[19] [TITLE:]HIV EVOLUTION DURING REPEATED SUPERVISED TREATMENT INTERRUPTIONS FOLLOWING EARLY ANTIRETROVIRAL TREATMENT OF ACUTE INFECTION

5th International Workshop on HIV Drug Resistance & Treatment Strategies

4-8 June 2001, Scottsdale, Arizona

[TITLE:] HIV EVOLUTION DURING REPEATED SUPERVISED TREATMENT INTERRUPTIONS FOLLOWING EARLY ANTIRETROVIRAL TREATMENT OF ACUTE INFECTION

[AUTHOR(S):] C Tremblay, J Hicks, L Sutton, MP DePasquale, N Kartsonis, F Giguel, E Rosenberg, BD Walker, MS Hirsch and RT D’Aquila
Massachusetts General Hospital and Harvard Medical School, Boston, Mass., USA
Antivir Ther. 2001;6 Suppl 1:17

OBJECTIVES: To evaluate whether the latent HIV-1 reservoir in peripheral blood mononuclear cells (PBMCs) is replenished during supervised treatment interruptions (STIs) following treatment of acute infection, to analyse virus evolution over the course of this treatment strategy, and to monitor for emergence of resistant virus during STIs.

METHODS: For seven of 14 subjects, HIV was quantitatively cultured from serial dilutions of PBMCs that were depleted of CD8+ cells by a bi-specific anti-CD3:8 monoclonal antibody when plasma HIV-1 RNA was <50 copies/ml on therapy. Levels of infectious virus (infectious units per million cells, IUPM) were compared at time points before and after an STI. Clonal genotypic analysis of env and pol was performed from viruses recovered from these cultures, as well as from plasmas with viral load >1000 copies/ml (Roche, ultrasensitive) at baseline and during STIs. For 14 subjects, population sequencing of pol was performed from off-drug plasmas with viral load >1000 copies/ml.

RESULTS: There was no increase in the level of infectious HIV-1 recovered from CD8+ cell-depleted PBMCs following an STI in any of the seven subjects studied. Furthermore, a >3-fold decrease in this virus reservoir was observed in four of seven subjects following an STI. Virus evolution over the course of this treatment strategy was apparent in some, but not all, subjects. In a retrospective analysis, one of 14 starting treatment with a lamivudine-containing regimen was found to have reverse transcriptase (RT) M184V initially detectable in the earliest specimen from the first STI. RT 184M soon dominated off-drug. HIV was re-suppressed when lamivudine was restarted along with other drugs, but 184V re-emerged at next STI.

CONCLUSION: In this cohort of HIV-1-infected subjects treated early during acute infection and then undergoing STIs that boosted HIV-specific immunity, an STI did not replenish the amount of HIV in the blood reservoir. Genetic data suggest virus evolution off-drug in some, but not all, subjects. The emergence of RT 184V in one of 14 subjects may have occurred at the start of an STI, suggesting that intracellular lamivudine triphosphate may sometimes persist longer than other drugs.

PRESENTING AUTHOR: C Tremblay

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