Best way to manage dolutegravir resistance in people with HIV
Investigating the Optimal Management of Dolutegravir Resistance: an Open-label Randomised Controlled Trial of Maintaining Dolutegravir or Switch to Ritonavir-boosted Darunavir
This trial will test whether staying on dolutegravir or switching to darunavir/ritonavir better controls HIV in people with dolutegravir-resistant virus and a viral load of 200 copies/mL or higher.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 392 (estimated) |
| Ages | 3 Years and up |
| Sex | All |
| Sponsor | University of Nairobi Academic / other |
| Locations | 9 sites (Kisumu and 8 other locations) |
| Trial ID | NCT06747507 on ClinicalTrials.gov |
What this trial studies
This randomized Phase 3 trial enrolls people aged 3 years and older from the Ndovu cohort who have HIV-1 RNA ≥200 copies/mL and at least one major dolutegravir-associated resistance mutation. Participants are randomized to either remain on their dolutegravir-based regimen or switch to darunavir plus ritonavir, with regular follow-up to compare viral suppression and safety outcomes. The trial is conducted at multiple Kenyan hospital sites and uses baseline drug resistance testing to define eligibility. Findings will clarify whether continuation of dolutegravir is acceptable or whether switching to a protease inhibitor improves virologic control in this population.
Who should consider this trial
Good fit: Ideal candidates are people with HIV aged 3 or older who are enrolled in the Ndovu cohort, have an HIV-1 RNA ≥200 copies/mL, and have at least one major dolutegravir-associated resistance mutation.
Not a fit: People who are pregnant or breastfeeding, have severe opportunistic infections or other clinical reasons to stop dolutegravir immediately, are taking contraindicated medications, or do not have major dolutegravir resistance mutations are unlikely to benefit from this trial.
Why it matters
Potential benefit: If successful, the trial could show whether people with dolutegravir-resistant virus can safely stay on dolutegravir or should switch to darunavir/ritonavir, helping clinicians avoid unnecessary or harmful regimen changes.
How similar studies have performed: Published data on outcomes for people with dolutegravir-associated resistance are limited, so this randomized comparison of continuing dolutegravir versus switching to darunavir/ritonavir is relatively novel, though resistance-guided switches to protease inhibitors have been used in other settings.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Enrolled in the Ndovu cohort study * Able and willing to understand and comply with the protocol requirements, instructions and restrictions * Able and willing to provide informed consent for the nested clinical trial (assent as appropriate and legal guardian consent if \< 18 years) * Age ≥ 3 years * Most recent HIV-1 RNA ≥ 200 copies/mL * At least one major DTG-associated DRM (substitution at codon 66K, 92Q, 118R, 138K/A/T, 140S/A/C, 148H/R/K, 155H or 263K) Exclusion Criteria: * Pregnant or breastfeeding * Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs * WHO stage 3 or 4 opportunistic infection which would prevent randomisation to either arm (e.g. due to drug interactions or significant liver or renal injury) within 4 weeks prior to RCT screening * Investigator opinion that the potential participant should discontinue DTG immediately for clinical reasons * Investigator opinion that the potential participant should not switch to DRV/r for clinical reasons
Where this trial is running
Kisumu and 8 other locations
- Jaramogi Oginga Odinga Teaching and Referral Hospital — Kisumu, Kenya (Recruiting)
- Bomu Hospital — Mombasa, Kenya (Not_yet_recruiting)
- Kenyatta National Hospital — Nairobi, Kenya (Recruiting)
- Butha-Buthe District Hospital — Butha-Buthe, Lesotho (Not_yet_recruiting)
- Mokhotlong District Hospital — Mokhotlong, Lesotho (Not_yet_recruiting)
- CS Ponta Gea — Beira, Sofala, Mozambique (Not_yet_recruiting)
- CS Machava II — Maputo, Mozambique (Not_yet_recruiting)
- CS Ndlavela — Maputo, Mozambique (Not_yet_recruiting)
- MUHAS Clinical Trial Unit — Dar es Salaam, Tanzania (Not_yet_recruiting)
Study contacts
- Principal investigator: Loice A Ombajo, MMed, MSc — University of Nairobi
- Study coordinator: Joseph Nkuranga, MBChB, MSc
- Email: dnkuranga@uonbi.ac.ke
- Phone: +254737223988
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.