Introduction

Doravirine (trade name: Pifeltro) has been approved in Germany since November 2018 for the treatment of HIV-1 infection in adults. It is combined with other treatments.

The human immunodeficiency virus (HIV) multiplies in cells of the immune system and destroys them. Without proper treatment, the immune system of most HIV patients is weakened so much over time that they become seriously ill. This stage is referred to as AIDS (acquired immune deficiency syndrome).

Although the currently available medications can't cure HIV, they can prevent immunodeficiency for many years. But the medication may become ineffective over time, allowing the viruses to multiply more again.

Doravirine inhibits certain proteins which the virus needs in order to multiply.

Application

Doravirine is taken once a day in tablet form (100 mg) with or without a meal. The drug is combined with other anti-HIV medications.

Other treatments

The first-line treatments for adults are the drugs rilpivirine or dolutegravir, which are each used in combination with two other drugs such as tenofovir alafenamide and emtricitabine or abacavir and lamivudine. Instead of tenofovir alafenamide, the drug tenofovir disoproxil is also an option.

Adults who have already taken medication for HIV are generally given individually tailored combination therapy for HIV. This type of treatment takes into consideration which treatments were tried before and why they were stopped. For instance, the previous treatment may have been ineffective or caused side effects that were too severe.

Assessment

In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) looked into the advantages and disadvantages of doravirine compared with the standard treatments for people who have HIV-1 infection.

The manufacturer only provided data to make an indirect comparison.

In scientific research, a direct comparison is a comparison made between two medications in a single study. Half of the participants in the study are given medication A, and the other half receive the standard treatment. After the study is completed, the numbers of certain events in each group – such as deaths, occurrences of symptoms or side effects – are compared.

Indirect comparisons, on the other hand, involve two different studies (in the simplest case): One study compares medication A with medication X. The other compares medication X with the standard treatment. Then the results for medication A from the first study are compared with the results for the standard treatment from the second study. The results of this kind of comparison are generally less reliable than a direct comparison.

Six studies were available for the purpose of the indirect comparison of doravirine. In three of the studies, doravirine was compared with efavirenz or darunavir. In the other three studies the standard treatment of dolutegravir was compared with either efavirenz or darunavir. Each of the medicines was combined with two more medications.

The indirect comparison showed the following results in people who have not yet taken any other medication to treat HIV:

What are the advantages and disadvantages of the fixed-dose combination?

The indirect comparison showed no advantages or disadvantages in comparison to the standard treatment of dolutegravir and two other medications.

No difference

  • Number of AIDS-related illnesses: Various bacterial, viral and fungal infections are more likely if the immune system is weakened due to HIV. Some types of tumors are also more common. The success of a particular treatment can be measured by whether these illnesses are less common in people who have the treatment. There was no difference between the treatments in the indirect comparison.
  • No difference was found in terms of the following, either:
    • Life expectancy
    • Severe side effects
    • Treatment stopped due to side effects

What remains unanswered?

Quality of life: The studies didn't look into quality of life.

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the review and the hearings received, the G-BA passed a resolution on the added benefit of doravirine (Pifeltro).