Delstrigo (doravirine, lamivudine, and tenofovir disoproxil fumarate)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved August 2018

Specific Treatments:

HIV-1 infection

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General Information

Delstrigo is a three-drug combination of doravirine (a nonnucleoside reverse transcriptase inhibitor [NNRTI]), lamivudine, and tenofovir disoproxil fumarate (both nucleoside analogue reverse transcriptase inhibitors).

Delstrigo is specifically indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior antiretroviral treatment history. The FDA expanded the indication in September of 2019 to include adult patients with HIV-1 infection who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of Delstrigo.

Desltrigo is supplied as a tablet for oral administration. Delstrigo is a fixed-dose combination product containing 100 mg of doravirine (DOR), 300 mg of lamivudine (3TC), and 300 mg of TDF. The recommended dosage in adults is one tablet taken orally once daily with or without food. 

Clinical Results

FDA Approval

The FDA approval of Delstrigo was based on 48-week data from a randomized, multicenter, double-blind, active controlled Phase III trial, DRIVE-AHEAD, in HIV-1 infected subjects with no antiretroviral treatment history. In DRIVE-AHEAD, 728 subjects were randomized and received at least 1 dose of either Delstrigo (DOR/3TC/TDF) or EFV 600 mg/FTC 200 mg/TDF 300 mg once daily. Delstrigo demonstrated sustained viral suppression through 48 weeks, meeting its primary endpoint of non-inferior efficacy compared to EFV/FTC/TDF (84% in the Delstrigo group achieved viral suppression of HIV-1 RNA <50 copies/mL vs. 81% in the EFV/FTC/TDF group; treatment difference: 3.5%). Of the 21 percent of study participants with a high viral load at baseline (HIV-1 RNA >100,000 copies/mL), 77% in the Delstrigo group and 72% in the EFV/FTC/TDF group achieved HIV-1 RNA <50 copies/mL at Week 48. Mean CD4+ T-cell counts in the Delstrigo and EFV/FTC/TDF groups increased from baseline by 198 and 188 cells/mm3, respectively.

The expanded approval of Delstrigo was based on DRIVE-SHIFT, the Phase 3 randomized, international, multicenter, open-label trial evaluating a switch to Delstrigo in virologically suppressed participants (HIV-1 RNA <50 copies/mL) on a baseline regimen for at least six months prior to trial entry with no history of virologic failure. The baseline regimen consisted of two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a protease inhibitor plus either ritonavir or cobicistat, or elvitegravir plus cobicistat, or an NNRTI. In DRIVE-SHIFT, 670 participants were randomized to begin treatment with Delstrigo immediately on Day 1 (immediate switch group, ISG; N=447) or after 24 weeks (delayed switch group, DSG; N=223). In the trial, the primary efficacy comparison was between the Delstrigo ISG at Week 48 and the baseline regimen DSG at Week 24. Two percent in the Delstrigo ISG had HIV-1 RNA ≥50 copies/mL at Week 48 compared to 1% in the baseline regimen DSG at Week 24. In addition, 91% of participants who switched to Delstrigo on Day 1 (ISG) had HIV-1 RNA <50 copies/mL at Week 48. Ninety-five percent of participants who continued on their baseline regimen (DSG) had HIV-1 RNA <50 copies/mL at Week 24.

Side Effects

Adverse effects associated with the use of Delstrigo may include, but are not limited to, the following:

dizziness

nausea

abnormal dreams

The Delstrigo drug label comes with the following Black Box Warning: Severe acute exacerbations of hepatitis B (HBV) have been reported in patients coinfected with HIV-1 and HBV who have discontinued lamivudine or tenofovir disoproxil fumarate (TDF), two of the components of Delstrigo. Closely monitor hepatic function in these patients. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

 

Mechanism of Action

Delstrigo is a three-drug combination of doravirine, lamivudine, and tenofovir disoproxil fumarate. Doravirine is a pyridinone non-nucleoside reverse transcriptase inhibitor of HIV-1 and inhibits HIV-1 replication by non-competitive inhibition of HIV-1 reverse transcriptase (RT). Lamivudine is a synthetic nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5´-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of RT via DNA chain termination after incorporation of the nucleotide analogue. Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Tenofovir diphosphate inhibits the activity of HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination.

Additional Information

For additional information regarding Delstrigo or HIV-1 infection, please visit https://www.delstrigo.com/