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5th International Workshop on HIV Drug Resistance & Treatment Strategies4-8 June 2001, Scottsdale, Arizona |
OBJECTIVE: To analyse the presence of HIV-1-resistant strains in viral RNA isolated from lymph node mononuclear cells (LNMC) in patients with plasma HIV-1 RNA suppression during highly active antiretroviral therapy (HAART).
METHODS: LNMC were taken by biopsy in 27 patients treated with a combination of two reverse transcriptase inhibitors (RTIs) plus one protease inhibitor (PI; indinavir: 11 cases, nelfinavir: 11 cases, lopinavir/r: 5 cases) and sustained plasma HIV-1 RNA levels <20 copies/ml. HIV-1 RNA was sequenced using the TruGene kit (Visible Genetics). In 12 cases, sufficient material was available to perform also an Antivirogram (Virco). In 15 patients, peripheral blood mononuclear cells (PBMC) taken the same day were also available for sequencing. Furthermore, frozen plasma samples taken just before the current HAART regimen initiation were available in 11 patients for sequencing.
RESULTS: Plasma HIV-1 RNA was consistently <20 copies/ml in the 27 patients for a mean duration of 97.16±63.32 weeks (range: 24–204 weeks) but detectable in all LNMC samples. Nine patients were on first line therapy and six of them did not have any mutation in LNMC. Eighteen patients had received prior sub-optimal combinations and 15 of them showed resistance mutations in HIV-1 RNA taken from LNMC. In 10 cases, these mutations were already present in plasma taken 24–180 weeks beforehand. Phenotypic resistance to at least one RTI or one PI was confirmed in eight out of 12 patients analysed. In seven out of 15 patients who had HIV-1 DNA sequenced from PBMC, differences were found between PBMC DNA and LNMC RNA, with more mutations in LNMC than in PBMC. Mean level of HIV-1 RNA in LNMC was 3.75±0.15 log copies/106 cells, with no differences between patients with or without resistance.
CONCLUSIONS: LNMC can produce resistant HIV-1, which was previously selected by sub-optimal combinations, during up to 180 weeks despite an effective HAART regimen. These data are concordant with recent studies showing continuous release of viral RNA by previously infected cells despite effective therapy.
PRESENTING AUTHOR: A Lafeuillade
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