Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2014

Open Access 01-12-2014 | 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

Authors: Suhaib Hattab, Amelie Guihot, Marguerite Guiguet, Slim Fourati, Guislaine Carcelain, Fabienne Caby, Anne-Geneviève Marcelin, Brigitte Autran, Dominique Costagliola, Christine Katlama

Published in: BMC Infectious Diseases | Issue 1/2014

Login to get access

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.
Literature
1.
Mocroft A, Ledergerber B, Katlama C, Kirk O, Reiss P, D’ Arminio Monforte A, Knysz B, Dietrich M, Phillips AN, Lundgren JD, EuroSIDA study group: Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003, 362 (9377): 22-29. 10.1016/S0140-6736(03)13802-0.CrossRefPubMed
2.
Delaugerre C, Ghosn J, Lacombe J-M, Pialoux G, Cuzin L, Launay O, Menard A, de Truchis P, Costagliola D: FHDH ANRS CO04. Trend over calendar time in virological failure in HIV-infected patients treated for at least six months with combined antiretroviral therapy in France (FHDH ANRS CO04). Paper presented at: 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. 2011, Rome, Italy: Abstract TUPDB0104
3.
4.
5.
French MA, King MS, Tschampa JM, da Silva BA, Landay AL: Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4+ T cells. J Infect Dis. 2009, 200 (8): 1212-1215. 10.1086/605890.CrossRefPubMed
6.
Neuhaus J, Jacobs DR, Baker JV, Calmy A, Duprez D, La Rosa A, Kuller LH, Pett SL, Ristola M, Ross MJ, Shlipak MG, Tracy R, Neaton JD: Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis. 2010, 201 (12): 1788-1795. 10.1086/652749.CrossRefPubMedPubMedCentral
7.
Mavigner M, Delobel P, Cazabat M, Dubois M, L’faqihi-Olive F-E, Raymond S, Pasquier C, Marchou B, Massip P, Izopet J: HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. PLoS One. 2009, 4 (10): e7658-10.1371/journal.pone.0007658.CrossRefPubMedPubMedCentral
8.
Hunt PW, Martin JN, Sinclair E, Epling L, Teague J, Jacobson MA, Tracy RP, Corey L, Deeks SG: Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis. 2011, 203 (10): 1474-1483. 10.1093/infdis/jir060.CrossRefPubMedPubMedCentral
9.
Petrara MR, Cattelan AM, Zanchetta M, Sasset L, Freguja R, Gianesin K, Cecchetto MG, Carmona F, De Rossi A: Epstein-Barr virus load and immune activation in human immunodeficiency virus type 1-infected patients. J Clin Virol. 2012, 53 (3): 195-200. 10.1016/j.jcv.2011.12.013.CrossRefPubMed
10.
Lane HC: Pathogenesis of HIV infection: total CD4+ T-cell pool, immune activation, and inflammation. Top HIV Med. 2010, 18 (1): 2-6.PubMed
11.
Terzieva V: Regulatory T, cells and HIV-1 infection. Viral Immunol. 2008, 21 (3): 285-291. 10.1089/vim.2008.0006.CrossRefPubMed
12.
Savès M, Raffi F, Capeau J, Rozenbaum W, Ragnaud J-M, Perronne C, Basdevant A, Leport C, Chêne G, Antiprotéases Cohorte (APROCO) Study Group: Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy. Clin Infect Dis. 2002, 34 (10): 1396-1405. 10.1086/339866.CrossRefPubMed
13.
Brown TT, Qaqish RB: Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS. 2006, 20 (17): 2165-2174. 10.1097/QAD.0b013e32801022eb.CrossRefPubMed
14.
Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, Boccara F, Bingham A, Costagliola D, French Hospital Database on HIV-ANRS CO4: Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population. AIDS. 2010, 24 (8): 1228-1230. 10.1097/QAD.0b013e328339192f.CrossRefPubMed
15.
