De-simplifying single-tablet regimens for HIV treatment

• A Calgary HIV clinic offered patients a cheaper drug regimen with more than one pill
• Over half of participants chose to switch and achieved high rates of viral suppression
• The clinic reduced drug costs 16% in 2017, and projected $3 million in savings in 2018

In the late 1980s, early formulations of HIV drugs required taking pills frequently, in one case, every four hours. In the mid-to-late 1990s, when potent combination HIV treatment (ART) became available, pill-taking became less frequent, usually three times daily. However, HIV-positive people often had to swallow a fistful of pills at each dosing interval.

About a decade ago, pharmaceutical companies began to put entire regimens in one pill (single-tablet regimens) that could be taken once daily. The marketing departments of these companies touted the “simplification” that such single-tablet regimens could bring to patients. Today, single-tablet regimens are widely used as first-line and even second-line treatment, as they simplify dosing and cut down the number of pills a patient needs to take. The latest versions of single-tablet regimens are also generally very well tolerated.

Growth, money and drug costs

In the aftermath of the financial-economic crisis in 2008, the rate of economic growth in Canada and other high-income countries generally fell and governments received less revenue. One policy response to the financial-economic crisis that many governments have chosen is the imposition of austerity programs. As a result, government spending on healthcare and other needed services is constrained compared to earlier decades when economic growth rates were more robust and inequality was less prominent. One important service that many governments in high-income countries provide is subsidized access to medicines for catastrophic conditions such as cancer, hepatitis C virus and HIV infection. As a result, the cost of drugs for these and other conditions tends to concern policy makers, hospitals, clinics and departments and ministries of health.

There are several steps that have been taken around the world to help reduce the burden of HIV drug prices on payers, such as the following:

• Low- and middle-income countries generally buy generic formulations.
• In some countries, particularly in southern Europe, some clinics privilege the use of functional mono- or dual-therapy in people who have a suppressed viral load with combinations such as darunavir (Prezista) + low-dose ritonavir or atazanavir (Reyataz) + low-dose ritonavir with or without the addition of 3TC (lamivudine).
• Canada’s provinces and territories engage in bargaining with pharmaceutical companies about the price of new drugs for HIV and many other conditions. Despite this bargaining, the resulting prices still eat a large amount of money from provincial and territorial healthcare budgets. As a result, some HIV clinics still strive to further reduce drug costs.

De-simplification

The Southern Alberta Clinic (SAC) in Calgary provides care and treatment for the majority of HIV-positive people in that region. Researchers at SAC have modelled the impact of what they call “de-simplification,” which they define as “switching a single-tablet formulation to two or more tablets of the same drugs with one or more drugs being generic…”

After surveying doctors and participants at SAC about de-simplifying HIV treatment, researchers at SAC began what they called a “soft rollout program of voluntary de-simplification.” That is, participants were offered the option of de-simplification. The researchers focused on one particular single-tablet regimen—Triumeq, which contains the following drugs: dolutegravir + abacavir + 3TC. They chose Triumeq because it was widely used in their clinic and is relatively easy to de-simplify, as generic abacavir + 3TC have been available in Canada for several years.

Researchers offered participants who were either on Triumeq or initiating ART with Triumeq the option of one of the following regimens:

• continue taking Triumeq (taken as one pill once daily)
• de-simplification – one pill containing dolutegravir (Tivicay) and one pill containing generic abacavir + 3TC; both pills taken once daily

The rollout began in November 2016 and data were collected up to April 1, 2018.

Participants were told of the price difference between the two regimens and were allowed to freely choose one of the regimens. Furthermore, if a participant later decided to change their mind, they were allowed to return to Triumeq (if their initial regimen was Triumeq).

Importantly, the researchers stated that the patient as well as their pharmacist and doctor all had to agree that the switch to or initiation with a de-simplified regimen was appropriate for the patient. The researchers stated: “No extra resources, incentives or reimbursement to the participants, physicians, pharmacists, before or after the program were offered.”

Results

Researchers approached different groups of participants about de-simplification, as follows:

• 321 participants who were already taking Triumeq. Of these people, 55% (177 people) agreed to de-simplify their regimen.
• 67 participants who were initiating ART with Triumeq. Of these people, 63% chose a de-simplified regimen.
• 41 participants who were talking multi-tablet regimens (usually based on protease inhibitors). All of these participants chose to switch to a de-simplified regimen.

Who switched?

According to the researchers, participants who chose to de-simplify their regimens were “more likely to be male, older and white and were gay or bisexual and lived longer with HIV” than participants who rejected de-simplification.

Why did some people not de-simplify?

A total of 144 people chose to not de-simplify their regimen; the most common reason (86%) for not de-simplifying was a preference for a single-tablet regimen. According to the researchers, participants who declined to de-simplify “were predominantly female, younger, people of colour, had fewer years of education, more likely to be heterosexual” compared to people who did switch their regimen.

Virological control

During the study, 3.4% of participants who were taking Triumeq developed viral loads greater than 500 copies/mL. Furthermore, two participants who initiated ART with Triumeq never achieved viral suppression. In contrast, among people who either switched to or initiated ART with a de-simplified regimen, only 1.2% had a viral load greater than 500 copies/mL three months after they began taking a de-simplified regimen.

Money saved

In 2017, the researchers found that moving to a de-simplified regimen resulted in a 16% decrease in drug costs for SAC. The clinic projects further savings in 2018 as the de-simplification process continues and expects to save $3 million.

Bear in mind

According to the research team, participants who decided to remain on or initiate treatment with Triumeq “valued the convenience of single-tablet regimens.”

Achieving and maintaining an undetectable viral load is the main goal of HIV care and treatment today. The researchers were pleased that the vast majority of participants taking a de-simplified regimen achieved and/or maintained a suppressed viral load.

Drug development in the private sector

Pharmaceutical companies, like all corporations, are by their nature profit driven. They will expand into therapeutic areas where their profit is high and avoid investment in therapeutic areas where profit is likely low. An example of this strategy is that more pharmaceutical companies are investing in developing and marketing novel anti-cancer drugs. The price for some of the latest cancer drugs can range from about US $100,000 to about $500,000 per person per year. Another example is the area of antibiotics. Most antibiotics that are commonly used now are generic and there has not been major large-scale private investment in the discovery and development of many new antibiotics as there has been with the development of new drugs for cancer. Any new antibiotic developed would have to compete against cheaper generic formulations. Also, antibiotics are usually used only for a short time, and doctors may reserve the use of new antibiotics only for very ill patients. All of these factors affect for-profit companies, which see them as disincentives for investment in antibiotic drug development.

In the area of HIV treatment, the main companies are Gilead Sciences, Merck and ViiV. They are still conducting research on new drugs and new formulations (long-acting) for the treatment of HIV and expect new drugs to be approved over the next several years. However, there will likely be pressure on these (and other companies) to keep prices for new drugs in a range that is sustainable for departments and ministries of health.

Resources

Will de-simplification of HIV treatment become common in high-income countries? – CATIE News

—Sean R. Hosein

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