Efficacy of a reduced dose of darunavir/ritonavir in a cohort of antiretroviral-naive and -experienced HIV-infected patients: a medium-term follow-up

Lanzafame, Massimiliano; Lattuada, Emanuela; Rigo, F.; Ferrari, Anna; Hill, Andrew; Vento, Sandro

doi:10.1093/jac/dku390

Cited by 10 publications

(5 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, another study from clinical practice recently showed that “unconventional” DRV/r dosage led to sustained virological suppression in treatment‐experienced patients . However, these results should be confirmed in a larger population in clinical practice.…”

Section: Discussionmentioning

confidence: 98%

“…In this regard, recent findings demonstrated that patients receiving first‐line treatment with a high pre‐therapy viral load (especially in the context of viraemia >100 000 HIV‐1 RNA copies/mL) had a lower chance of achieving virological success . Furthermore, although different DRV/r dosages are recommended according to the patient's treatment history and the presence/absence of PI resistance , few data on the impact of DRV/r dosage on virological response are available from clinical practice .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Virological response and resistance profile in HIV‐1‐infected patients starting darunavir‐containing regimens

et al. 2016

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Virological response and resistance profile in HIV‐1‐infected patients starting darunavir‐containing regimens

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The results of our retrospective study indicate that reduced dose antiretroviral regimens are effective in progressively decreasing immune activation similarly to standard cART [3,[13][14][15][16][17].…”

Section: Discussionmentioning

confidence: 79%

Lack of Difference between the Reduced Dose and Full-Dose of Antiretroviral Therapy in Terms of the Decrease in Immune Activation

Nicolè¹,

Cucchetto²,

Lanzafame³

et al. 2017

Ann Antivir Antiretrovir

View full text Add to dashboard Cite

Virological and immunological effectiveness of reduced doses of antiretrovirals has been shown in two randomized trials and smaller studies. We have now evaluated immune activation in patients on reduced doses of antiretroviral therapy (ART) using HLA-DR+CD8+ lymphocytes as a marker of activation. In an observational, retrospective study we assessed 113 HIV-infected patients who switched from standard combined ART (cART) to reduced dose combinations (cohort 1), while maintaining virological suppression (<20 copies/mL). After a mean time of 36 months on reduced dose therapy, the mean increase in CD4+ lymphocyte numbers was 100 cell/μL (p<0.01) and the mean reduction of HLA-DR+ lymphocytes was 103 cells/μL (p<0.01). We also compared cohort 1 with a cohort of 113 virologically suppressed patients on standard cART (cohort 2). We found no signifi cant differences in the number of CD4+ lymphocytes or in immune activation (mean values of HLA-DR+ absolute number and percentage of total CD8+ lymphocytes). The results of this retrospective study did not identify any immunological differences between reduced antiretroviral dose regimens and standard cART and suggest that reduced dose regimens can progressively reduce immune activation similarly to standard cART.

show abstract

“…involving fewer drugs or lower doses have gained attention as they could help to reduce toxicity, reduce costs (therefore increasing access to the drug in developing countries), and improve convenience and patient compliance. A reduction in the daily dose of DRV/RTV from 800/100 to 600/100 mg q24h was demonstrated to be safe in virologically suppressed patients [24,25], as was a further reduction to 400/100 mg q24h [26,27]. Additionally, DRV 400 mg plus a NRTI backbone was found to be non-inferior to standard dose lopinavir plus a NRTI backbone [27].…”

Section: Key Pointsmentioning

confidence: 94%

Exploration of Reduced Doses and Short-Cycle Therapy for Darunavir/Cobicistat in Patients with HIV Using Population Pharmacokinetic Modeling and Simulations

et al. 2020

View full text Add to dashboard Cite

Background and objectives Protease inhibitors such as darunavir are an important therapeutic option in the anti-human immunodeficiency virus arsenal. Current dosage guidelines recommend using cobicistat- or ritonavir-boosted darunavir 800 mg every 24 h (q24h) in protease inhibitor-naïve patients, or ritonavir-boosted darunavir 600 mg q12h in experienced patients. However, darunavir displays a large, poorly characterized, inter-individual pharmacokinetic variability. The objectives of this study were to investigate the pharmacokinetics of darunavir and to elucidate the sources of its inter-individual variability using population pharmacokinetic modeling. Then, to determine the appropriateness of current treatment guidelines and the feasibility of alternative dosing regimens in a representative cohort of adult patients using simulations. Methods Sparse pharmacokinetic samples were collected in 127 patients with human immunodeficiency virus type 1 infection, then supplemented with rich sampling data from a subset of 12 individuals. Data were analyzed using the nonlinear mixed-effects modeling software NONMEM. The effect of reduced doses (600 mg q24h and 400 mg q24h) or reduced frequency of administration (800 mg q24h for 5 days followed by 2 days of treatment interruption) was simulated. Results Our model adequately described the pharmacokinetics of darunavir. Predictors of individual exposure were CYP3A5*3 and SLCO3A1 rs8027174 genotypes, sex, and alpha-1 acid glycoprotein level. No relationship was apparent between darunavir area under the curve and treatment efficacy or safety. For reduced dose regimens, darunavir concentrations remained above the protein binding-corrected EC 50 in the majority of subjects. More stringent pharmacokinetic targets were not reached in a significant proportion of patients. Conclusions These results add to the growing body of evidence that darunavir-based therapy could be simplified to reduce costs and toxicity, as well as to improve patient compliance. However, the heterogeneity in pharmacokinetic response should be considered when assessing whether individual patients could benefit from a particular regimen, for instance through the use of population pharmacokinetic models. Clinical Trial Registration ClinicalTrials.gov identifier: NCT03101644, date of registration: 5 April, 2017. Electronic supplementary material The online version of this article (10.1007/s40262-020-00920-z) contains supplementary material, which is available to authorized users.

show abstract

Efficacy of a reduced dose of darunavir/ritonavir in a cohort of antiretroviral-naive and -experienced HIV-infected patients: a medium-term follow-up

Cited by 10 publications

References 8 publications

Virological response and resistance profile in HIV‐1‐infected patients starting darunavir‐containing regimens

Virological response and resistance profile in HIV‐1‐infected patients starting darunavir‐containing regimens

Lack of Difference between the Reduced Dose and Full-Dose of Antiretroviral Therapy in Terms of the Decrease in Immune Activation

Exploration of Reduced Doses and Short-Cycle Therapy for Darunavir/Cobicistat in Patients with HIV Using Population Pharmacokinetic Modeling and Simulations

Contact Info

Product

Resources

About