Lanoy E, Spano J-P, Bonnet F, Guiguet M, Boué F, Cadranel J, Carcelain G, Couderc LJ, Frange P, Girard PM, Oksenhendler E, Poizot-Martin I, Semaille C, Agut H, Katlama C, Costagliola D, ONCOVIH study group: The spectrum of malignancies in HIV-infected patients in 2006 in France: the ONCOVIH study. Int J Cancer. 2011, 129 (2): 467-475. 10.1002/ijc.25903.CrossRefPubMed
16.
Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, Berti A, Rossi E, Roverato A, Palella F: Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011, 53 (11): 1120-1126. 10.1093/cid/cir627.CrossRefPubMed
17.
Lang S, Mary-Krause M, Simon A, Partisani M, Gilquin J, Cotte L, Boccara F, Costagliola D, French Hospital Database on HIV (FHDH)–ANRS CO4: HIV replication and immune status are independent predictors of the risk of myocardial infarction in HIV-infected individuals. Clin Infect Dis. 2012, 55 (4): 600-607. 10.1093/cid/cis489.CrossRefPubMed
18.
Lang S, Mary-Krause M, Cotte L, Gilquin J, Partisani M, Simon A, Boccara F, Costagliola D, Clinical Epidemiology Group of the French Hospital Database on HIV: Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med. 2010, 170 (14): 1228-1238. 10.1001/archinternmed.2010.197.CrossRefPubMed
19.
Brown TT, Tassiopoulos K, Bosch RJ, Shikuma C, McComsey GA: Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care. 2010, 33 (10): 2244-2249. 10.2337/dc10-0633.CrossRefPubMedPubMedCentral
20.
Pradhan AD, Manson JE, Rifai N, Buring JE, Ridker PM: C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA J Am. 2001, 286 (3): 327-334. 10.1001/jama.286.3.327.CrossRef
21.
Clearfield MB: C-reactive protein: a new risk assessment tool for cardiovascular disease. J Am Osteopath Assoc. 2005, 105 (9): 409-416.PubMed
22.
Schuett H, Luchtefeld M, Grothusen C, Grote K, Schieffer B: How much is too much? Interleukin-6 and its signalling in atherosclerosis. Thromb Haemost. 2009, 102 (2): 215-222.PubMed
23.
Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Neuhaus J, Nixon D, Paton NI, Neaton JD, INSIGHT SMART Study Group: Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med. 2008, 5 (10): e203-10.1371/journal.pmed.0050203.CrossRefPubMedPubMedCentral
24.
Hunt PW, Sinclair E, Rodriguez B, Shive C, Clagett B, Funderburg N, Epling L, Van Natta M, Medvik K, Huang Y, Deeks SG, Martin JN, Meinert C, Lederman MM: Gut epithelial barrier dysfunction, inflammation and coagulation predict higher mortality during treated HIV/AIDS. Paper presented at: 19th Conference on Retroviruses and Opportunistic Infections. 2012, Washington, USA: Abstract 278
25.
De Luca A, de Gaetano DK, Colafigli M, Cozzi-Lepri A, De Curtis A, Gori A, Sighinolfi L, Giacometti A, Capobianchi MR, D'Avino A, Iacoviello L, Cauda R, D'Arminio MA: The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: a nested case–control study. BMC Infect Dis. 2013, 13 (1): 414-10.1186/1471-2334-13-414.CrossRefPubMedPubMedCentral
26.
Trenorio AR, Yu Z, Bosch RJ, Deeks SG, Benigno R, Supriya K, Hunt PW, Cara W, Lederman MM, Landy AL, AIDS Clinical Trials Group: Soluble markers of inflammation and coagulation, but not T-cell activation predict non-AIDS defining events during suppressive antiretroviral therapy. 20th Conference on Retroviruses and Opportunistic Infections. 2013, Atlanta, GA: Abstract 790
27.
Martínez E, D’Albuquerque PM, Llibre JM, Gutierrez F, Podzamczer D, Antela A, Berenguer J, Domingo P, Moreno X, Perez I, Pich J, Gatell JM, SPIRAL Trial Group: Changes in cardiovascular biomarkers in HIV-infected patients switching from ritonavir-boosted protease inhibitors to raltegravir. AIDS. 2012, 26 (18): 2315-2326. 10.1097/QAD.0b013e328359f29c.CrossRefPubMed
