Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia.
BACKGROUND
To identify potential causes and clinical implications of transient increases in plasma viral load (hereafter, "blips").


METHODS
M99-056 and M02-418 were prospective, randomized trials evaluating the safety and efficacy of lopinavir/ritonavir (LPV/r) capsules administered twice per day or once per day to subjects infected with human immunodeficiency virus-1 (HIV-1). Plasma viral load was measured every 4 weeks (from baseline through week 24, excluding week 12 and week 20 in M02-418), every 8 weeks (from week 24 through week 48), and every 12 weeks (from week 48 through week 96). Blips were defined by 1 plasma viral load measurement of between 50-1000 copies/mL, immediately preceded and immediately followed by a measurement of <50 copies/mL. A medication event monitoring system was used to record the date and time subjects administered a dose of LPV/r.


RESULTS
Of 228 subject enrolled, event monitor data were available for 223 (98%) subjects (92 of whom received twice-daily LPV/r therapy, and 131 of whom received once-daily therapy). Viral load blips (median plasma viral load, 82 copies/mL [range, 51-858 copies/mL]) were identified in 60 (27%) of the subjects (21 in the LPV/r twice-daily group and 39 in the LPV/r once-daily group). Neither the baseline plasma viral load nor the CD4(+) T cell count were associated with blips. During the week prior to a blip, the mean number of days that the subject administered the prescribed number of doses was lower than the number during a matched period for the same subject during which a blip did not occur (5.55 vs. 6.22 days; P = .007). Blips were not associated with virologic failure or the development of drug resistance.


CONCLUSIONS
Blips were associated with decreased adherence, but not with virologic failure or development of drug resistance in these studies of LPV/r.


BACKGROUND
Clinicaltrials.gov identifier: NCT00043966 .
Podsadecki
Thomas J
TJ
Global Pharmaceutical Research and Development, Abbott Laboratories, 200 Abbott Park Road, Abbott Park, IL 60064, USA. thomas.podsadecki@abbott.com
Vrijens
Bernard C
BC
Tousset
Eric P
EP
Rode
Richard A
RA
Hanna
George J
GJ
D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011744:Pyrimidinones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016312:Treatment Refusal; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000821:virology
D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir