Dolutegravir in HIV-1 infection: Added benefit in adult patients

May 21, 2014, Institute for Quality and Efficiency in Health Care

Dolutegravir has been approved since January 2014 in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) infected adults and adolescents above 12 years of age. 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) now examined whether the new drug offers an added benefit over the appropriate comparator therapy.

The dossier compiled by the drug manufacturer provided proof of a considerable added benefit in adults without pretreatment and an indication of a minor added benefit in pretreated adults who require integrase inhibitors (INIs) (i. e. whose should include an INI). These patients have fewer side effects with the new drug than with the respective comparator therapy.

No added benefit could be determined for pretreated adults who do not require INIs (i. e. in whom no integrase inhibitor is indicated) and for adolescents above 12 years of age, because there were no study data.

Comparator therapy depends on pretreatment and age

Dolutegravir is a so-called integrase inhibitor (INI) and aims to prevent the integration of viral DNA into the nucleus of human cells. The Federal Joint Committee (G-BA) distinguished between adults and adolescents depending on the pretreatment, and specified different appropriate comparator therapies for the different patient groups:

In adults without pretreatment (treatment-naive), dolutegravir was to be compared with efavirenz (NNRTI drug class) in combination with two nucleoside/nucleotide analogues (NRTI drug class), tenofovir plus emtricitabine or abacavir plus lamivudine. In treatment-naive adolescents, the new drug was to be compared with efavirenz in combination with abacavir plus lamivudine.

For adolescents and adults who have already been treated for HIV-1 with other drugs, the G‑BA specified an individual antiretroviral treatment depending on their prior therapy and the reason for the treatment switch. Particularly treatment failure because of a lack of antiviral effect (possibly associated with resistance of the virus to some drugs) or side effects were relevant.

In case of resistance to other drug classes in pretreated patients, treatment should include a drug of a further drug class. When resistance to NRTIs or NNRTI has been proven, for example, an INI is a commonly chosen treatment.

Treatment-naive adults: considerable added benefit

Two randomized controlled trials (RCTs), SPRING-1 and SINGLE, with a study duration of 96 weeks each and a total of almost 1000 study participants, were included in the assessment. The results of these 2 studies showed no differences between the treatment groups with regard to mortality and morbidity.

Neither HIV symptoms nor the outcome "quality of life" was recorded in the SPRING-1 study, and the SINGLE study produced no evaluable data for these two outcomes. Hence an added benefit of dolutegravir is not proven for these patient-relevant outcome criteria.

Untreated adults had noticeably fewer side effects under dolutegravir, however: Study discontinuations due to side effects and skin rash occurred less frequently in both sexes, and in men, nervous system disorders were less common under treatment with dolutegravir.

As no indication of considerably worse results can be inferred from the data on morbidity in treatment-naive adults, proof of a considerable added benefit can be derived for dolutegravir in the overall assessment of the results on side effects.

Different comparator therapies depending on individual pretreatment

In the only study (SAILING) that investigated pretreated adults, dolutegravir was compared with another INI (raltegravir). The study participants were not pretreated with INIs and all of them had resistance to various drugs. They received dolutegravir or raltegravir in addition to an individual antiretroviral treatment, which depended on the respective resistance and which was already individually specified before randomization.

Pretreated adults requiring INI: minor added benefit

In pretreated adults with HIV-1 infection with mandatory INI treatment, the study groups in the SAILING study did not differ with regard to mortality and symptoms (morbidity). HIV symptoms were not recorded in the study, which also produced no evaluable data on quality of life. Hence no added benefit of dolutegravir can be determined for these patient-relevant outcomes.

However, dolutegravir had advantages with respect to side effects for patients who require INIs: Severe side effects like infection were less common, and nervous system disorders were also less frequent in patients over the age of 50 years. Overall, there is an indication of a minor added benefit of dolutegravir because there were fewer than under the comparator therapy.

In contrast, no conclusions can be derived from the results of the SAILING study for pretreated patients in whom INI was possible but not mandatory.

No data on adolescents

As no study could be identified that investigated HIV-1 infected adolescents aged 12 years or older – neither treatment-naive nor pretreated – there were no data on the comparison of dolutegravir with the appropriate comparator therapy. Hence an added benefit of dolutegravir is not proven for adolescent patients.

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 decides on the extent of the added benefit, thus completing the early benefit assessment.

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

Related Stories

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 ...

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 the fixed combination of dapagliflozin and metformin is not proven

May 15, 2014
The fixed combination of the drugs dapagliflozin and metformin (trade name: Xigduo) has been approved since January 2014 for adults with type 2 diabetes in whom diet and exercise do not provide adequate glycaemic control. ...

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 ...

Sofosbuvir: Indication of added benefit for specific patients

May 2, 2014
The drug sofosbuvir has been available since January 2014 as a treatment for chronic hepatitis C infection. In an early benefit assessment pursuant to the Act on the Reform of the Market for Medicinal Products (AMNOG), the ...

Trastuzumab emtansine: Indication of major added benefit in one subpopulation

April 7, 2014
The antibody-drug conjugate trastuzumab emtansine (trade name: Kadcyla) has been approved since November 2013 for the treatment of patients with unresectable, locally advanced or metastatic breast cancer that is HER2-positive, ...

Recommended for you

In most surgery patients, length of opioid prescription, number of refills spell highest risk for misuse

January 17, 2018
The possible link between physicians' opioid prescription patterns and subsequent abuse has occupied the attention of a nation in the throes of an opioid crisis looking for ways to stem what experts have dubbed an epidemic. ...

Patients receive most opioids at the doctor's office, not the ER

January 16, 2018
Around the country, state legislatures and hospitals have tightened emergency room prescribing guidelines for opioids to curb the addiction epidemic, but a new USC study shows that approach diverts attention from the main ...

FDA bans use of opioid-containing cough meds by kids

January 12, 2018
(HealthDay)—Trying to put a dent in the ongoing opioid addiction crisis, the U.S. Food and Drug Administration on Thursday slapped strict new restrictions on the use of opioid-containing cold and cough products by kids.

Taking ibuprofen for long periods found to alter human testicular physiology

January 9, 2018
A team of researchers from Denmark and France has found that taking regular doses of the pain reliever ibuprofen over a long period of time can lead to a disorder in men called compensated hypogonadism. In their paper published ...

Nearly one-third of Canadians have used opioids: study

January 9, 2018
Nearly one in three Canadians (29 percent) have used "some form of opioids" in the past five years, according to data released Tuesday as widespread fentanyl overdoses continue to kill.

Growing opioid epidemic forcing more children into foster care

January 8, 2018
The opioid epidemic has become so severe it's considered a national public health emergency. Addiction to prescription painkillers, such as oxycodone and morphine, has contributed to a dramatic rise in overdose deaths and ...

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.