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formerly Central European Journal of Medicine

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Differential course of HIV-1 infection and apolipoprotein E polymorphism

1Center for Demographic Studies, Duke University, 2117 Campus Drive, Durham, NC, 27708-0408, USA

2Laboratorio Analisi e Diagnostica Molecolare I.N.R.C.A.-IRCCS, 60100, Ancona, Italy

3Direzione Scientifica I.N.R.C.A.-IRCCS, 60100, Ancona, Italy

4Dept. of Biomedical Sciences, University of Modena and Reggio Emilia, 41100, Modena, Italy

5Infectious Diseases Clinics, Azienda Policlinico, 41100, Modena, Italy

6Dept.of Clinical Medicine, University “La Sapienza”, Rome, Italy

7Dept.of Medicine and Sciences of Aging, University “G. d’Annunzio” Chieti, Italy

8Diatech Laboratories, Jesi, Italy

© 2007 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. (CC BY-NC-ND 3.0)

Citation Information: Open Medicine. Volume 2, Issue 4, Pages 404–416, ISSN (Online) 2391-5463, DOI: 10.2478/s11536-007-0039-x, December 2007

Publication History

Published Online:


We studied the course of infection with human immunodeficiency virus type 1 (HIV-1) in relation to apolipoprotein E (APOE) polymorphism found for 209 Italians treated at Infectious Disease Clinics in Rome and Modena. Clinically, patients were classified into four groups according to the yearly rate of decline in CD4+ cell count (LTNP: long-term non-progression; SLOW, ’NORMAL’ or RAPID). Patients at both extremes of the clinical spectrum, i.e. those who rapidly progressed to AIDS and those with stable high CD4 cell counts, had few APOE ɛ4 and ɛ2 alleles (P = 0.04). Detailed clinical information was then used to construct four model-based clinical profiles using grade-of-membership analysis (GoM), predictive of APOE genotypic frequencies: 1. The clinical profile associated with good long-term prognosis lacked ɛ2 (P=0.01); 2. Disease progression to AIDS was associated with ɛ4 and ɛ2, most evident for zidovudine-lamivudine regimens without a protease inhibitor (P = 0.03); and, 3. AIDS patients had low ɛ4 and ɛ2 frequencies, consistent with a high mortality rate among ɛ4+ and ɛ2+ AIDS patients. These findings suggest allele-specific immunomodulatory effects involving inherited APOE isoform important enough to alter the clinical course of HIV infection and, possibly, drug efficacy. They imply a connection between lipid metabolism and immunity potentially relevant to common disorders.

Keywords: HIV-1 infection; APOE; genetic epidemiology; grade-of-membership analysis; immunomodulation

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