17th International HIV Drug Resistance Workshop 11-14 June 2008, Sitges, Spain

VIROLOGICAL EVOLUTION IN HIV TREATMENT-EXPERIENCED PATIENTS WITH RALTEGRAVIR-BASED SALVAGE REGIMENS

Antivir Ther. 2008; 13(Suppl. 3):A13 (abstract no. 11)

C Katlama¹, F Caby¹, RM Andrade¹, L Schneider¹, A Canestri¹, N Ktorza¹, R Tubiana¹, MA Valantin¹, M Wirden², I Mallet² and V Calvez^2
1Infectious Diseases Department, Pitié-Salpêtrière Hospital, Paris, France; ²Virology Department, Pitié-Salpêtrière Hospital, Paris, France

BACKGROUND: Raltegravir (RAL) belongs to a new class of anti-HIV drugs that has been studied in multidrug failure situations mainly through clinical trials with excellent results. However, little is known about resistance to RAL in patients with persistent viraemia.

METHODS: All patients in multidrug failure who initiated RAL between November 2006 and September 2007 were prospectively followed for at least 24 weeks. The CD4+ T-cell count and pHIV-RNA values were collected at baseline and at weeks (W) 4, 12, 24, 36 and 48 after RAL introduction. HIV genotype was performed just before RAL introduction for each patient and later in case of virological failure.

RESULTS: Fifty patients were included. Prior antiretroviral drug therapy contained enfuvirtide (57%), darunavir (68%), etravirine (37%) and foscarnet (12%). Median baseline characteristics were as follows: CD4+ T-cell count=169 cells/mm³ (1–833); pHIV-RNA=15,136 copies/ml (339–724,436). Baseline mutation number was NRTI=7 (1–10), NNRTI=1 (0–4) and PI=13 (8–20). RAL was used in combination with enfuvirtide (35%), darunavir (84%), etravirine (74%), atazanavir (29%) and foscarnet (6%). The median follow-up was W36 (6–15). Thirty-four patients (68%) had virological success with pHIV-RNA <40 at W24. Eleven patients (22%) had low persistent viral load (40< pHIV-RNA <400) and three (6%) had high persistent viraemia (pHIV-RNA >400). The viral load of the remaining two patients were between 40 and 400 copies/ml at W24, but one of them became undetectable at W28 and the other reached levels above 400 copies/ml. Among the patients in virological failure, genotype resistance testing was successfully performed in 13 patients and RAL resistance mutations were detected in four. G140S+Q148H were detected in two patients, N155H in one patient and a mutation switch from N155H to G140S+Q148H was observed in the last one. Three of these four patients had pHIV-RNA >400.

CONCLUSIONS: In our experience, the majority of patients in virological failure to RAL-based regimens showed low viraemia for a prolonged period without exacerbation. The presence of RAL-resistance mutations was associated to the highest viral replication rates. A longer follow-up of such patients will allow a better understanding of the evolution of RAL resistance profile.

2008-06-11
11

Copyright © 2008 - International Medical Press Ltd.. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the International Medical Press Ltd. 2-4 Idol Lane, London EC3R 5DD UK.