Virologic rebound on HAART in the context of low treatment adherence is associated with a low prevalence of antiretroviral drug resistance.
The contributions of viral drug resistance, drug pharmacokinetics, and treatment adherence to failure of protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) have been explored in isolation. We examined the interactions between these factors. Patients on their first PI-based HAART combination for >6 months with plasma HIV viral load (VL) >1000 copies/mL ("viremic" group) were compared with patients with a stable VL <50 copies/mL ("nonviremic" group). Data were collected on adherence (measured electronically), PI plasma levels (sampled randomly, at trough and twice after an observed dose), viral genotype, and phenotype. Mean adherence was significantly lower in the viremic group (84.3% versus 100.1%; p =.005). In the viremic group, substitutions in HIV protease were detected most frequently in the following positions in subjects on indinavir (IDV): L10I/V (35.7%), M46I/L (35.7%), A71T/V (35.7%), V82A (42.9%); and for subjects on nelfinavir (NFV): D30N (50.0%), V77I (56.3%), N88D (37.5%). Phenotypic resistance was detected in 20% of isolates from patients on IDV and 42% on NFV. Lower adherence was associated with detection of fewer resistance substitutions (r = 0.52; p =.005) and less phenotypic resistance (rho = 0.56, p =.005). There were no differences between the groups in pharmacokinetics. However, in viremic subjects, lower postdose NFV levels were associated with higher resistance (rho = -0.61, p =.02).
St. Stephen's Center, Chelsea and Westminster Hospital, London, UK. John.Walsh@St-Marys.nhs.uk
John Christopher
JC
Walsh
Anton Louis
AL
Pozniak
Mark Richard
MR
Nelson
Sundhiya
S
Mandalia
Brian George
BG
Gazzard
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics; D006801:Humans; D019469:Indinavir / Q000493:pharmacokinetics; D008297:Male; D019888:Nelfinavir / Q000493:pharmacokinetics; D010349:Patient Compliance; D019562:Viral Load
D017320:HIV Protease Inhibitors; D019469:Indinavir; D019888:Nelfinavir