The advent of generic HIV medications in the 2000s had a dramatic effect on improving outcomes in developing countries with a high HIV/AIDS burden. Before that, death rates were skyrocketing because people did not have access to the expensive antiretroviral agents that were already available in developed nations, and testing and prevention efforts were limited because of a lack of resources and the challenges of the HIV/AIDS stigma. The situation was so dire that in 2000, the United Nations released a report that predicted half of teenagers in Africa would die of AIDS before they reached age 50 years, with estimates reaching as high as two-thirds of teenagers in the hardest hit African nations, such as Botswana.1 Because of this gap in access to HIV medication, AIDS-related deaths in Africa did not start declining until 2007, whereas outcomes in patients with HIV/AIDS in the United States started to improve in the mid- to late 1990s, after approval of the first antiretroviral drugs.2,3 Although generic antiretroviral agents have had a dramatic effect on HIV/AIDS outcomes in developing nations, where the unmet need was great and their availability was spurred by compassionate use lobbying, their niche in developed countries such as the United States have yet to be worked out.
The first generic antiretroviral therapy, didanosine delayed-release capsules for use in combination with other antiretroviral agents, was approved by the US Food and Drug Administration in December 2004.4 Since then, several other generic antiretroviral agents have come onto the US market, including lamivudine, abacavir, and efavirenz, with availability of a generic version of tenofovir disoproxil announced by Teva in December 2017.4-6 Other drug manufacturers are expected to market their own generic versions of tenofovir disproxil fumarate, including Laurus Labs Ltd, a major supplier of the key ingredients in many HIV antiretroviral agents, which received approval for its generic version of tenofovir disoproxil in March 2018 after its formulations unit passed US Food and Drug Administration inspection.7
Although the US market is poised to be flooded by generic antiretroviral agents from numerous drug manufacturers as antiretroviral drugs continue to come off patent, there are barriers to their use. Questions remain about their potential cost-savings, and there are concerns about whether patients will adhere to generic regimens.
The estimated discounted lifetime cost of HIV treatment in the United States is $326,500, with antiretroviral agents making up about 60% of those costs.5 A cost comparison of 4 regimens currently recommended by the US Department of Health and Human Services showed costs could often be cut by substituting available generics.5 For example, a switch from a brand name to a generic formulation of the 3-drug combination of dolutegravir, abacavir, and lamivudine could save $667 in wholesale acquisition costs and $553 in federal supply schedule costs for a 30-day supply.5 But not all substitutions yielded such significant price reductions. Switching to generic formulations of dolutegravir, tenofovir disoproxil fumarate, and emtricitabine yielded a savings of only $5 for public payers.5
In some cases, switching from brand-name antiretroviral drugs might not yield any cost savings to patients. This is because many combination antiretroviral agents have components that are not off patent in the United States. Patients receiving such regimens might need to have their prescribed regimens broken into multiple pills, which can lead to multiple insurance copayments, adding to patient cost burden.5 Furthermore, with many drug manufacturers offering copay programs for brand-name drugs, there might be little incentive for patients to make the switch to generics.
Treating HIV/AIDS remains a big business. It is anticipated that the global market for HIV-1 therapeutics alone will reach 15.8 billion USD by 2025.8 Every manufacturer’s goal is to grab as much of that market as possible, whether they are selling brand-name or generic antiretroviral agents. For the brand-name manufacturers, preserving and boosting the bottom line often means employing tactics to stifle competition from the generics manufacturers.
