Rilpivirine combination product in pretreated HIV-1 patients: Added benefit not proven

April 7, 2014

The German Institute for Quality and Efficiency in Health Care (IQWiG) reassessed the antiviral drug combination rilpivirine/emtricitabine/tenofovir. In early 2012, the combination was approved for the treatment of adults infected with human immunodeficiency virus type 1 (HIV-1) who have not received previous antiretroviral treatment. For men, the Institute then found proof, and for women, indications of a considerable added benefit of the fixed combination in comparison with the appropriate comparator therapy.

In the end of 2013, the approval was expanded to people with previous , and the drug manufacturer submitted a dossier for this new therapeutic indication, in which it claimed an added benefit again. IQWiG came to a different conclusion: The only study cited in the dossier was too short for the assessment of an added benefit, and the appropriate comparator therapy was not implemented. Hence an added benefit of rilpivirine/emtricitabine/tenofovir in the treatment of adults infected with HIV-1 with previous antiretroviral treatment is not proven.

New therapeutic indication, new comparator therapy

According to the expansion of approval from November 2013, the fixed can now also be used in HIV-1 infected adults with a viral load of no more than 100,000 RNA copies per millilitre who have already received antiretroviral treatment – provided that their virus has no mutations associated with known resistance to the drugs.

Since these patients had already received antiretroviral treatment, which possibly did not have a satisfactory effect or had to be discontinued, the Federal Joint Committee (G-BA) specified a different appropriate comparator therapy than in 2012 for non-pretreated patients: Antiretroviral treatment was now to be specified individually, depending on the previous treatment and the reason for treatment switching, e.g. treatment failure or side effects.

Comparator therapy not implemented

In its dossier, the manufacturer presented one single study, in which the drug combination was compared with an individual antiretroviral treatment. However, no switch of treatment was possible in the control group. Instead, the patients continued their previous treatment – although approximately 10% of them complained of side effects in the beginning, and about 20% claimed to be worried about longterm side effects of their previous treatment.

Randomized controlled phase far too short

Moreover, the rilpivirine/emtricitabine/tenofovir combination was only compared with the appropriate comparator therapy for 24 weeks in the study. But the research question of the benefit assessment cannot be answered on the basis of such a short study; this would require at least one to two years.

For these reasons, an added benefit of rilpivirine/emtricitabine/tenofovir is not proven for HIV-1 infected adults with previous antiretroviral whose viruses do not have mutations associated with resistance.

G-BA decides on the extent of added benefit

The dossier assessment is part of the overall procedure for early benefit assessments supervised by the G-BA. After publication of the manufacturer's dossier and IQWiG's assessment, the G-BA conducts a commenting procedure, which may provide further information and result in a change to the benefit assessment. The G BA then decides on the extent of the added benefit, thus completing the early benefit assessment.

Explore further: Ipilimumab in advanced melanoma: Added benefit for non-pretreated patients not proven

More information: An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website " www.gesundheitsinformation.de, published by IQWiG, provides easily understandable and brief German-language information on rilpivirine/emtricitabine/tenofovir.

The G-BA website contains both general English-language information on benefit assessment pursuant to §35a Social Code Book (SGB) V and specific German-language information on the assessment of rilpivirine/emtricitabine/tenofovir. More English-language information will be available soon (Sections 2.1 to 2.6 of the dossier assessment as well as subsequently published health information on " www.informedhealthonline.org).

Related Stories

Ipilimumab in advanced melanoma: Added benefit for non-pretreated patients not proven

March 18, 2014
The German Institute for Quality and Efficiency in Health Care (IQWiG) already assessed the added benefit of ipilimumab in advanced melanoma in 2012. A considerable added benefit was found for patients who had already received ...

Elvitegravir fixed combination in HIV: Lesser benefit for treatment-naive patients

September 20, 2013
The drug combination of elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil (elvitegravir fixed combination, trade name: Stribild) has been approved in Germany since May 2013 for the treatment of adults infected ...

Added benefit of saxagliptin as monotherapy is not proven

December 5, 2013
The drug saxagliptin (trade name: Onglyza) has been approved also as monotherapy in Germany since July 2013 for certain adults with type 2 diabetes mellitus. It is an option when drug treatment is needed, but the drug metformin ...

Enzalutamide: IQWiG assessed data subsequently submitted by the manufacturer

February 21, 2014
Enzalutamide (trade name: Xtandi) has been approved since June 2013 for men with metastatic prostate cancer in whom the commonly used hormone blockade is no longer effective and who have already been treated with the cytostatic ...

Aflibercept in AMD: No proof of added benefit

June 5, 2013
It is not proven that patients with wet age-related macular degeneration benefit from the new drug aflibercept, as the drug manufacturer did not present any suitable data for a comparison with the current standard therapy ...

Radium-223 dichloride in prostate cancer: Major added benefit for certain patients

April 3, 2014
Radium-223 dichloride (radium-223 for short, trade name: Xofigo) has been approved since November 2013 for men with advanced prostate cancer, in whom hormone blockade is no longer effective, and symptomatic bone metastases, ...

Recommended for you

Paris spotlight on latest in AIDS science

July 21, 2017
Some 6,000 HIV experts gather in Paris from Sunday to report advances in AIDS science as fading hopes of finding a cure push research into new fields.

Scientists elicit broadly neutralizing antibodies to HIV in calves

July 20, 2017
Scientists supported by the National Institutes of Health have achieved a significant step forward, eliciting broadly neutralizing antibodies (bNAbs) to HIV by immunizing calves. The findings offer insights for HIV vaccine ...

Heart toxin reveals new insights into HIV-1 integration in T cell genome

July 20, 2017
Human immunodeficiency virus (HIV)-1 may have evolved to integrate its genetic material into certain immune-cell-activating genes in humans, according to new research published in PLOS Pathogens.

Scientists capture first high-resolution image of key HIV protein transitional state

July 13, 2017
A new, three-dimensional snapshot of HIV demonstrates the radical structural transformations that enable the virus to recognize and infect host cells, according to a new study led by scientists at The Scripps Research Institute ...

Barrier to autoimmune disease may open door to HIV, study suggests

July 11, 2017
Researchers from the University of Colorado School of Medicine have discovered that a process that protects the body from autoimmune disease also prevents the immune system from generating antibodies that can neutralize the ...

Team tests best delivery mode for potential HIV vaccine

June 20, 2017
For decades, HIV has successfully evaded all efforts to create an effective vaccine but researchers at The Scripps Research Institute (TSRI) and the La Jolla Institute for Allergy and Immunology (LJI) are steadily inching ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.