Short- and Long-Term Optimal Control of a Mathematical Model for HIV Infection of $$CD4^{+}T$$ C D 4 + T Cells

Croicu, Ana-Maria

doi:10.1007/s11538-015-0114-4

Cited by 14 publications

(9 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This has been described by Rosenberg et al for the supervised treatment interruption strategies, or in the pharmacokinetic‐pharmacodynamic field . The optimal control theory can be applied for globally optimizing the treatment regime, which has been proposed by Castiglione and Piccoli, and applied to optimizing the treatment of HIV infected patients . However, as noted by Chakraborty and Murphy these works do not sufficiently take into account the statistical issues of the problem, ie, model parameters have to be estimated and for efficient estimation and random effects have to be introduced in the statistical model.…”

Section: Introductionmentioning

confidence: 99%

“…17,31 The optimal control theory can be applied for globally optimizing the treatment regime, which has been proposed by Castiglione and Piccoli, 32 and applied to optimizing the treatment of HIV infected patients. 33,34 However, as noted by Chakraborty and Murphy 35 these works do not sufficiently take into account the statistical issues of the problem, ie, model parameters have to be estimated and for efficient estimation and random effects have to be introduced in the statistical model. Such random effect mechanistic model has been applied to tune the dose of an antiretroviral treatment by Prague et al 36 In the present paper, we aim to find efficient adaptive protocols for IL7 administration based on predictions from a random effect mechanistic model proposed in the work of Jarne et al 21 Here, we propose realistic protocols that shorten the time spent under the limit of 500 CD4 cells/ L and limit the number of IL7 injections.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts

Villain

Commenges

Pasin

et al. 2018

Statistics in Medicine

View full text Add to dashboard Cite

In human immunodeficiency virus–infected patients, antiretroviral therapy suppresses the viral replication, which is followed in most patients by a restoration of CD4+ T cells pool. For patients who fail to do so, repeated injections of exogenous interleukin 7 (IL7) are experimented. The IL7 is a cytokine that is involved in the T cell homeostasis and the INSPIRE study has shown that injections of IL7 induced a proliferation of CD4+ T cells. Phase I/II INSPIRE 2 and 3 studies have evaluated a protocol in which a first cycle of three IL7 injections is followed by a new cycle at each visit when the patient has less than 550 CD4 cells/μL. Restoration of the CD4 concentration has been demonstrated, but the long‐term best adaptive protocol is yet to be determined. A mechanistic model of the evolution of CD4 after IL7 injections has been developed, which is based on a system of ordinary differential equations and includes random effects. Based on the estimation of this model, we use a Bayesian approach to forecast the dynamics of CD4 in new patients. We propose four prediction‐based adaptive protocols of injections to minimize the time spent under 500 CD4 cells/μL for each patient, without increasing the number of injections received too much. We show that our protocols significantly reduce the time spent under 500 CD4 over a period of two years, without increasing the number of injections. These protocols have the potential to increase the efficiency of this therapy.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts

Villain

Commenges

Pasin

et al. 2018

Statistics in Medicine

View full text Add to dashboard Cite

show abstract

“…Control theory is a potentially useful approach to address the problem of optimizing the dosage, timing, and composition of therapeutic agents. For example, control theory has been applied to optimize antiretroviral drug therapy for HIV infections [Culshaw et al, 2004, Jang et al, 2011, Croicu, 2015, Croicu et al, 2017, minimize resistance in antibiotic treatment [Peña-Miller et al, 2012], and determine the optimal dosing schedule of antimalarial medications [Thibodeaux and Schlittenhardt, 2011] and cancer therapies [Castiglione and Piccoli, 2006, de Pillis et al, 2008, Ledzewicz et al, 2012. These applications of control theory have focused on modeling the within-host disease dynamics using a set of coupled nonlinear differential equations describing the population dynamics of disease agents such as pathogens or tumor cells, as well as host cells that include immune cells and/or cells targeted by pathogens.…”

mentioning

confidence: 99%

Optimizing the Timing and Composition of Therapeutic Phage Cocktails: A Control-theoretic Approach

