De-simplifying treatment is acceptable and cost-saving, if a choice is offered

Mandatory de-simplification was unpopular and failed to save money
Mareike Günsche |

Although a voluntary switch from a single-tablet combination to taking multiple pills each day proved acceptable to people with HIV in the Netherlands, an enforced switch to save money proved unacceptable and led to a paradoxical increase in costs after one year, Dutch researchers report in two studies published this month.

Over the past 15 years, pharmaceutical companies have prioritised the development of fixed-dose single-tablet antiretroviral regimens, to simplify taking antiretroviral treatment and improve adherence. Treatment guidelines recommend their use in most circumstances, to promote treatment adherence and simplify prescribing and supply.

But as several of the main components of antiretroviral treatment have become available as generic products at much lower cost than branded products, health systems and insurers have been keen to reduce HIV treatment costs by encouraging the use of generics wherever possible.



In relation to medicines, a drug manufactured and sold without a brand name, in situations where the original manufacturer’s patent has expired or is not enforced. Generic drugs contain the same active ingredients as branded drugs, and have comparable strength, safety, efficacy and quality.


Cost-effectiveness analyses compare the financial cost of providing health interventions with their health benefit in order to assess whether interventions provide value for money. As well as the cost of providing medical care now, analyses may take into account savings on future health spending (because a person’s health has improved) and the economic contribution a healthy person could make to society.

This means ‘de-simplifying’ treatment by switching from a single tablet that contains three drugs to a regimen consisting of two tablets, one containing tenofovir disoproxil fumarate (TDF) and emtricitabine (or abacavir and lamivudine), the other containing a branded product such as rilpivirine (Edurant) or dolutegravir (Tivicay).

Although single-centre studies in Canada and France have reported cost savings from de-simplification, it’s not clear if these savings can be replicated in other settings, or if de-simplification affects patient outcomes.

Researchers in the Netherlands wanted to assess the acceptability and cost savings associated with de-simplification when it was offered as a voluntary option to people with HIV receiving care at five large HIV clinics in 2019.

Patients at participating clinics taking Triumeq (abacavir / lamivudine / dolutegravir), Eviplera (tenofovir disoproxil fumarate/emtricitabine / rilpivirine) or Atripla (tenofovir disoproxil fumarate / emtricitabine / efavirenz) were offered the option of switching to a generic NRTI backbone and the branded form of the third agent, or to continue taking the single-tablet regimen.

The study recruited 283 people, mostly male (89%), with a median age of 52 years. Participants had been taking antiretroviral treatment for a median of nine years.

Just over half (55%) of those recruited to the study agreed to switch to a two-tablet regimen. Those who chose to switch tended to be older, to have lived with an HIV diagnosis for longer and were more likely to be taking co-medications. There was no difference in self-reported adherence or time on antiretroviral treatment between those who switched and those who continued a single-tablet regimen. Nor was there any difference in agreement to switch by regimen.

On the other hand, willingness to switch differed significantly between centres. Two clinics were significant outliers from the overall switch rate in the study (55%). Only 41% agreed to switch at one clinic, whereas 74% agreed to switch at another centre. The study investigators say that the way in which individual healthcare providers communicated the de-simplification strategy may have influenced willingness to switch.

Sixty percent of participants answered a questionnaire on their physical and mental health at the beginning of the study and 12 months later. After adjusting for age, gender, time of HIV diagnosis, time on current ART and use of Atripla, there was no significant difference in patient-reported outcomes.

If all participants had continued their existing treatment, the total treatment cost would have been €2.6 million. Switching reduced the overall treatment cost in the study population by just under 18%, similar to the cost reduction observed in a Canadian study. The study investigators estimate that if the switch option had been taken up at the same level throughout the Netherlands, de-simplification would save approximately €9 million a year.

The same research group also looked at the consequences of a Dutch health insurer’s requirement that everyone taking the single-pill combination Eviplera (tenofovir disoproxil fumarate / emtricitabine / rilpivirine) should switch to a generic pill containing tenofovir disoproxil fumarate / emtricitabine plus branded rilpivirine (Edurant) in 2021.

The mandatory de-simplification was expected to save an average of €368 a month per patient. The policy was implemented despite objections from physicians, pharmacists and patient groups. Pharmacists were required to dispense the prescription as two tablets unless patients had medical reasons to stay on the single-pill combination.

The decision affected 128 people insured by the specific health insurer. Just under half (46%) de-simplified treatment, but only 17 out of 59 were taking the de-simplified regimen 18 months later. Twenty-seven switched to another regimen within three months of de-simplifying treatment, in almost all cases to a single-tablet branded regimen. Frequently this was Odefsey, which has the same components as the original regimen, except for the replacement of tenofovir disoproxil fumarate with tenofovir alafenamide.

Prior to the introduction of the de-simplification policy, the monthly cost of treatment for those taking Eviplera was €73,000. After mandatory de-simplification was introduced, the monthly cost of treatment increased to €76,000.

“Engaging people with HIV and their prescribers is critical for successful implementation of cost-effective treatment changes,” the study investigators conclude. They say that prescribers are in a position to reassure their patients about the effectiveness of generic drugs and two-tablet regimens.