Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients

Cahn, Pedro; Fourie, Jan; Grinsztejn, Beatriz; Hodder, Sally; Molina, Jean‐Michel; Ruxrungtham, Kiat; Workman, Cassy; Casteele, Tom Van de; Doncker, P. De; Lathouwers, Erkki; Tomaka, Frank

doi:10.1097/qad.0b013e328345ee95

Cited by 106 publications

(102 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The total darunavir concentrations found in our cirrhotic patients are also similar to those observed in prior studies in noncirrhotic patients with the same darunavir dose (15,(25)(26)(27). In all of these studies, including ours, the C min values are well above the darunavir 50% effective concentration (EC 50 ) for wild-type virus (55 ng/ml) (27) and even the EC 50 for viruses with a 10-fold change in resistance for darunavir (550 ng/ml).…”

Section: Discussionsupporting

confidence: 88%

Darunavir and Ritonavir Total and Unbound Plasmatic Concentrations in HIV-HCV-Coinfected Patients with Hepatic Cirrhosis Compared to Those in HIV-Monoinfected Patients

Curran

Martí

López

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

dOur objective was to describe the pharmacokinetic (PK) parameters of total and unbound darunavir and ritonavir concentrations in HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis, as ritonavir-boosted darunavir is mainly metabolized in the liver, and hepatic cirrhosis might modify darunavir-ritonavir concentrations. This was a prospective, case-control, and unicenter study. HIV-HCV-coinfected patients with compensated cirrhosis (cases) and HIV-monoinfected patients with normal liver function (controls) were included. Darunavir-ritonavir was given at 800/100 mg once daily. Patients were followed for 24 weeks to assess safety and efficacy. A steady-state 12-h PK study was performed. Total and unbound concentrations were determined by liquid chromatography-tandem mass spectrometry. The unbound fraction was obtained by ultrafiltration. The plasma area under the concentration-time curve (AUC) and oral clearance (CL/F) were assessed by noncompartmental models. Thirty patients (20 cases and 10 controls) were included. Among cirrhotic patients, the Child-Pugh score was C in 4 cases, B in 1 case, and A in 15 cases; the median (interquartile range) transient elastography values were 20 kPa (14 to 26 kPa), and 5 patients had prior clinical decompensations. There were no significant differences in the darunavir PK parameters between cases and controls except for longer time to maximum plasma concentrations (T max ) and half-lives in the cirrhotic patients. There were no significant differences in ritonavir total concentrations, but the unbound concentrations were higher in cirrhotic patients. There were significant correlations between the darunavir total and unbound concentrations in both cirrhotic patients and controls. There were no differences in PK parameters based on Child-Pugh score, liver elasticity, gender, or use of concomitant medications. In conclusion, in HIV-HCV-coinfected patients with clinically compensated cirrhosis receiving darunavir-ritonavir at 800/100 mg once daily, the darunavir total and unbound concentrations are similar to those observed in noncirrhotic patients, and dose adjustments are not necessary.

show abstract

Section: Discussionsupporting

confidence: 88%

Darunavir and Ritonavir Total and Unbound Plasmatic Concentrations in HIV-HCV-Coinfected Patients with Hepatic Cirrhosis Compared to Those in HIV-Monoinfected Patients

Curran

Martí

López

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…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

View full text Add to dashboard Cite

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.

show abstract

“…The effectiveness of DRV/COBI was based on the analysis data at week 48 obtained from the study GS-US-216-130 [12] and the ARTEMIS [6] and ODIN [7] clinical trials. In the GS-US-216-130 [12], of the 397 patients screened, 313 were enrolled and included in the intent-to-treat (ITT) population.…”

Section: Discussionmentioning

confidence: 99%

“…Although IP have a high genetic barrier and a good tolerability and safety profile, RTV is associated with gastrointestinal adverse effects, numerous interactions with other drugs, insulin resistance, lipoatrophy and hyperlipidemia [4,5]. Different studies have evaluated the efficacy of DRV/r once daily in combination with other ART (ARTEMIS [6] study in naive patients and ODIN [7] study in pretreated patients) or monotherapy in pretreated patients (MONET, MONOI, Monarch and PROTEA studies) [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

