The Quad Pill: Improving Medication Adherence

Gilead Sciences, the pharmaceutical leader in the development of treatments for HIV/AIDS, has been actively developing and testing the Quad pill, a combination of four HIV regimens in one pill.  The much-hyped Quad pill comes only five years after Gilead released Atripla, a pill that combines two of Gilead’s already developed HIV drugs with an HIV drug from Bristol-Myers Squibb.  Atripla and the Quad pill are fixed-dose combinations that combine multiple antiretroviral drugs into a single pill.  They represent a growing trend in the pharmaceutical industry to combine therapies in order to improve patient compliance, lower manufacturing costs, simplify distribution, and potentially reduce the development of resistance to treatment.  While most of these benefits also translate into increased efficiency and profits for the pharmaceutical companies, they can also result in more effective treatment of disease.

The Quad pill, by combining four HIV treatments into one pill, addresses the issue of medication nonadherence which can many times undermine the success of a treatment for HIV.  According to one study, antiretroviral nonadherence is the second strongest predictor of progression of HIV to AIDS and death.  Most results from studies on adherence of antiretrovirals in HIV patients usually hover around 70%.  Furthermore, the optimal level of adherence for durable virologic and clinical success – taking over 95% of antiretroviral medications – was reached by only 6% of HIV patients.  These results indicate the extent to which nonadherence of antiretrovirals is a problem and in many cases preventing the successful management of HIV.  A meta-analysis of studies on fixed-dose combinations found that they resulted in a 26% decrease in noncompliance.  Gilead, in developing fixed-dose combinations such as Atripla and the Quad pill, has clearly recognized the widespread problem of nonadherence in HIV patients and have focused their R&D efforts accordingly.

The Quad pill is currently in the clinical trial stage of development and could gain FDA approval by mid-2012.  In the clinical trials, Gilead is seeking only to establish the non-inferiority of the pill in comparison to already-approved treatments for HIV.  Gilead’s strategy is centered around the idea that an equally efficacious drug that also allows for better adherence would be preferred by patients and thereby result in better outcomes.  Analysts seem to agree and are already forecasting that the drug could achieve blockbuster drug status (more than $1 billion in annual sales).

While the approval of the Quad pill would be an obvious victory for Gilead, it would also provide a better option for many HIV patients who struggle with taking their medications on a daily basis.  I believe that the development of the Quad pill is an example of how the oft-maligned pharmaceutical industry, at times, is able to create profits while also serving the needs of patients.  Profits and the public good are not mutually exclusive.  In fact, one could argue that if it weren’t for other pharmaceutical companies like Merck and GlaxoSmithKline trying to cut into their share of the HIV drug market, Gilead may never have been compelled to create the Quad pill.  Still, simply developing and distributing the Quad pill is not enough.  Gilead would be wise to also promote programs on a local level that educate HIV patients about their disease and how they can successfully manage it by taking their medication as directed.  In doing so, they should understand the cultural factors that are at play in regions of the world where HIV is highly prevalent.  Additionally, they should work closely with the governments of developing countries that have large HIV populations in order to make sure the drug is affordable.  R&D is not where it ends for pharmaceuticals – pricing, marketing, and distribution are just as important in providing effective (and profitable) treatments for patients.


Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. “Fixed-dose combinations improve medication compliance: a meta-analysis.” American Journal of Medicine. 2007 Aug;120(8):713-9.

Beasley, Deena. “Lofty Hopes Confront Gilead’s 4-Drug HIV Pill.” Reuters Online. 9 September 2011.

García de Olalla  P, Knobel  H, Carmona  A, Guelar  A, López-Colomés  JL, Caylà  JA. “Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients.” J Acquir Immune Defic Syndr. 2002 May;30(1):105-10.

Golin  CE, Liu  H, Hays  RD, Miller  LG, Beck  CK, Ickovics  J, Kaplan  AH, Wenger  NS. “A prospective study of predictors of adherence to combination antiretroviral medication.” J Gen Intern Med. 2002 Oct;17(10):756-65.


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