Comparative impact of antiretroviral drugs on markers of inflammation and immune activation during the first two years of effective therapy for HIV-1 infection: an observational study

Abstract

BackgroundFew studies have compared the impact of different antiretroviral regimens on residual immune activation and inflammation with discordant results. Aim of the study was to investigate the impact of various antiretroviral regimens on markers of immune activation and inflammation during the first two years of effective therapy.MethodsWe studied HIV-infected antiretroviral-naïve patients who began cART with either abacavir/lamivudine or tenofovir/emtricitabine, combined with ritonavir-boosted lopinavir (LPV/r), atazanavir (ATV/r) or efavirenz (EFV). All the patients had a virological response within 6 months, which was maintained for 2 years with no change in their ART regimen. C-reactive protein (hs-CRP), interleukin-6 (IL-6), soluble CD14 (sCD14), monokine induced by interferon-γ (MIG) and interferon-γ-inducible protein-10 (IP-10) were measured in stored plasma obtained at cART initiation and 24 months later. Mean changes from baseline were analyzed on loge-transformed values and multivariable linear regression models were used to study the effect of the treatment components, after adjusting for factors that might have influenced the choice of ART regimen or biomarker levels. Differences were expressed as the mean fold change percentage difference (Δ).ResultsSeventy-eight patients (91% males) with a median age of 43 years met the inclusion criteria. Their median baseline CD4 cell count was 315/mm3 and HIV-1 RNA level 4.6 log10 copies/ml. During the 2-years study period, IL-6, IP-10 and MIG levels fell significantly, while hs-CRP and sCD14 levels remained stable. IP-10 and MIG levels declined significantly less strongly with ATV/r than with EFV (IP-10Δ -57%, p = 0.011; MIGΔ -136%, p = 0.007), while no difference was noted between LPV/r and EFV. The decline in IL-6 did not differ significantly across the different treatment components.ConclusionsAfter the first 2 years of successful cART, IL-6, IP-10 and MIG fell markedly while hs-CRP and sCD14 levels remained stable. The only impact of ART regimen was a smaller fall in markers of immune activation with ATV/r than with EFV. Our results suggest that these markers could be worthwhile when evaluating new antiretroviral drugs.

Could CD8/38 predict virological response to antiretroviral therapy (ART) in human immunodeficiency virus (HIV) infected patients?

“…In addition, co-infection from other viruses, such as cytomegalovirus and Epstein-Barr virus, are a consequence of mucosal immune dysfunction due to decreased CD4 T-cells in the acute phase and the loss of intestinal barriers that may translocate bacteria to systemic circulation. 12 The results from this study align with Maartens et al 11 after initiating ART, the VL levels decreased below the equipment's minimum limit of detection in almost all of the patients during the 3 months of ART. 11 These results support the antigen stimulation theory.…”

Ιn Vivo Effects of Tenofovir-DF/Emtricitabine and Abacavir/Lamivudine with Atazanavir-R on Platelet Activating Factor Metabolism in HIV Naive Patients

“…The in vivo study showed that treatment with tenofovir-DF/ emtricitabine with atazanavir boosted ritonavir does not significantly affect PAF metabolism according to published data suggesting that this combination decreases inflammatory and coagulation markers [17][18][19]. On the contrary, abacavir/lamivudine with atazanavir boosted ritonavir exhibited a gradual increase in bound and total PAF levels with a pronounced effect at the end of the study.…”

“…Some of those have demonstrated that plasma levels of inflammatory markers significantly fell while others have reported no significant change. In most cases, hsCRP remains unchanged or even increases [17,18,25]. Mechanism by which abacavir containing regimens affects inflammatory pathways is not clear.…”

“…A number of studies also suggest that treatment with tenofovir-DF/ emtricitabine with atazanavir-r decreases inflammatory and hypercoagulation markers [17][18][19] but tenofovir-DF has been associated with renal impairment especially when combined with PIs such as atazanavir-r [20][21][22][23]. On the other hand, conflicting results occur concerning the effect of abacavir/lamivudine/atazanavir-r regimen on markers of systemic and/or chronic inflammation [17,18,24,25].…”

“…On the other hand, conflicting results occur concerning the effect of abacavir/lamivudine/atazanavir-r regimen on markers of systemic and/or chronic inflammation [17,18,24,25].…”