“Manufacturers have used various strategies to delay generic competition, such as developing coformulations with medications that have longer patent lives (e.g., coformulating tenofovir disoproxil fumarate with emtricitabine), changing inactive drug components (e.g., adding a new binding agent to the combination of efavirenz, emtricitabine, and tenofovir to resist degradation), filing for approval for additional indications that introduce new patent claims and extend market exclusivity (e.g., obtaining [US Food and Drug Administration] approval to market lamivudine to treat hepatitis B virus), and obtaining patents on pediatric formulations (e.g., patenting the combination of lopinavir and ritonavir),” wrote Martin and Schackman in a recently published article in the New England Journal of Medicine.5
But brand-name manufacturers are not the only ones employing tactics to enhance their bottom line. In 2016, Turing Pharmaceuticals received considerable criticism after it raised the price of the antiparasitic medication pyrimethamine, which is often used to prevent and treat various infections in patients with HIV. The cost of the medication increased 5000%, from $13.50 a pill before Turing acquired the drug to $750 a pill after they rebranded it as Daraprim. In spite of significant media attention and pushback, the current price is reported to exceed $800 per pill in many pharmacies, despite Turing promising it would reduce drug costs.9
Although the Turing example is extreme, it shows what can happen when competition is eliminated or stifled through company mergers or drug acquisitions. To address such concerns, some state legislators are proposing various bills aimed at preventing price gouging and ensuring price transparency.10 In Illinois in February 2018, House Bill 4900 was proposed, also known as the Illinois Generic Drug Pricing Fairness Act. If enacted, the state attorney general could subpoena any generic drug company that significantly increases the cost of essential off-patent or generic drugs (≥30% in 1 year, ≥50% in 3 years, ≥75% in 5 years), and those found in violation of the act could face various penalties, including restitution to patients who paid the increased prices.11
To add to this marketplace mayhem, brand-name and generic drug pricing can vary significantly between pharmacies, depending on what is negotiated between pharmacy benefits managers and retailers. A 2017 issue of Consumer Report found that the cost of the same prescription drug can vary by hundreds of dollars at different pharmacies, even within the same town.12 Therefore, the retailer can factor just as heavily into the cost equation, and patients might have to shop around to determine the most cost-effective route for them.
Adherence and Acceptance Arguments
Concerns over patients accepting or adhering to generics have been raised, especially if the regimen leads to an increase in pill burden. In a French survey-based study assessing perception of antiretroviral generic medicines among patients and physicians, only 17% of patients surveyed would accept generic antiretroviral agents if their use would increase the pill burden.13 Among the physicians surveyed, only 26% said they would prescribe generics even if a regimen had to be broken into multiple pills.
It has also been suggested that patients might perceive switching from 1 combination pill to multiple pills as a step backward, and that they may have concerns over an increased risk for adverse effects with generics.5 “In promoting their brand-name products, manufacturers may emphasize the side effects of older products as compared with newer brand-name alternatives, thereby increasing the general mistrust of generics,” wrote Martin and Schackman.
The Bottom Line
Generic antiretroviral agents have had a dramatic effect on changing the dismal outcomes of HIV-infected patients in developing nations and are providing more treatment options to those in developed countries, including the United States. Although generics may not always be less expensive than their brand-name counterparts, they are providing patients with more options and spurring competition in the process, which may ultimately help UNAIDS achieve its 90:90:90 goal, making 90% of HIV-positive patients aware of their disease, giving 90% of HIV-positive patients treatment, and having 90% of patients receiving treatment achieve undetectable viral loads by 2020.
- UN predicts half the teenagers in Africa will die of AIDS. BMJ. 2000;321(7253):72.
- Thirty years of HIV/AIDS: snapshots of an epidemic. amfAR. Accessed April 2, 2018.
- UNAIDS Special Report Update. Published May 2013. Accessed April 2, 2018.
- HIV/AIDS Historical Time Line 2000-2010. US Food and Drug Administration. Updated January 5, 2018. Accessed April 2, 2018.
- Martin EG, Schackman BR. Treating and preventing HIV with generic drugs—barriers in the United States. N Engl J Med. 2018; 378:316-319.
- Teva announces exclusive launch of a generic version of Viread in the United States. Teva Pharmaceutical Industries, Ltd. Released December 15, 2017. Accessed April 2, 2018.
- Laurus Labs received gViread approval, unit clears USFDA inspection. IIFL Group. Published March 5, 2018. Accessed April 3, 2018.
- HIV-1 therapeutics market size to reach USD 15.8 billion by 2025. Grand View Research. Published October 2016. Accessed April 6, 2018.
- Daraprim prices still an obstacle for patients. Healio. Published March 26, 2018. Accessed April 6, 2018.
- Checking in: are your state legislators concentrating on drug-price transparency? Policy and Medicine. Published February 28, 2018. Accessed April 6, 2018.
- Mesa B. House bill aims to gouge the gougers. Columbia Chronicle. Published March 4, 2018. Accessed April 6, 2018.
- Gill LL. How to pay less for your meds. Consumer Reports. Published April 5, 2018. Accessed April 6, 2018.
- Jacomet C, Allavena C, Peyrol F, et al. Perception of antiretroviral generic medicines: one-day survey of HIV-infected patients and their physicians in France. PLoS ONE. 2015;10(2):e0117214.