Elvitegravir belongs to the class of antiretroviral drugs known as integrase inhibitors. The drug works against HIV's integrase protein, blocking its ability to integrate its genetic code into human cells.
As an individual drug (Vitekta), elvitegravir was given marketing approval in Europe in November 2013. However, marketing authorisation was removed at the request of the drug's maker, Gilead Sciences, in late 2016. Gilead decided to stop marketing the drug for commercial reasons.
Elvitegravir is now available as part of the combination products Stribild (combined with tenofovir disoproxil fumarate, emtricitabine and cobicistat) and Genvoya (combined with tenofovir alafenamide, emtricitabine and cobicistat).
Elvitegravir showed an equivalent rate of viral suppression to the integrase inhibitor raltegravir in Study 145, a 96-week randomised trial in treatment-experienced people. Participants had experience of agents in at least two antiretroviral drug classes and a majority had resistance to agents in two classes. Optimised background regimens were selected after resistance testing. In this study, elvitegravir was dosed with a boosted protease inhibitor, which boosted blood levels of elvitegravir. At 96 weeks, 48% of elvitegravir recipients and 45% of raltegravir recipients had viral load below 50 copies/ml. Virological failure (defined as never suppressed, viral rebound or drug discontinuation due to non-efficacy) was observed in 26% and 29% of participants, respectively. Among the one-quarter of participants who underwent resistance testing due to suboptimal response or viral rebound, 7% in both arms showed evidence of primary integrase resistance mutations. (Elion)
Study 236-0102 compared a fixed-dose regimen of elvitegravir boosted by cobicistat, tenofovir disoproxil fumarate (TDF) and emtricitabine to the fixed-dose regimen of efavirenz, TDF and emtricitabine (Atripla) in previously untreated people. After 48 weeks, 88% of participants in the elvitegravir arm and 84% of those on Atripla had a viral load below 50 copies and viral suppression was maintained at 96 weeks (84% vs 82%). Virological failure was seen in 7% of participants in both arms at week 48. (Zolopa)
Study 236-0103 compared a fixed-dose regimen of elvitegravir boosted by cobicistat, TDF and emtricitabine to ritonavir-boosted atazanavir plus TDF and emtricitabine in previously untreated people. Ninety per cent of people in the elvitegravir arm and 87% in the boosted atazanavir arm had viral loads below 50 copies/ml at 48 weeks, a non-significant difference. (Rockstroh)
In Study 104 and Study 111, previously untreated people received elvitegravir boosted with cobicistat, emtricitabine and either TDF or TAF, a new formulation of tenofovir. At 48 weeks, 92% of people in the TAF arm and 90% in the TDF arm achieved viral suppression (HIV RNA <50 copies/ml) in the combined analysis. In both studies, 4% of participants experienced virological failure. (Sax)
Common side effects (occurring in > 1% of trial participants):
- Headache, weakness, dizziness, difficulty sleeping, abnormal dreams, fatigue
- Nausea, vomiting, diarrhoea, decreased appetite, indigestion, feeling bloated, constipation, flatulence
- Skin rash, itching, dark skin patches (often starting on the hands or soles of feet)
- Changes in some blood test results, including liver and kidney tests, blood sugar and cholesterol.
An analysis of eight clinical trials of new drugs introduced after 2003 found that weight gain was significantly greater in people taking an integrase inhibitor and that dolutegravir or bictegravir were associated with a higher risk of substantial weight gain (> 10% of body mass) than elvitegravir. (Sax 2019)
Elvitegravir is not active against HIV that is resistant to raltegravir or other integrase inhibitors. Dolutegravir may still be active against HIV that is resistant to elvitegravir. (Anstett) (Eron)
As with other agents boosted with cobicistat, the use of elvitegravir during pregnancy is not recommended due to lower drug levels during the third trimester. (Momper) (Boyd)
Elion R et al. A randomized phase 3 study comparing once-daily elvitegravir with twice-daily raltegravir in treatment-experienced subjects with HIV-1 infection: 96-week results. Journal of Acquired Immune Deficiency Syndromes, 63: 494-7, 2013.
Zolopa A et al. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. Journal of Acquired Immune Deficiency Syndromes, 63: 96-100, 2013.
Rockstroh J et al. A randomized, double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. Journal of Acquired Immune Deficiency Syndromes, 62: 483-6, 2013.
Sax P et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. The Lancet, 385: 2606-15, 2015.
Anstett K et al. HIV drug resistance against strand transfer integrase inhibitors. Retrovirology, 14: 36, 2017.
Eron J et al. Safety and efficacy of dolutegravir in treatment-experienced subjects with raltegravir-resistant HIV type 1 infection: 24-week results of the VIKING Study. Journal of Infectious Diseases, 207: 740-8, 2013.
Momper J et al. Elvitegravir/cobicistat pharmacokinetics in pregnant and postpartum women with HIV. AIDS, 32: 2507-2516, 2018.
Boyd SD et al. Cobicistat-containing antiretroviral regimens are not recommended during pregnancy: viewpoint. AIDS, 33: 1089-1093, 2019.