Similar Safety and Efficacy of Once- and Twice-Daily Lopinavir/Ritonavir Tablets in Treatment-Experienced HIV-1–Infected Subjects at 48 Weeks

Zajdenverg, Roberto; Podsadecki, Thomas; Badal-Faesen, Sharlaa; Andrade-Villanueva, Jaime; Gathe, Joseph; Mingrone, Horacio; Fredrick, Linda; Gaultier, I.; Woodward, William C.; Bernstein, Barry

doi:10.1097/qai.0b013e3181cbd21e

Cited by 33 publications

(28 citation statements)

References 19 publications

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“…These results are comparable to recently reported studies in modestly treatment-experienced patients who received modern ritonavir-boosted PIs. 20,21 The number of early second cART virologic failures observed among patients who had a suppressed HIV RNA at the time of switch from first to second cART regimens was surprising. These findings emphasize caution when switching cART in successfully treated patients.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Second Combination Antiretroviral Therapy Regimens Among HIV-Infected Persons in Clinical Care: A Multicenter Cohort Study

Napravnik

Eron

Juday

et al. 2013

AIDS Research and Human Retroviruses

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Data on the effectiveness of second-line combination antiretroviral therapy (cART) are limited. We evaluated virologic outcomes of second cART in a multicenter cohort collaboration. The study population initiated first and second modern cART between 1996 and 2010. The second cART required a switch in at least the anchor agent of first cART. We evaluated time to virologic failure of second cART and factors associated with greater risk of failure using multivariable Cox proportional hazards models. Of 488 patients who switched to second-line cART, 67% were black and 32% were women. The median HIV-1 RNA at second cART initiation was 9,565 copies/ml [interquartile range (IQR); 123, 94,108]. The time to virologic failure of second cART was longer if HIV-1 RNA was undetectable at switch ( p = 0.001), although 12% and 17% of patients with undetectable and detectable HIV-1 RNA experienced virologic failure within 6 months of second cART initiation, respectively. A lower CD4 cell count at second cART initiation was associated with a greater risk of virologic failure. Failure rates decreased in more recent calendar years [adjusted relative hazard of 0.40 comparing 2008 to 2010 with 1996 to 1998 (95% confidence interval; 0.15, 1.00)]; however, type of anchor agent was not associated with failure. In conclusion, virologic failure of second cART was less likely if patients switched with undetectable HIV-1 RNA, although risk of early failure was similar. The effectiveness of second cART regimens improved over calendar time and was independent of the anchor agent in the regimen.

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Section: Discussionmentioning

confidence: 99%

Outcomes of Second Combination Antiretroviral Therapy Regimens Among HIV-Infected Persons in Clinical Care: A Multicenter Cohort Study

Napravnik

Eron

Juday

et al. 2013

AIDS Research and Human Retroviruses

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“…Study 5 was a randomized, open-label phase 3 study comparing the pharmacokinetics and pharmacodynamics of LPV/r tablets at 800/200 mg QD and 400/100 mg BID in 599 treatment-experienced HIV-infected male and nonpregnant female subjects (23). Data from 261 subjects receiving the 400/100-mg BID regimen were included in this analysis.…”

Section: Methodsmentioning

confidence: 99%

No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

Salem

Jones

Santini-Oliveira

et al. 2016

Antimicrob Agents Chemother

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Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC 0 -12 ) and concentration prior to dosing (C predose ) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC 0 -12 or C predose values observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pregnancy.T he use of combination antiretroviral therapy (cART) is recommended in all pregnant women with HIV infection for prevention of perinatal transmission as well as for maternal health. Such use has resulted in a significant reduction of perinatal transmission from 25% to 0 -3.6% (1, 2). Treatment guidelines include the use of protease inhibitors in combination with two nucleoside reverse transcriptase inhibitors (NRTIs) (3-7).Lopinavir (LPV) is a peptidomimetic HIV type 1 (HIV-1) protease inhibitor. When LPV is coadministered with low-dose ritonavir (RTV), which acts as a pharmacokinetic enhancer by blocking the cytochrome P450 3A (CYP3A)-mediated metabolism of LPV, serum levels of LPV are significantly increased, and half-life is prolonged. The high LPV exposures achieved with coformulated lopinavir-ritonavir (LPV/r) have the advantage of providing a pharmacologic barrier to the emergence of HIV-1 viral resistance in patients with wild-type virus, as well as enhanced activity against some forms of drug-resistant HIV-1 (8).Because of the potency of ...

