[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100573532":3},{"organization":4,"outcomesModule":7,"designInfo":69,"detailedDescription":76,"studyPopulation":68,"armGroups":77,"interventions":90,"overallOfficials":102,"centralContacts":106,"locations":112,"responsibleParty":217,"collaborators":220,"id":230,"slug":231,"hasResults":232,"nctId":233,"briefTitle":234,"officialTitle":235,"acronym":68,"eligibilityCriteria":236,"healthyVolunteers":232,"sex":237,"minAge":238,"maxAge":68,"enrollmentInfo":239,"targetDuration":68,"studyType":242,"phases":243,"briefSummary":245,"conditions":246,"keywords":248,"overallStatus":115,"whyStopped":68,"lastUpdateSubmitDate":255,"lastUpdatePostDateStruct":256,"startDateStruct":259,"completionDateStruct":261,"leadSponsor":263,"locationsCount":264},{"fullName":5,"class":6},"University of Nairobi","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":68},[9],{"measure":10,"description":11,"timeFrame":12},"Proportion of participants with HIV-1 RNA of \u003C200 copies\u002FmL at 6 months","The comparative efficacy of switching to a DRV\u002Fr-based regimen after confirmed virologic failure and of remaining on DTG-based ART in achieving viral suppression of \\\u003C200 copies\u002FmL at 6 months from randomization among participants with ≥1 major DTG-associated DRM","6 months",[14,18,21,25,28,31,34,37,40,43,46,49,52,55,58,61,64],{"measure":15,"description":16,"timeFrame":17},"Proportion of participants with HIV-1 RNA of \u003C200 copies\u002FmL at 12 months","Viral suppression to HIV-RNA of \\\u003C200 copies\u002FmL at 12 months from randomization","12 months",{"measure":19,"description":20,"timeFrame":12},"Superiority of switch to DRV\u002Fr","Evaluate if switching to DRV\u002Fr-based ART after virologic failure is superior to remaining on DTG-based ART in achieving viral suppression to \\\u003C200 copies\u002FmL at 6 months from randomization",{"measure":22,"description":23,"timeFrame":24},"Viral suppression with cut-off of 50 copies\u002FmL","Evaluate the difference in viral suppression using HIV-RNA cut-off of \\\u003C50 copies\u002FmL at 6 and 12 months from randomization","6 and 12 months",{"measure":26,"description":27,"timeFrame":24},"Viral suppression with cut-off of 1,000 copies\u002FmL","Evaluate the difference in viral suppression using HIV-RNA cut-off of \\\u003C1,000 copies\u002FmL at 6 and 12 months from randomization",{"measure":29,"description":30,"timeFrame":24},"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",{"measure":32,"description":33,"timeFrame":24},"Viral suppression by sex at birth","Viral load suppression based on participant's sex",{"measure":35,"description":36,"timeFrame":24},"Incidence of adverse events by study arm","Incidence and severity of adverse events and laboratory abnormalities",{"measure":38,"description":39,"timeFrame":12},"Association between adherence and suppression","Adherence levels, based on DBS TFV-DP levels, associated with suppression and selection of treatment-emergent DRMs",{"measure":41,"description":42,"timeFrame":24},"Incidence of drug resistant mutations (DRMs)","Incidence of treatment-emergent DRMs over 12 months of follow-up",{"measure":44,"description":45,"timeFrame":24},"Patterns of accumulated drug resistant mutations (DRMs)","Describe the patterns of accumulated drug resistant mutations over 12 months of follow-up",{"measure":47,"description":48,"timeFrame":24},"Drug resistant mutations (DRM) patterns associated with non-suppression","Evaluate drug resistant mutation patterns that are associated with sustained non-suppression",{"measure":50,"description":51,"timeFrame":24},"Predictors of DTG-associated drug resistant mutations (DRMs)","Investigate the predictors of selection of DTG-associated drug resistant mutations",{"measure":53,"description":54,"timeFrame":24},"Viral suppression by pre-enrolment nucleoside reverse transcriptase inhibitor (NRTI)","Assess viral suppression based on pre-enrolment NRTI",{"measure":56,"description":57,"timeFrame":24},"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",{"measure":59,"description":60,"timeFrame":24},"Change in cluster of