Switching to doravirine/tenofovir/lamivudine for people with controlled HIV and a past M184V/I mutation

DOR/TDF/3TC Maintenance Therapy Among Patients Harboring M184V/I Mutation: a Pilot Open-label Study

This trial will test whether switching to a single-pill doravirine/lamivudine/tenofovir regimen keeps viral load suppressed in adults with HIV who previously had the M184V/I mutation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Caen (Academic / other)
• Locations: 4 sites (Caen and 3 other locations)
• Trial ID: NCT06034938 on ClinicalTrials.gov

What this trial studies

This is a phase 2, single-arm pilot in which eligible adults with suppressed HIV and a prior M184V/I mutation will switch their antiretroviral regimen to a fixed-dose doravirine/lamivudine/tenofovir tablet (Delstrigo) and be followed for 48 weeks. The primary outcome is the proportion of participants with HIV RNA <50 copies/mL at 24 weeks after the switch, with continued virologic monitoring to week 48. Secondary endpoints include changes in metabolic and weight parameters and tracking of HIV-DNA mutations over time using proviral genotyping. Participants must have had viral suppression for at least 6 months and a documented past M184V/I on plasma genotype while lacking that mutation on current proviral DNA Sanger testing.

Who should consider this trial

Good fit: Adults with HIV who have been virologically suppressed (HIV RNA <50 cp/mL) for at least 6 months, are on a stable ART regimen for ≥3 months, have a documented past M184V/I on plasma genotype but no M184V/I on current proviral DNA, and can give informed consent.

Not a fit: People with current virologic failure, documented resistance mutations to doravirine or tenofovir per the listed ANRS criteria, or contraindications/allergies to the drugs are unlikely to benefit from this switch.

Why it matters

Potential benefit: If successful, this approach could offer a well‑tolerated, single‑tablet maintenance option that preserves viral suppression despite a prior M184V/I mutation.

How similar studies have performed: Some prior switch studies have shown maintained suppression despite archived M184V/I with certain regimens, but using doravirine/tenofovir/lamivudine specifically in this population is relatively untested and being piloted here.

Eligibility criteria

Inclusion Criteria:

* Adult living with HIV
* Receiving stable antiretroviral treatment for at least 3 months
* HIV RNA VL\<50cp/mL for at least 6 months
* Presence of the M184V/I mutation in at least one previous genotype performed on plasma HIV RNA but absent from the genotype on current standard pro-viral DNA (Sanger technique)
* Signed informed consent

Exclusion Criteria:

* History of genotypic mutation associated with resistance to DOR or TDF according to the ANRS version 32 algorithm, i.e. :
* For DOR : V106A/M; Y188L; G190E/S; M230L; L100I + K103N; K103N + Y181C; K103N + P225H; F227C; At least 3 amongst: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y
* For TDF : At least 3 mutations among: M41L, E44D, D67N, T69D/N/S, L74V/I, L210W, T215A/C/D/E/G/H/I/L/N/S/V/Y/F; K65R/E/N ; Insertion at codon 69; K70E
* Contraindications to the use of DOR/TDF/3TC
* Hypersensitivity to doravirine, tenofovir, lamivudine or any of the excipients (lactose in particular)
* Current or recent treatment with a strong CYP3A4 inducer
* Breast-feeding
* Patients already on DOR
* Pregnant or breast-feeding women
* Patients under guardianship or trusteeship

Where this trial is running

Caen and 3 other locations

• CHU de Caen — Caen, France (Recruiting)
• CHU Orléans — Orléans, France (Recruiting)
• CHU Rouen — Rouen, France (Recruiting)
• CH Tourcoing — Tourcoing, France (Recruiting)

Study contacts

• Study coordinator: Jean-Jacques Parienti, MD, PhD

Conditions Hiv; doravirine; M184 mutation; Maintenance therapy; PLWH