ABSTRACT
Novel strategies are necessary to decrease inflammatory parameters in successfully treated HIV-infected patients. Our aim was to evaluate the maintenance of viral suppression and potential changes in inflammatory, immune-activation and coagulation biomarkers in virologically suppressed HIV-infected patients switched to a nucleoside reverse transcriptase inhibitor-sparing (NRTI) and maraviroc (MVC)-containing combined antiretroviral therapy (cART). Fifty-eight HIV-infected patients were observed after their treatment regimens were changed to MVC 150mg/once daily plus ritonavir-boosted protease inhibitor therapy. Activation-, inflammation- and coagulation-associated biomarkers and mitochondrial (mt)DNA were analyzed after a median of 24weeks of follow-up. We observed that after changing to an NRTI-sparing regimen, 96.6% of HIV-patients on viral suppressive cART maintained viral suppression and their CD4+ T cell counts did not change significantly (median of 31weeks of follow-up). This cART switch reduced soluble CD40 ligand (p=0.002), beta-2 microglobulin (p=0.025), and soluble CD14 (p=0.009) in patients with higher baseline levels of these inflammation biomarkers after a median of 24weeks of follow-up. The results of our study show that changing to NRTI-sparing dual therapy decreased the levels of inflammatory biomarkers and maintained the immune-virologic efficacy. The potential benefits of this regimen warrant further investigation to uncover the association of this therapy with the potential decrease in the morbidity and mortality of HIV-infected patients from non-AIDS-defining illnesses.
Subject(s)
CD40 Ligand/blood , Cyclohexanes/administration & dosage , HIV Infections/drug therapy , HIV-1/drug effects , Lipopolysaccharide Receptors/blood , Reverse Transcriptase Inhibitors/administration & dosage , Triazoles/administration & dosage , beta 2-Microglobulin/blood , Adult , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , Drug Therapy, Combination , Female , HIV Infections/blood , HIV Infections/virology , HIV-1/genetics , HIV-1/isolation & purification , HIV-1/physiology , Humans , Male , Maraviroc , Middle AgedABSTRACT
Levels of soluble CD14 (sCD14) were longitudinally measured in 85 human immunodeficiency virus (HIV)-infected subjects during long-term receipt of suppressive combined antiretroviral therapy (cART) and compared to those in young and elderly HIV-negative control subjects. cART did not normalize sCD14 levels; rather, the HIV-infected group displayed a significantly higher sCD14 level at baseline (ie, before cART initiation), 1 year after cART initiation, and 5 years after cART initiation, compared with both control groups. Furthermore, the baseline CD4(+) T-cell count was inversely associated with the baseline sCD14 level. Our results point to the necessity of complementary therapies to treat the activated/inflamed status associated with chronic HIV infection and to the benefits of early initiation of cART.
Subject(s)
Anti-Retroviral Agents/therapeutic use , Cyclohexanes/therapeutic use , HIV Infections/drug therapy , Lipopolysaccharide Receptors/blood , Triazoles/therapeutic use , Adult , Aged , Anti-Retroviral Agents/pharmacology , CD4 Lymphocyte Count , Case-Control Studies , Cyclohexanes/pharmacology , Female , HIV Infections/blood , HIV Infections/immunology , HIV-1/pathogenicity , Humans , Longitudinal Studies , Male , Maraviroc , Middle Aged , RNA, Viral/blood , Solubility , Time Factors , Treatment Outcome , Triazoles/pharmacology , Viral LoadABSTRACT
The potential effect of blocking the CCR5 receptor on HIV disease progression biomarkers is not well understood. We showed that an 8-day maraviroc (MVC) monotherapy clinical test (MCT) can be used in selecting patients to receive MVC-containing combined antiretroviral therapy (cART). Using this MCT model, we assessed the effect of MVC on several HIV disease progression biomarkers during the MCT (MVC-specific effect) and following short-term (12-week) cART. We compared 45 patients on MVC monotherapy with a control group of 25 patients on MVC-sparing cART. We found that MVC did not modify any biomarkers in patients that had no virological response after the MCT. MVC-specific effects in patients with virological responses included increased CD8(+) T-cell activation and senescence levels, preservation of an increase in soluble CD14 (sCD14), and a decrease in D dimer levels. After 12 weeks, MVC-containing cART increased CD8(+) T-cell counts and preserved CD4(+) T-cell senescence levels compared with MVC-sparing cART. Moreover, there was a decrease in sCD14 levels in patients that received MVC-containing cART. In conclusion, effects compatible with CD8(+) T-cell redistribution in peripheral blood were observed after MVC therapy. However, MVC was associated with a favorable profile in HIV disease progression biomarkers only in patients with a virological response. These results support a potential clinical benefit of a therapy which includes MVC in HIV-infected patients.
Subject(s)
CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , Cyclohexanes/therapeutic use , HIV Fusion Inhibitors/therapeutic use , HIV Infections/drug therapy , HIV-1/drug effects , RNA, Viral/antagonists & inhibitors , Triazoles/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Biomarkers/metabolism , CCR5 Receptor Antagonists , CD4-Positive T-Lymphocytes/virology , CD8-Positive T-Lymphocytes/virology , Cyclohexanes/pharmacology , Disease Progression , Female , Fibrin Fibrinogen Degradation Products/analysis , HIV Fusion Inhibitors/pharmacology , HIV Infections/metabolism , HIV Infections/virology , HIV-1/physiology , Humans , Lipopolysaccharide Receptors/metabolism , Lymphocyte Activation/drug effects , Lymphocyte Count , Male , Maraviroc , Middle Aged , RNA, Viral/biosynthesis , Receptors, CCR5/metabolism , Triazoles/pharmacology , Viral Load/drug effectsABSTRACT
The maraviroc clinical test (MCT) is a clinical approach to establish the indication of maraviroc treatment. In this study, we analysed the long-term outcome of patients receiving a combined antiretroviral therapy (cART) selected according to MCT results. Ninety-two consecutive HIV-infected patients underwent MCT. A virological response (<40 HIV-RNA copies/ml after 24 weeks) was observed in 76/92 patients (82.6%). These patients (n=76) were included in a time to treatment failure analysis; after a mean follow-up period of 88 weeks, treatment failure was confirmed in 14 patients (18.4%). Tropism switch during MCT was observed in 3/35 patients (8.6%); these patients experienced excellent long-term outcome on cART. In conclusion, MCT should be considered as an additional method before CCR5-antagonists prescription.