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“…The simplification of LPV/r dosage from 400/100 mg BID to 800/200 mg QD was studied initially in ARV-naïve adults and recently in experienced adults and did not show any difference in therapeutic efficacy in randomized controlled studies (7,23). The QD regimen option is now officially recommended in naïve adult patients (10).…”

mentioning

confidence: 99%

Pharmacokinetics and Virological Efficacy after Switch to Once-Daily Lopinavir-Ritonavir in Treatment-Experienced HIV-1-Infected Children

Foissac

Urien

Hirt

et al. 2011

Antimicrob Agents Chemother

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Lopinavir-ritonavir (LPV/r) is a protease inhibitor that is used twice daily (BID) in the treatment of HIV infection in children.In the context of a single-center observational study, a switch to a once-a-day (QD) LPV/r regimen was proposed for considerations of convenience and to support adherence. The aims of this study were to compare the pharmacokinetics, viral loads, percentages of CD4 ؉ T cells, and lipid profiles after switching from a twice-daily to a once-daily regimen of LPV/r in experienced children. For this purpose, LPV concentrations, viral loads, CD4؉ T cells, and biochemistry data were measured in routine therapeutic drug monitoring procedures in 45 children and adolescents. Thirty-six children were switched to the QD regimen. Nine children on the BID or QD regimen were added for pharmacokinetic-study purposes only. The QD trough concentrations (C trough ) of lopinavir in plasma were significantly lower than those observed with the BID regimen (P < 0.0001), but the 24-h exposure levels were not significantly lower with the QD than with the BID regimen (P ‫؍‬ 0.09). Among 34 evaluable patients who switched from the BID to the QD regimen, the virological efficacy of LPV/r appeared to differ (P < 0.001), with 74% and 57% of viral loads, respectively, being <50 copies/ml (mean follow-up times, 33 and 20 months). Among 22 patients with stable virological control before the switch, 12 experienced either failure or blip (one observation of detectable viral load between two observations of undetectable viral load) after the switch. The change from the BID to the QD regimen did not result in significant differences in CD4 ؉ T cell percentages or total cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels. The switch from the BID to the QD LPV/r regimen led to equivalent exposure and lower C trough values and resulted in lower levels of virological control in these antiretroviral-experienced children.Lopinavir-ritonavir (LPV/r) is the protease inhibitor that is most used in children today, administered twice daily (BID) and usually combined with two nucleoside analogues. The protease inhibitor LPV/r has been approved by the European Medicines Agency (EMEA) for children aged at least 2 years (8) and by the U.S. Food and Drug Administration (FDA) for children aged at least 14 days and older (1). LPV/r has demonstrated durable antiviral activity in antiretroviral (ARV)-naïve and protease inhibitor-experienced children, with viral suppression (HIV-1 RNA at Ͻ50 copies/ml) in more than 60% of the population treated (60 to 80% of adults demonstrated suppression in previous studies) (6,20). Since 2006, LPV/r has been available as an oral solution or tablet, 200/50 mg or 100/25 mg, respectively.There is a general trend toward the simplification of treatment with once-a-day (QD) administration to improve convenience and patient adherence (13). The simplification of LPV/r dosage from 400/100 mg BID to 800/200 mg QD was studied initially in ARV-naïve adults and recently in experienced adults ...

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Similar Safety and Efficacy of Once- and Twice-Daily Lopinavir/Ritonavir Tablets in Treatment-Experienced HIV-1–Infected Subjects at 48 Weeks

Abstract: LPV/r dosed QD resulted in increased treatment adherence and was as efficacious as BID LPV/r while providing similar safety, tolerability, and limited resistance evolution.

Cited by 33 publications

References 19 publications

Outcomes of Second Combination Antiretroviral Therapy Regimens Among HIV-Infected Persons in Clinical Care: A Multicenter Cohort Study

Outcomes of Second Combination Antiretroviral Therapy Regimens Among HIV-Infected Persons in Clinical Care: A Multicenter Cohort Study

No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

Pharmacokinetics and Virological Efficacy after Switch to Once-Daily Lopinavir-Ritonavir in Treatment-Experienced HIV-1-Infected Children

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