Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study

Abstract

BackgroundProtease inhibitor monotherapy is associated with more frequent episodes of viral rebounds above 50 copies/mL than triple therapy. Objective: To evaluate if, compared to triple-drug therapy, protease inhibitor monotherapy is associated with increased levels of inflammatory/procoagulant markers and more frequent plasma residual viremia detection.MethodsIn this cross-sectional study, we included patients treated for ≥ 1 year with darunavir/ritonavir or lopinavir/ritonavir as monotherapy (n = 72) or with two nucleos(t)ides (n = 74). All samples were tested for CRP, IL-6, fibrinogen and D-dimer. Residual viremia was determined using an ultrasensitive qualitative nested-PCR of the HIV pol gene with a limit of detection of 1 copy of HIV-RNA.ResultsWe found no differences in levels of inflammatory/procoagulant markers or in the proportion of patients with plasma residual viremia detection by treatment group.ConclusionThe long-term treatment with protease inhibitor monotherapy in the setting of routine clinical practice is not associated with a higher prevalence of plasma residual viremia or more elevated inflammatory/procoagulant markers levels than triple drug therapy.

Systemic inflammation and residual viraemia in HIV-positive adults on protease inhibitor monotherapy: a cross-sectional study

“…We did not find any evidence of increased levels of inflammatory biomarkers or higher prevalence of residual viraemia in patients with HIV viral loads <50 copies/ml while treated with PImono as compared with patients on cART which is consistent with previous studies where PI monotherapy has been compared to PI-based cART [ 14 , 15 ]. However, Torres et al have reported higher monocyte activation, inflammation and residual viraemia in patients on PI monotherapy compared to PI-based cART [ 16 ].…”

“…In our study the majority of subjects showed low plasma levels of hsCRP and SAA as expected in well suppressed patients with no major co-morbidities. However, the levels of CRP and IL6 reported in previous studies with less stringent exclusion criteria were much higher and the proportion of participants with known co-morbidities such as hepatitis C was about 20% [ 15 , 16 ]. Increased monocyte activation, systemic inflammation and immune activation markers have all been associated with a number of inflammatory conditions, including HCV infection [ 17 ], and some of these could have been contributed to partially explain controversial results.…”

Inflammatory effects of atazanavir/ritonavir versus darunavir/ritonavir in treatment naïve, HIV-1-infected patients

“…In conclusion, our analysis provides further data examining the association between the modulation of vascular inflammatory and of activation markers with specific PI-based treatments over one year of exposure to these drugs. The data show little evidence for an association, supporting the notion that ART has generally poor efficiency in downregulating these soluble markers [14][15][16][17]. In contrast, ox-LDL appeared to be elevated in people who received ATV/r as compared to DRV/r.…”

“…Antiretroviral therapy (ART) is able to induce the control of HIV replication, but immune activation persists in people living with HIV (PLWHIV) [8][9][10][11]. Limited studies have compared the impact of different ART on residual immune activation and soluble markers of inflammation with discordant results [12][13][14][15][16][17][18][19]. However, the effects of different ART on cellular or soluble markers of activation are unclear.…”

No Differences of Immune Activation and Microbial Translocation Among HIV-infected Children Receiving Combined Antiretroviral Therapy or Protease Inhibitor Monotherapy

“…Our observation is supported by recently published data from adult patients receiving mtPI/rtv or cART, demonstrating no differences in the levels of inflammatory and procoagulant markers including CRP, interleukin-6, fibrinogen and d -dimer. 14 Furthermore, in a 2-year follow-up study of adult patients who were switched from cART to mtPI/rtv, cellular IA (measured as the expression of HLA-DR + CD38 + on CD4 + and CD8 + T cells) and systemic IA (measured as soluble CD14 and d -dimer) markers did not change among patients remaining on viral suppression along follow-up. 8 Owing to a higher risk of viral rebound, the International Antiviral Society-USA Panel does not recommend the use of mtPI/rtv in adult patients when other options are available.…”