Impact of intensification with raltegravir on HIV-1-infected individuals receiving monotherapy with boosted PIs

Impact of intensification with raltegravir on HIV-1-infected individuals receiving monotherapy with boosted PIs

Data de publicació online: 04/04/2018 Data de publicació en paper: 1 Juliol 2018 Revista: Journal of Antimicrobial Chemotherapy



Monotherapy with ritonavir-boosted PIs (PI/r) has been used to simplify treatment of HIV-1-infected patients. In previous studies raltegravir intensification evidenced ongoing viral replication and reduced T cell activation, preferentially in subjects receiving PI-based triple ART. However, data about low-level viral replication and its consequences in patients receiving PI/r monotherapy are scarce.


We evaluated the impact of 24 weeks of intensification with raltegravir on markers of viral persistence, cellular immune activation and inflammation biomarkers in 33 patients receiving maintenance PI/r monotherapy with darunavir or lopinavir boosted with ritonavir. identifier: NCT01480713.


The addition of raltegravir to PI/r monotherapy resulted in a transient increase in 2-LTR (long-terminal repeat) circles in a significant proportion of participants, along with decreases in CD8+ T cell activation levels and a temporary increase in the expression of the exhaustion marker CTLA-4 in peripheral T lymphocytes. Intensification with raltegravir also reduced the number of samples with intermediate levels of residual viraemia (10-60 HIV-1 RNA copies/mL) compared with samples taken during PI/r monotherapy. However, there were no changes in cell-associated HIV-1 DNA in peripheral CD4+ T cells or soluble inflammatory biomarkers (CD14, IP-10, IL-6, C-reactive protein and D-dimer).


Intensification of PI/r monotherapy with raltegravir revealed persistent low-level viral replication and reduced residual viraemia in some patients during long-term PI/r monotherapy. The concomitant change in T cell phenotype suggests an association between active viral production and T cell activation. These results contribute to understanding the lower efficacy rates of PI/r monotherapies compared with triple therapies in clinical trials.

Autors: Puertas MC, Gómez-Mora E, Santos JR, Moltó J, Urrea V, Morón-López S, Hernández-Rodríguez A, Marfil S, Martínez-Bonet M, Matas L, Muñoz-Fernández MA, Clotet B, Blanco J, Martinez-Picado J

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