Cheap AIDS Pills & Shorter Lives Or Broken Budgets?

Should a lower-cost combination of mostly generic pills for treating AIDS replace a more expensive, but convenient brand-name pill? By doing so, the US healthcare system could save an estimated $920 million the first year if every eligible patient switched. At the same time, the change in regimens and lessened effectiveness of one of the generics could increase risks, and shave approximately four months off a patient's lifespan.

Such a choice points up the stark direction the societal healthcare discussion is increasingly taken. And the details in comparing HIV treatments are weighed in a study in the Annals of Internal Medicine, which examined the advantages and disadvantages of taking Atripla, which combines three brand-name antiretrovirals - tenofovir (Viread), emtricitabine (Emtriva) and efavirenz (Sustiva) - or a soon-to-be-available option featuring generics.

Specifically, the study notes that a generic form of Epivir, or lamivudine, an antiretroviral with a similar mechanism of action as Emtriva, became available a year ago. And a generic version of Sustiva is expected in the near future. Along with Viread, the two generics could offer a lower-cost alternative to Atripla. For the record, Viread and Emtriva are sold by Gilead Sciences (GILD), while Sustiva is sold by Bristol-Myers Squibb (BMY). Both drugmakers market Atripla.

Given that the cost of antiretrovirals in the US was roughly $9 billion in 2011, a lower-cost combination may be a tempting option for third-party payers. Using a mathematical model, the researchers found that switching all HIV-infected patients in the US to the generic-based combo would produce lifetime savings of $42,500 per patient. And to mollify concerns about lifespans and risks, they say savings could be used to attack chronic hepatitis C.

"In an era in which dedication to the national HIV mission requires 'redirected' financing, the potential $1 billion savings from generic-based regimens might be an efficient source available for national reinvestment," write the authors. How so? For every 15 people switched to a generic-based regimen - with potential annual savings of $6,100 per patient - one person co-infected with HIV and HCV could be potentially cured of chronic hepatitis C.

The study noted that the Atripla branded regiman yields a so-called quality-adjust life year cost of $114,800, which exceeds the $100,000 benchmark that is generally preferred for weighing cost effectiveness of medicines. And while the study did not calculate societal savings beyond the first year, lead author Rochelle Walensky says the annual savings thereafter could be expected to be similar (here is the abstract).

Looked at another way, the approximate cost of Atripla is $15,000 per patient per year, compared with about $9,000 for the generic-based regimen, a $6,000 difference. To reach these calculations, the researchers made various assumptions about pricing, since generic versions of Sustiva are not yet available in the US, explains Walensky, a Harvard University medical school professor and infectious diseases physician at Massachusetts General Hospital.

Of course, the study does note the potential downside. For one thing, patient adherence could suffer as three pills, instead of one, would be required, leading to treatment failure. And laboratory studies have also found that Epivir may be slightly less effective and more vulnerable to the development of drug-resistant viral strains than Emtriva. And then there is the loss of four months of life, on average, that may occur.

"It's a societal fix," Walensky tells us. "No one wants to put their nickel on what they want to pay for QALY. Some would argue this ratio is beyond what we should be paying for the branded ART (antiretroviral therapy). But the generic ART (cost) is attractive. Maybe the answer is that we should be paying for generic ART. One might not be happy to think about what were losing with generic ART, but we might be able to gain a lot more from that same money spent. We put numbers on things that people are curious about.

"I think we need to be empowered to know how this is can be a win- win for our patients and pocketbooks. Patients have to be the ones to take a higher pill burden. Wouldn’t it be nice if they were getting some benefit? Such as easier treatment for hepatitis C or assistance in paying for their co-pay? We conducted this analysis from a policy perspective to open the discussion to think about how we can save a lot of money and what that means for our patients. When I speak to a patient, I want to know if they can tolerate taking three instead of one pill, or will they fail? That's something I sure want to know," she says.

