The Promise of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are the Data?

Scarsi, Kimberly K; Swindells, Susan

doi:10.1177/23259582211009011

Cited by 51 publications

(55 citation statements)

References 51 publications

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“…Recently, long-acting injectable ARV therapy containing rilpivirine and cabotegravir has been demonstrated to be non-inferior to oral ARV therapy and was approved for use in Europe and USA. Being administered directly to the systemic circulation, long-acting injectable ARV therapy may solve many absorption and bioavailability challenges post-BS [ 100 ]. However, multi-level barriers slow down the large-scale implementation of long-acting ART.…”

Section: Successful Arv Candidates Post-bsmentioning

confidence: 99%

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

et al. 2022

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Bariatric surgery is increasingly applied among people living with HIV to reduce obesity and the associated morbidity and mortality. In people living with HIV, sufficient antiretroviral exposure and activity should always be maintained to prevent development of resistance and disease progression. However, bariatric surgery procedures bring various gastrointestinal modifications including changes in gastric volume, and acidity, gastrointestinal emptying time, enterohepatic circulation and delayed entry of bile acids. These alterations may affect many aspects of antiretroviral pharmacokinetics. Some drug characteristics may result in subtherapeutic exposure and the potential related risk of treatment failure and resistance. Antiretrovirals that require low pH, administration of fatty meals, longer intestinal exposure, and an enterohepatic recirculation for their absorption may be most impacted by bariatric surgery procedures. Additionally, some antiretrovirals can interact with the polyvalent cations in supplements or drugs inhibiting gastric acid, thereby preventing their use as these comedications are commonly prescribed post-bariatric surgery. Predicting pharmacokinetics on the basis of drug characteristics solely proved to be challenging, therefore pharmacokinetic studies remain crucial in this population. Here, we discuss general implications of bariatric surgery on antiretroviral outcomes in people living with HIV as well as drug properties that are relevant for the choice of antiretroviral treatment in this special patient population. Additionally, we summarise studies that evaluated the pharmacokinetics of antiretrovirals post-bariatric surgery. Finally, we performed a comprehensive analysis of theoretical considerations and published pharmacokinetic and pharmacodynamic data to provide recommendations on antiretrovirals for people living with HIV undergoing bariatric surgery.

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Section: Successful Arv Candidates Post-bsmentioning

confidence: 99%

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

et al. 2022

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“…While participant satisfaction with long-acting ART has been largely positive [ 2 ▪ , 25 – 28 ], provider enthusiasm has been more cautious. Concerns include the need for patients to adhere to injection visits for treatment to be successful [ 26 ].…”

Section: Cabotegravir and Rilpivirine For The Treatment Of Hivmentioning

confidence: 99%

“…Although effective and well tolerated [ 1 ], the need for high levels of adherence to daily oral regimens remains a barrier to the success of both treatment and prevention. Challenges related to daily oral adherence include pill fatigue, the need for discretion, self-stigma, and other factors [ 2 ▪ ]. Long-acting injectable antiretrovirals have the potential to improve adherence with less frequent dosing, greater confidentiality/privacy, and reduced risk of undesired disclosure.…”

Section: Introductionmentioning

confidence: 99%

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV

Bares¹,

Scarsi

2021

Current Opinion in HIV and AIDS

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Purpose of review Cabotegravir (CAB) and rilpivirine (RPV) is the first long-acting injectable antiretroviral therapy (ART) option approved for virologically suppressed adults with HIV-1. In addition, long-acting CAB is a promising agent for HIV preexposure prophylaxis (PrEP). This review focuses on phase 3 clinical trial results and implementation considerations for these long-acting ART and PrEP strategies. Recent findings Long-acting CAB and RPV administered every 4 weeks demonstrated noninferiority to oral ART through week 96 in both the ATLAS and FLAIR studies, whereas ATLAS-2M found similar efficacy through 96 weeks when the long-acting injectable ART was administered every 8 weeks instead of every 4 weeks. For prevention, two phase 3 trials were stopped early due to fewer incident HIV infections in participants receiving long-acting CAB every 8 weeks compared with daily oral tenofovir disoproxil fumarate–emtricitabine for PrEP. The long-acting therapies were well tolerated across all clinical trials. Summary Clinical trial results support the use of long-acting CAB for HIV PrEP and long-acting CAB and RPV as a switch strategy for adults with HIV-1 who are first virologically suppressed with oral ART. Implementation challenges persist, and data are urgently needed in populations who may benefit most from long-acting therapy, including adolescents, pregnant individuals, and those with barriers to medication adherence.

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“…In contrast, LA oral and subcutaneous formulations are self-administered and may increase patient autonomy, but also potentially lower adherence. Patients' social contexts must be acknowledged to address known challenges to adherence, such as oral lead-in concerns, and issues related to long pharmacokinetic tails and the potential need to return to oral medications [4,85]. Patients have expressed concerns about switching from oral to LA ART as it requires a new drug regimen, may have different adverse effects, and it limits their control over daily dosing [77,86,87].…”

Section: The Need To Ensure Global Availabilitymentioning

confidence: 99%

“…Each new LA modality is an important tool in an ever-expanding toolkit and offers novel strategies to reduce barriers to daily pill taking [4,5]. Although LA modalities have the potential to change the course of the epidemic if provided as an option for all, they are not a panacea.…”

Section: Introductionmentioning

confidence: 99%

Promise, perils and cautious optimism: the next frontier in long-acting modalities for the treatment and prevention of HIV

Philbin

Perez-Brumer

2022

Current Opinion in HIV and AIDS

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Purpose of reviewThis paper provides a critical review of recent therapeutic advances in long-acting (LA) modalities for human immunodeficiency virus (HIV) treatment and prevention. Recent findingsLA injectable antiretroviral therapy (ART) has been approved in the United States, Canada and Europe; the United States also has approved LA injectable preexposure prophylaxis (PrEP) and the World Health Organization has recommended the vaginal PrEP ring. Current LA PrEP modalities in clinical trials include injections, films, rings, and implants; LA ART modalities in trials include subcutaneous injections and longterm oral pills. Although LA modalities hold incredible promise, global availability is inhibited by longstanding multilevel perils including declining multilateral funding, patent protections and lack of political will. Once available, access and uptake are limited by factors such as insurance coverage, clinic access, labor markets, stigma, and structural racism and sexism. These must be addressed to facilitate equitable access for all. SummaryThere have been tremendous recent advances in the efficacy of LA ART and PrEP modalities, providing renewed hope that 'ending the HIV epidemic' is within reach. However, pervasive socio-structural inequities limit the promise of LA modalities, highlighting the need for cautious optimism in light of the embedded inequities in the trajectory of research, development, and population-level implementation.

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The Promise of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are the Data?

Cited by 51 publications

References 51 publications

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

Implications of Bariatric Surgery on the Pharmacokinetics of Antiretrovirals in People Living with HIV

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV

Promise, perils and cautious optimism: the next frontier in long-acting modalities for the treatment and prevention of HIV

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