[67] THE LYMPHOCYTE HIV RESERVOIR IN PATIENTS ON PROLONGED HAART IS A MEMORY OF VIRUS EVOLUTION

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] THE LYMPHOCYTE HIV RESERVOIR IN PATIENTS ON PROLONGED HAART IS A MEMORY OF VIRUS EVOLUTION

[AUTHOR(S):] O Lambotte¹, ML Chaix², B Gubler³, N Nasreddine¹, C Wallon¹, C Goujard⁴, C Rouzioux², Y Taoufik^1,3 and JF Delfraissy^1,4
¹INSERM E-109, Faculté de Médecine de Bicêtre, Université Paris XI, Bicêtre; ²Laboratory of Virology, EA MRT CHU Necker, Paris; ³Laboratory of Immunology; and ⁴Department of Internal Medicine, Bicêtre Hospital, Bicêtre, France

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 67
Antiviral Therapy 2003; 8(Suppl. 1):S201

[ABSTRACT:] Objective: To investigate the dynamic of the HIV lymphocyte reservoir in patients on prolonged and effective highly active antiretroviral therapy (HAART)

Methods: Nine HAART highly-adherent patients were selected on the basis of prolonged infection and long-term undetectable plasma viral RNA. Five had received prior HAART antiretroviral therapy. We compared a polymorphic region of env gene, C2V4, and the part of pol gene coding for the reverse transcriptase (RT) in a pre-HAART plasma, in the reservoir lymphocytes purified on HAART and, in three patients, in the first plasma after a structured treatment interuption (STI). Both regions were amplified from plasma HIV RNA and cellular proviral DNA, cloned and sequenced. Phylogenetic analysis was performed.

Results: Diversity of the lymphocyte reservoir was found in six of nine patients. Archiving of pre-HAART plasma clones was observed in six of nine patients. Among the pre-HAART treated patients, the co-existence of ‘wild-type’ and AZT-resistant strains was found in reservoir T cells in two patients. In three patients, no resistant virus was found in the reservoir T cells despite the presence of resistant virus in pre-HAART plasmas. However, in two of these three patients, a virus archivage was documented according to C2V4 analysis. In the patients with STI, the latently infected T cells were one source of the plasmatic viraemia rebound but not the sole cause.

Conclusions: The HIV lymphocyte reservoir is dynamic with a diversity mainly resulting from the successive archiving of plasma viruses circulating during the HIV infection course. The archiving of resistant virus must be taken into account in therapeutic decisions.

030714
67