28.
Smith KY, Patel P, Fine D, Bellos N, Sloan L, Lackey P, Kumar PN, Sutherland-Phillips DH, Vavro C, Yau L, Wannamaker P, Shaefer MS, HEAT Study Team: Randomized, double-blind, placebo-matched, multicenter trial of abacavir/lamivudine or tenofovir/emtricitabine with lopinavir/ritonavir for initial HIV treatment. AIDS. 2009, 23 (12): 1547-1556. 10.1097/QAD.0b013e32832cbcc2.CrossRefPubMed
29.
McComsey GA, Kitch D, Daar ES, Tierney C, Jahed NC, Melbourne K, Ha B, Brown TT, Bloom A, Fedarko N, Sax PE: Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir. AIDS. 2012, 26 (11): 1371-1385. 10.1097/QAD.0b013e328354f4fb.CrossRefPubMedPubMedCentral
30.
Funderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, Mayer H, Rajicic N, Valdez H, Lederman MM: Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients. PLoS One. 2010, 5 (10): e13188-10.1371/journal.pone.0013188.CrossRefPubMedPubMedCentral
31.
Wohl DA, Arnoczy G, Fichtenbaum CJ, Campbell T, Taiwo B, Hicks C, McComsey GA, Koletar S, Sax P, Tebas P, Ha B, Massengale K, Walsh K, Stein JH: Comparison of cardiovascular disease risk markers in HIV-infected patients receiving abacavir and tenofovir: the nucleoside inflammation, coagulation and endothelial function (NICE) study. Antivir Ther. 2013, doi:10.3851/IMP2681
32.
Deeks SG, Tracy R, Douek DC: Systemic effects of inflammation on health during chronic HIV infection. Immunity. 2013, 39 (4): 633-645. 10.1016/j.immuni.2013.10.001.CrossRefPubMedPubMedCentral
33.
Pine SR, Mechanic LE, Enewold L, Chaturvedi AK, Katki HA, Zheng YL, Bowman ED, Engels EA, Caporaso NE, Harris CC: Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer. J Natl Canc Inst. 2011, 103 (14): 1112-1122. 10.1093/jnci/djr216.CrossRef
34.
Boulware DR, Hullsiek KH, Puronen CE, Rupert A, Baker JV, French MA, Bohjanen PR, Novak RM, Neaton JD, Sereti I, INSIGHT Study Group: Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis. 2011, 203 (11): 1637-1646. 10.1093/infdis/jir134.CrossRefPubMedPubMedCentral
35.
Sandler NG, Wand H, Roque A, Law M, Nason MC, Nixon DE, Pedersen C, Ruxrungtham K, Lewin SR, Emery S, Neaton JD, Brenchley JM, Deeks SG, Sereti I, Douek DC: INSIGHT SMART Study Group. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011, 203 (6): 780-790. 10.1093/infdis/jiq118.CrossRefPubMedPubMedCentral
36.
Cassol E, Malfeld S, Mahasha P, van der Merwe S, Cassol S, Seebregts C, Alfano M, Poli G, Rossouw T: Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy. J Infect Dis. 2010, 202 (5): 723-733. 10.1086/655229.CrossRefPubMed
37.
Kamat A, Misra V, Cassol E, Ancuta P, Yan Z, Li C, Morgello S, Gabuzda D: A plasma biomarker signature of immune activation in HIV patients on antiretroviral therapy. PLoS One. 2012, 7 (2): e30881-10.1371/journal.pone.0030881.CrossRefPubMedPubMedCentral
38.
Sandler NG, Douek DC: Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol. 2012, 10 (9): 655-666. 10.1038/nrmicro2848.CrossRefPubMed
39.
D’Ettorre G, Paiardini M, Zaffiri L, Andreotti M, Ceccarelli G, Rizza C, Indinnimeo M, Vella S, Mastroianni CM, Silvestri G, Vullo V: HIV persistence in the gut mucosa of HIV-infected subjects undergoing antiretroviral therapy correlates with immune activation and increased levels of LPS. Curr HIV Res. 2011, 9 (3): 148-153. 10.2174/157016211795945296.CrossRefPubMed
40.
