Tivicay: a new once-daily HIV integrase inhibitor

Tivicay (dolutegravir) is a new once-daily integrase inhibitor licensed for the treatment of HIV-1 infection in combination with other antiretrovirals.

Tivicay (dolutegravir) is given once daily without requiring a concomitant pharmacokinetic boosting drug
Tivicay (dolutegravir) is given once daily without requiring a concomitant pharmacokinetic boosting drug

PHARMACOLOGY

Dolutegravir inhibits HIV integrase to block viral replication.1

CLINICAL STUDIES

Dolutegravir was investigated in 5 key pivotal studies for the treatment of HIV-1 infection in adults and children aged 12 years and older in combination with other antiretrovirals. In treatment-naïve patients, it was compared with raltegravir (SPRING-2), efavirenz (SINGLE) and darunavir (FLAMINGO).1–3

Once-daily dolutegravir has also been compared to raltegravir in treatment-experienced patients in the SAILING study and it was investigated administered twice-daily in highly pre-treated patients with evidence of integrase inhibitor resistance in the single-arm VIKING-3 study.4,5

Versus raltegravir

The SPRING-2 study showed that dolutegravir (50mg once daily) was non-inferior to raltegravir (400mg twice daily) when used in combination with a fixed-dose dual NRTI background regimen in 822 treatment-naïve patients with HIV-1 infection. At week 48, the percentage of patients with an undetectable viral load (HIV-1 RNA <50 copies/ml) was 88% in the dolutegravir group compared with 85% in the raltegravir group.2

Versus efavirenz

The SINGLE study (n=833) also recruited treatment-naïve HIV-1 infected patients but compared once-daily dolutegravir, in combination with lamivudine and abacavir, to efavirenz + emtricitabine + tenofovir (Atripla). A significantly higher proportion of patients achieved virological suppression (HIV-1 RNA <50 copies/ml) in the dolutegravir group compared with the triple combination tablet group at week 48: 88% vs 81% (p=0.003).3

Treatment-experienced patients

Dolutegravir was compared with raltegravir, both in combination with an optimised background regimen, in treatment-experienced patients with at least two-class drug resistance who had not yet received an integrase inhibitor in the SAILING study (n=719). On analysis after meeting the pre-specified non-inferiority criteria, dolutegravir (50mg once daily) was superior to raltegravir with a significantly higher proportion of patients with plasma HIV-1 RNA <50 copies/ml at week 48 (p=0.003).4

Dolutegravir displayed efficacy in highly pre-treated patients with resistance to multiple classes of antiretrovirals including integrase inhibitors (raltegravir and/or elvitegravir) in the single-arm, phase IIb VIKING-3 study (n=183). When dolutegravir (50mg twice daily) was added to their background regimen, 63% of patients achieved virological suppression (HIV-1 RNA <50 copies/ml).

Versus darunavir

The open-label FLAMINGO study compared dolutegravir with ritonavir-boosted darunavir in 484 treatment-naïve patients. In the interim analysis at week 48, a significantly higher proportion of patients treated with dolutegravir had an HIV-1 RNA viral load of <50 copies/ml than patients treated with darunavir: 90% vs 83% (p=0.025).6

Safety profile

The adverse effects associated with dolutegravir showed similar incidences across all treatment populations. Nausea, diarrhoea and headache were most commonly observed.1  

References:

  1. Tivicay Summary of Product Characteristics, January 2014.
  2. Raffi F et al. Lancet 2013; 381: 735–43.
  3. Walmsley SL et al. N Engl J Med 2013; 369: 1807–18.
  4. Cahn P et al. Lancet 2013; 382: 700–8.
  5. Eron JJ et al. J Infect Dis 2013; 207: 740–8.
  6. Clotet B et al. Abstract LBPS4/6 presented at European AIDS Clinical Society (EACS), 17 October 2013, Brussels, Belgium. 

View Tivicay drug record

Further information: ViiV Healthcare

Follow MIMS on Twitter


MIMS Clinics

Prescribing news and resources for key therapeutic areas, collated by the MIMS editors.

Register or Subscribe to MIMS

GPs can get MIMS print & online and GPonline for free when they register online – take 2 minutes, and make sure you get your free MIMS access! If you're not a GP, you can subscribe to MIMS for full access.

Register or subscribe

MIMS bulletins

News and updates straight to your inbox.

Prescribing Update: Fortnightly news bulletin
Alert:
Urgent prescribing updates
Spotlight: Disease-themed monthly round-up

Sign me up

MIMS Dermatology

Read the latest issue online exclusively on MIMS Learning.

Read MIMS Dermatology

Mobile apps

MIMS: access the full drug database and quick-reference tables on the go

MIMS Diagnosis and Management: concise information on signs and symptoms, investigations and diseases

Promo Image

Clinical calculators

Handy calculators and conversions for primary care.