Tenofovir disoproxil fumarate and emtricitabine maintenance strategy in virologically controlled adults with low HIV-1 DNA: 48 week results from a randomized, open-label, non-inferiority trial

Abstract

Objectives Low HIV reservoirs may be associated with viral suppression under a lower number of antiretroviral drugs. We investigated tenofovir disoproxil fumarate/emtricitabine as a maintenance strategy in people living with HIV (PLHIV) with low HIV-DNA. Methods TRULIGHT (NCT02302547) was a multicentre, open-label, randomized trial comparing a simplification to tenofovir disoproxil fumarate/emtricitabine versus a triple regimen continuation (tenofovir disoproxil fumarate/emtricitabine with a third agent, control arm) in virologically suppressed adults with HIV-DNA <2.7 log10 copies/106 PBMCs and no prior virological failure (VF). The primary endpoint (non-inferiority margin 12%) was the percentage of participants with a plasma viral load (pVL) <50 copies/mL in ITT (Snapshot approach) and PP analyses at Week 48 (W48). Results Of the 326 participants screened, 223 (68%) were randomized to the tenofovir disoproxil fumarate/emtricitabine arm (n = 113) or control arm (n = 110). At W48, the tenofovir disoproxil fumarate/emtricitabine and control arms maintained a pVL < 50 copies/mL in 100/113 (88.5%) and 100/110 (90.9%) participants, respectively (ITT difference 2.4%, 95% CI –5.9 to 10.7; PP difference 3.4%, 95% CI –4.2 to 11.0). Six VFs occurred in the tenofovir disoproxil fumarate/emtricitabine arm (two with emerging mutations M184V and K65R) versus two in the control arm (ITT difference 3.5%, 95% CI –1.9 to 9.4). All VFs were resuppressed after treatment modification. Conclusions Although non-inferiority was shown, simplification to tenofovir disoproxil fumarate/emtricitabine should not be used for most PLHIV because of a low risk of VF with resistance.

Dolutegravir Monotherapy as Maintenance Strategy: A Meta-Analysis of Individual Participant Data From Randomized Controlled Trials

“…The threshold of 2.7 log 10 per million PBMC corresponds to the median of the HIV DNA measured in PWH with sustained virological suppression [ 44 ]. Human immunodeficiency virus DNA below this threshold was associated with a good virological response in a randomized clinical trial with another suboptimal strategy, compared with a triple therapy [ 6 ]. Our study supports the concept that in a therapeutic situation of extreme simplification, such as DTG-m, the existence of a small viral reservoir is associated with the maintenance of good virological suppression, whereas in mirror, a large reservoir is associated with a high risk of virological failure.…”

“…Regarding individual-level variables, the data manager of each qualified study performed a deidentified individual data extraction including the prespecified following variables: trial arm, date of inclusion, sex, age at inclusion, ethnicity, HIV transmission risk, nadir CD4 T-cell count, date of HIV diagnosis, prior exposure to INSTI, previous genotypic resistance to any ART, previous genotypic resistance to any INSTI, presence of a polymerase chain reaction (PCR) signal below the quantification threshold, CD4 T-cell count, total HIV-1 DNA—at baseline and at week 48—virologic failure, and HIV integrase mutations. A binary variable HIV DNA count at baseline was created with a cutoff at 2.7 log/10 6 peripheral blood mononuclear cells (PBMCs) according to Trulight study [ 6 ]. We built a binary variable nadir of CD4 T-cell count with a cutoff of 350 cells/mm 3 and a time before first ART with a cutoff at 90 days according to the medians.…”

“…However, the antiretroviral treatment (ART) of human immunodeficiency virus (HIV) infection requires life-long therapy, which can be associated with side effects, toxicities, pill burden, drug-drug interactions, and long-term complications particularly for aging PWH [ 4 , 5 ]. In an effort to improve quality of life and tolerance and decrease healthcare-related costs, several ART simplification maintenance strategies have been investigated [ 6–16 ].…”