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

Online publication: 04/04/2018 Printed publication: 1 July 2018 Journal: Journal of Antimicrobial Chemotherapy

Abstract:

BACKGROUND:

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.

METHODS:

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. ClinicalTrials.gov identifier: NCT01480713.

RESULTS:

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).

CONCLUSIONS:

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.

Authors: 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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