The use of and response to second-line protease inhibitor regimens: results from the EuroSIDA study.
OBJECTIVE
To describe the use of second line protease-inhibitor (PI) regimens across Europe and to determine factors associated with virological and immunological response.


METHODS
Analysis of data from 984 patients with a median follow-up of 21 months enrolled in EuroSIDA. Patients started their second PI-containing regimen at least 16 weeks after starting the first PI-containing regimen and with viral load > 1000 copies/ml.


METHODS
Virological response was defined as a viral load < 500 copies/ml and immunological response as an increase of 50 x 10(6)/l or more in CD4 lymphocyte count.


RESULTS
The median CD4 cell count at starting the second PI was 171 x 10(6) cells/l; viral load was 4.45 log copies/ml. As a second PI regimen, 45% were using a dual PI, while of those on one PI, indinavir (42%) and nelfinavir (34%) were most common. In multivariate Cox models, a higher viral load at starting the second PI [relative hazard (RH), 0.67 per 1 log higher; 95% confidence interval (CI), 0.58-0.77; P < 0.0001) and a lower CD4 cell count (RH, 1.15 per 50% higher; 95% CI, 1.06-1.26; P = 0.0014) were associated with a reduced probability of virological response. Those who had achieved viral suppression on the first PI-regimen were more likely to respond to the second (RH, 1.65; 95% CI, 1.30-2.10; P < 0.0001) as were those who added one or two new nucleosides to their second PI.


CONCLUSIONS
Patients who initiate a second PI regimen at lower viral load, higher CD4 cell count or who added new nucleosides tended to be more likely to achieve a viral load < 500 copies/ml. The roles of cross-resistance and adherence in response to second-line regimens needs further investigation.
Mocroft
A
A
Royal Free Centre for HIV Medicine, Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK.
Phillips
A N
AN
Miller
V
V
Gatell
J
J
van Lunzen
J
J
Parkin
J M
JM
Weber
R
R
Roge
B
B
Lazzarin
A
A
Lundgren
J D
JD
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008297:Male; D019888:Nelfinavir / Q000627:therapeutic use*; D011446:Prospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir; D019258:Saquinavir; D019438:Ritonavir