Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

Persistence of HIV-1 replication and genotypic resistance in sanctuary sites after 3 years of effective HAART: relevance of Protease Inhibitors diffusion

A. Lafeuillade¹, C. Solas², G. Hittinger¹, S. Chadapaud¹, H. Khiri³, P. Halfon³, B. Lacarelle^2
1 Infect. Dis., Chalucet Hospital, 83056 Toulon; ² Lab. Pharmacokinetic, ³ Lab. Virol., Marseilles, France

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL4.4
AIDS 2000, Oct 22-26;14(Suppl. 4); S4

PURPOSE OF THE STUDY: HAART failure results from viral resistance, adherence problems and pharmacological factors. Poor penetration of Protease Inhibitors (Pis) in various compartments could contribute to the selection of drug resistance. However, PIs diffusion in sanctuary sites has not been extensively studied, particularly in lymph nodes.

METHODS: 25 patients on 2 NRTI + Indinavir (IDV, 15 cases) or Nelfinavir (NFV, 10 cases) for up to 3 years were evaluated for IDV or NFV concentrations in CSF, semen and lymph nodes. Plasma HIV-1 RNA was <50 copies/ ml in 20 patients and 50–1000 copies/ml in 5 patients. CSF and semen samples were collected prior drug intake, lymph nodes biopsies were done 3–5 h after dose with a concomitant plasma sample. In 7 cases, frozen plasma samples just before HAART initiation were also available. IDV or NFV concentrations were assessed by HPLC. HIV-1 RNA was quantified using the Amplicor Monitor™ kit. Sequencing of RT and Protease genes was done on HIV-1 RNA using the TruGene™ kit.

SUMMARY OF RESULTS: Median plasma through concentrations were 263 ng/ml and 1835 ng/ml for IDV and NFV. Median IDV values were 75 ng/ml in CSF (Plasma ratio: 0.16), 788 ng/ml in semen (Plasma ratio: 1.9) and 920 ng/ g in lymph nodes (Plasma ratio: 2.0). NFV was undetectable in CSF and at low concentrations in 4/9 semen samples (Plasma ratio: 0.06). In lymph nodes, NFV was present at lower concentrations than IDV (Plasma ratio: 0.58). HIV-1 RNA was detected in all lymph nodes (15/25 with mutations). HIV-1 RNA was detected in 3 semen samples (2 with mutations) from patients taking NFV. All CSF samples were <50 copies/ml. In most cases, mutations found in lymph nodes HIV-1 RNA were already present in plasma before HAART, at a time when patients received sub-optimal double NRTI combinations.

CONCLUSIONS: A large inter-individual variability of IDV and NFV concentrations was found in the different sanctuary sites. Residual viral replication and resistance appear to be related with PIs diffusion in semen but not in CSF and lymph nodes.

Presenting author: A. Lafeuillade

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2000-10-22
PL4-4

Originally published in AIDS Volume 14, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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