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Vpr and HIV-1 disease progression: R77Q mutation is associated with long-term control of HIV-1 infection in different groups of patients

Mologni, Danielaa; Citterio, Paolaa; Menzaghi, Barbaraa; Poma, Barbara Zanonea; Riva, Chiaraa; Broggini, Valentinaa; Sinicco, Alessandroc; Milazzo, Lauraa; Adorni, Fulviob; Rusconi, Stefanoa; Galli, Massimoa; Riva, Agostinoa; for the rHoPeS Group

doi: 10.1097/01.aids.0000210611.60459.0e
Clinical Science

Background: Vpr (viral protein R) is a 96 amino acids soluble protein that is expressed late during viral replication. Recent studies have focused on the role of a mutation at position 77 that might be associated with the condition of long-term non-progression, but data are still controversial.

Patients and methods: Fifteen long-term non-progressors (LTNP), 19 therapy-naive HIV-1-infected patients with progressive disease (Pr), 23 HIV-1-infected patients receiving sub-optimal therapy with dual nucleoside [nucleoside reverse transcriptase inhibitor (NRTI)] therapy but efficiently controlling viral replication (STP) and 19 antiretroviral therapy multi-experienced patients with actively replicating virus (MEP) were analysed. HIV-RNA was extracted from plasma samples, the Vpr region was amplified, cloned and sequenced. The Pol gene was amplified, directly sequenced and analysed using Sequence Navigator software.

Results: A significantly higher prevalence of the R77Q mutation was evidenced both in LTNP (86.7%) and STP (73.9%) in comparison with Pr (42.1%) and MEP (42.1%), (P = 0.007). Comparing groups of patients with progressive disease (Pr + MEP) and groups with non-progressive disease (LTNP + STP) the probability of harbouring the R77Q mutation was significantly higher in non-progressors (odds ratio, 5.16; P = 0.001).

Conclusions: Our results support the hypothesis of the association of R77Q mutation in the Vpr gene with delayed progression of HIV-1 disease. R77Q does not seem to be linked to a particular viral strain but might be associated to immunologic selection. The R77Q mutation might reduce CD4+ T-cell depletion possibly affecting T-cell survival in vivo by altering the pro-apoptotic activity of Vpr.

From the aInstitute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Milan

bInstitute of Biomedical Technologies–National Research Council, Milan

cClinica di Malattie Infettive, Amedeo di Savoia Hospital, Turin, Italy.

*See Appendix.

Received 28 April, 2005

Revised 1 July, 2005

Accepted 24 August, 2005

Correspondence to Dr Agostino Riva, Institute of Infectious and Tropical Diseases, University of Milan, L. Sacco Hospital, Via GB Grassi 74, 20157 Milan, Italy. E-mail: agostino.riva@unimi.it

© 2006 Lippincott Williams & Wilkins, Inc.