scholarly journals A drug pharmacodynamics and pharmacokinetics based approach towards stabilization of HIV infection dynamics

2015 ◽  
Vol 30 (5) ◽  
Author(s):  
Rufina M. Tretyakova ◽  
Andreas Meyerhans ◽  
Gennady A. Bocharov
Keyword(s):  
Drug Administration ◽  
Drug Efficacy ◽  
Drug Dosage ◽  
Antiretroviral Drugs ◽  
Loop Control ◽  
Infection Dynamics ◽  
Antiretroviral Drug ◽  
Optimal Drug ◽  
Drug Pharmacokinetics ◽  
Efficacy Function

AbstractIn our study we developed a computational algorithm for finding optimal dosages of antiretroviral drug administration for the stabilization of HIV load at low levels. The novelty is that the pharmacokinetics and pharmacodynamics of the antiretroviral drugs were taken into account. A standard closed-loop control of HIV dynamics was constructed that stabilizes the viral load and the optimal drug administration mode was formulated. We analyze the appropriateness of the ‘drug efficacy’ based control and its relationship to a realistic drug dosage and kinetic models in the human body. The translation of the efficacy function into drug concentration is implemented via the pharmacodynamics model of the drug effect. Optimal approximation of the idealized concentration functions is based on the orthogonal projection on linear subspace of drug pharmacokinetics functions.

Stochastic Programming on Optimal Drug Administration for Two Stage Cancer Treatment Problems

2012 ◽  
Vol 3 (1) ◽  
pp. 1-10
Author(s):  
P. Tirupathi Rao ◽  
D. Flora Evangil ◽  
K. Madhavi
Keyword(s):  
Drug Administration ◽  
Dosage Level ◽  
Drug Dosage ◽  
Drug Dose ◽  
Drug Usage ◽  
Optimal Decisions ◽  
Optimal Drug ◽  
Vacation Period ◽  
Lower Limits ◽  
Care Decision

Either Continuous drug administration or continuous drug vacation for long spells of cancer chemotherapy is not suggestible. Similarly the quantum of administered drug dose either above the required level or below the wanted level is also not advised. Effective drug administration has to consider the optimal threshold limits on the drug administration/drug vacation times; upper and lower limits of drug quantity; along with the suitable number of drug administration/drug vacation cycles; and the number of spells within the cycle of drug usage/stoppage. This paper develops an optimization programming problem for designing drug administration strategies for a cancer patient under chemotherapy. This study will help in exploring the decision parameters at the targeted objectives. Optimal decisions on drug dosage level, drug administration period, drug vacation period, number of drug administration cycles; number of drugs applied within a cycle, etc., can be obtained with the model. Sensitivity analysis is carried out for understanding the model behavior. This work has a scope for developing health care Decision Support Systems.

Comparison of particle swarm and bacterial foraging optimization algorithms for therapy planning in HIV/AIDS patients

2016 ◽  
Vol 09 (02) ◽  
pp. 1650024 ◽  
Author(s):  
K. Kamalanand ◽  
P. Mannar Jawahar
Keyword(s):  
Viral Load ◽  
Immune System ◽  
Drug Dosage ◽  
Antiretroviral Drugs ◽  
Therapy Planning ◽  
Cd4 Cells ◽  
Bacterial Foraging Optimization ◽  
Aids Patients ◽  
Optimal Drug ◽  
Hiv Aids

In HIV/AIDS patients, antiretroviral therapy (ART) is used for reducing the viral load and helps in increasing the life span of the individual. However, severe side effects are associated with the use of antiretroviral drugs. Hence, a treatment schedule, using minimal amount of drugs, is required for maintaining a low viral load and a healthy immune system. The objective of this work is to compute the optimal dosage of antiretroviral drugs for therapy planning in HIV/AIDS patients, using intelligent optimization techniques. In this work, two computational swarm intelligence techniques known as the particle swarm optimization (PSO) and bacterial foraging optimization (BFO) in conjunction with the three-dimensional mathematical model of HIV/AIDS have been used for estimating the optimal drug dosage for administering therapy by minimization of viral load as well as the total drug concentration. Results demonstrate that, using the proposed method, it is possible to achieve minimal viral load and an improved immune system, with the estimated drug dosage. Further, it was observed that the efficiency of BFO (CD4 cells [Formula: see text][Formula: see text]cells/mm3 at seventh year of infection) for estimation of optimal drug dosage is higher than the PSO method (CD4 cells [Formula: see text][Formula: see text]cells/mm3 at seventh year of infection). This work seems to be of high clinical relevance since, at present, ART is the widely used procedure for treatment of HIV infected patients.

