Abacavir/lamivudine fixed-dose combination antiretroviral therapy for the treatment of HIV

Achenbach, Chad J.; Scarsi, Kimberly K.; Murphy, Robert L.

doi:10.1007/s12325-010-0006-9

Cited by 14 publications

(11 citation statements)

References 57 publications

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“…However, numerous studies have concluded that adherence (defined as the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen [ 3 ]) to injectable DMTs for patients with MS is suboptimal [ 4 , 5 ]. Studies in patients with MS [ 4 – 10 ] have reported rates of medication adherence ranging from 27 to 83 %, depending on the methodology and whether the study used claims data to calculate indirect measures of adherence [ 6 , 7 , 11 , 12 ] or surveys to collect self-reported measures of adherence [ 4 , 5 , 8 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…These results imply that experiences and/or perceptions of discomfort and inconvenience affect the choice of and the adherence to self-administered injectable DMTs. Several authors have suggested that improvements in administration of these treatments, such as a reduced dosing frequency, may reduce patient burden and improve adherence, as well as having economic benefits through fewer hospitalizations and emergency room visits [ 4 , 6 , 7 , 12 , 18 ]. Improvements in the dosing frequency and tolerability of DMTs may therefore improve adherence and directly reduce the number of injection-related adverse events.…”

Section: Introductionmentioning

confidence: 99%

“…Patient preference studies for features of injectable DMTs provide information on the relative importance of these treatment features with respect to patient treatment choice and adherence. Collectively, data from these studies inform physicians on what features of treatment regimens and modalities are important to their patients and the associated burden of treatment [ 5 , 8 , 14 ], as well as informing healthcare providers and payors of any potential (direct and indirect) economic benefits that may arise from increased treatment efficacy and adherence [ 7 ]. Therefore, the objective of this study was to quantify the relative importance of the features of injectable DMTs that are associated with treatment choice and medication adherence in patients with MS.…”

Section: Introductionmentioning

confidence: 99%

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Patient Preferences for Injectable Treatments for Multiple Sclerosis in the United States: A Discrete-Choice Experiment

Poulos

Kinter

Yang

et al. 2015

Patient

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Background and ObjectivePatients’ perceptions and experiences of medication efficacy, medication adverse events, dosing frequency, and dosing complexity have been found to influence adherence to injectable disease-modifying treatments (DMTs) in patients with multiple sclerosis (MS). The aim of this study was to quantify patient preferences for features of injectable DMTs for MS.MethodsAdult patients in the United States (US) with a self-reported diagnosis of MS completed an online discrete-choice experiment survey to assess preference for a number of features of a hypothetical injectable DMT. Patients chose hypothetical treatments in paired comparisons, where each treatment was described by features or attributes, including the number of years until disability progression, the number of relapses in the next 4 years, injection time, the frequency of injections, the occurrence of flu-like symptoms (FLS), and severity of injection-site reactions. Random-parameters logit regression parameters were used to calculate preference weights of attribute levels and the relative importance of changes in treatment features.ResultsOf the 205 patients who completed the survey, 192 provided sufficient data for analysis. The results indicated a broad range of tradeoffs that patients would be willing to make. With regard to this, the relative importance of an improvement in the number of years until disability progression from 1 to 2 (i.e., vertical distance between preference weights for these attribute levels) was 0.9 [95 % confidence interval (CI) 0.5–1.2], the relative importance of this change was approximately equivalent to that of an improvement from 12 injections per month to two (mean 0.8, 95 % CI 0.4–1.2), or approximately equivalent to a decrease from four to one relapses in the next 4 years (mean 0.8, 95 % CI 0.5–1.2), or FLS 3 days after every injection to 3 days after some injections (mean 1.0, 95 % CI 0.6–1.4).ConclusionsThese results suggest that an improvement in treatment efficacy may be as important as a reduction in injection frequency or a reduction in some adverse events for patients who self-administer injectable DMTs for MS. Understanding the preferences of patients who use injectable treatments will inform the development of such treatments, which may in turn improve patient medication adherence and well-being.Electronic supplementary materialThe online version of this article (doi:10.1007/s40271-015-0136-x) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Patient Preferences for Injectable Treatments for Multiple Sclerosis in the United States: A Discrete-Choice Experiment

Poulos

Kinter

Yang

et al. 2015

Patient

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“…While atazanavir (ATV) has demonstrated little dyslipidemic impact as compared with certain other protease inhibitors (PIs), there are concerns regarding ritonavir (/r)-boosted PI regimens as potentially increasing CHD risk, although whether this would be associated with any change in inflammatory biomarker concentrations is unclear. [13][14][15][16] Abacavir (ABC) is a generally well-tolerated nucleoside reverse transcriptase inhibitor (NRTI) that has been used in combination antiretroviral regimens since the 1990s, 17 and while the majority of studies [18][19][20][21][22] have not demonstrated an increased ABC-attributable CHD risk in the absence of confounding factors, two recent analyses of observational cohorts 23,24 reported a statistically increased incidence in MI in HIV-infected patients receiving ABC-based therapy with various third agents.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory Biomarker Changes and Their Correlation with Framingham Cardiovascular Risk and Lipid Changes in Antiretroviral-Naive HIV-Infected Patients Treated for 144 Weeks with Abacavir/Lamivudine/Atazanavir with or without Ritonavir in ARIES

