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Abstract
DISCREPANCIES BETWEEN VIRAL LOAD, RESISTANCE PROFILE AND PROTEASE INHIBITORS' CONCENTRATION IN HIV-1 RESERVOIRS AND SANCTUARIES
CHADAPAUD S, HITTINGER G, SOLAS C, HALFON P, KHIRI H, LACARELLE B, LAFEUILLADE A
Objective: To assess viral load, genotypic resistance and protease inhibitors’(PI) diffusion in viral reservoirs and sanctuaries during highly active antiretroviral therapy (HAART).
Design: Cross-sectional analysis of sanctuary samples from 35 HIV-infected patients on stable HAART regimens containing Indinavir (16) or Nelfinavir (14) or Lopinavir/r (5).
Methods: Plasma, CSF, genital fluid and a lymph node (LN) biopsy were taken on the same day in each case. Samples were assayed for HIV-1 RNA, sequencing of the RT and PR genes and PI concentration. Frozen plasma was also available just before HAART initiation in 8 cases.
Results: Plasma HIV-1 RNA was detectable in 13 patients and <50 copies/ml in others. HIV-1 RNA was detectable in 3 CSF and 3 semen samples, and in all LNs. Mutations were found in HIV-1 RNA from CSF and semen, even in the 2 cases where viral load was detectable in semen but not in plasma. Similar mutations were found in plasma and LNs for patients having detectable viraemia. Mutations were also found in 19 LNs from patients with long-term undetectable viraemia. In 9 cases, these mutations were already present in plasma before HAART, during sub-optimal combinations of nucleoside analogues. The CSF/plasma ratio was 0.14 for Indinavir. Nelfinavir and Lopinavir were undetectable in CSF. The semen/plasma ratio was 1.9 for Indinavir, 0.08 for Nelfinavir and for 0.45 for Lopinavir. The LN/plasma ratio was 2.07 for Indinavir, 0.58 for Nelfinavir and 0.21 for Lopinavir.
Conclusions: Major differences exist between PIs in terms of diffusion in viral reservoirs and sanctuaries. In CSF, HIV-1 RNA is frequently <50 copies/ml even when the PI is undetectable. In LNs, persistent RNA despite effective HAART frequently harbours resistance mutations reflecting previous sub-optimal regimens. Analysing additional cases will determine whether poor penetration of PIs in semen can lead to compartmentalization of resistant viral strains.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
27
Suggested Citation
"CHADAPAUDS, et al.
DISCREPANCIES BETWEEN VIRAL LOAD, RESISTANCE PROFILE AND PROTEASE INHIBITORS' CONCENTRATION IN HIV-1 RESERVOIRS AND SANCTUARIES.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
27"
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