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Effect of Combined Antiretroviral Therapy (cART) on Bacterial Translocation, Inflammation, Coagulation and Immune Activation in Advanced (<100 CD4+ cells/mm3) Antiretroviral-Naïve Patients at Week 48 (EFV or Reyataz/r)
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Reported by Jules Levin
CROI 2012 March 5-8 Seattle WA
Jose M. Miro1, Christian Manzardo1, Alberto C. Guardo1, Francisco Lozano1, Elena Ferrer 2, Pere Domingo3, Adria Curran4, Bonaventura Clotet5, Montserrat Plana1, Jose M. Gatell1
and the Advanz-3 Investigators*
1Hospital Cl’nic-IDIBAPS- University of Barcelona, Barcelona, Spain 2Hospital de Bellvitge-IDIBELL-University of barcelona, Spain; 3Hospital de Sant
CONCLUSIONS
In antiretroviral-naïve patients with very advanced disease, we observed the following:
· Values for inflammation, immune activation, and apoptotic markers-but not D-dimer-declined
significantly after 48 weeks of effective cART (from Jules: but did not normalize for all only for some apparently). There were no statistically significant differences in the decline of these markers between patients taking a PI/r-based regimen and patients taking
an EFV-based regimen.
· A significant decline in bacterial translocation (srCD14) was also observed. The impact on
bacterial translocation of a PI/r-based regimen was similar to that of an EFV-based regimen,
even though each regimen is metabolized differently in the gut.
Abstract
Background: Data on the impact of cART on bacterial translocation, inflammation, coagulation, and immune activation in advanced HIV-1 infection are limited. Moreover, it is unknown whether impact on bacterial translocation could vary with the type of cART regimen, since protease inhibitors (PI) and efavirenz (EFV) have different patterns of metabolism in the gut.
Methods: In the Advanz-3 trial (NCT00532168), 90 HIV-1-infected antiretroviral-naïve patients with <100 CD4+ cells/mm3 were randomly assigned in a 1:1:1 ratio to EFV, atazanavir-ritonavir, or lopinavir-ritonavir plus tenofovir plus emtricitabine at standard doses. For the present study, we selected those patients with virological
suppression (<50 copies/mL) at 24 and 48 weeks. We determined serum levels (baseline and 48 weeks) of soluble receptor of CD14 (srCD14, the lipopolysaccharide ligand), tumor necrosis factor alpha (TNF-alpha), high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer, as well as the proportion of CD8+CD38+/DR+ T cells and CD3+ T-cell apoptosis levels (annexin-V). Results were compared using the Mann-Whitney test.
Results: Of the 56 eligible patients, 16 had received an EFV-based regimen (group EFV) and 40 a ritonavir-boosted PI regimen (group PI/r). At 48 weeks, we recorded significantly decreased median delta values for srCD14 (-0.73 μg/mL, P=0.008), TNF-alpha (-6.00 pg/mL, P<0.001), IL-6 (-3.00 pg/mL, P<0.001), hsCRP (-0.07 μg/mL, P=0.036), annexin-V (-36.81%, P<0.001), CD8+CD38+ T cells (-26.04%, P<0.001) or CD8+CD38+DR+ (-21.69%, P<0.001). D-dimer levels remained unchanged (P=0.45). Results for baseline bacterial translocation, inflammation, coagulation, immune activation, and apoptotic markers were similar in both groups (P>0.05 for all comparisons). After 48 weeks of cART, there were no differences in
the fall in median delta values of these markers between the groups, although there was a trend towards a greater reduction in srCD14 in patients treated with a PI/r-based regimen (-8.28% in the EFV group vs. -30.11% in the PI/r group, P=0.15).
Conclusions: In antiretroviral-naïve patients with advanced disease, values for bacterial translocation, inflammation, immune activation, and apoptotic markers- but not D-dimer-declined significantly after 48 weeks of effective cART. The impact on bacterial translocation of a PI/r-based regimen was similar to that of an EFV-based regimen.
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