differentiation 4 (CD4) Count","The impact of regimen on change in cluster of differentiation 4 (CD4) count",{"measure":62,"description":63,"timeFrame":12},"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",{"measure":65,"description":66,"timeFrame":67},"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","Month 6",null,{"allocation":70,"interventionModel":71,"interventionModelDescription":72,"primaryPurpose":73,"observationalModel":68,"timePerspective":68,"maskingInfo":74},"RANDOMIZED","PARALLEL","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\u002Fr among PLWH age ≥ 3 years who are failing DTG-based ART with HIV-1 RNA ≥ 200 copies\u002FmL and ≥ 1 major DTG-associated DRM (substitution at codon 66K, 92Q, 118R, 138K\u002FA\u002FT, 140S\u002FA\u002FC, 148H\u002FR\u002FK, 155H or 263K ), and most recent prior HIV-1 RNA ≥1,000 copies\u002FmL after at least 6 months on DTG-based ART.","TREATMENT",{"masking":75,"maskingDescription":68,"whoMasked":68},"NONE","BACKGROUND:\n\nThe 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\u002FmL 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.\n\nGOAL:\n\nTo assess the efficacy and safety of remaining on DTG compared to switching to DRV\u002Fr among people failing DTG-based ART with at least one major DTG DRM.\n\nMETHODS:\n\nThis 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\u002Fr among PLWH age ≥ 3 years who are failing DTG-based ART with HIV-1 RNA ≥ 200 copies\u002FmL and ≥ 1 major DTG-associated DRM (and most recent prior HIV-1 RNA ≥ 1,000 copies\u002FmL after at least 6 months on DTG-based ART). The primary efficacy endpoint is the proportion of participants with HIV-1 RNA \\\u003C 200 copies\u002FmL 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\u002FmL after at least six months on DTG-based ART.",[78,84],{"label":79,"type":80,"description":81,"interventionNames":82},"Continue on DTG-based Therapy","EXPERIMENTAL","Participants in this arm will continue their pre-randomization DTG-based ART regimen",[83],"Drug: Dolutegravir Pill",{"label":85,"type":86,"description":87,"interventionNames":88},"Switch to PI-based Therapy","ACTIVE_COMPARATOR","Participants in this arm will be switched to ritonavir-boosted darunavir (DRV\u002Fr)-based ART regimen on the day of randomization",[89],"Drug: Darunavir+Ritonavir",[91,96],{"type":92,"name":93,"description":94,"armGroupLabels":95,"otherNames":68},"DRUG","Dolutegravir Pill","Dose will be based on weight; brand names will be as supplied through the respective national programs",[79],{"type":92,"name":97,"description":98,"armGroupLabels":99,"otherNames":100},"Darunavir+Ritonavir","Dose will be based on weight",[85],[101],"Durart",[103],{"name":104,"affiliation":5,"role":105},"Loice A Ombajo, MMed, MSc","PRINCIPAL_INVESTIGATOR",[107],{"name":108,"role":109,"phone":110,"phoneExt":68,"email":111},"Joseph Nkuranga, MBChB, MSc","CONTACT","+254737223988","dnkuranga@uonbi.ac.ke",[113,128,140,151,164,174,188,198,205],{"facility":114,"status":115,"city":116,"state":68,"zip":68,"country":117,"countryCode":118,"cosmosGeoPoint":119,"geoPoint":124,"contacts":125},"Jaramogi Oginga Odinga Teaching and Referral Hospital","RECRUITING","Kisumu","Kenya","KE",{"type":120,"coordinates":121},"Point",[122,123],34.76171,-0.10221,{"lat":123,"lon":122},[126],{"name":127,"role":109,"phone":110,"phoneExt":68,"email":111},"Joseph Nkuranga",{"facility":129,"status":130,"city":131,"state":68,"zip":68,"country":117,"countryCode":118,"cosmosGeoPoint":132,"geoPoint":136,"contacts":137},"Bomu Hospital","NOT_YET_RECRUITING","Mombasa",{"type":120,"coordinates":133},[134,135],39.66359,-4.05466,{"lat":135,"lon":134},[138],{"name":139,"role":109,"phone":68,"phoneExt":68,"email":68},"Nashina Admani",{"facility":141,"status":115,"city":142,"state":68,"zip":143,"country":117,"countryCode":118,"cosmosGeoPoint":144,"geoPoint":148,"contacts":149},"Kenyatta National Hospital","Nairobi","00100",{"type":120,"coordinates":145},[146,147],36.81667,-1.28333,{"lat":147,"lon":146},[150],{"name":127,"role":109,"phone":110,"phoneExt":68,"email":111},{"facility":152,"status":130,"city":153,"state":68,"zip":68,"country":154,"countryCode":155,"cosmosGeoPoint":156,"geoPoint":160,"contacts":161},"Butha-Buthe