Low-doses of indinavir boosted with ritonavir in HIV-infected Thai patients: pharmacokinetics, efficacy and tolerability.
OBJECTIVE
To assess the steady-state pharmacokinetics of two reduced doses of indinavir boosted with ritonavir (indinavir/ritonavir) in HIV-infected Thai patients.


METHODS
Thirteen immunocompromised antiretroviral-naive patients (6 males, 7 females) initiated 600/100 mg indinavir/ritonavir, zidovudine and lamivudine, every 12 h. After 1 month, blood samples were taken at pre-dose, and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8 and 12 h after drug intake. Indinavir dosing was then reduced to 400 mg (twice daily) and 1 week later an identical series of samples were drawn. Patients then resumed 600 mg of indinavir. HIV-1 RNA viral load was determined at 8, 24 and 48 weeks. Indinavir plasma levels were determined by HPLC and pharmacokinetic parameters by non-compartmental analysis.


RESULTS
Median (range) weight was 58 kg (51-73) for men and 53 kg (46-59) for women. On 600 mg of indinavir, median indinavir AUC, C(max), and C(min) were 39.3 mg.h/L (20.6-50.5), 6.2 mg/L (3.7-9.0) and 0.41 mg/L (0.12-0.77), respectively, and on indinavir 400 mg, 18.3 mg.h/L (11.1-33.0), 3.8 mg/L (2.2-7.8) and 0.17 mg/L (0.10-0.39), respectively. No renal complications were observed. At 48 weeks, 6/13 (46%) patients had stopped 600 mg of indinavir due to intolerability (gastrointestinal and cutaneous), and 5/7 (71%) patients had a HIV-1 viral load <50 copies/mL.


CONCLUSIONS
Reduced doses of indinavir/ritonavir maintained adequate indinavir plasma levels compared to current guidelines suggesting that these doses are efficacious in this setting. Considering the poor tolerability of 600 mg of indinavir, the 400 mg of indinavir may be preferred due to its lower exposure indices but long-term efficacy data are needed.
Cressey
Tim R
TR
Harvard School of Public Health, Harvard University, Boston, MA, USA. tim@phpt.org
Leenasirimakul
Prattana
P
Jourdain
Gonzague
G
Tod
Michel
M
Sukrakanchana
Pra-Ornsuda
PO
Kunkeaw
Suparat
S
Puttimit
Chutima
C
Lallemant
Marc
M
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D019469:Indinavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D019438:Ritonavir / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
D019380:Anti-HIV Agents; D012367:RNA, Viral; D019469:Indinavir; D019438:Ritonavir