Sixth International Congress Drug Therapy in HIV Infection 17-21 November, 2002 Glasgow, UK

Purpose: We report about two patients who had a virological break-through after a switch in remission.

Methods: Methods Two male patients, 43 (patient A) and 51 (patient B) years of age with CDC states B2 and C3 respectively. They were pretreated with several therapies containing zidovudine (AZT), lamivudine (3TC) and different Protease Inhibitors (PI) before switching to the regimen with EFV due to virological failure. Both of them had a good therapy adherence. Due to quality of life both changed their more than 24-months successful (viral load ≤ 50 copies/ml) antiretroviral therapy by replacing EFV to TDF. Backbone drugs were abacavir (ABC) with 3TC (A) or stavudine (d4T) (B). At switching time-point the CD4+-cell counts were 376 (23%) (A) and 659 (18%) (B) cells/µl.

Summary of Results: After receiving TDF for 4 (A) and 12 (B) weeks a virological break through was observed for both patients [87.400 (A) and 7.020 copies/ml (B)]. The CD4+-cell counts decreased for patient A to 257 cells/µl (9%) and for patient B to 534 cells/µl (18%). In genotypic resistance analyses the following mutations were detected: M41L, M184V, L210W, T215Y (A) and M41L, V118I, L210W, T215Y (B), respectively. Due to the resistance analyses the patients got a boostered double PI-regimen with lopinavir/r (LPV/r) and saquinavir (SQV). After 8 weeks the viral load decreased below the limit of detection.

Conclusions: Conclusions Both here described cases were pretreated with drugs that select NAMs. Apparently in some cases the mutations M41L and L210W plus one or two NRTI-associated mutations (NAMs) are sufficient to cause resistance to TDF. The regimen with EFV was potent enough to suppress the virus. Although the viral load was suppressed for a period of 24 months, certain NAMs probably persisted in a minority population or in viruses in latent reservoirs. With the switch to TDF the virus got the chance to break through.

It is important in the treatment of therapy experienced patients to keep the whole therapy history in mind.

Presenting author: Heribert Knechten

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1 PZB, Aachen, Germany.

2002-11-17

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