Dual combination therapy for HIV-1 infected patients

A Randomized Comparative Phase II Trial Evaluating the Capacity of the Dual Combination Doravirine/Raltegravir to Maintain Virological Success in HIV-1 Infected Patients With an HIV-RNA Plasma Viremia Below 50 Copies/mL Under a Current Antiretroviral Regimen

This study tests if a new combination of two HIV medications can help people who have their virus under control feel better and avoid side effects from their current treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Paris, Île-de-France Region)
• Trial ID: NCT04513626 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a dual combination therapy using doravirine and raltegravir in HIV-1 infected patients. The study focuses on patients who have achieved viral suppression and are on a stable antiretroviral regimen. By assessing the long-term safety and efficacy of this combination, the trial aims to address the cumulative toxicities associated with traditional antiretroviral therapies. Participants will be monitored for their HIV-RNA levels and overall health outcomes over the course of the trial.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with documented HIV-1 infection who have maintained viral suppression on a stable antiretroviral regimen.

Not a fit: Patients who are not naive to doravirine or have documented resistance to doravirine and/or raltegravir may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a safer and more effective treatment option for patients living with HIV.

How similar studies have performed: Other studies have shown promising results with dual combination therapies in HIV treatment, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years
* Patients with HIV-1 documented infection
* CD4 ≥ 200/mm3
* On stable combined ART regimen with at least 2 drugs for at least 6 months
* HIV-RNA plasma VL ≤ 50 copies/mL during the last 12 months prior to screening visit (W-6/W-4), documented by at least 2 time-points with no more than one blip (defined as one HIV-RNA plasma VL between 51 and 200 copies/mL followed by one HIV-RNA plasma VL ≤ 50 copies/mL)
* Naive to doravirine
* Absence of resistance to doravirine\* and/or raltegravir\*\*(see list mutations below)

  * on all HIV-genotypes with available RT and integrase gene sequences allowing resistance interpretation in case of previous virological failure
  * or on DNA genotype performed at screening if HIV genotype is not available in case of prior virological failure.
* Signed informed consent form.
* Patient affiliated to a social insurance regimen. For French patients only: subject enrolled in or a beneficiary of a Social Security programme (State Medical Aid or AME is not a Social Security programme).

  * Mutations associated to doravirine resistance are: V106A/M, Y188L, G190E/S, M230L, F227C, at least 2 among: A98G, L100I, K101E, V106I, E138K, Y181C/V, G190A or H221Y

    * Mutations associated to raltegravir resistance are: T66A/K, E92Q, G118R, F121Y, G140A/S Y143A/C/G/H/R/S, Q148E/G/H/K/R, V151L, N155H/S/T, E157Q, S230R, R263K, L74 F/I + V75I.

Exclusion Criteria:

* Absence of RT and INI HIV sequence available (past genotypes or failure of amplification of DNA at screening)
* HBV co-infection
* Hemoglobin \<9 g/dL
* Platelets \<80,000/mm3
* Creatinine clearance \<60 mL/min (MDRD)
* AST or ALT ≥5N
* Concomitant DAA for anti-HCV therapy
* Any severe concomitant illness
* Any drug with potential drug-drug interaction with doravirine
* Concomitant treatment using interferon, interleukins or any other immune-therapy or chemotherapy
* Concomitant prophylactic or curative treatment for an opportunistic infection
* All conditions (use of alcohol, drugs, etc.) judged by the investigator to possibly interfere with trial protocol compliance, adherence and/or trial treatment tolerance
* Subjects under "sauvegarde de justice" (judicial protection due to temporarily and slightly diminished mental or physical faculties), or under legal guardianship
* Subjects participating in another clinical trial evaluating different therapies and including an exclusion period that is still in force during the screening phase
* Pregnant women or breastfeeding women

Where this trial is running

Paris, Île-de-France Region

• Christine KATLAMA — Paris, Île-de-France Region, France (RECRUITING)

Study contacts

• Principal investigator: Christine Katlama, MD — Pitie-Salpetriere Hospital
• Study coordinator: Yasmine Dudoit

Conditions: HIV Infections