Clinical trial NCT05373758: A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure on TLD in Sub-Saharan Africa
Official title: A Randomized Clinical Trial to Evaluate Solutions for the Management of Virologic Failure for Individuals on Tenofovir, Lamivudine, and Dolutegravir (TLD) in Sub-Saharan Africa
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: HIV Infections
AIDS
Virologic Failure
Keywords: ART
Medication Adherence
Drug resistance
Dolutegravir
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Mbarara University of Science and Technology
name: University of KwaZulu
name: University of California, San Francisco
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2022-05-13
Enrollment: 648
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Viral suppression at 48 weeks
timeFrame: 48 weeks post-enrollment (visit window spanning 42 to 54 weeks post-enrollment)
Secondary outcomes:
Other outcomes:
Locations:
city: Durban
country: South Africa
facility: RK Khan Hospital Clinic
city: Mbarara
country: Uganda
facility: Mbarara City Clinic
city: Mbarara
country: Uganda
facility: Mbarara Regional Referral Hospital Immune Suppression Syndrome Clinic
Study officials:
affiliation: Massachusetts General Hospital
name: Suzanne McCluskey, MD
role: PRINCIPAL_INVESTIGATOR
References: