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Virological Response to a Second-Line Protease Inhibitor (PI) Regimen: Laboratory Markers and Choice of Treatment A. MOCROFT*1, A. N. PHILLIPS, V. MILLER, J. GATELL, J. VAN LUNZEN, A. LAZZARIN, and J. D. LUNDGREN2.
1Royal Free Ctr. for HIV Med., UK; and 2The EuroSIDA Coordinating Ctr. Denmark Introduction: Studies of patients on second line regimens tend to be based on small series of patients and the factors associated with virological response are poorly understood.
Aim: To investigate factors associated with virological response (viral load (VL) < 500 copies/ml) to a second PI regimen among 942 patients in EuroSIDA.
Patients: Patients starting second PI regimen at least 16 weeks after starting first line regimen and with VL > 1000 copies/ml.
Results: The median CD4 at starting the second PI regimen was 160; VL was 4.6 log copies/ml, median follow-up is 12 months. As a second PI regimen, almost 50% were using a dual PI (47%), while of those on one PI, indinavir (45%) and nelfinavir (31%) were the most common. In a multivariate Cox model, those with a higher VL at starting the second PI regimen were less likely to achieve virological success (relative hazard (RH) per 1 log higher VL 0.66, p < 0.0001), while those who achieved virological success on the first PI regimen were more likely to succeed in the second PI regimen (RH 1.67, p < 0.0001). Patients starting a second PI regimen at a higher CD4 were more likely to succeed (RH per 50% higher CD4 1.11, p = 0.017, as were those who added 1 or 2 new nucleosides (i.e., previously naive) to their second PI regimen. Patients who started saquinavir as first line had a greater chance of virological success in the second PI regimen (RH 1.93, p < 0.0001). There were no differences in the RH of success when comparing PI’s used as part of the second PI regimen, or when comparing combinations of nucleosides used. Among patients who stayed on a single PI as second PI treatment, those who swapped from saquinavir-indinavir had a higher chance of virological success compared to those who swapped from ritonavir-indinavir (RH 2.13, p = 0.0064).
Conclusions: Virological response depended on the first line regimen used. Patients who initiate a second PI regimen at lower VL, higher CD4 or who had new nucleosides added had a better response. The relationship between cross-resistance and adherence will undoubtedly also play a role. Updated results, including further follow-up on more patients will be presented.
Key Words: protease inhibitors, salvage therapy, treatment responses
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