District Hospital","Butha-Buthe","Lesotho","LS",{"type":120,"coordinates":157},[158,159],28.24937,-28.76659,{"lat":159,"lon":158},[162],{"name":163,"role":109,"phone":68,"phoneExt":68,"email":68},"Irene Ayakaka",{"facility":165,"status":130,"city":166,"state":68,"zip":68,"country":154,"countryCode":155,"cosmosGeoPoint":167,"geoPoint":171,"contacts":172},"Mokhotlong District Hospital","Mokhotlong",{"type":120,"coordinates":168},[169,170],29.06751,-29.28939,{"lat":170,"lon":169},[173],{"name":163,"role":109,"phone":68,"phoneExt":68,"email":68},{"facility":175,"status":130,"city":176,"state":177,"zip":68,"country":178,"countryCode":179,"cosmosGeoPoint":180,"geoPoint":184,"contacts":185},"CS Ponta Gea","Beira","Sofala","Mozambique","MZ",{"type":120,"coordinates":181},[182,183],34.83889,-19.84361,{"lat":183,"lon":182},[186],{"name":187,"role":109,"phone":68,"phoneExt":68,"email":68},"Nalia Ismael",{"facility":189,"status":130,"city":190,"state":68,"zip":68,"country":178,"countryCode":179,"cosmosGeoPoint":191,"geoPoint":195,"contacts":196},"CS Machava II","Maputo",{"type":120,"coordinates":192},[193,194],32.58322,-25.96553,{"lat":194,"lon":193},[197],{"name":187,"role":109,"phone":68,"phoneExt":68,"email":68},{"facility":199,"status":130,"city":190,"state":68,"zip":68,"country":178,"countryCode":179,"cosmosGeoPoint":200,"geoPoint":202,"contacts":203},"CS Ndlavela",{"type":120,"coordinates":201},[193,194],{"lat":194,"lon":193},[204],{"name":187,"role":109,"phone":68,"phoneExt":68,"email":68},{"facility":206,"status":130,"city":207,"state":68,"zip":68,"country":208,"countryCode":68,"cosmosGeoPoint":209,"geoPoint":213,"contacts":214},"MUHAS Clinical Trial Unit","Dar es Salaam","Tanzania",{"type":120,"coordinates":210},[211,212],39.26951,-6.82349,{"lat":212,"lon":211},[215],{"name":216,"role":109,"phone":68,"phoneExt":68,"email":68},"Patricia Munseri",{"type":105,"investigatorFullName":218,"investigatorTitle":219,"investigatorAffiliation":5,"oldNameTitle":68,"oldOrganization":68},"Loice Achieng Ombajo","Chief Investigator",[221,224,226,228],{"name":222,"class":223},"Instituto Nacional de Saúde, Mozambique","OTHER_GOV",{"name":225,"class":6},"Muhimbili University of Health and Allied Sciences",{"name":227,"class":6},"SolidarMed",{"name":229,"class":6},"London School of Hygiene and Tropical Medicine","100573532","phase-3-ndovu-rct-investing-the-optimal-management-of-dolutegravir-resistance-100573532",false,"NCT06747507","Ndovu RCT: Investing the Optimal Management of Dolutegravir Resistance","Investigating the Optimal Management of Dolutegravir Resistance: an Open-label Randomised Controlled Trial of Maintaining Dolutegravir or Switch to Ritonavir-boosted Darunavir","Inclusion Criteria:\n\n* Enrolled in the Ndovu cohort study\n* Able and willing to understand and comply with the protocol requirements, instructions and restrictions\n* Able and willing to provide informed consent for the nested clinical trial (assent as appropriate and legal guardian consent if \\\u003C 18 years)\n* Age ≥ 3 years\n* Most recent HIV-1 RNA ≥ 200 copies\u002FmL\n* At least one major DTG-associated DRM (substitution at codon 66K, 92Q, 118R, 138K\u002FA\u002FT, 140S\u002FA\u002FC, 148H\u002FR\u002FK, 155H or 263K)\n\nExclusion Criteria:\n\n* Pregnant or breastfeeding\n* Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs\n* 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\n* Investigator opinion that the potential participant should discontinue DTG immediately for clinical reasons\n* Investigator opinion that the potential participant should not switch to DRV\u002Fr for clinical reasons","ALL","3 Years",{"count":240,"type":241},392,"ESTIMATED","INTERVENTIONAL",[244],"PHASE3","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.",[247],"HIV-1-infection",[249,250,251,252,253,254],"HIV","Dolutegravir","Treatment failure","Drug resistant mutations","Dolutegravir resistance","Re-suppression","2025-09-04",{"date":257,"type":258},"2025-09-11","ACTUAL",{"date":260,"type":258},"2025-09-01",{"date":262,"type":241},"2027-07",{"name":5,"class":6},9]