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Open Access Highly Accessed Research article

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

Suhaib Hattab12*, Amelie Guihot345, Marguerite Guiguet12, Slim Fourati126, Guislaine Carcelain345, Fabienne Caby17, Anne-Geneviève Marcelin126, Brigitte Autran345, Dominique Costagliola12 and Christine Katlama127

Author Affiliations

1 INSERM, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris F-75013, France

2 Sorbonne Universities, UPMC Univ Paris 06, UMR_S 1136, Pierre Louis Institute of Epidemiology and Public Health, Paris F-75013, France

3 INSERM, UMR_S 1135, CIMI, Paris F-75013, France

4 Sorbonne Universities, UPMC Univ Paris 06, UMR_S 1135, CIMI, Paris F-75013, France

5 AP-HP, Hôpital Pitié-Salpêtrière, Département d’immunologie, Paris F-75013, France

6 AP-HP, Hôpital Pitié-Salpêtrière, Service de virologie, Paris F-75013, France

7 AP-HP, Hôpital Pitié-Salpêtrière, Service des maladies infectieuses et tropicales, Paris F-75013, France

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BMC Infectious Diseases 2014, 14:122  doi:10.1186/1471-2334-14-122

Published: 4 March 2014

Abstract

Background

Few 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.

Methods

We 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).

Results

Seventy-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.

Conclusions

After 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.

Keywords:
HIV; cART; Immune activation; Inflammation; Markers