Generic HIV Drugs Could Save Millions, But May Reduce Effectiveness

Using separate generic pills instead of a brand-name 3-in-1 coformulation could save more than $900 million during the first year, but such a switch could also lead to reduced adherence to antiretroviral therapy (ART) and poorer treatment outcomes, according to a mathematical model described in the January 15, 2013, Annals of Internal Medicine.

Generic antiretroviral drugs are widely used in low-income countries, but most popular modern medications are still under patent protection in the U.S. The picture will change, however, when efavirenz (marketed as Sustiva by Bristol-Myers Squibb) goes off patent later this year.

This would allow people with HIV to switch from Gilead Science's Atripla (tenofovir/emtricitabine/efavirenz) once-daily single-tablet regimen to a combination of generic efavirenz, generic lamivudine or 3TC (a drug similar to emtricitabine), and branded tenofovir (marketed as Viread). But patients may maintain better adherence when they only have to take 1 pill, and some research has shown that lamivudine has a lower barrier to resistance than emtricitabine.

Rochelle Walensky from Massachusetts General Hospital and colleagues devised a mathematical model to predict the effects of such a switch, looking at overall cost-savings, incremental cost-effectiveness, and changes in treatment outcomes. The analysis was funded by the National Institute of Allergy and Infectious Diseases.

They found that compared with no treatment at all, generic ART has an incremental cost-effectiveness ratio, or ICER, of $21,100 per quality-adjusted life-year, or QALY. Compared with generic ART, brand-name therapy increases lifetime costs by $42,500 per person. The estimated first-year savings if all eligible patients start or switch to generic ART would be $920 million. "Most plausible assumptions about generic-based ART efficacy and costs lead to branded ART ICERs greater than $100,000 [per] QALY," the researchers concluded.

The model projected the cost savings over a patient's lifetime, but once a generic formulation of tenofovir also becomes available, people will be able to construct an all-generic regimen that is even cheaper. An additional issue, for people with insurance, is that 3 separate drugs may require 3 copays, which could actually lead to higher out-of-pocket costs when using the generics.

Below is an edited excerpt from a press release jointly issued by Massachusetts General Hospital and Weill Cornell Medical College describing the analysis in more detail.

 

Generic HIV Treatment Strategy Could Save Nearly $1 Billion Annually but May Be Less Effective

 

January 14, 2013 -- Replacing the combination of brand-name, antiretroviral drugs currently recommended for control of HIV infection with soon-to-be-available generic medications could save the U.S. health care system almost $1 billion a year but may diminish the effectiveness of HIV treatment. A study led by Massachusetts General Hospital (MGH) and Weill Cornell Medical College investigators, appearing in the January 15 Annals of Internal Medicine, examines the potential impact of such a change. 

 

"The switch from branded to generic antiretrovirals would place us in the uncomfortable position of trading some losses of both quality and quantity of life for a large potential dollar savings," says Rochelle Walensky, MD, MPH, of the MGH Medical Practice Evaluation Center, lead author of the study. "By estimating the likely magnitude of these offsetting effects now -- before generic antiretrovirals actually hit the shelves -- we can confront our willingness as clinicians, patients and as a society to make these difficult choices." 

 

In 2011 the cost of antiretroviral drugs in the U.S. was around $9 billion, most of which was paid for by government sources. The currently recommended treatment for newly diagnosed patients is a single pill (Atripla) taken daily that combines three brand-name antiretrovirals: tenofovir (Viread), emtricitabine (Emtriva) and efavirenz (Sustiva). A generic form of the antiretroviral drug lamivudine, which has a similar mechanism of action to emtricitabine, became available in January 2012, and a generic version of efavirenz is expected in the relatively near future.  

 

Replacing two of the three branded drugs with generics could significantly reduce costs, the authors note, but such a strategy would also have disadvantages. A more complicated treatment regimen, requiring three daily pills instead of one, increases the risk that some patients will miss doses, leading to the loss of antiretroviral effectiveness called treatment failure. Laboratory studies have also found that lamivudine may be slightly less effective and more vulnerable to the development of drug-resistant viral strains than emtricitabine. 

 

To evaluate the impact of a switch to a generic-based antiretroviral regimen, the research team used a widely used mathematical model of HIV progression to simulate the effects of a daily three-pill regimen of generic efavirenz and lamivudine plus brand-name tenofovir, compared with the current one-pill combination drug. They adopted a worst-case scenario to project the efficacy of the generic drugs and their impact on viral resistance

 

Their results indicated that switching all HIV-infected patients in the U.S. to the three-drug generic strategy would produce lifetime savings of $42,500 per eligible patient. In the first year alone, the nationwide savings would reach nearly $1 billion. However, the quality-adjusted loss of life expectancy could be as much as 4.5 months.

 

The study's senior author, Bruce Schackman, PhD, chief of the Division of Health Policy and associate professor of Public Health at Weill Cornell Medical College, says, "Diverting patients from the most effective, branded treatment alternative could be made more acceptable if the savings were directed to other HIV-related needs. For example, fewer than half the state-funded AIDS Drug Assistance Programs include the effective protease-inhibitor-based treatment for hepatitis C virus (HCV), which infects up to 25 percent of HIV-infected individuals.  We calculated that, for every 15 patients switched to the generic-based regimen, one who is also infected with HCV could be treated and potentially cured of that infection."

 

Adds Walensky, a professor of Medicine at Harvard Medical School, "For patients who take their medications well and adhere to the medical regimen, the generic option will be a bit more complex but could be as effective as the standard regimen. But a patient who relies heavily on the simplicity of taking a single pill is more likely to suffer detrimental effects, since missing doses will increase the risk of treatment failure."

 

"There's no getting around the fact that savings from generics will only be realized if we deliberately route patients away from the most effective, branded treatment alternative," she stresses. "This is a trade-off that many of us will find emotionally difficult, and perhaps even ethically impossible, to recommend. All of us -- consumers, providers and advocates -- would be far likelier to embrace such a policy change if we knew the savings would be redirected towards other aspects of HIV medicine." 

 

1/15/13

References

 

RP Walensky, PE Sax, YM Nakamura, et al. Economic Savings Versus Health Losses: The Cost-Effectiveness of Generic Antiretroviral Therapy in the United States. Annals of Internal Medicine 158(2):84-92. January 15, 2013.

R Sherer. Generic Antiretrovirals and the Uncertain Future of HIV Care in the United States. Annals of Internal Medicine 158(2):133-134. January 15, 2013.

Other Source

 

Massachusetts General Hospital and Weill Cornell Medical College. Generic HIV Treatment Strategy Could Save Nearly $1 Billion Annually but May Be Less Effective. Press release. January 14, 2013.