The HIV integrase inhibitor raltegravir (RAL) can exacerbate autoimmune diseases in genetically predisposed mice. To evaluate whether this may occur in clinical practice, we clinically monitored HIV-positive patients treated with RAL and measured a panel of autoantibodies (auto-Abs) during the first year of RAL treatment.
Methods
This was a longitudinal study in 109 antiretroviral-experienced patients who started a RAL-based regimen and were followed up for more than 2 years. A total of 45 patients were tested at baseline (before starting RAL) and after 12 months for the presence of the following auto-Abs: anti-nuclear antibodies, anti-double-stranded DNA, anti-smooth-muscle antibodies, anti-thyreoglobulin and anti-thyroid peroxidase antibodies, anti-cardiolipin immunoglobulin G and immunoglobulin M and anti-nuclear extractable antigens, including anti-SM ribonucleoprotein antigen, anti-Ro antigen and anti-La antigen.
Results
A low rate of clinically relevant autoimmune diseases was observed at study entry (3/109; 2.8%; 95% CI 0.004, 0.059). No exacerbations were observed during follow-up. During the second year of RAL-based therapy a previously healthy patient developed psoriasis. At baseline, 17/45 (37.8%) patients tested for the presence of auto-Abs were positive. Most patients (n=13) were positive for anti-cardiolipin. After 12 months of RAL exposure, 9/45 patients were positive (20%; P=0.063). A positive correlation was found between HIV-1 RNA and anti-cardiolipin antibody concentration (P=0.010).
Conclusions
According to these results, RAL does not promote antibody-mediated immune disorders, at least not in the mid-term. A prolonged follow-up and an extension of the panel of auto-Abs are recommended to support these results.
References
1.
CooperD.A., SteigbigelR.T., GatellJ.M.Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med2008; 359: 355–365.
2.
SteigbigelR.T., CooperD.A., KumarP.N.Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med2008; 359: 339–354.
3.
Beck-EngeserG.B., EilatD., HarrerT., JäckH.M., WablM.Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir. Proc Natl Acad Sci U S A2009; 106: 20865–20870.
4.
DreyfusD.H.Autoimmune disease: a role for new anti-viral therapies?Autoimmun Rev2011; 11: 88–97.
BucciardiniR., D'EttorreG., BaroncelliS.Virological failure at one year in triple-class experienced patients switching to raltegravir-based regimens is not predicted by baseline factors. Int J STD AIDS2012; 23: 459–463.
7.
CastroK.G., WardJ.W., SlutskerL.1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Repcomm Rep1992; 41: 1–19.
8.
NguyenB.Y., ReveilleJ.D.Rheumatic manifestations associated with HIV in the highly active antiretroviral therapy era. Curr Opin Rheumatol2009; 21: 404–410.
BreenE.C., HussainS.K., MagpantayL.B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma. Cancer Epidemiol Biomarkers Prev2011; 20: 1303–1314.
17.
HaynesB.F., FlemingJ., St ClairE.W.Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science2005; 308: 1906–1908.
18.
MartinezV., DiemertM.C., BraibantM.Anticardiolipin antibodies in HIV infection are independently associated with antibodies to the membrane proximal external region of gp41 and with cell-associated HIV DNA and immune activation. Clin Infect Dis2009; 48: 123–132.
19.
Panel on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.Department of Health and Human Services. (Updated 28 February 2012. Accessed 05 April 2012.) Available from http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