Leung

Wardi

et al. 2019

Preprint

View full text Add to dashboard Cite

Viruses that infect bacteria, i.e., bacteriophage or 'phage', are increasingly considered as treatment options for the control and clearance of bacterial infections, particularly as compassionate use therapy for multi-drug resistant infections. In practice, clinical use of phage often involves the application of multiple therapeutic phage, either together or sequentially. However, the selection and timing of therapeutic phage delivery remains largely ad hoc. In this study, we evaluate principles underlying why careful application of multiple phage (i.e., a 'cocktail') might lead to therapeutic success in contrast to the failure of single-strain phage therapy to control an infection. First, we use a nonlinear dynamics model of within-host interactions to show that a combination of fast intra-host phage decay, evolution of phage resistance amongst bacteria, and/or compromised immune response might limit the effectiveness of single-strain phage therapy. To resolve these problems, we combine dynamical modeling of phage, bacteria, and host immune cell populations with control-theoretic principles (via optimal control theory) to devise evolutionarily robust phage cocktails and delivery schedules to control the bacterial populations. Our numerical results suggest that optimal administration of single-strain phage therapy may be sufficient for curative outcomes in immunocompetent patients, but may fail in immunodeficient hosts due to phage resistance. We show that optimized treatment with a two-phage cocktail that includes a counter-resistant phage can restore therapeutic efficacy in immunodeficient hosts.

show abstract

“…резкое снижение заболеваемости и смертности среди пациентов, зараженных ВИЧ [6,7]. В этой связи ак-туальным становится вопрос реализации репродук-тивной функции у ВИЧ-инфицированных женщин, но не всегда желанная беременность наступает спон-танно.…”

unclassified

Somatic and gynecologic anamnesis in HIV-infected patients in ART programms

Medvedeva¹,

Malgina²

2016

Probl. reprod.

View full text Add to dashboard Cite

Вирусом иммунодефицита человека (ВИЧ) зара-жены более чем 40 млн во всем мире, половина из них женщины [1]. Сегодня отношение к ВИЧ меня-ется -ВИЧ-инфекция воспринимается не как смер-e-mail: Medvedeva-V-V@mail.ru тельное состояние, а как терапевтически контроли-руемое хроническое заболевание [2][3][4][5].С момента внедрения высокоактивной антире-тровирусной терапии (ВААРТ) в 1996 г. отмечено Цель исследования -оценка особенностей соматического, акушерско-гинекологического анамнеза у Вич-инфицированных пациенток с бесплодием. Материал и методы. В исследование включены 97 пациенток с бесплодием, инфицированных Вич (основная группа), и 90 сероотрицательных по Вич пациенток (контрольная группа), обратившиеся в клинику Врт для коррекции бесплодия. результаты. наиболее значимые различия получены в таких факторах, как прием наркотиков в анамнезе (в основной группе в 28 раз чаще), наличие патологии желудочно-кишечного тракта (в 2 раза чаще) и щитовидной железы (в 3,2 раза чаще). у пациенток с Вич-инфекцией превалировало вторичное бесплодие (59,7% против 30%; p<0,05) на фоне предшествующих абортов (40,2% против 16,7%; p<0,05), самопроизвольных выкидышей (14,4% против 5,5%; p<0,05). значимые различия получены также в частоте патологии шейки матки, перенесенных инфекций, передаваемых половым путем, и заболеваемости аднекситом. генез бесплодия у Вич-инфицированных пациенток представлен в основном трубно-перитонеальным фактором. Кроме того, у пациенток основной группы более чем в 3 раза чаще наблюдалась комбинация лабораторных и ультразвуковых признаков снижения овариального резерва. Выводы. учитывая выявленные особенности социального, соматического и акушерско-гинекологического анамнеза у бесплодных пациенток с Вич-инфекцией, можно предполагать как прямое воздействие вируса на яичниковую ткань и эндометрий, так и влияние персистирующих инфектов на фоне иммунодефицита и токсическое влияние антиретровирусной терапии на органы репродуктивной системы, желудочно-кишечный тракт и щитовидную железу. Objective -to evaluate thr somatic, obstetric-gynecologic anamnesis in HIv-infected patients with infertility. Material and methods. the study included 97 patients with infertility and HIv (core group) and 90 HIv-seronegative patients (control group) in Art programs. Results. the most significant differences are obtained in such factors as drug use history, gastrointestinal diseases and thyroid cancer. Patients with HIv more often had secondary infertility and artificial abortions as well as spontaneous abortion in anamnesis. significant differences are obtained in cervical pathology, stIs and adnexitis rates. genesis of infertility in HIv-infected individuals is represented mainly tubal-peritoneal factor. In addition the patients of the main group more often had decreased ovarian reserve. Conclusions. Infertile patients with HIv infection can have direct impact of the virus on the ovarian tissue and endometrium, the influence of persistent infecton on the background of immunodeficiency and toxic effects of antiretroviral therapy on th...

show abstract

Short- and Long-Term Optimal Control of a Mathematical Model for HIV Infection of $$CD4^{+}T$$ C D 4 + T Cells

Cited by 14 publications

References 21 publications

Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts

Adaptive protocols based on predictions from a mechanistic model of the effect of IL7 on CD4 counts

Optimizing the Timing and Composition of Therapeutic Phage Cocktails: A Control-theoretic Approach

Somatic and gynecologic anamnesis in HIV-infected patients in ART programms

Contact Info

Product

Resources

About