Virological Outcome After Choice of Antiretroviral Regimen Guided by Proviral HIV-1 DNA Genotyping in a Real-Life Cohort of HIV-Infected Patients

Abstract

Issues have been raised concerning clinical relevance of HIV-1 proviral DNA genotypic resistance test (DNA GRT). To assess impact of DNA GRT on choice of antiretroviral therapy (ART) and subsequent virological outcome, we retrospectively reviewed decision-making and viral load (VL) evolution following DNA GRT performed in our center between January 2012 and December 2017, except those prescribed within the framework of a clinical trial. A total of 304 DNA GRTs were included, 185 (62%) performed in a context of virological success. Only 34% of tests were followed by ART change, more frequently in situation of virological success (39% vs. 26%, p = 0.02). In this situation, ART change guided by DNA GRT led to VL >20 copies/mL after 6 months in 5% of cases. In multivariate analysis, higher HIV DNA quantification (p = 0.01) was associated with occurrence of viremia. A higher nadir of CD4 count (p = 0.04) and a longer time with VL <20 copies/mL (p = 0.04) were independently associated with a lower risk of viremia. In situation of low-level viremia, ART change guided by DNA GRT led to VL <20 copies/mL after 6 months in 52% of cases, while decision to maintain the same treatment led to VL <20 copies/mL in 74% of cases. In multivariate analysis, longer time with VL >20 copies/mL (p = 0.02) was associated with persistence of virological replication. In conclusion, in situation of virological success, use of DNA GRT in addition to analysis of historical RNA GRT to guide ART optimization appears safe. Its prescription framework in situation of low-level viremia deserves to be better defined.

High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I

“…Furthermore, a recent retrospective observational study demonstrated that DNA genotype-guided regimen changes were well tolerated with no increased risk of virologic failure [ 42 ]. In a similar study conducted in France, DNA genotype-guided regimen changes increased the probability of maintaining viral suppression; however, the inclusion of APOBEC-mediated hypermutated sequences in their dataset confounds interpretation [ 43 ]. As GenoSure Archive removes hypermutated sequences from assay results, our dataset does not over-report resistance substitutions caused by hypermutation, such as M184I, which was detected at low frequency (1%).…”

“…Furthermore, a recent retrospective observational study demonstrated that DNA genotype-guided regimen changes were well tolerated with no increased risk of virologic failure [42]. In a similar study conducted in France, DNA genotype-guided regimen changes increased the probability of maintaining viral suppression; however, the inclusion of APOBEC-mediated hypermutated sequences in their dataset confounds interpretation [43].…”

HIV DNA Sequencing to Detect Archived Antiretroviral Drug Resistance

“…The authors suggested that HIV DNA sequencing may provide value for decision-making for selected patients, including those with multiple previous or foreseen ART adjustments due to comorbidities, medication interactions, difficulty accessing care, hesitancy regarding ART switches or other factors that could increase risk when switching therapy. Maybeck et al also provided cohort data in support of HIV DNA sequencing to guide treatment decisions alongside historical data based on plasma HIV RNA sequencing [ 36 ]. Armenia et al found that among virologically suppressed patients, detection of RAMs in HIV DNA, together with a low nadir CD4 cell count and a short duration of virological control, was predictive of virological rebound after switching therapy [ 37 ].…”

Enhancing care for people living with HIV: current and future monitoring approaches

“…A general limitation of all of the currently available and future candidate markers is the almost exclusive application to the blood compartment. While the analysis of blood markers has clearly allowed establishment of highly effective treatment strategies, the vast majority of HIV species reside in lymphatic tissue in multiple anatomical sites that are hardly accessible [31]. Although blood will necessarily remain the material of choice in routine patient management, studies addressing the added value of sampling these sites are required to gain a full profile of the HIV reservoir and its dynamics under different treatment strategies.…”