Taiwo B, Matining RM, Zheng L, Lederman MM, Rinaldo CR, Kim PS, Berzins BI, Kuritzkes DR, Jennings A, Eron JJ, Wilson CC: Associations of T cell activation and inflammatory biomarkers with virological response to darunavir/ritonavir plus raltegravir therapy. J Antimicrob Chemother. 2013, 68 (8): 1857-1861. 10.1093/jac/dkt120.CrossRefPubMedPubMedCentral
41.
Lederman MM, Calabrese L, Funderburg NT, Clagett B, Medvik K, Bonilla H, Gripshover B, Salata RA, Taege A, Lisgaris M, McComsey GA, Kirchner E, Baum J, Shive C, Asaad R, Kalayjian RC, Sieg SF, Rodriguez B: Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis. 2011, 204 (8): 1217-1226. 10.1093/infdis/jir507.CrossRefPubMedPubMedCentral
42.
Hunt PW, Brenchley J, Sinclair E, McCune JM, Roland M, Page-Shafer K, Hsue P, Emu B, Krone M, Lampiris H, Douek D, Martin JN, Deeks SG: Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis. 2008, 197 (1): 126-133. 10.1086/524143.CrossRefPubMedPubMedCentral
43.
Moser B, Loetscher M, Piali L, Loetscher P: Lymphocyte responses to chemokines. Int Rev Immunol. 1998, 16 (3–4): 323-344.CrossRefPubMed
44.
Juompan LY, Hutchinson K, Montefiori DC, Nidtha S, Villinger F: Analysis of the immune responses in chimpanzees infected with HIV type 1 isolates. AIDS Res Hum Retroviruses. 2008, 24 (4): 573-586. 10.1089/aid.2007.0182.CrossRefPubMed
45.
Liovat A-S, Rey-Cuillé M-A, Lécuroux C, Jacquelin B, Girault I, Petitjean G, Zitoun Y, Venet A, Barré-Sinoussi F, Lebon P, Meyer L, Sinet M, Müller-Trutwin M: Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection. PLoS One. 2012, 7 (10): e46143-10.1371/journal.pone.0046143.CrossRefPubMedPubMedCentral
46.
Edén A, Andersson L-M, Andersson O, Flamholc L, Josephson F, Nilsson S, Ormaasen V, Svedhem V, Säll C, Sönnerborg A, Tunbäck P, Gisslén M: Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients. AIDS Res Hum Retroviruses. 2010, 26 (5): 533-540. 10.1089/aid.2009.0177.CrossRefPubMed
47.
Katlama C, Deeks SG, Autran B, Martinez-Picado J, van Lunzen J, Rouzioux C, Miller M, Vella S, Schmitz JE, Ahlers J, Richman DD, Sekaly RP: Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet. 2013, 381 (9883): 2109-2117. 10.1016/S0140-6736(13)60104-X.CrossRefPubMed
Metadata
Title
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
Authors
Suhaib Hattab
Amelie Guihot
Marguerite Guiguet
Slim Fourati
Guislaine Carcelain
Fabienne Caby
Anne-Geneviève Marcelin
Brigitte Autran
Dominique Costagliola
Christine Katlama
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/1471-2334-14-122

Other articles of this Issue 1/2014

BMC Infectious Diseases 1/2014 Go to the issue

Research article

A novel polyclonal antibody-based sandwich ELISA for detection of Plasmodium vivaxdeveloped from two lactate dehydrogenase protein segments

Research article

Characterization of Neisseria gonorrhoeaeisolates detected in Switzerland (1998–2012): emergence of multidrug-resistant clones less susceptible to cephalosporins

Research article

Host cytokine responses distinguish invasive from airway isolates of the Streptococcusmilleri/anginosis group

Research article

Sex-specific disease outcomes of HIV-positive and HIV-negative drug users admitted to an opioid substitution therapy program in Spain: a cohort study

Research article

Quantifying the clinical virulence of Klebsiella pneumoniae producing carbapenemase Klebsiella pneumoniae with a Galleria mellonellamodel and a pilot study to translate to patient outcomes

Research article

A qualitative study of senior hospital managers’ views on current and innovative strategies to improve hand hygiene
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits