Beyond one pill, once daily: current challenges of antiretroviral therapy management in the United States

Masters, Mary Clare; Krueger, Karen; Williams, Janna; Morrison, Lindsay R.; Cohn, Susan E.

doi:10.1080/17512433.2019.1698946

Cited by 19 publications

(13 citation statements)

References 166 publications

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“…Developing long-acting injectable formulations that achieve extended-duration pharmacokinetics for antiretrovirals is a currently topical problem in the fight against HIV/AIDS [ 2 , 56 ]. In the case of TFV, such formulations may be obtained by preparing salts of a TFV base with a polymeric acid; their intramuscular administration would then form tissue depots, gradually releasing the base and making it available for internalization by cells.…”

Section: Discussionmentioning

confidence: 99%

A New Approach to Developing Long-Acting Injectable Formulations of Anti-HIV Drugs: Poly(Ethylene Phosphoric Acid) Block Copolymers Increase the Efficiency of Tenofovir against HIV-1 in MT-4 Cells

Nifant’ev

Siniavin

Карамов

et al. 2020

IJMS

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Despite the world’s combined efforts, human immunodeficiency virus (HIV), the causative agent of AIDS, remains one of the world’s most serious public health challenges. High genetic variability of HIV complicates the development of anti-HIV vaccine, and there is an actual clinical need for increasing the efficiency of anti-HIV drugs in terms of targeted delivery and controlled release. Tenofovir (TFV), a nucleotide-analog reverse transcriptase inhibitor, has gained wide acceptance as a drug for pre-exposure prophylaxis or treatment of HIV infection. In our study, we explored the potential of tenofovir disoproxil (TFD) adducts with block copolymers of poly(ethylene glycol) monomethyl ether and poly(ethylene phosphoric acid) (mPEG-b-PEPA) as candidates for developing a long-acting/controlled-release formulation of TFV. Two types of mPEG-b-PEPA with numbers of ethylene phosphoric acid (EPA) fragments of 13 and 49 were synthesized by catalytic ring-opening polymerization, and used for preparing four types of adducts with TFD. Antiviral activity of [mPEG-b-PEPA]TFD or tenofovir disoproxil fumarate (TDF) was evaluated using the model of experimental HIV infection in vitro (MT-4/HIV-1IIIB). Judging by the values of the selectivity index (SI), TFD exhibited an up to 14-fold higher anti-HIV activity in the form of mPEG-b-PEPA adducts, thus demonstrating significant promise for further development of long-acting/controlled-release injectable TFV formulations.

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Section: Discussionmentioning

confidence: 99%

A New Approach to Developing Long-Acting Injectable Formulations of Anti-HIV Drugs: Poly(Ethylene Phosphoric Acid) Block Copolymers Increase the Efficiency of Tenofovir against HIV-1 in MT-4 Cells

Nifant’ev

Siniavin

Карамов

et al. 2020

IJMS

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“…Efforts to further simplify HIV treatment have sparked recent interest in the use of two‐drug regimens. It is becoming increasingly clear that, in carefully selected patients, dual therapy is efficacious, with potential to reduce drug toxicity and cost 36 . There is growing evidence to support a switch to dual therapy once viral suppression is maintained on a standard three‐drug regimen 34,37,38 .…”

Section: Managementmentioning

confidence: 99%

“…It is becoming increasingly clear that, in carefully selected patients, dual therapy is efficacious, with potential to reduce drug toxicity and cost. 36 There is growing evidence to support a switch to dual therapy once viral suppression is maintained on a standard three-drug regimen. 34,37,38 However, it is important to note that none of the currently available two-drug regimens has anti-hepatitis B virus (HBV) activity.…”

Section: Two-drug Regimensmentioning

confidence: 99%

HIV: the changing paradigm

Raubinger

Lee

Pinto

2022

Internal Medicine Journal

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The past four decades have seen enormous progress in the diagnosis and management of human immunodeficiency virus (HIV) infection. There have been significant advances spanning the approval of the first antiretroviral agents, the advent of combination antiretroviral therapy to single tablet regimens with minimal toxicity. Although these remarkable developments have on the surface led to the 'end of AIDS', there are still key populations being left behind. This clinical update will describe the diagnosis and management of HIV, and the changing paradigms that have seen HIV transform from a life-limiting condition to a manageable chronic disease over a few decades.

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“…Instead, it is now a manageable chronic condition due in large part to significant advances in antiretroviral therapy (ART) over the past four decades [ 1 – 3 ]. People with HIV (PWH) who are adherent to ART have a life expectancy near that of the general population [ 4 , 5 ]. Yet despite highly potent and effective ART, UNAIDS estimated that approximately 41% of PWH remain unsuppressed among countries with reportable data in 2019 [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Ethical and practical considerations for HIV cure-related research at the end-of-life: a qualitative interview and focus group study in the United States

et al. 2022

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Background One of the next frontiers in HIV research is focused on finding a cure. A new priority includes people with HIV (PWH) with non-AIDS terminal illnesses who are willing to donate their bodies at the end-of-life (EOL) to advance the search towards an HIV cure. We endeavored to understand perceptions of this research and to identify ethical and practical considerations relevant to implementing it. Methods We conducted 20 in-depth interviews and 3 virtual focus groups among four types of key stakeholders in the United States (PWH, biomedical HIV cure researchers, HIV clinicians, and bioethicists) to obtain triangulated viewpoints because little was known about the ethics of this topic. Each group was queried as to ethical considerations, safeguards, and protections for conducting HIV cure-related research at the EOL to ensure this research remains acceptable. Results All four key stakeholder groups generally supported HIV cure-related research conducted at the EOL because of the history of altruism within the PWH community and the potential for substantial scientific knowledge to be gained. Our informants expressed that: (1) Strong stakeholder and community involvement are integral to the ethical and effective implementation, as well as the social acceptability of this research; (2) PWH approaching the EOL should not inherently be considered a vulnerable class and their autonomy must be respected when choosing to participate in HIV cure-related research at the EOL; (3) Greater diversity among study participants, as well as multi-disciplinary research teams, is necessitated by HIV cure-related research at the EOL; (4) The sensitive nature of this research warrants robust oversight to ensure a favorable risk/benefit balance and to minimize the possibility of therapeutic misconception or undue influence; and (5) Research protocols should remain flexible to accommodate participants’ comfort and needs at the EOL. Conclusion Because of the ethical issues presented by HIV cure-related research at the EOL, robust ethical safeguards are of utmost importance. The proposed ethical and practical considerations presented herein is a first step in determining the best way to maximize this research’s impact and social value. More much inquiry will need to be directed towards understanding context-specific and cultural considerations for implementing EOL HIV cure research in diverse settings.

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Beyond one pill, once daily: current challenges of antiretroviral therapy management in the United States

Cited by 19 publications

References 166 publications

A New Approach to Developing Long-Acting Injectable Formulations of Anti-HIV Drugs: Poly(Ethylene Phosphoric Acid) Block Copolymers Increase the Efficiency of Tenofovir against HIV-1 in MT-4 Cells

A New Approach to Developing Long-Acting Injectable Formulations of Anti-HIV Drugs: Poly(Ethylene Phosphoric Acid) Block Copolymers Increase the Efficiency of Tenofovir against HIV-1 in MT-4 Cells

HIV: the changing paradigm

Ethical and practical considerations for HIV cure-related research at the end-of-life: a qualitative interview and focus group study in the United States

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