General Information

Juluca is specifically indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen for at least 6 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Juluca.

Juluca is supplied as tablets for oral administration. The recommended dosage is one tablet taken orally once daily with a meal. One tablet of Juluca contains 50 mg of dolutegravir and 25 mg of rilpivirine. If Juluca is coadministered with rifabutin, take an additional 25-mg tablet of rilpivirine with Juluca once daily with a meal for the duration of the rifabutin coadministration.

Clinical Results

FDA Approval

The FDA approval of Juluca was based on two pivotal phase III clinical trials, SWORD-1 and SWORD-2, which evaluated the efficacy, safety, and tolerability of switching to dolutegravir plus rilpivirine from current integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based antiretroviral regimen in HIV-1-infected adults who are virologically suppressed with a three or four-drug regimen. SWORD-1 and SWORD-2 were replicate 148-week, randomized, open-label, non-inferiority studies designed assess the antiviral activity and safety of a two-drug, daily oral regimen of dolutegravir plus rilpivirine compared with current antiretroviral therapy. The primary endpoint was the proportion of patients with plasma HIV-1 RNA <50 copies per millilitre (c/mL) at Week 48. Results showed the 2-drug regimen achieved non-inferior viral suppression (HIV-1 RNA less than 50 copies per mL) at 48 weeks compared with a three- or four-drug regimen in both pooled and individual analyses of the SWORD-1 and SWORD-2 studies (CAR 485/511 [95%], dolutegravir + rilpivirine 486/513 [95%] [adjusted difference -0.2% (95% confidence interval CI: 3.0%, 2.5%), pooled analysis]). Virologic suppression rates were similar between treatment arms.

Mechanism of Action

Juluca is a two-drug combination of dolutegravir, a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and rilpivirine, a HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI). Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Strand transfer biochemical assays using purified HIV-1 integrase and pre-processed substrate DNA resulted in IC50 values of 2.7 nM and 12.6 nM. Rilpivirine is a diarylpyrimidine NNRTI of HIV-1 and inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase (RT). Rilpivirine does not inhibit the human cellular DNA polymerases α, β, and γ.