Predictors of virological success and ensuing failure in HIV-positive patients starting highly active antiretroviral therapy in Europe: results from the EuroSIDA study.
BACKGROUND
Predictors of virological response to highly active antiretroviral therapy (HAART) have never been systematically evaluated in a large continental multicenter cohort of unselected human immunodeficiency virus (HIV)-infected people.


OBJECTIVE
To determine the factors related to achieving and maintaining undetectable plasma HIV-1 RNA levels among HIV-1-infected patients first starting protease inhibitor- or nonnucleoside retrotranscriptase inhibitor-containing HAART in Europe.


METHODS
Prospective multicenter cohort study.


METHODS
Fifty-two clinical centers in 17 European countries included in the EuroSIDA Study Group, from August 1996 to April 1999.


METHODS
A total of 1469 HIV-positive patients first starting HAART recruited from an unselected cohort of more than 7300 HIV-positive patients.


METHODS
Detection of factors related to virological success after first starting HAART (baseline) and ensuing failure by standard survival techniques, including Kaplan-Meier techniques and Cox proportional hazards models. All analyses were intention to treat.


RESULTS
Most patients (80%) achieved plasma HIV-1 RNA levels of less than 500 copies/mL during follow-up (60.4% at 6 months from the onset of HAART). Patients with higher baseline HIV-1 RNA levels (relative hazard [RH], 0.76 per log higher; 95% confidence interval [CI], 0.69-0.84; P<.001) and those taking saquinavir mesylate hard gel as a single protease inhibitor (RH, 0.62; 95% CI, 0.47-0.82; P<.001) were less likely to reach undetectable HIV-1 RNA levels. Conversely, higher CD4+ lymphocyte counts (RH per 50% higher, 1.09; 95% CI, 1.02-1.16; P = .008) and the initiation of 3 or more new antiretroviral drugs (RH, 1.29; 95% CI, 1.03-1.61; P = .02) were independent predictors of higher success. Once success was achieved, HIV-1 RNA levels rebounded in more than one third of all patients during follow-up (24% at 6 months). Antiretroviral-naive patients (RH, 0.50; 95% CI, 0.29-0.87; P = .01), older patients (RH, 0.86 per year older; 95% CI, 0.75-0.99; P = .04), and those starting a protease inhibitor other than saquinavir hard gel (RH, 0.66; 95% CI, 0.44-0.98; P = .04) were at decreased hazard for virological failure. Higher baseline HIV-1 RNA level (RH, 1.18 per log higher; 95% CI, 0.99-1.40; P = .06) and a longer time to achieve virological success (RH per 12 months, 1.53; 95% CI, 0.99-2.38; P = .06) were marginally significant predictors of a decreased hazard of ensuing virological failure.


CONCLUSIONS
HAART is associated with a favorable virological response if started when the baseline HIV-1 RNA level is low, if at least 2 new nucleoside retrotranscriptase inhibitors are added, and if standard doses of saquinavir hard gel capsule are avoided as a single protease inhibitor. Older patients are more likely to achieve virological success. Thereafter, the higher durability of virological response is predicted by an antiretroviral-naive status and by the use of specific regimens. Lower baseline HIV-1 RNA levels and rapid maximal viral suppression seem to be other important factors in the durability of virological response.
Paredes
R
R
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain. 34120rpd@comb.es
Mocroft
A
A
Kirk
O
O
Lazzarin
A
A
Barton
S E
SE
van Lunzen
J
J
Katzenstein
T L
TL
Antunes
F
F
Lundgren
J D
JD
Clotet
B
B
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D005060:Europe; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000032:analysis; D017211:Treatment Failure
D019380:Anti-HIV Agents; D012367:RNA, Viral