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

More AIDS-defining illnesses and severe side effects than with appropriate comparator therapy

2013-09-20

(Press-News.org) 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 with human immunodeficiency virus type 1 (HIV-1). In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the German Institute for Quality and Efficiency in Health Care (IQWiG) examined whether an added benefit is proven for this combination over the current standard therapy.

This is not the case: No informative data are available for pretreated patients, and for treatment-naive patients, the disadvantages predominate. Particularly, AIDS-defining illnesses and serious side effects occur more frequently than with the appropriate comparator therapy.

Two appropriate comparator therapies

The Federal Joint Committee (G-BA) specified two appropriate comparator therapies according to the approval status: Treatment-naive patients, i.e. patients who had not been treated for HIV before, were to receive efavirenz in combination with tenofovir and emtricitabine or in combination with abacavir and lamivudine. Therapy in treatment-experienced patients was to be tailored to the individual depending on factors such as resistance or severe side effects in their prior treatment.

More AIDS-defining illnesses in treatment-naive patients

Two suitable randomized controlled trials of sufficient duration (48 and 96 weeks) in patients who had not been treated for HIV before were available. Regarding deaths (outcome "mortality"), there was no statistically significant difference between the elvitegravir fixed combination and the efavirenz combination. For the outcome "morbidity", there was an indication of a lesser benefit because more AIDS-defining events occurred under the elvitegravir fixed combination: about 23 out of 1000 versus 3 out of 1000 under the comparator therapy. The studies did not provide any information on health-related quality of life.

Advantages and disadvantages regarding side effects

The picture regarding side effects and treatment discontinuations is complex: The studies used by the drug manufacturer were conducted in the United States and in Puerto Rico and included both white and non-white patients. The frequency of several side effects depended on the patients' ethnic group. Hence the advantages and disadvantages of the fixed combination versus the comparator therapy were assessed separately for these two subgroups.

Skin rash and nervous system disorders such as dizziness or headache occurred less frequently under the elvitegravir fixed combination in patients without prior treatment. Non-white study participants also discontinued treatment due to side effects less frequently than in the comparator group. On the other hand, serious adverse events and renal disorders occurred more frequently under treatment with the elvitegravir fixed combination.

Negative effects predominate

The extent of the negative effects of the fixed combination considerably outweighs the extent of the advantages. Overall, there is an indication of a lesser benefit of the elvitegravir fixed combination versus the efavirenz combination for treatment-naive patients.

The manufacturer did not submit any studies for pretreated patients in which the comparator therapies were notably adapted to the results of the prior treatment. A small selection of pre-specified antiviral substances was used instead. In addition, only patients without prior treatment were investigated in the studies. An added benefit for pretreated patients is therefore not proven.

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.

### An overview of the results of IQWiG's benefit assessment is given by a German-language executive summary. In addition, the website gesundheitsinformation.de, published by IQWiG, provides easily understandable and brief German-language information on elvitegravir fixed combination.

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 the elvitegravir combination.

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 informedhealthonline.org). If you would like to be informed when these documents are available, please send an e-mail to info@iqwig.de.

ELSE PRESS RELEASES FROM THIS DATE:

Blood pressure cuff may save lives in patients with acute heart attack

2013-09-20

In patients with an acute heart attack, remote ischemic conditioning – intermittent inflation of a blood pressure cuff to cut off blood flow to the arm during transportation to hospital for acute balloon dilatation – reduces subsequent cardiac symptoms and mortality after acute heart attack. The results are presented by researchers from Aarhus University Hospital and Aarhus University in European Heart Journal on-line 12 September 2013. Activating the body's defense mechanism Lack of oxygen for short periods of time in a distant organ by intermittently stopping blood ...

Promising new alloy for resistive switching memory

2013-09-20

WASHINGTON, D.C. Sept. 20, 2013 -- Memory based on electrically-induced "resistive switching" effects have generated a great deal of interest among engineers searching for faster and smaller devices because resistive switching would allow for a higher memory density. Researchers have tested a number of oxide materials for their promise in resistive switching memories, and now a team of researchers in Singapore have demonstrated how conductive nano-filaments in amorphous titanium dioxide (TiO2) thin films could be utilized for resistive switching device applications. Yuanmin ...

