Efficacy, Safety and Tolerability of Switching to DTG/3TC Single Tablet Regimen from B/F/TAF in Older Persons Living with HIV in Kenya

Background: The standard treatment for HIV comprises three or four drugs in order to achieve viral suppression. However, the use of some of these drugs may affect the kidneys, bone and other body systems. For example, an ongoing study in Kenya has demonstrated high rates of kidney and bone disease in older persons living with HIV aged 60 years old or more.

Recent studies have shown that two-drug regimens such as a combination of dolutegravir (DTG) and lamivudine (3TC) may achieve the same rates of viral suppression after switching from other treatment regimens containing three drugs. The use of a two-drug regimen means that there will be a lower drug burden that may have less harmful effects including improving bone health and kidney function. 

Objective: The purpose of the study is to determine whether older persons living with HIV (60 years old or above) who are currently virally suppressed on their first line antiretroviral regimen containing bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) can safely be switched to a two-drug regimen of dolutegravir (DTG) and lamivudine (3TC).

Participants and Methods: We will enroll 240 participants in two sites in Kenya: Kenyatta National Hospital in Nairobi and Jaramogi Oginga Odinga Teaching and Referral Hospital in Kisumu. After providing written informed consent, participants will be evaluated for eligibility. Those who are enrlled will have their treatment regimen changed to a combined pill containing DTG and 3TC taken once daily for the duration of the study. Thereafter, each person will be followed up for 96 weeks (about two years). All participants will have scheduled visits at weeks 4, 12, 24, 36, 48, 60, 72, 84 and 96. During follow-up, the amount of HIV virus in blood will be checked alongside other laboratory and radiological tests assessing for safety.

Background

Three drug regimens for the treatment of HIV are widely used and successful in achieving viral suppression. However, they are associated with various adverse events including renal and bone disease, anemia, mitochondrial toxicity, and possible association with increased cardiovascular events. Data from the ongoing BFTAF Elderly Switch Study has demonstrated high rates of renal insufficiency and osteoporosis in people living with HIV aged 60 years or more, hence the need for safe treatment options. Two drug regimens (2DR) have demonstrated non-inferiority to three drug regimens in patients who are treatment naïve as well as in those who are virally suppressed on a first-line regimen and potentially have lower toxicity, fewer adverse drug events and a lower drug burden.

Objectives

To assess the efficacy and safety of switch to dolutegravir and lamivudine (DTG/3TC) single tablet regimen from bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in persons living with HIV aged 60 years old or more.

Methods

This is a phase 3b, multi-center, open-label, single arm clinical trial over 96 weeks. The study will take place at two sites in Kenya: Kenyatta National Hospital (KNH) and Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). Study visits will take place at screening, baseline, and weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 (with a 6-week extension as required for confirming HIV-1 RNA levels). A target of 240 participants from the ongoing BFTAF Elderly Switch Study will be enrolled. Eligible participants will be switched from B/F/TAF to DTG/3TC at enrollment and followed up for 96 weeks. The primary endpoint will be the proportion of participants with plasma HIV-1 RNA ≥ 50 copies/mL (Snapshot algorithm) at Week 48. Analysis of the primary endpoint will be performed for the ITT-E population using the FDA snapshot method.

Data Management: The collection and processing of personal data from s 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

Study Utility

The Kenyan national HIV program currently recommends tenofovir disoproxil fumarate (TDF) as the preferred nucleoside reverse transcriptase inhibitor (NRTI). TDF is associated with both renal and bone toxicity and in the absence of safer tenofovir pro-drugs such as tenofovir alafenamide (TAF), it is important to consider regimens that exclude the toxic NTRIs such as the two-drug regimen of lamivudine and dolutegravir, especially in populations that are at risk of multiple comorbidities. This will provide useful data to inform policy and programming.