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Objective: To investigate the dynamics of the lymphocyte HIV reservoir in patients on prolonged and effective highly active antiretroviral therapy (HAART)., Design: Nine HAART-treated patients were selected on the basis of long-term infection and long-term undetectable plasma viral RNA. Five patients had received antiretroviral therapy before HAART. We compared a polymorphic region of the env gene (C2V4), and the part of the pol gene encoding the reverse transcriptase in pre-HAART plasma and in the reservoir lymphocytes during HAART; the first plasma sample taken after structured treatment interruption was also studied in three patients., Methods: Both regions of interest were amplified from plasma HIV RNA and cellular proviral DNA, then cloned, sequenced and subjected to phylogenetic analysis., 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. 'Wild-type' and zidovudine-resistant strains co-existed in reservoir T cells of two pre-HAART treated patients. In three patients, no resistant virus was found in the T-cell reservoir despite the detection of resistant virus in pre-HAART plasmas. However, virus archiving was documented in two of these three patients on the basis of C2V4 analysis. Latently infected T cells only partly accounted for the plasma viral load rebound after structured treatment interruption., Conclusions: The HIV lymphocyte reservoir is dynamic. Its diversity results mainly from successive archiving of circulating plasma viruses during the course of HIV infection. Archiving of resistant virus must be taken into account in therapeutic decisions.

Objectives: To examine the antigen specificities of HIV reservoir CD4 T cells in patients on prolonged and effective highly active antiretroviral therapy (HAART)., Design: Five HIV-infected patients, who were highly adherent to antiretroviral treatment, were selected on the basis of long-term undetectable plasma viral RNA on unmodified HAART. To investigate the antigen specificities of infected memory CD4 T cells, we examined the capacity of recall antigens, including HIV antigens, to induce virus production by peripheral blood mononuclear cells (PBMC)., Methods: To quantify CD4 T cells infected by replication-competent virus, and to determine their antigen specificities, we used a limiting dilution-based culture assay. CD8 T cell-depleted PBMC at several cell densities were activated by using Tuberculin purified protein derivative, cytomegalovirus, or HIV-1 p24 with and without HIV-1 Nef., Results: We found that the pool of infected CD4 T cells includes HIV-specific cells with apparent frequencies between 5- and 100-fold higher than those of the common specificities for cytomegalovirus or Tuberculin., Conclusion: Our findings suggest that a significant proportion of replication-competent HIV-infected CD4 T cells in these patients are memory cells directed against HIV determinants. This may provide a rationale for the therapeutic use of recombinant HIV antigens to reduce the pool of HIV-reservoir cells., (Copyright 2002 Lippincott Williams & Wilkins)