Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT06155019 |
Other study ID # |
CREPATS 16 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
December 15, 2023 |
Est. completion date |
June 15, 2024 |
Study information
Verified date |
February 2024 |
Source |
Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida |
Contact |
Yasmine DUDOIT, Mrs |
Phone |
00 33 1 42 16 41 81 |
Email |
yasmine.dudoit[@]aphp.fr |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
The main objective of the SWEED study is to determine whether doravirine containing ART is
able to maintain viral suppression at W48 in HIV-1 infected people living with HIV (PLWH)
receiving etravirine containing ART:
- An ARV strategy containing doravirine as a replacement for etravirine can maintain
virological suppression in participants with controlled viral replication under ARV
treatment containing etravirine, with a virological success rate >90%
- This strategy can maintain virological suppression even in the event of NNRTI resistance
mutations acquired in the past
- This strategy is well tolerated
- The emergence of resistance to NNRTIs is uncommon in the event of virological failure
under the ARV regimen containing doravirine
Description:
The evolution of HIV infection from fatal to chronic has been enabled by advances in
development and access of antiretroviral treatment (ART), which has also resulted in life
expectancy of PLWH approaching that of those uninfected.In addition, over the past few years,
new drugs and news regimens have offered improved efficacy, safety and tolerability. The
95-95-95 UNAIDS target, i.e. to diagnose 95% of PLWHIV (1st 95), provide ART to 95% of those
diagnosed with HIV (2nd 95), and to reach viral suppression in 95% of patients on ART (3rd
95), is being achieved in several countries. Calls to add a fourth target, i.e. to improve
the quality of life for PLWHIV, have grown stronger since the concept was introduced in 2016.
The twin aims are long-term treatment durability and improved quality of life with a focus on
personalized treatment.
Switching or simplifying ART in the setting of HIV suppression may improve pill burden,
dosing frequency, safety, tolerability, and/or food requirements. At times, ART switch or
simplification is elective, such as consolidating a multiple-tablet to a single-tablet
regimen (STR). Other times, it is necessary to eliminate drug-drug interactions (DDIs) and/or
minimize active or potential treatment-associated adverse events (AEs). The fundamental
principle of switching or simplifying ART is to preserve virologic suppression without
jeopardizing future ART options.
Etravirine, a second generation NNRTI, has been demonstrated to be effective on HIV strains
with prior resistance mutations on reverse transcriptase impacting other NNRTIs, such as
nevirapine, efavirenz or rilpivirine. It has even been used in salvage therapy, in
association with darunavir and raltegravir, in uncontrolled patients with multiresistant
strains. Etravirine is mostly prescribed twice daily, and is a strong enzymatic inducer
providing many DDIs, complicating its use.
Doravirine, a last generation NNRTI, is approved in treatment-naïve and experienced
HIV-infected individuals. In the DRIVE-FORWARD study, doravirine 100 mg QD, in combination
with either TDF/FTC or ABC/3TC, achieved high virologic success at week 48 and was
non-inferior to DRV/r + 2 NRTIs regardless of baseline HIV-RNA. In the DRIVE-AHEAD study, in
treatment-naïve adults with HIV-1 infection, doravirine + 3TC/TDF administered once daily
demonstrated a high antiviral potency with non-inferior efficacy to EFV/FTC/TDF regardless of
baseline HIV-RNA, and a low rate of resistance, with only 1.6% of participants developing
resistance to any study drug through W48. For virologically suppressed patients considering a
change in therapy, switching to DOR/3TC/TDF was shown to be a well-tolerated option which was
non-inferior to continuation of the previous regimen, with high rates of virologic
suppression and low rates of virologic rebound. Long term results from the DRIVE-SHIFT trial
showed that doravirine maintained virologic suppression and was generally well tolerated
through 144 weeks of treatment. DOR/3TC/TDF as switch therapy showed a favorable lipid
profile compared with previous regimens and results in minimal weight gain. The convenience
achieved through switching to a DOR based regimen serves to achieve regimen simplification
and could respond to patient demands for increased tolerability.
The DOR resistance profile is distinct from that of other NNRTIs with the in vitro selection
of mutations at reverse transcriptase (RT) positions 106, 108, 188, 227, 230, 234 and 236. In
vitro studies have also suggested that DOR has activity against viruses with certain
mutations selected by other NNRTIs, including the K103N and Y181C mutations. In the
DRIVE-SHIFT trial, conducted in virologically suppressed patients, 24 participants had a
virus with baseline NNRTI mutations (K103N, Y181C and G190A) and 23/24 who switched to
DOR/3TC/TDF remained virologically suppressed at the 48-week follow-up. This suggests that
the most frequent NNRTI mutations at RT mutation positions 103, 181 and 190 probably not
impact DOR activity in vivo.
Due to its virological properties, we believe that doravirine can advantageously replace
etravirine, maintaining control of viral replication, in combination with other
antiretrovirals, in virologically controlled patients, despite possible exposure to NNRTIs in
the pass. Furthermore, doravirine is taken as a single tablet once a day, and causes almost
no drug interactions, unlike etravirine.