not expert in HIV medicine may continue to prescribe to naive patients, and that such prescriptions will have an adverse fiscal impact on the state.

We therefore urge that the TAR process be implemented to restrict Trizivir's use for patients who are naive to ARV therapy.

Trizivir is a fixed dose combination ("FDC") tablet that contains the following HIV/AIDS medications: AZT, 3TC, and abacavir. One of the presumed benefits of Trizivir -- taking these three drugs in one pill -- is that, because it purportedly lowers the pill burden, there will be better compliance and adherence to a medication regimen. This, the theory goes, will result in increased health outcomes for patients, as well as increased ease of use and treatment by doctors. For these reasons, FDC products have experienced a growth in use and popularity and are now produced in various forms by a number of pharmaceutical companies.

The problem with Trizivir is that, while the individual medications comprising it may be effective in treating HIV/AIDS, the specific combination has been shown to have minimal effectiveness. The National Institutes of Health ("NIH") conducted a study to measure the effectiveness of various AIDS drug combinations, including Trizivir (ACTG 5095). In March of 2003, however, the NIH suspended a portion of its study comparing Trizivir to other regimens.

The NIH study compared treatment naive patients on Trizivir alone with patients who took a combination of Trizivir and Bristol-Myers Squibb Co.'s ("BMS") Sustiva, or Sustiva and a two-drug tablet called Combivir, also made by GSK. Twice the number of Trizivir-only patients saw their HIV levels climb again within about eight months of starting therapy. According to a Kaiser Daily HIV/AIDS Report on the issue, the researchers stopped one arm of the study because patients taking Trizivir experienced virologic failure -- defined as having a viral load level above 200 copies/ml at least four months after beginning the treatment -- sooner and more often than patients in the other two arms of the study.

The finding that Trizivir is less effective for treatment naive patients with HIV/AIDS recently was stated again in a study published in the April 29, 2004 issue of The New England Journal of Medicine (Volume 350, Number 18, pages 32-43).

Trizivir's lack of effectiveness renders it unsafe for treatment naive patients. It is apparent that Trizivir may be effective only if it taken with other HIV/AIDS drugs. However, Trizivir is marketed and used to treat HIV alone. The potential harm to these patients is increased as many are treated by general practitioners who may not be aware of the most recent findings and continue to prescribe Trizivir to treatment naive patients. This will result in reduced health outcomes for those who take the promise of the FDC to heart and use only Trizivir.

While Trizivir may be effective when taken in combination with other HIV/AIDS medications, the necessity of taking additional medications appears to defeat the purpose and benefit of fixed dose combination therapy -- reducing pill burden to increase regimen adherence and compliance. Therefore, the chief benefit of Trizivir is lost.

The end result of the continued presence of Trizivir on the market is confusion, decreased health outcomes, and drug resistance. Given the effectiveness of the three drugs comprising Trizivir, and the existence of numerous other AIDS medications, including other FDC's, the continued use of Trizivir for treatment naive patients presents a real danger to those people afflicted with HIV/AIDS.