TY - JOUR
T1 - Dynamics of Low-Level Viremia and Immune Activation after Switching to a Darunavir-Based Regimen
AU - LOWERIT Study Team
AU - Stam, Arjen J
AU - Buchholtz, Ninée V E J
AU - Bierman, Wouter F W
AU - van Crevel, Reinout
AU - Hoepelman, Andy I M
AU - Claassen, Mark A A
AU - Ammerlaan, Heidi S M
AU - van Welzen, Berend J
AU - van Kasteren, Marjo E E
AU - van Lelyveld, Steven F L
AU - de Jong, Dorien
AU - Tesselaar, Kiki
AU - van Luin, Matthijs
AU - Nijhuis, Monique
AU - Wensing, Annemarie M J
PY - 2024/1/25
Y1 - 2024/1/25
N2 - There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV.
AB - There is an ongoing debate regarding whether low-level viremia (LLV), in particular persistent LLV, during HIV treatment with optimal adherence originates from low-level viral replication, viral production, or both. We performed an observational study in 30 individuals with LLV who switched to a boosted darunavir (DRV)-based therapy. In-depth virological analyses were used to characterize the viral population and the (activity) of the viral reservoir. Immune activation was examined using cell-bound and soluble markers. The primary outcome was defined as the effect on HIV-RNA and was categorized by responders (<50 cp/mL) or non-responders (>50 cp/mL). At week 24, 53% of the individuals were considered responders, 40% non-responders, and 7% could not be assigned. Sequencing showed no evolution or selection of drug resistance in the non-responders. Production of defective virus with mutations in either the protease (D25N) or RT active site contributed to persistent LLV in two individuals. We show that in about half of the study participants, the switch to a DRV-based regimen resulted in a viral response indicative of ongoing low-level viral replication as the cause of LLV before the switch. Our data confirm that in clinical management, high genetic barrier drugs like DRV are a safe choice, irrespective of the source of LLV.
KW - Humans
KW - Darunavir/therapeutic use
KW - Viremia
KW - HIV Infections/drug therapy
KW - Antiretroviral Therapy, Highly Active
KW - Sequence Analysis
KW - Viral Load
KW - Anti-HIV Agents/pharmacology
U2 - 10.3390/v16020182
DO - 10.3390/v16020182
M3 - Article
C2 - 38399959
SN - 1999-4915
VL - 16
JO - Viruses
JF - Viruses
IS - 2
M1 - 182
ER -