Differential course of HIV-1 infection and apolipoprotein E polymorphism

• Authors: Elizabeth Corder , Luciano Galeazzi , Claudio Franceschi , Andrea Cossarizza , Roberto Paganelli , Marcello Pinti , Cristina Mussini , Vanni Borghi , Elena Pinter , Rita Cristofaro , Roberta Galeazzi , Marino Perini , Fernando Aiuti , Sergio Giunta
• Languages of publication: EN

Abstracts

EN

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

EN

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

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2007
• Volume: 2
• Issue: 4
• Pages: 404-416

Dates

published

1 - 12 - 2007

online

1 - 12 - 2007

Contributors

author

Elizabeth Corder

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

author

Luciano Galeazzi

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

author

Claudio Franceschi

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

author

Andrea Cossarizza

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

author

Roberto Paganelli

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

author

Marcello Pinti

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

author

Cristina Mussini

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

author

Vanni Borghi

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

author

Elena Pinter

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

author

Rita Cristofaro

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

author

Roberta Galeazzi

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

author

Marino Perini

• Diatech Laboratories, Jesi, Italy

author

Fernando Aiuti

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

author

Sergio Giunta

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

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Identifiers

DOI

10.2478/s11536-007-0039-x