Background: Currently the recommend treatment for all adults with HIV is a combination of tenofovir, lamivudine and dolutegravir (TDF/3TC/DTG in short). This combination has limitations for elderly people living with HIV who are more likely to have other long-term diseases and have higher risk of developing other ailments like bone and kidney disease. Other treatment options in Kenya include a drug called Abacavir that may result in increased risk of heart disease which limits its use in the elderly. The combination we are using in this study also comprises three drugs: bictegravir, emtricitabine and tenofovir alafenamide, B/F/TAF in short. This combination has been shown to be as good as other regimens in managing HIV disease (efficacy), has few side effects (safety), is given as a single small pill that is easy to swallow, and does not have the same risks of bone, kidney or heart disease as other regimens in use in the country. We are not aware of any research that compared different treatment options for elderly people living with HIV whose numbers are continuously increasing.

 

Objective: We will compare the efficacy, safety, and effect on bone health of B/F/TAF against the treatment regimens that elderly people (60 years old or greater) living with HIV are currently using. The results from this study may have far reaching implications in informing management of elderly persons living with HIV in Kenya and globally.

 

Participants and Methods: We will enroll 516 participants from the outpatient HIV clinics at Kenyatta National Hospital and Jaramogi Oginga Odinga Teaching and Referral Hospital in Kisumu. Half of them will have their HIV treatment changed to B/F/TAF while the other half will remain on the treatment they have been using; the choice will be made randomly at the time each person starts the study. Thereafter, each person will be followed up for 48 weeks. During this time, the amount of HIV virus in blood will be checked at weeks 4, 12, 24 and 48 alongside other laboratory and radiological tests assessing for safety. Procedures to minimize risk of COVID-19 infection amongst subjects and staff will be implemented.

Study Background: Current Kenya National ARV Guidelines and WHO Guidelines recommend first line therapy of TDF/3TC/DTG for adult PLHIV. This regimen has limitations, particularly for the aging PLHIV who are more likely to have pre-existing comorbidities and higher risk of developing comorbidities, including osteopenia, osteoporosis, and renal insufficiency. Abacavir, the preferred alternative NRTI in Kenya, is associated with increased cardiovascular risk that also limits its use in elderly populations. B/F/TAF is highly efficacious, well tolerated, co-formulated in a small pill, and does not have the same bone, renal or cardiovascular risks associated with currently recommended regimens in Kenya. We are not aware of any clinical trial to date that has been fully powered to compare ARV regimens for the increasing population of elderly PLHIV.

 

Broad Objective: We will compare the efficacy, safety, and impact on bone mineral density of switching to B/F/TAF to that of remaining on current ARV regimen in a population of elderly patients (60 years old or greater) with no prior confirmed treatment failure in Kenya.

 

Study Design and Sites: This is a phase IV, multi-center, open-label, randomized trial over 48 weeks, describing the efficacy and safety of switching from current ARV regimen to B/F/TAF in virally suppressed HIV-1 infected elderly adults (≥ 60 years) who have been on ART for at least 24 weeks and having achieved virological suppression (HIV-1 RNA < 50 copies/ml) for at least 12 weeks, with no prior confirmed virological failure. The study will take place at Kenyatta National Hospital (KNH) and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH).

 

Participants and Methods: The study will enroll 516 subjects from the outpatient HIV clinics at KNH and JOOTRH. Subjects will be randomized to remain on their current ART regimen or switch to B/F/TAF, and will be followed for 48 weeks. HIV-1 RNA viral load will be measured at weeks 4, 12, 24 and 48. Serum creatinine, CD4 count, fasting glucose, fasting lipids and patient satisfaction will be measured at baseline and weeks 24 and 48, along with other safety investigations. Procedures to minimize risk of COVID-19 infection amongst subjects and staff will be implemented.

 

The primary efficacy endpoint of HIV-1 RNA ≥ 50 copies/ml at week 48 will be analyzed for non-inferiority using the FDA snapshot method. The primary safety endpoint of mean percentage change in lumbar spine bone mineral density DXA values from baseline to 48 weeks will be assessed using analysis of variance (ANOVA).

 

Data Management: The collection and processing of personal data from subjects enrolled in this study will be limited to those data that are necessary to investigate the primary and secondary objectives. These data will be collected using electronic Case Report Forms and processed with adequate precautions to ensure confidentiality and compliance with data privacy and protection laws and regulations.

 

Expected Main Outcome Measure/Study Utility: As the first fully powered clinical trial comparing ARV regimens in the elderly, these results may have far reaching implications in informing management of elderly patients in Kenya and globally. B/F/TAF is currently undergoing registration with the Pharmacy and Poisons Board of Kenya, and Kenya is one of the countries included in Gilead’s licensing agreement with the Medicines Patent Pool, so there is potential to scale up a generic product in the public sector with government and donor funding if B/F/TAF is found to result in non-inferior virological outcomes while leading to an improvement in bone mineral density and preservation of renal function.