scholarly journals Maternal and infant health is protected by antiretroviral drug strategies that preserve breastfeeding by HIV-positive women

2012 ◽  
Vol 13 (1) ◽  
Author(s):  
Louise Kuhn
Keyword(s):  
South African ◽  
Infant Formula ◽  
Infant Health ◽  
Antiretroviral Drugs ◽  
Hiv Positive ◽  
Infant Survival ◽  
Department Of Health ◽  
Hiv Positive Women ◽  
Antiretroviral Drug ◽  
Maternal And Infant Health

The South African Department of Health is justified in withdrawing support for free infant formula. By so doing, it recognises that any intervention that might detract from breast feeding poses a serious threat to infant survival. Since evidence is now strong that antiretroviral drugs used during lactation prevent transmission of infection from a seropositive mother, strategies that promote breastfeeding can now be recommended for enhancing the health of mothers and infants.

scholarly journals A biological model of scabies infection dynamics and treatment informs mass drug administration strategies to increase the likelihood of elimination

2019 ◽  
Vol 309 ◽  
pp. 163-173 ◽  
Author(s):  
M.J. Lydeamore ◽  
P.T. Campbell ◽  
D.G. Regan ◽  
S.Y.C. Tong ◽  
R.M. Andrews ◽  
...  
Keyword(s):  
Drug Administration ◽  
Mass Drug Administration ◽  
Biological Model ◽  
Infection Dynamics

15 Optimal Drug Administration Based on a Compartmental System

2015 ◽  
pp. 166-174
Author(s):  
Hideo Kusuoka ◽  
Hajime Maeda ◽  
Shinzo Kodama ◽  
Michitoshi Inoue ◽  
Hiroshi Abe ◽  
...  
Keyword(s):  
Drug Administration ◽  
Compartmental System ◽  
Optimal Drug

scholarly journals A comparison between different anti-retroviral therapy regimes on soluble inflammation markers: a pilot study

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Martina Maritati ◽  
Trentini Alessandro ◽  
Nunzia Zanotta ◽  
Manola Comar ◽  
Tiziana Bellini ◽  
...  
Keyword(s):  
Drug Regimen ◽  
Antiretroviral Drugs ◽  
Serum Samples ◽  
The Third ◽  
Cytokines And Chemokines ◽  
Antiretroviral Drug ◽  
Group 3 ◽  
Group 2 ◽  
Inflammatory Profile ◽  
Group 1

Abstract Background Although HIV-related deaths have decreased dramatically following the introduction of antiretroviral therapy (ART), HIV infection itself causes increased morbidity and mortality for both non-AIDS-related events or chronic inflammation and immune activation. The use of certain antiretroviral drugs can contribute to this process. Methods We investigated 26 potential biomarkers in serum samples from HIV-1 infected patients virologically suppressed under ART. The main objective of our study was to evaluate if virological suppression achieved with a triple drug regimen containing tenofovir disoproxil fumarate co-formulated with emtricitabine (TDF/FTC) as backbone, could correlate with a better immunological and inflammatory profile in relation to the third class of antiretroviral drug administered. The eligible patients were then divided into 3 groups in relation to the third drug associated with TDF/FTC: nucleoside reverse transcriptase inhibitors (NNRTI) (Group 1, n = 16), protease inhibitors (PI) (Group 2, n = 17) and integrase inhibitors (INI) (Group 3, n = 16). Results Inflammatory cytokines and chemokines were more represented in Group 2 than in Group 3 (IL-1Ra, p = 0.013; IL-12p70 p = 0.039; TNF-α p = 0.041; IL-8, p = 0.027; MIP1 β, p = 0.033). Eotaxin showed lower levels in Group 1 compared to Group 2 (p = 0.010), while IP-10 was significantly lower in Group 1 compared to both Group 2 and Group 3 (p = 0.003 and p = 0.007, respectively). Conclusions Our results seem to discourage the administration of PI as a third drug in a virologically effective antiretroviral regimen, as its use is linked to the detection of higher levels of pro-inflammatory mediators in comparison with INI and NNRTI.