“…The study evaluates the efficacy and safety of the components separately, mainly in "naive" patients who were given as starting ART regimen: DRV/COBI+2 NRTIs which was equivalent in virological efficacy compared to the ARTEMIS [6] and ODIN [7] studies. In a Phase III study was evaluated the degree of satisfaction of patients on COBI-containing co-formulations versus RTV, as well as the incidence of gastrointestinal side effects.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

One Year Follow-Up of Darunavir/Cobicistat Monotherapy in Pretreated HIV Patients

Yunquera-Romero¹,

Diez²,

Rio-Valencia³

et al. 2017

J AIDS Clin Res

View full text Add to dashboard Cite

IntroductionThe availability of antiretroviral treatment (ART) has made it possible to consider HIV-1 infection as a chronic disease. This has led to a change in the objectives of ART with a greater importance in improving the patient's quality of life and more efficient use of the resources, without compromising the effectiveness of treatments. In ART naive patients, on the first and successive lines after ART failure, preferred regimens remain the combination of three active drugs against HIV: Two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), a protease inhibitor (PI) with a pharmacokinetic (PK) enhancer (booster) (cobicistat or ritonavir), integrase strand transfer inhibitor (INSTI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) [1][2][3].Currently, boosted protease inhibitor monotherapy (PI/r): Darunavir/ritonavir (DRV/r) or Lopinavir/ritonavir (LPV/r) is only contemplated in the main treatment guidelines in pretreated patients to avoid toxicity associated with NRTIs, reduce costs and simplify ART. PI/r monotherapy with Atazanavir/ritonavir (ATV/r) is not recommended because of the worst results obtained in clinical trials. To initiate monotherapy based on PI/r, the patient must meet the following criteria: absence of chronic hepatitis B, plasma HIV-RNA viral load <50 copies/mL for at least 6 months and absence of mutations in the protease gene or virological failures (VF) prior to PI/r. PI/r are drugs that have a high genetic barrier and are used in monotherapy to maintain virological suppression in most patients, but with lower rates than triple therapy. The use of monotherapy with Lopinavir/ritonavir (LPV/r) and Darunavir/ritonavir (DRV/r) is associated with a higher frequency of "blips", defined as isolated and transient viral load values between 50 and <200 copies/mL. The "blips", although in most studies are not related to the increased risk of virological failure, do recommend re-evaluation of ART (degree of adhesion and genetic barrier) and in some patients may select resistant mutants [1]. Virological failure occurs when, in a patient with strict adherence and optimal tolerability to ART, there are any of the following two situations: a) Viral load detectable after 24 weeks of initiation of ART; B) if after reaching undetectability, th e viral load returns to >50 copies/mL in two consecutive determinations (separated by 2-4 weeks), excluding intercurrent vaccinations or infections (they may produce transient elevations of viral load). Virologic a l failure is AbstractIntroduction: Boosted protease inhibitor monotherapy (PI/r ) : Darunavir/ritonavir (DRV/r) or Lopinavir/ritonavir (LPV/r) monotherapy is only provided in the major treatment guidelines in pre-treated HIV patients to prevent toxicity associated with nucleoside/nucleotide reverse transcriptase inhibitor (NRTIs), reduce costs and simplify antiretroviral treatment. To start PI/r monotherapy, according to GESIDA g uidelines 2016, patients need to meet the following criteria: absence of chronic hepatitis B, pla...

show abstract

Week 48 analysis of once-daily vs. twice-daily darunavir/ritonavir in treatment-experienced HIV-1-infected patients

Abstract: Once-daily DRV/r 800/100 mg was noninferior in virologic response to twice-daily DRV/r 600/100 mg at 48 weeks in treatment-experienced patients with no DRV RAMs, and with a more favorable lipid profile. These findings support use of once-daily DRV/r in this population.

Cited by 106 publications

References 16 publications

Darunavir and Ritonavir Total and Unbound Plasmatic Concentrations in HIV-HCV-Coinfected Patients with Hepatic Cirrhosis Compared to Those in HIV-Monoinfected Patients

Darunavir and Ritonavir Total and Unbound Plasmatic Concentrations in HIV-HCV-Coinfected Patients with Hepatic Cirrhosis Compared to Those in HIV-Monoinfected Patients

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

One Year Follow-Up of Darunavir/Cobicistat Monotherapy in Pretreated HIV Patients

Contact Info

Product

Resources

About