AIDS, HIV Infections, Virologic Failure
Conditions
Keywords
ART, Medication Adherence, Drug resistance, Dolutegravir
Brief summary
The RESOLVE trial is an open, parallel arm, randomized clinical trial which aims to determine the optimal strategy for management of virologic failure on antiretroviral therapy (ART) with tenofovir, lamivudine, and dolutegravir (TLD) in sub-Saharan Africa. The primary outcome of interest will be viral suppression to \<50 copies/mL at 48 weeks using the FDA snapshot definition. The study will be conducted in Uganda and South Africa.
Detailed description
The RESOLVE trial is an open, parallel arm, randomized clinical trial which will be conducted at public-sector HIV clinics in Uganda and South Africa. We will enroll individuals with HIV age 15 and above who have had two HIV-1 RNA viral load results \>1,000 copies/mL while on TLD and who have been on TLD for at least 12 months. Participants will be randomized using an equal allocation ratio of 1:1:1 across three study arms: a) Standard of Care (regimen guided by genotypic resistance tests and care as per guidelines in Uganda; and with regimen selection and possible genotypic resistance testing (GRT) and care as per guidelines in South Africa), 2) Individualized Care with regimen choice based on results of genotypic resistance tests and urine tenofovir adherence assays, or 3) Immediate Switch to PI-based second-line ART. Randomization will be stratified by clinic, prior exposure to non-nucleoside reverse transcriptase inhibitors, and virologic failure history. We will follow participants for one year with study visits at enrollment, Week 24, and Week 48. The primary outcome of interest will be viral suppression to \<50 copies/mL at 48 weeks using the FDA snapshot definition.
Interventions
OTHERStandard of Care treatment strategy
Management of virologic failure on TLD using the Standard of Care strategy
OTHERIndividualized Care treatment strategy
Management of virologic failure on TLD using the Individualized Care strategy
OTHERImmediate Switch
Management of virologic failure on TLD using the Immediate Switch strategy
Sponsors
Massachusetts General Hospital
Mbarara University of Science and Technology
University of KwaZulu
University of California, San Francisco
National Institute of Allergy and Infectious Diseases (NIAID)
Bill and Melinda Gates Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 15 years and above * Enrolled in HIV care at one of the study clinics * History of two HIV-1 RNA viral load measurements \>1,000 copies/mL while on TLD * On TLD for at least 12 months * Lives within 100 kilometers of study clinic * Pregnant women are eligible for enrollment.
Exclusion criteria
* Plans to transfer out of the clinic within the next 48 weeks * Plans to move out of the study catchment area within the next 48 weeks * As determined by chart review, we will exclude those with known virologic failure on protease inhibitors or exposure to integrase strand transfer inhibitors other than dolutegravir.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Viral suppression at 48 weeks | 48 weeks post-enrollment (visit window spanning 42 to 54 weeks post-enrollment) | A plasma HIV-1 RNA viral load \<50 copies/mL (FDA-snapshot definition) |
Countries
South Africa, Uganda
Contacts
CONTACTSuzanne McCluskey, MD
PRINCIPAL_INVESTIGATORSuzanne McCluskey, MD
Massachusetts General Hospital
Outcome results
None listed