Densest array of carbon nanotubes grown to date

2013-09-20

WASHINGTON, D.C. Sept. 20, 2013 -- Carbon nanotubes' outstanding mechanical, electrical and thermal properties make them an alluring material to electronics manufacturers. However, until recently scientists believed that growing the high density of tiny graphene cylinders needed for many microelectronics applications would be difficult. Now a team from Cambridge University in England has devised a simple technique to increase the density of nanotube forests grown on conductive supports about five times over previous methods. The high density nanotubes might one day replace ...

Microfluidic platform gives a clear look at a crucial step in cancer metastasis

2013-09-20

CAMBRIDGE, Mass-- Cancer cells metastasize in several stages -- first by invading surrounding tissue, then by infiltrating and spreading via the circulatory system. Some circulating cells work their way out of the vascular network, eventually forming a secondary tumor. While the initial process by which cancer cells enter the bloodstream -- called intravasation -- is well characterized, how cells escape blood vessels to permeate other tissues and organs is less clear. This process, called extravasation, is a crucial step in cancer metastasis. Now researchers at MIT ...

Personality a key factor in health care use

2013-09-20

Psychiatrists and psychologists have long understood that an individual's personality can define how he or she views the world around them, reacts to situations, and interacts with others. It now appears that personality traits can be linked to the frequency with which older adults use expensive health care services. A study, published today in the journal The Milbank Quarterly, finds that certain measurable personality characteristics can be correlated to health care consumption, in some instances increasing use high cost health care services such as emergency room ...

3 new species of tiny frogs from the remarkable region of Papua New Guinea

2013-09-20

Three new species of tiny frogs from Papua New Guinea are described in the latest issue of Zookeys. Dr Fred Kraus, University of Michigan, who in 2011 in Zookeys described the world's smallest frogs Paedophryne dekot and Paedophryne verrucosa, now adds another 3 species from the genus Oreophryne to the remarkable diversity of this region. The three new species Oreophryne cameroni, Oreophryne parkopanorum and Oreophryne gagneorum are all rather minute, with total body lengths of around 20 mm. These tiny frogs, however are still substantially larger than the species that ...

NASA sees super-rapid intensification of Supertyphoon Usagi

2013-09-20

The radar on the Tropical Rainfall Measuring Mission (TRMM) satellite captured an image of Supertyphoon Usagi near the end of a 24-hour period in which Usagi intensified by 65 knots. This is more than twice the commonly used 30-knot threshold for defining rapid intensification. The TRMM data was used to create a 3-D image. The data was collected at 1035 UTC/6:35 a.m. EDT on Thursday, September 19, 2013, when Usagi was at category 3 on the Saffir-Simpson hurricane intensity scale. A few hours later, Usagi completed its lightning-fast intensification to category 5, the ...

NSF report details increase in business research and development

2013-09-20

According to a recent study published by the National Science Foundation (NSF), businesses spent more on research and development (R&D) in 2011 than they did in 2010. Companies spent $294 billion on R&D performed in the United States during 2011, compared with $279 billion during 2010. Data are from the Business and R&D and Innovation Survey (BRDIS), which is co-sponsored by NSF and the U.S. Census Bureau. BRDIS revealed that during 2011, companies in manufacturing industries performed $201 billion, or 68 percent, of domestic R&D. Companies in nonmanufacturing industries ...

Lithosphere interprets earth

2013-09-20

Boulder, Colo., USA -- The October 2013 Lithosphere is now online. Locations studied include the Central Iberian Massif in Spain; Arctic Alaska; the Wet Mountains of Central Colorado, USA; the Basgo Formation in northwest India; Crystal Geyser in southeastern Utah, USA; Knight Inlet in the southwestern Coast Mountains Batholith, British Columbia, Canada; and three crustal-scale shear zones in the western Canadian Shield of northern Saskatchewan. Lithosphere is published bimonthly in hardcopy; articles are posted online as they become available. Abstracts are online at ...

Researchers identify a switch that controls growth of most aggressive brain tumor cells

2013-09-20

DALLAS -- Researchers at UT Southwestern Medical Center have identified a cellular switch that potentially can be turned off and on to slow down, and eventually inhibit the growth of the most commonly diagnosed and aggressive malignant brain tumor. Findings of their investigation show that the protein RIP1 acts as a mediator of brain tumor cell survival, either protecting or destroying cells. Researchers believe that the protein, found in most glioblastomas, can be targeted to develop a drug treatment for these highly malignant brain tumors. The study was published online ...

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

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: