Ndovu RCT: Investing the Optimal Management of Dolutegravir Resistance

NCT06747507 | Recruiting Phase 3 DMC

• 1 other identifier: Ndovu RCT
• Study Type: interventional
• Target: 392
• Locations: 4 countries
• Sites: 9

Brief Summary

This clinical trial will address the gap in published data on the effect of dolutegravir (DTG)-associated drug-resistant mutations on viral suppression among people remaining on DTG-based antiretroviral therapy. It will also address the gap in the optimal management strategy for this population.

Conditions

HIV-1-infection

Keywords

HIV; Dolutegravir; Treatment failure; Drug resistant mutations; Dolutegravir resistance; Re-suppression

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with HIV-1 RNA of <200 copies/mL at 6 months

  The comparative efficacy of switching to a DRV/r-based regimen after confirmed virologic failure and of remaining on DTG-based ART in achieving viral suppression of \<200 copies/mL at 6 months from randomization among participants with ≥1 major DTG-associated DRM

  6 months

Secondary Outcomes (17)

• Proportion of participants with HIV-1 RNA of <200 copies/mL at 12 months

  12 months

• Superiority of switch to DRV/r

  6 months

• Viral suppression with cut-off of 50 copies/mL

  6 and 12 months

• Viral suppression with cut-off of 1,000 copies/mL

  6 and 12 months

• Viral suppression by age strata

  6 and 12 months

Study Arms (2)

Continue on DTG-based Therapy

EXPERIMENTAL

Participants in this arm will continue their pre-randomization DTG-based ART regimen

Drug: Dolutegravir Pill

Switch to PI-based Therapy

ACTIVE COMPARATOR

Participants in this arm will be switched to ritonavir-boosted darunavir (DRV/r)-based ART regimen on the day of randomization

Drug: Darunavir+Ritonavir

Interventions

Dolutegravir Pill DRUG

Dose will be based on weight; brand names will be as supplied through the respective national programs

Continue on DTG-based Therapy

Darunavir+Ritonavir DRUG

Dose will be based on weight

Also known as: Durart

Switch to PI-based Therapy

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nairobi: lead
• Instituto Nacional de Saúde, Mozambique: collaborator
• Muhimbili University of Health and Allied Sciences: collaborator
• SolidarMed: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (9)

Jaramogi Oginga Odinga Teaching and Referral Hospital

Kisumu, Kenya

RECRUITING

Bomu Hospital

Mombasa, Kenya

NOT YET RECRUITING

Kenyatta National Hospital

Nairobi, 00100, 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

MeSH Terms

Interventions

dolutegravir

Study Officials

• Loice A Ombajo, MMed, MSc

  University of Nairobi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph Nkuranga, MBChB, MSc

CONTACT

+254737223988; dnkuranga@uonbi.ac.ke

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Investigator

Model Details: This is a phase 3b, multi-country, open-label, two-arm, active-controlled randomized clinical trial over 12 months describing the efficacy and safety of switching from DTG to DRV/r among PLWH age ≥ 3 years who are failing DTG-based ART with HIV-1 RNA ≥ 200 copies/mL and ≥ 1 major DTG-associated DRM (substitution at codon 66K, 92Q, 118R, 138K/A/T, 140S/A/C, 148H/R/K, 155H or 263K ), and most recent prior HIV-1 RNA ≥1,000 copies/mL after at least 6 months on DTG-based ART.

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: December 24, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 6 months after publication of the final manuscript and for a period of 36 months
• Access Criteria: Access to IPD will be subject to the University of Nairobi data sharing requirements. Written requests should be submitted to the Chief Investigator providing a brief description of the individual or group making the request and detailing the reason for the same. Prior to sharing the data, the requestor will be required to sign a data access and sharing agreement.

Locations

TA (1); KE (3); LE (2); MO (3)