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

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