By IDSE News Staff
The FDA approved an expanded indication for dolutegravir-lamivudine (DTG/3TC; Dovato, ViiV Healthcare) for appropriate virologically suppressed adults living with HIV who want to switch treatments to reduce the number of antiretroviral (ARV) therapies they take.
A complete two-drug regimen for virologically suppressed adults with HIV-1 with no history of treatment failure or resistance to its components, DTG/3TC originally was approved in April 2019 for treatment-naive adults living with HIV.
The once-daily, single-tablet, two-drug regimen of DTG 50 mg and 3TC 300 mg allows adults living with HIV the option to manage their virus without a third ARV agent. It is free of tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate and abacavir.
The approval of DTG/3TC in adults who are virologically suppressed is based on week 48 results from the phase 3, randomized, open-label, active-controlled, multicenter TANGO study. Study participants were HIV-1–infected adults on a TAF-containing regimen with HIV-1 RNA less than 50 copies/mL for at least six months, without prior virologic failure, no historical nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitor (INSTI) major resistance mutation, and no evidence of hepatitis B infection. Participants were randomized to switch to DTG/3TC or continue on the TAF-containing regimen through week 48. The primary end point was the proportion of participants with a viral load less than 50 copies/mL at week 48 (FDA Snapshot algorithm) for the intention-to-treat–Exposed population.
In the primary analysis, no participants on DTG/3TC and one participant (<1%) on the TAF-containing regimen met confirmed virologic failure criteria, with no resistance mutations observed at failure.
“This expanded approval for Dovato is particularly important for my virologically suppressed patients living with HIV who are seeking a new option that can reduce the number of drugs they are exposed to each day,” said Charlotte-Paige Rolle, MD, MPH, the director of research operations at the Orlando Immunology Center, in Florida.
“The data supporting the approval demonstrates how virologically suppressed adults with no known resistance to dolutegravir or lamivudine were able to switch from a TAF-containing regimen of at least three drugs to Dovato while maintaining similar efficacy with zero cases of treatment-emergent resistance through 48 weeks.”
Dolutegravir is an INSTI for use in combination with other ARV agents for the treatment of HIV-1. INSTIs work by blocking HIV replication. They prevent the viral DNA from integrating into the genetic material of T cells. This step is essential in the HIV replication cycle and is responsible for establishing chronic infection.
Lamivudine is a nucleoside analog, which is a synthetic modified nucleoside that mimics naturally occurring endogenous nucleosides. It works by blocking cellular division or viral replication by preventing DNA/RNA synthesis or by inhibiting cellular or viral enzymes involved in nucleoside/tide metabolism.
The Adult and Adolescent Antiretroviral Treatment Guidelines from the Department of Health and Human Services (DHHS) included DTG/3TC in the list of recommended initial regimens for most people with HIV, which is the first time a complete two-drug regimen has been recommended by the DHHS in the first-line setting, except in individuals with HIV RNA greater than 500,000 copies/mL, HBV coinfection, or in whom ARV agents are started before the results of the HIV genotypic resistance testing for reverse transcriptase or HBV testing are available.
