Low‐dose indinavir in combination with low‐dose ritonavir: steady‐state pharmacokinetics and long‐term clinical outcome follow‐up

Justesen, Ulrik Stenz; Levring, AM; Thomsen, Anna M; Lindberg, JA; Pedersen, Court; Tauris, P

doi:10.1046/j.1468-1293.2003.00153.x

Cited by 20 publications

(12 citation statements)

References 10 publications

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“…In another small retrospective trial, Justesen et al . found that 70% of 21 patients (either ART‐naive or IDV 800 mg tid experienced subjects) treated with IDV/RTV 400/100 mg bid achieved a viral load <20 copies/mL after a median of 116 weeks [16]. Both studies found low rates of adverse events, but no comparison was made with other dosages of IDV.…”

Section: Discussionmentioning

confidence: 99%

Indinavir/ritonavir‐based therapy in HIV‐1‐infected antiretroviral therapy‐naive patients: comparison of 800/100 mg and 400/100 mg twice daily

et al. 2005

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Objectives To compare the efficacy and tolerability of indinavir (IDV)/ritonavir (RTV) at 800/100 and 400/100 mg twice daily (bid) in antiretroviral therapy (ART)‐naive patients. Methods An open comparison of two groups of ART‐naive patients treated with IDV/RTV 800/100 or 400/100 mg bid plus two nucleoside analogues was carried out. Viral load, CD4 cell count and tolerability were measured at baseline and at weeks 4, 12, 24 and 48. IDV plasma concentrations were measured retrospectively. Results A total of 107 patients were included in the study. Of these, 57 were treated with 800/100 and 50 with 400/100 mg IDV/RTV bid. At week 48, a viral load of <50 HIV‐1 RNA copies/mL was achieved by 77 and 64% of the patients, respectively, and the median CD4 cell count increases were +171 and +164 cells/μL (intent‐to‐treat; P not significant), respectively. Side effects leading to protease inhibitor discontinuation occurred in 61% of subjects in the 800/100 mg group vs. 20% in the 400/100 mg group (P<0.0001). Switching from 800/100 to 400/100 mg dosage improved adverse events in 16 of 20 patients. IDV concentrations were above 0.15 mg/L in 89% of the 28 patients tested in the 400/100 mg group. Conclusions Indinavir/ritonavir 400/100 mg bid provided the same efficacy as 800/100 mg bid at 48 weeks in an ART‐naive population, but safety and tolerance were significantly better for 400/100 mg, while convenience was also improved and cost was reduced.

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Section: Discussionmentioning

confidence: 99%

Indinavir/ritonavir‐based therapy in HIV‐1‐infected antiretroviral therapy‐naive patients: comparison of 800/100 mg and 400/100 mg twice daily

et al. 2005

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“…14,15 Apart from this, various other studies also support clinical usefulness of low-dose IDV/r-based treatment. 8,14,15,17,18 PK data also suggest that low-dose IDV/rbased treatment may not be adequate for patients weighing >55 kg. 14 Results of our study confirms that PI/r-based treatment is a good choice for second line in treatment of first-line NNRTIbased treatment failure with 14.8% of overall treatment failure with second-line regimen during the follow-up period.…”

Section: Visits (In Months)mentioning

confidence: 99%

“…12,13 Recent studies suggested that lowering of IDV/r dosage to 400/100 mg BID has retained same potency and has improved pharmacokinetic profiles. 8,[14][15][16][17][18] Atazanavir boosted with ritonovir (ATV/r) is an advantageous PI due to its oncedaily dosage and reduced effect on patient's lipid profile. 19,20 Some study findings suggest that these drugs have the same efficacy as LPV/r.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effectiveness of Low-Dose Indinavir/Ritonavir (IDV/r)- versus Atazanavir/Ritonavir (ATV/r)-Based Generic Antiretroviral Therapy in NNRTI-Experienced HIV-1-Infected Patients in India

Patel

Naik

et al. 2011

Journal of the International Association of Physicians in AIDS

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Background: Currently, data on the effectiveness of second-line antiretroviral regimens using indinavir/ritonavir (IDV/r) and atazanavir/ritonavir (ATV/r) along with 2 nucleoside reverse transcriptase inhibitor (NRTI) in resource-poor settings is limited. Methods: Observational follow-up study on 441 patients who experienced treatment failure to first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based treatment. Multivariate Cox Proportional Hazards Model was used to assess comparative effectiveness of treatment regimens. Results: A total of 63 patients (14.8%) had failed second line treatments, of which 53 patients (17.2%) were using IDV/r while 10 patients (8.5%) were on ATV/r. After adjusting for age, weight, gender, and baseline CD4 count, patients who took IDV/r were more than twice as likely to experience treatment failure as compared to those who were on ATV/r (hazard ratio [HR] 2.18; 95% confidence interval [CI] 1.14, 4.15). Successful response to second-line therapy was not different between the 2 treatment groups when patients weighed less than 55 kg at baseline (log rank P value ¼ 1.00) in contrast to the individuals weighing 55 kg (P < .0001). Conclusion: We found that successful response to second-line therapy was twice as likely in the ATV/r group; however, this difference was eliminated in patients less than 55 kg.

