A Phase 3 interventional study of Dolutegravir Pill and Darunavir+Ritonavir in HIV-1-infection, sponsored by University of Nairobi. Recruiting at 9 sites in 4 countries. Open to participants aged 3 Years and older. Per ClinicalTrials.gov, last updated 2025-09-11.
Sponsored by University of Nairobi · Phase 3, Interventional, and Treatment
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.
BACKGROUND:
The majority of people living with HIV (PLWH) on first-line antiretroviral therapy (ART) in low- and middle-income countries are on dolutegravir (DTG)-containing regimens. Different countries have adopted different approaches in the management of people on DTG-based first-line ART with repeat HIV viral load (VL) of > 1,000 copies/mL after 3 months of enhanced adherence counselling. For example, Kenya recommends a drug resistance test (DRT) to guide on switch and the optimal second-line regimen; Mozambique and Tanzania recommend switch to 2 nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) without drug resistance testing; South Africa does not recommend switch from DTG or DRT for those who are on first-line DTG-containing regimens within the first 2 years of treatment, after which management is guided by possible DRT and expert opinion. The World Health Organization has recognised the role of drug resistance testing (DRT) in a treatment failure algorithm for people living with HIV receiving DTG-based treatment to minimise unnecessary switches from this regimen. The switch to PI has disadvantages including higher cost, higher pill burden, less convenient administration (often should be taken with food), more potential drug-drug interactions, poorer tolerability and more long-term toxicities.
GOAL:
To assess the efficacy and safety of remaining on DTG compared to switching to DRV/r among people failing DTG-based ART with at least one major DTG DRM.
METHODS:
This is a phase 3b, multi-country, open-label, two-arm, active-controlled randomized clinical trial (RCT) 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 (and most recent prior HIV-1 RNA ≥ 1,000 copies/mL after at least 6 months on DTG-based ART). The primary efficacy endpoint is the proportion of participants with HIV-1 RNA \< 200 copies/mL at month 6. The study will be conducted in 9 sites in Kenya, Mozambique, Tanzania and Lesotho targeting 392 participants including 30 children aged between 3 and 14 years old. The primary efficacy analysis will assess the difference in the proportion of participants with viral suppression at month 6 using the Cochran-Mantel-Haenszel method. This RCT is nested within an observational cohort study describing HIV-1 viral suppression of people with HIV-1 RNA value of ≥ 1,000 copies/mL after at least six months on DTG-based ART.
University of Nairobi is the lead sponsor of 11 studies on the registry; 2 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants in this arm will continue their pre-randomization DTG-based ART regimen
Drug: Dolutegravir Pill
Participants in this arm will be switched to ritonavir-boosted darunavir (DRV/r)-based ART regimen on the day of randomization
Drug: Darunavir+Ritonavir
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
Time frame: 6 months
Proportion of participants with HIV-1 RNA of <200 copies/mL at 12 months
Viral suppression to HIV-RNA of \<200 copies/mL at 12 months from randomization
Time frame: 12 months
Superiority of switch to DRV/r
Evaluate if switching to DRV/r-based ART after virologic failure is superior to remaining on DTG-based ART in achieving viral suppression to \<200 copies/mL at 6 months from randomization
Time frame: 6 months
Viral suppression with cut-off of 50 copies/mL
Evaluate the difference in viral suppression using HIV-RNA cut-off of \<50 copies/mL at 6 and 12 months from randomization
Time frame: 6 and 12 months
Viral suppression with cut-off of 1,000 copies/mL
Evaluate the difference in viral suppression using HIV-RNA cut-off of \<1,000 copies/mL at 6 and 12 months from randomization
Time frame: 6 and 12 months
Viral suppression by age strata
Viral load suppression rate by age strata: 3-9, 10-19, ≥20, 20-24, 25-34, 35-44, and ≥45 years old
Time frame: 6 and 12 months
Viral suppression by sex at birth
Viral load suppression based on participant's sex
Time frame: 6 and 12 months
Incidence of adverse events by study arm
Incidence and severity of adverse events and laboratory abnormalities
Time frame: 6 and 12 months
Association between adherence and suppression
Adherence levels, based on DBS TFV-DP levels, associated with suppression and selection of treatment-emergent DRMs
Time frame: 6 months
Incidence of drug resistant mutations (DRMs)
Incidence of treatment-emergent DRMs over 12 months of follow-up
Time frame: 6 and 12 months
Patterns of accumulated drug resistant mutations (DRMs)
Describe the patterns of accumulated drug resistant mutations over 12 months of follow-up
Time frame: 6 and 12 months
Drug resistant mutations (DRM) patterns associated with non-suppression
Evaluate drug resistant mutation patterns that are associated with sustained non-suppression
Time frame: 6 and 12 months
Predictors of DTG-associated drug resistant mutations (DRMs)
Investigate the predictors of selection of DTG-associated drug resistant mutations
Time frame: 6 and 12 months
Viral suppression by pre-enrolment nucleoside reverse transcriptase inhibitor (NRTI)
Assess viral suppression based on pre-enrolment NRTI
Time frame: 6 and 12 months
Viral suppression by tenofovir disoproxil fumarate versus tenofovir alafenamide
Assess viral suppression based on tenofovir disoproxil fumarate (TDF) versus tenofovir alafenamide (TAF) as the study nucleoside reverse transcriptase inhibitor
Time frame: 6 and 12 months
Change in cluster of differentiation 4 (CD4) Count
The impact of regimen on change in cluster of differentiation 4 (CD4) count
Time frame: 6 and 12 months
Patient satisfaction as measured using the HIV Treatment Satisfaction Questionnaire - Status version (HIVTSQs) which scores 10 variables on a 7-point likert score ranging from 0 to 6 with a higher score representing a better outcome
Patient satisfaction (HIVTSQs) at baseline
Time frame: 6 months
Change in patient satisfaction as measured using the HIV Treatment Satisfaction Questionnaire - Change version (HIVTSQc) which scores 10 variables on a 7-point likert score ranging from -3 to +3 with a higher score representing a better outcome
Patient satisfaction (HIVTSQc) at month 6
Time frame: Month 6
Plan to share: Yes — The investigators will share the individual patient data (IPD) that underlie the results reported after de-identification (text, tables, figures and appendices).
Supporting information: Study protocol, Statistical analysis plan, 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.
Started Sep 2025 (actual). Primary completion is estimated for Dec 2026, 15 months after the start.
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