scholarly journals Hyperthyroidism in the personalized medicine era: the rise of mathematical optimization

2019 ◽  
Vol 16 (155) ◽  
pp. 20190083 ◽  
Author(s):  
Fanwen Meng ◽  
Enlin Li ◽  
Paul Michael Yen ◽  
Melvin Khee Shing Leow
Keyword(s):  
Personalized Medicine ◽  
Rapid Determination ◽  
Mathematical Optimization ◽  
Optimal Dose ◽  
Equation System ◽  
Drug Dosage ◽  
Dose Titration ◽  
Synthesis Rate ◽  
Efficient Treatment ◽  
Optimal Drug

Thyroid over-activity or hyperthyroidism constitutes a significant morbidity afflicting the world. The current medical practice of dose titration of anti-thyroid drug (ATD) treatment for hyperthyroidism is relatively archaic, being based on arbitrary and time-consuming trending of thyroid function that requires multiple clinic monitoring visits before an optimal dose is found. This prompts a re-examination into more deterministic and efficient treatment approaches in the present personalized medicine era. Our research project seeks to develop a personalized medicine model that facilitates optimal drug dosing via the titration regimen. We analysed 49 patients' data consisting of drug dosage, time period and serum free thyroxine (FT4). Ordinary differential equation modelling was applied to describe the dynamic behaviour of FT4 concentration. With each patient's data, an optimization model was developed to determine parameters of synthesis rate, decay rate and IC 50 . We derived the closed-form time- and dose-dependent solution which allowed explicit estimates of personalized predicted FT4. Our equation system involving time, drug dosage and FT4 can be solved for any variable provided the values of the other two are known. Compared against actual FT4 data within a tolerance, we demonstrated the feasibility of predicting the FT4 subsequent to any prescribed dose of ATD with favourable accuracy using the initial three to five patient-visits' data respectively. This proposed mathematical model may assist clinicians in rapid determination of optimal ATD doses within allowable prescription limits to achieve any desired FT4 within a specified treatment period to accelerate the attainment of euthyroid targets.

scholarly journals Association between lipodystrophy and length of exposure to ARTs in adult HIV-1 infected patients in Montreal

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ahmad Alikhani ◽  
Helene Morin ◽  
Stephanie Matte ◽  
Pouriya Alikhani ◽  
Cécile Tremblay ◽  
...  
Keyword(s):  
Cross Sectional Study ◽  
Continuous Variable ◽  
Antiretroviral Drugs ◽  
Cumulative Exposure ◽  
Sectional Study ◽  
Cross Sectional ◽  
Centre Hospitalier Universitaire ◽  
Antiretroviral Drug ◽  
Trunk Limb ◽  
Hiv 1

Abstract Background The aim of this study was to establish the prevalence of lipodystrophy and its association to cumulative exposure to antiretroviral drugs. Method We conducted a cross sectional study in all HIV- infected patients attending the HIV clinic in the Centre hospitalier universitaire de Montréal (CHUM) with DEXA scan. Lipodystrophy was defined as a trunk/limb fat ratio ≥ 1.5. Association between cumulative exposure to antiretroviral (measured in years of use) with trunk/limb fat ratio (coded as a continuous variable) was assessed using univariate and multivariate linear regression for each antiretroviral drug with at least 40 exposed patients. Results One hundred sixty-six patients were included. Seventy-five percent were male, median age was 56 years, 67% were Caucasian. Overall, prevalence of lipodystrophy was 47%, with a mean trunk/limb fat ratio of 1.87, SD = 1.03, min = 0.6 and max = 5.87. Each 10-year increase in age and HIV infection duration was associated with an average increase of 0.24 and 0.34 for the trunk/limb fat ratio respectively. (p = 0.003, p = 0.002, respectively) Patients classified as lipodystrophic were more likely to be diabetic (50 vs. 28%, p = 0.07) and to have dyslipidemia (47 vs. 19%, p = 0.01). According to viral load at DEXA test, each one log increase was associated with less probability (0.7) of lipodystrophy. (p = 0.01) Among ARV drugs tested, there was an association between years of use of d4T, ritonavir and raltegravir and higher trunk/limb fat ratio (indicating more lipodystrophy) (p < 0.05). Conclusion Lipodystrophy is very common in HIV infected patients and is correlated with duration of some new antiretroviral drugs.

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