3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

HIV-PROVIRAL DNA AND PLASMA-RNA SEQUENCING FOR DETECTION OF DRUG RESISTANCE MUTATIONS IN ANTIRETROVIRAL NAÏVE PATIENTS

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuPp0304

Parisi S.G.¹, Mazzi R.², Zazzi M.³, Manfrin V.⁴, Nicolini G.⁵, Carolo G.⁶, Boldrin C.¹, Franchin E.¹, Dal Bello F.¹, Gatti F.², Palù G.^1
1University Hospital, Padua, Italy, ²Hospital, Verona, Italy, ³University Hospital, Siena, Italy, ⁴Hospital, Vicenza, Italy, ⁵Hospital, Schio, Italy, ⁶Hospital, Legnago, Italy

INTRODUCTION: Genotypic analisys is commonly used in drug naïve HIV-patients (pts), and plasma-RNA (PL) is taken as representative of viral population. However, in the absence of drug pressure, resistant variants may revert to or be outcompeted by more fit wild-type viruses. We tested if DNA obtained from peripheral blood mononuclear cells (PBMC) provides complementary informations to PL about drug resistance primary mutations (DRPM) in naïve pts.

METHODS: PL and PBMCs from 60 pts diagnosed in 2004 as HIV-infected were analyzed. The protease (PR) and the reverse transcriptase (RT) were sequenced by in-house method, and analyzed for the presence of DRPMs and for drug susceptibility profile.

RESULTS: In 45 pts both genotype and subtype were concordant (Copt); several DRPMs were detected, conferring resistance to NRTI (3 pts), to NRTI+NNRTI (1), to PI (2). 15 pts showed substancial differences between PL-virus and PBMCs-virus (Dipt). 5 Dipts showed RT-DRPMs and resistance to NRTI (3) and NNRTI (2) in PL; in their PBMCs-DNA also PR-DRPMs were found, conferring PI-resistance. 6 Dipts revealed in PBMCs both RT and PR-DRPMs, and NRTI and PI-resistance, with drug sensitive viruses in PL. 3 out of these 6 Dipts had CRF02_AG subtype in PBMC, and B-subtype in PL. 4 Dipt showed RT and PR-DRPMs in PL, and wild-type viruses in PBMCs.

CONCLUSIONS: We found drug resistance in 21 out of 60 naïve-pts (35%), but only in 6 Copts and 9 Dipts (25%) this resistance was at least partially evident with conventional PL-analysis. A substantially different virus was found in PBMCs of 10 Dipts, revealing a dual infection, a recent superinfection or a reversion of an originally infecting resistant virus, with the storage of the less fit variant, still detectable as transient prevalent population in the PBMC-archive. We suggest that PBMCs analysis is useful in naïve pts to detect stored resistant variants that may compromise future therapy options.

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050724
Clinical | TuPp0304 | Saverio Giuseppe Parisi
4.4 670 4.4 Resistance testing in clinical practice

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