"If we don’t quantify trade offs for the day when generics come out, we’re playing in a data-free zone. There's a lot of money at stake here and how we negotiate this and what do with those dollars is an important discussion to have. I have no judgment as to how well these generics will work – that's not the point of the study. The point was to demonstrate that, even if they didn’t work as well, genrics would still come out ahead in terms of cost effectiveness," she continues.

"And even if generics don’t do as well and adherence is to blame, it's because drug companies are not working together to formulate generics into a single pill. And that’s something that society has the power to fix. Whether we can exert enough pressure is unclear. That's not scientifically grounded, but politically grounded."

[UPDATE: Doctors Without Borders notes that the patents on Viread "are what block the production of combinations... and prevent patients in the US from accessing generic versions..." The advocacy group adds that Gilead obtained additional patents after the basic patent expired. As a result, generic versions will not be available in the US before 2018.]

Certainly, this is a provocative notion and offers a more specific example of the broader discussion that has been taking place in recent years. Making such decisions, however, will not be easy, especially as ethical considerations come into play. Who wants to be the one to decide whether four months of life is worth 'x' dollars and could be subtracted from a lifetime? At the same time, the ability to provide life-saving medicines to the largest population possible may well be compromised if savings are not realized. What do you think?

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[UPDATE: A few days later, Gottfried Hirnschall, director of the HIV/AIDS Department at the World Health Organization, and Cornelis de Joncheer, director of the Department of Essential Medicines and Health Products at the WHO, wrote this letter to the Annals of Internal Medicine:

"Rochelle Walensky and colleagues provide important estimates of the potential cost savings associated with the introduction of generic-based antiretroviral therapy (ART) in the US. Using conservative ssumptions, they estimate first-year savings of up to US$ 920 million and lifetime average savings of $42,500 per eligible patient. However, the authors of the study caution that this may require a tradeoff between drug efficacy and cost savings, as the regimens proposed in the model are not available fixed-dose combinations and may have inferior efficacy and could lead to poor adherence.

"We would like to highlight three points related to this analysis.First, the assumption of inferior efficacy is based on the suggesting that lamivudine (3TC) has poorer efficacy than emtricitabine (FTC). This assumption is in contrast to a recent systematic review that found no evidence of any difference between the two drugs in terms of efficacy and safety. Second, the assumption of poorer adherence is based on the fact that generic formulations are not available as fixed-dose combinations. This may be the case in the United States, but quality-assured generic fixed-dose combinations of tenofovir, emtricitabine and efavirenz (TDF+FTC+EFV) do exist and are used in other parts of the world. Third, each of the scenarios includes the originator TDF product because TDF is patented in the US, and the estimated cost of this regimen is US$ 9,200 per patient/year. However, a fixed-dose combination of TDF+FTC+EFV including generic TDF is currently available internationally and costs less than US$ 200 per patient/year.

"Taken together, these points suggest that potential cost savings in the United States of using generic regimens could be even greater than concluded by this analysis, with no negative consequences in terms of efficacy or adherence. It is important to also highlight that in this analysis, presumed differences between generic and originator regimens are associated with the use of different drugs (3TC versus FTC), and formulations (separate tablets rather than fixed-dose combinations), and not the use of generic drugs per se: "Walensky et al rightly consider quality-assured generic and originator drugs to be equivalent in terms of safety and efficacy. Despite ongoing doubts and controversies about the use of generic antiretrovirals over the last decade, comparative studies have found no differences in safety or efficacy between originator and quality-assured generic antiretrovirals. Ensuring access to affordable antiretroviral therapy has been an essential precondition of the global scale up of antiretroviral therapy, and both generic and originator companies have an important role to play in ensuring that current and future antiretroviral regimens are accessible and affordable for all who need them.

"The study by Walensky et al opens an important discussion about the extent to which patients in the United States are able to access more affordable, fixed-dose antiretroviral regimens that are already available in many other countries. Unfortunately, the findings of the modeling study are being portrayed as indicative of the need to make an ethical trade-off between cost savings and efficacy. Such an interpretation is misleading and is not supported by the extensive global evidence of the efficacy of quality-assured generic ART."]