Antiviral potency of HAART regimens and clinical success are not strictly coupled in real life conditions: evidence from the MASTER-1 study.
HIV Clin Trials
; 2(5): 399-407, 2001.
Article
in En
| MEDLINE
| ID: mdl-11673814
ABSTRACT
PURPOSE:
To compare in a real clinical setting the largely unknown midterm clinical effectiveness of two protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) regimens with different potency and tolerability profiles in naïve patients.METHOD:
This study was a multicenter, open-label, randomized trial in naïve patients with less than 400 CD4+ cell count/microL, regardless of viral load. Treatment arms were hard gel capsule saquinavir (HGC-SQV)-based HAART (Arm A), with an expected more favorable tolerability profile, and indinavir (IDV)-based HAART (Arm B), with more potent virologic activity. While viro-immunological surrogate markers and World Health Organization (WHO) grade III toxicity (secondary endpoints) were regularly monitored, primary endpoints of the study were clinical and defined as any AIDS-defining event, AIDS-related death, WHO grade IV toxicity, drop outs, and protocol violations.RESULTS:
262 consecutive patients were enrolled in the study from March 1, 1997 to December 31, 1997, in 24 different Italian clinical centers (132, Arm A; 130, Arm B). After 24 months of follow-up, patients who were enrolled in Arm B showed a significantly higher rate of virological success (75% had viremia below 500 copies/mL, CI = 12.9%, in the on-treatment analysis) and immunological gain (mean CD4+ cell count increase of 274 CD4+ cells/microL, SD = 234) when compared to patients enrolled in arm A (57%, CI = 15.5% and 223 CD4+ cells/microL, SD = 192; p =.0353 and.026, respectively). Despite the significant difference observed in surrogate markers, the number of total primary endpoints did not differ in the two groups (55 out of 132 in Arm A vs. 58 out of 130 person-years in Arm B; p =.86).CONCLUSION:
Our results suggest that, after 24 months of follow-up in a real clinical setting, a PI-based HAART induces significant clinical benefits in naïve patients even in the absence of a complete suppression of viral replication. However, the long-term clinical impact of the possible accumulation of viral mutations in the presence of low-grade viral replication remains to be elucidated.
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Collection:
01-internacional
Health context:
2_ODS3
/
4_TD
Database:
MEDLINE
Main subject:
HIV Infections
/
HIV Protease Inhibitors
/
Anti-HIV Agents
Type of study:
Clinical_trials
/
Etiology_studies
/
Guideline
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
Country/Region as subject:
Europa
Language:
En
Journal:
HIV Clin Trials
Year:
2001
Document type:
Article