As researchers and clinicians attempt to grapple with the ever-growing threat of antimicrobial resistance, they’d be wise not to ignore a frequently overlooked contributor – poor drug adherence.

While a pathogen’s development of drug resistance can be influenced by a plethora of factors unrelated to how antimicrobial agents are prescribed, poor adherence to treatment is almost universally associated with negative clinical outcomes, including the emergence of antimicrobial resistance.

To tackle this important issue, drug manufacturers have been striving to develop novel regimens aimed at improving adherence by reducing the pill burden, with two completely different indications – malaria and human immunodeficiency virus (HIV) – exemplifying this trend.

In the case of HIV, poor adherence to antiretroviral therapy (ART) is associated with treatment-emergent resistance and negative long-term outcomes, despite the ability of modern drugs to effectively suppress the virus if taken as prescribed. In an effort to combat this growing problem, ViiV Healthcare, in collaboration with Janssen, is currently advancing the first long-acting injectable formulation, composed of cabotegravir/rilpivirine. If successful, the drug would require a single injection every four weeks, which would be beneficial for those living with HIV who cannot comply with once-daily oral regimens.

Similarly, the parasite causing malaria – a mosquito-borne disease that caused an estimated 429,000 deaths worldwide in 2015 – has over time become resistant to each medicine developed to kill it. As a result, there is an increasing trend to develop single-dose formulations of antimalarials to reduce the duration of treatment as much as possible.

When an individual infected with malaria begins feeling better after receiving the first dose of an artemisinin-based combination treatment (ACT), often he/she does not comply with the three-day regimen required to kill all the remaining parasites in the human body. This may happen more frequently in remote areas of developing countries, where access to medicines is challenging. In fact, rather than completing the treatment, subjects prefer saving some doses of a drug for their relatives or for future infections. Studies indicate that this poor adherence to ACT contributes to causing parasite mutations, which ultimately lead to drug resistance.

In recognition of this problem, Takeda Pharmaceuticals, Novartis, and the Medicines for Malaria Venture (MMV) are currently conducting Phase II studies to evaluate novel compounds DSM265, KAF156, and artefenomel, respectively, which all hold the potential of single-dose administration.

Recently, a study published in the New England Journal of Medicine reported the first case of partial resistance to artemisinin, a key component of ACT (the universally recommended treatment for uncomplicated malaria), in Africa. The event has been a confirmation of what malaria experts have feared, and has increased awareness of the importance of preventing the spread of artemisinin resistance through novel drugs and preventative strategies, as no other alternative treatments are currently available.

While the emergence of antimicrobial resistance cannot be blamed solely on poor adherence, there is little doubt that failure to take drugs as prescribed does contribute to the problem. Although new promising and single-dose treatments to help increase adherence across a wide array of infectious diseases are on the horizon, GlobalData believes that these would not be sufficient, unless effective strategies can be implemented in parallel through collaborations between healthcare providers, policy makers, public institutions and nonprofit organizations.