Simplifying protease inhibitor therapy with once-daily dosing of saquinavir soft-gelatin capsules/ritonavir (1600/100 mg): HIVNAT 001.3 study.
OBJECTIVE
To determine the feasibility of switching therapy for HIV-1-infected patients with plasma viral loads of <50 HIV-1 RNA copies/mL who are receiving twice-daily saquinavir soft-gelatin capsules (SQV-SGC) plus dual nucleoside reverse transcriptase inhibitors (NRTIs) to a regimen containing once-daily SQV-SGC/ritonavir (RTV).


METHODS
Therapy for patients with plasma viral loads of <50 copies/mL after 2 years of treatment with twice-daily SQV-SGC (1400 mg) plus zidovudine/lamivudine or didanosine/stavudine was switched to once-daily SQV-SGC/RTV (1600/100 mg) with continuing NRTI treatment.


METHODS
Safety and efficacy (determined by plasma viral load and CD4 cell count) were evaluated (week 24). For 12 patients, steady-state plasma pharmacokinetics of SQV was determined (week 4).


RESULTS
Once-daily SQV-SGC/RTV was well tolerated. No patient changed regimens. After 24 weeks, 64 (93%) of 69 patients had plasma viral loads of <50 copies/mL (the remaining 5 patients had plasma viral loads of <300 copies/mL). The median CD4 cell count increased from 534/mL at the start of once-daily SQV-SGCs/RTV to 695/mL after 24 weeks (p <.001). Compared with the preceding 24 weeks of treatment with twice-daily SQV-SGC, the CD4 cell count improved significantly during once-daily SQV-SGC/RTV therapy (p <.001). All patients maintained SQV trough concentrations (C(24h)) of >0.05 mg/L. Median values for the area under the plasma concentration-versus-time curve from 0 to 24 hours (AUC(0-24h)), maximal concentration (C(max)), and C(24h) for SQV were 48.1 (h.mg)/L, 6.98 mg/L, and 0.17 mg/L, respectively. Body weight was inversely correlated with SQV AUC(24h) and C(24h) (p <.01).


CONCLUSIONS
Clinical and pharmacokinetic data support once-daily SQV-SGC/RTV (1600/100 mg) with two NRTIs as a convenient and safe therapeutic regimen to maintain viral suppression and immune function in HIV-1-infected patients with plasma viral loads of <50 copies/mL.
Cardiello
Peter G
PG
HIV Netherlands-Australia-Thailand Research Collaborative (HIVNAT), The Thai Red Cross AIDS Research Center, Bangkok, Thailand. Peter.Cardiello@post.harvard.edu
van Heeswijk
Rolf P
RP
Hassink
Elly A
EA
Srasuebkul
Preeyaporn
P
Mahanontharit
Apicha
A
Samor
Tarika M
TM
Worarien
Wassana
W
Beijnen
Jos H
JH
Hoetelmans
Richard M
RM
Ruxrungtham
Kiat
K
Cooper
David A
DA
Lange
Joep M
JM
Phanuphak
Praphan
P
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002214:Capsules / Q000008:administration & dosage; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D005780:Gelatin / Q000008:administration & dosage; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015497:HIV-1 / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D019438:Ritonavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019258:Saquinavir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D002214:Capsules; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D005780:Gelatin; D019258:Saquinavir; D019438:Ritonavir