609 Evolution of Protease and Reverse Transcriptase Inhibitor-associated Mutations in HIV-1 Protease Inhibitor-treated Patients with Persistent Low Viremia X. Duval, S. Darmon, P. Longuet, D. Descamps, J.L. Ecobichon, S. Delarue, G. Peytavin, C. Leport, J.L. Vildé, F. Brun-Vezinet* CHU Bichat-Claude Bernard, Paris, France
Background: Drug resistant viruses can emerge rapidly in a setting of incomplete viral suppression. The aim of our study was to monitor longitudinally the emergence of additional protease (PI) and reverse transcriptase (RT) inhibitor-associated mutations in HIV-1 treated patients (pts) with persistent low viremia.
Methods: Pts who developed a persistent low viremia between 1997-2002 after an initial response to PI (achievement of undetectable viral load (VL) and/or decrease of more than 2 log) were recruited. The study period started with the first low VL and ended with the last VL below 10,000 copies/ml in pts remaining on the same PI containing regimen. Longitudinal HIV protease (PR) and RT gene sequences (n = 80) were performed in 14 pts on stored plasma.
Results: Before treatment, median CD4 cell count nadir and VL zenith were 191/mm3 (5-418) and 108,000 copies/ml (26,000-1,201,000), respectively. At the time of the first low viremia, median duration of HAART, CD4 cell count and HIV VL were 12.5 (6-46) months (mos), 377 (11-736)/mm3 and 1,060 (400-5,493) copies/ml, respectively. Median study period was 18 mos (6-53) during which HIV-VL increased in 7 pts (median increase of 1,300 copies/ml) and decreased in 7 pts (median decrease of 1,080 copies/ml); CD4 cell count increased in 11 pts (median increase of 50 cells/mm3) and decreased in 3 pts (median decrease of 54 cells/mm3). At the end of the study period, no additional PI-associated mutations were detected in 6 pts; additional major PI-associated mutations were found in 4 pts (29%) (NFV n = 2, IDV or RTV n = 2), combined with minor PI-associated mutations in 1; additional minor PI-associated mutations, mainly mixtures, were found in the 4 other pts. Acquisition of RT-associated mutations occurred in 2/14 pts. During the low viremia period, acquired mutations that were no longer detected in the last low viremic sample were noted in 6 pts. There was no association between the acquisition of mutations and the variations in CD4 count or HIV-VL. Overall, no major impact on further therapeutic options was noted.
Conclusion: In this selected population with high CD4 cell counts, additional major PI-associated mutations were detected in less than 1/3 of pts during the period of persistent low viremia. In the view of long-term management of HIV therapy, this data do not support the necessity of a rapid modification in the therapeutic regimen when low viremia is detected.
