Comparing two HIV treatment regimens for maintaining viral suppression

MODULO Trial: Doravirine/Lamivudine (DOR/3TC) as a Maintenance ART in Comparison With Dolutegravir/Lamivudine (DTG/3TC) in PLWH Successfully Treated With Three-drug Regimens at Inclusion

This study is testing whether two different HIV treatment combinations can help people who have their virus under control stay healthy without using certain types of medications.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 408 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida (Academic / other)
• Locations: 1 site (Paris, Île-de-France Region)
• Trial ID: NCT06774872 on ClinicalTrials.gov

What this trial studies

This trial aims to compare the effectiveness of two antiretroviral therapy regimens, Doravirine/Lamivudine (DOR/3TC) and Dolutegravir/Lamivudine (DTG/3TC), in maintaining virological success in people living with HIV who have achieved viral suppression. Participants must have a stable three-drug regimen prior to inclusion and will be monitored for virological failure over a 48-week period. The study seeks to evaluate a dual therapy option that avoids integrase inhibitors and boosted protease inhibitors, addressing the needs of patients with specific treatment histories or comorbidities.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older living with HIV-1 who have maintained a suppressed viral load for at least 24 months on a stable three-drug regimen.

Not a fit: Patients co-infected with HIV-2 or hepatitis B, or those with documented resistance mutations to the study drugs may not benefit from this trial.

Why it matters

Potential benefit: If successful, this study could provide an effective alternative treatment option for patients living with HIV who have limitations with current therapies.

How similar studies have performed: Previous studies have shown success with dual therapy approaches in HIV treatment, but this specific comparison of DOR/3TC versus DTG/3TC is novel.

Eligibility criteria

Inclusion Criteria:

* Adults ≥18 years;
* Living with HIV-1;
* With pVL \<50 copies/mL for at least 24 months;
* Under stable three-drug regimen including 2 NRTIs + 1 NNRTI or 1 INSTI or 1 boosted PI for at least 12 months;
* Affiliated to the French Social Insurance;
* Who have given their written consent to participate in the study

Exclusion Criteria:

* HIV-2 co-infection;
* Co-infection with hepatitis B virus (positive HBsAg and/or positive anti-HBc antibody with negative anti-HBs antibody);
* Documented resistance mutation or association of resistance mutations, associated with partial or full resistance to doravirine, dolutegravir or lamivudine;
* At least one resistance genotype is mandatory to include the patient:

  * If there was no virological failure under NRTI, NNRTI and INSTI in the past:

    * Pretherapeutic HIV-RNA genotype,
    * OR, in case of no available HIV-RNA genotype, genotype on proviral HIV-DNA to performed before inclusion,
  * In case of virological failure under NRTI, NNRTI and INSTI in the past:

    * HIV-RNA genotype at time of virological failure,
    * OR, in case of no available HIV-RNA genotype at time of failure, genotype on proviral HIV-DNA to performed before inclusion to be sure that the virus is fully sensitive to the study treatments,
  * Past virological failure is defined as: 2 consecutive pVL ≥50 copies/mL or one pVL ≥200 copies/mL,
  * Resistance genotypes will be interpretated with the last available ANRS algorithm.
* Glomerular filtration rate \<50 mL/min (CKD-EPI formula);
* Comedications leading to drug-drug interaction with one of the 3 study drugs (cf. detailed protocol);
* Pregnant or breastfeeding women, and women with age to be pregnant but refusing effective contraception, whether or not a desire for pregnancy is expressed;
* Any clinal condition limiting the participation in a clinical trial: Immunocompromised conditions including active cancer or hematological malignancy, organ transplant or with transplant rejection within the last 6 months, immunosuppressive therapy, or other condition that in the opinion of the investigator could cause impaired host immunity
* Protected adults (persons under legal guardianship or under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties)

Where this trial is running

Paris, Île-de-France Region

• Hôpital Pitié-Salpêtrière — Paris, Île-de-France Region, France (Recruiting)

Study contacts

• Principal investigator: Romain PALICH, MD — Pitié-Salpêtrière Hospital
• Study coordinator: Yasmine DUDOIT

Conditions HIV-1-infection