Young¹,

Squires

Ross

et al. 2013

AIDS Research and Human Retroviruses

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Propensity for developing coronary heart disease (CHD) is linked with Framingham-defined cardiovascular risk factors and elevated inflammatory biomarkers. Cardiovascular risk and inflammatory biomarkers were evaluated in ARIES, a Phase IIIb/IV clinical trial in which 515 antiretroviral-naive HIV-infected subjects initially received abacavir/lamivudine + atazanavir/ritonavir for 36 weeks. Subjects who were virologically suppressed by week 30 were randomized 1:1 at week 36 to either maintain or discontinue ritonavir for an additional 108 weeks. Framingham 10-year CHD risk scores (FRS) and risk category of <6% or ≥6%, lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were assessed at baseline, week 84, and week 144. Biomarkers were stratified by FRS category. When ritonavir-boosted/nonboosted treatment groups were combined, median hsCRP did not change significantly between baseline (1.6 mg/liter) and week 144 (1.4 mg/liter) in subjects with FRS <6% (p=0.535) or with FRS ≥6% (1.9 mg/liter vs. 2.0 mg/liter, respectively; p=0.102). Median IL-6 was similar for subjects with FRS <6% (p=0.267) at baseline (1.6 pg/ml) and week 144 (1.4 pg/ml) and for FRS ≥6% (2.0 pg/ml vs. 2.2 pg/ml, respectively; p=0.099). Median Lp-PLA(2) decreased significantly (p<0.001) between baseline (197 nmol/min/ml) and week 144 (168 nmol/min/ml) in subjects with FRS <6% and with FRS ≥6% (238 nmol/min/ml vs. 175 nmol/min/ml, respectively; p<0.001). In conclusion, in antiretroviral-naive subjects treated with abacavir-based therapy for 144 weeks, median inflammatory biomarker levels for hsCRP and IL-6 generally remained stable with no significant difference between baseline and week 144 for subjects with either FRS <6% or FRS ≥6%. Lp-PLA(2) median values declined significantly over 144 weeks for subjects in either FRS stratum.

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“…Lamivudine (3TC), a nucleoside reverse transcriptase inhibitor commonly used in combination antiretroviral therapy to HIV‐infected children , was initially administered twice daily in both adults and children. Lamivudine enters infected lymphocytes and is progressively phosphorylated by intracellular enzymes to the active moiety, which has a long half‐life (16–19 h) relative to the half‐life of parent lamivudine in plasma (7–9 h) .…”

Section: Introductionmentioning

confidence: 99%

A model‐based approach for the evaluation of once daily dosing of lamivudine in HIV‐infected children

Piana

Zhao

Adkison

et al. 2014

Brit J Clinical Pharma

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AIMLittle attention has been paid to the effects of compliance and prescription practice on treatment outcome in HIV-infected children. In this context, an evaluation of the role of covariates on pharmacokinetics is required to establish the impact of differences in dosing regimens. Here we investigate whether a once daily dosing regimen of lamivudine provides comparable exposure to the currently approved paediatric regimen. METHODSA hypothetical group of 180 patients between 3 months and 12 years old was used to evaluate the impact of body weight on systemic exposure to lamivudine. Simulation scenarios were evaluated using AUC and Cmax as parameters of interest. The analysis was performed using a population pharmacokinetic model previously implemented in NONMEM v.6.2. RESULTSThe simulations show that once daily dosing of lamivudine yields comparable exposure to historical values observed in children and adults, both for liquid and solid dosage forms. Simulated steady-state AUC(0-24 h) and Cmax values after once daily doses ranged respectively from 9.95 mg l −1 h and 1.9 mg l −1 for children lighter than 14 kg to 13.75 mg l −1 h and 3.0 mg l −1 for children heavier than 30 kg. These values are comparable or higher than historical values observed after once daily dosing in children and adults. CONCLUSIONSOur findings illustrate how dosing regimens can be evaluated taking into account the effects of developmental growth on drug disposition. Most importantly, they suggest that the reduction in dosing frequency to once daily leads to comparable lamivudine exposure, as observed after administration of a twice daily dosing regimen. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Lamivudine is currently administered as a once daily dosing regimen in adults and twice daily in children.• Recent studies in a subgroup of HIV-infected children have shown similar pharmacokinetics after once and twice daily dosing with either of the available dosage forms of lamivudine (i.e. tablet and solution).• Empirical evidence of drug exposure, efficacy and safety in controlled clinical trials has been required for the evaluation and approval of novel dosing regimens for a licensed product, thereby exposing children to potentially unnecessary trials. WHAT THIS STUDY ADDS• Although simulated exposures varied across the paediatric weight range, children in all weight bands showed predicted lamivudine AUC(0-24 h) values after once daily administration comparable with or higher than the reference values previously observed in children on twice daily regimen or adults on once daily or twice daily dosing regimens.• The predicted increase in Cmax after once daily administration is unlikely to result in a higher risk of adverse events.• The use of model-based extrapolations allows the assessment of novel dosing regimens based on the underlying pharmacokinetic and pharmacokinetic-pharmacodynamic properties of the drug(s) under investigation.

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Abacavir/lamivudine fixed-dose combination antiretroviral therapy for the treatment of HIV

Cited by 14 publications

References 57 publications

Patient Preferences for Injectable Treatments for Multiple Sclerosis in the United States: A Discrete-Choice Experiment

Patient Preferences for Injectable Treatments for Multiple Sclerosis in the United States: A Discrete-Choice Experiment

Inflammatory Biomarker Changes and Their Correlation with Framingham Cardiovascular Risk and Lipid Changes in Antiretroviral-Naive HIV-Infected Patients Treated for 144 Weeks with Abacavir/Lamivudine/Atazanavir with or without Ritonavir in ARIES

A model‐based approach for the evaluation of once daily dosing of lamivudine in HIV‐infected children

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