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“…The difference was observed consistently on all three study days, and the same result was found in subjects admitted the previous day, when we timed their evening dose. This difference most likely reflects diurnal variation in indinavir concentrations, a phenomenon that has been previously noted for indinavir as well as for other protease inhibitors (PIs) (7,8). In light of this difference, it would be advisable for all future research studies of PIs to include measurements of both morning and evening C min s.…”

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confidence: 95%

“…A small group of patients with undetectable virus loads switching from unboosted indinavir to 400 mg of indinavir with ritonavir given twice daily maintained viral suppression at 48 weeks (5). In contrast, in patients with detectable viral loads and previous PI exposure, switching to 400 mg of indinavir resulted in some treatment failures (7). Therefore, the 400-mg dose of indinavir may best be avoided for patients who have previously experienced PI failure, in whom the 95% inhibitory concentration may be raised above that for a wild-type virus (4).…”

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confidence: 99%

Pharmacokinetics of Indinavir at 800, 600, and 400 Milligrams Administered with Ritonavir at 100 Milligrams and Efavirenz in Ethnic Chinese Patients Infected with Human Immunodeficiency Virus

Lee

Panchalingam

Yap

et al. 2004

Antimicrob Agents Chemother

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We assessed the pharmacokinetics of three different doses of indinavir in five patients. All doses achieved trough concentrations above efficacy thresholds. Toxic trough concentrations were observed in all patients receiving 800 mg, in two patients receiving 600 mg, and in none receiving 400 mg. Indinavir at 400 mg may be efficacious and less toxic in patients taking ritonavir and efavirenz.Coadministration of ritonavir increases concentrations of indinavir and prolongs indinavir's half-life (10, 13). Indinavir (800 mg) is now commonly prescribed with ritonavir in doses of 100 mg twice daily. The higher drug concentrations of indinavir in ritonavir-boosted regimens may increase toxicity, especially nephrolithiasis (2). Lower doses of indinavir may provide clinically efficacious drug concentrations while minimizing toxicity and lowering costs.The combination of efavirenz and indinavir has durable efficacy similar to that of dual nucleosides and indinavir (6, 12). However, efavirenz reduces levels of indinavir by about 20% (1); it is recommended that indinavir be increased to 1,000 mg when coadministered with efavirenz (Crixivan product monograph, Merck & Co.). However, boosting with ritonavir may allow indinavir doses to be maintained or even reduced. Two studies show adequate trough levels but potentially toxic peak levels with 800 mg of indinavir boosted with ritonavir, even when this combination is coadministered with efavirenz (1, 3). Dose reductions of indinavir may provide better toxicity profiles.We recruited human immunodeficiency virus-infected patients on a regimen of indinavir, ritonavir, and efavirenz and with undetectable viral loads. The study was performed at Tan Tock Seng Hospital, Singapore, Republic of Singapore, and approved by the local Ethics Committee.Patients ' doses were established at 800 mg of indinavir and 100 mg of ritonavir twice daily for at least 1 week before the study. Twelve-hour pharmacokinetic protocols were performed at baseline and 1 week after dose reductions to 600 and 400 mg of indinavir twice daily. Subjects then returned to taking indinavir (800 mg).Patients arrived before 8 a.m. on each pharmacokinetic profile day, some on the day before. They were given their morning doses of indinavir and ritonavir with standardized mediumfat, medium-calorie breakfasts consisting of 465 kcal (33% fat, 20% protein, and 47% carbohydrate). Blood was collected for drug concentration measurements at 0 (baseline), 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 h post-indinavir ingestion.Indinavir concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry as previously described (10a). Pharmacokinetic parameters, including peak and trough concentrations (C max s and C min s, respectively) of indinavir, areas under the curve, half-lives, and times to maximum concentration, were obtained by using TOPFIT software (Gustav Fischer Verlag, Stuttgart, Germany).We used the efficacy threshold indinavir C min of 100 ng/ml, based on Department of Health and Human Services conse...

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Low‐dose indinavir in combination with low‐dose ritonavir: steady‐state pharmacokinetics and long‐term clinical outcome follow‐up

Abstract: Treatment with the IDV/RTV 400/100 mg regimen appears to be efficacious for up to 2 years. However, rather low IDV Cmin suggests that the regimen should be evaluated further before its widespread use and that the regimen probably should be guided by pharmacokinetic evaluation.

Cited by 20 publications

References 10 publications

Indinavir/ritonavir‐based therapy in HIV‐1‐infected antiretroviral therapy‐naive patients: comparison of 800/100 mg and 400/100 mg twice daily

Indinavir/ritonavir‐based therapy in HIV‐1‐infected antiretroviral therapy‐naive patients: comparison of 800/100 mg and 400/100 mg twice daily

Comparison of the Effectiveness of Low-Dose Indinavir/Ritonavir (IDV/r)- versus Atazanavir/Ritonavir (ATV/r)-Based Generic Antiretroviral Therapy in NNRTI-Experienced HIV-1-Infected Patients in India

Pharmacokinetics of Indinavir at 800, 600, and 400 Milligrams Administered with Ritonavir at 100 Milligrams and Efavirenz in Ethnic Chinese Patients Infected with Human Immunodeficiency Virus

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