Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study

Orkin, Chloe; Morell, Enrique Bernal; Tan, Darrell H. S.; Katner, Harold; Stellbrink, Hans‐Jürgen; Belonosova, Elena; DeMoor, Rebecca; Griffith, Sandy; Thiagarajah, Shanker; Solingen‐Ristea, Rodica Van; Ford, Susan L.; Crauwels, Herta; Patel, Parul; Cutrell, Amy; Smith, Kimberly Y.; Vandermeulen, Kati; Birmingham, Eileen; Clair, Marty St.; Spreen, William; D’Amico, Ronald

doi:10.1016/s2352-3018(21)00184-3

Cited by 76 publications

(104 citation statements)

References 27 publications

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“…Patients with CVF had RPV RAMs in proviral DNA, HIV-1 subtype A6/A1, or body mass index ≥30 kg/m 2 . At week 124, 1 (<1%) patient in each arm had ≥50 HIV RNA copies/mL, consistent with non-inferiority demonstrated at week 48 [ 16 ]. Adverse events were similar across all groups in severity and frequency, and ISRs were the most common (21% in the injection group) adverse events.…”

Section: Cabotegravir: Integrase Strand Transfer Inhibitorsupporting

confidence: 63%

“…The 2-drug regimen of CAB and rilpivirine (RPV), an agent of non-nucleoside reverse transcriptase inhibitors (NNRTIs), has demonstrated potent antiviral activity for the maintenance of viral suppression in both ART-naïve and experienced patients [ 12 13 14 15 16 17 ]. The phase-2 Long-Acting Antiretroviral Treatment Enabling Trial (LATTE) study provided the regimen of oral CAB with RPV has an antiviral activity similar to efavirenz combined with dual NRTIs through week 96 [ 12 ].…”

Section: Cabotegravir: Integrase Strand Transfer Inhibitormentioning

confidence: 99%

Section: Cabotegravir: Integrase Strand Transfer Inhibitormentioning

confidence: 99%

“…The phase 3 First Long-Acting Injectable Regimen (FLAIR) and Antiretroviral Therapy as Long-Acting Suppression (ATLAS) trials evaluated the 2-drug regimen of LA CAB with RPV for ART- naïve patients and those suppressed with the current oral regimen, respectively [ 15 16 17 ]. ART-naïve patients received oral induction therapy with DTG/lamivudine (3TC)/abacavir (ABC) for 20 weeks in FLAIR trial [ 15 16 ]. Participants whose viral load was undetectable after 16 weeks of oral induction therapy, were randomized to either continue the current oral regimen or switch to LA monthly therapy following a 4-week oral lead-in therapy with CAB and RPV.…”

Section: Cabotegravir: Integrase Strand Transfer Inhibitormentioning

confidence: 99%

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Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention

Kim

2021

Infect Chemother

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Current oral antiretroviral agents provide highly effective treatment for patients infected with human immunodeficiency virus (HIV), and can be used as pre-exposure prophylaxis (PrEP) to prevent new HIV infections. Several single-tablet regimens with excellent antiviral efficacy have dramatically improved the quality of life of patients who can adhere to daily oral therapy. However, there is increasing demand on long-acting injectable antiretroviral agents for patients who cannot take oral agents or feel fatigue related to daily pill burden. Monthly long-acting (LA) cabotegravir (CAB) combined with rilpivirine (RPV) has recently been listed as optimizing agent for maintenance of HIV suppression in treatment-experienced patients whose viral load is undetectable for 3 to 6 months. Novel agents with different mechanism of action and long half-life extending dosing interval are being tested in phase 2 and 3 clinical trials. This review summarizes the data of efficacies and safety profiles of LA CAB with RPV regimen, and also new long-acting injectable antiretroviral agents in pipeline.

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Section: Cabotegravir: Integrase Strand Transfer Inhibitorsupporting

confidence: 63%

Section: Cabotegravir: Integrase Strand Transfer Inhibitormentioning

confidence: 99%

Section: Cabotegravir: Integrase Strand Transfer Inhibitormentioning

confidence: 99%

Section: Cabotegravir: Integrase Strand Transfer Inhibitormentioning

confidence: 99%

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Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention

Kim

2021

Infect Chemother

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“…Long-acting CAB and RPV are currently recommended with an OLI to ensure the medications are well tolerated before transition to the long-acting formulations. Given there were no safety signals during the OLI in the clinical trials, direct to injection options are currently being evaluated in ongoing studies, and early data suggest that an ART switch to long-acting therapy is safe and effective when administered without an OLI [ 24 ▪ ].…”

Section: Cabotegravir and Rilpivirine For The Treatment Of Hivmentioning

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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Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

Gandhi

Bedimo

Hoy

et al. 2023

JAMA

251

148

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ImportanceRecent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice.ObjectiveBased on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection.Evidence ReviewA panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered.FindingsInitiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor–containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential.Conclusions and RelevanceAdvances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.

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Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study

Cited by 76 publications

References 27 publications

Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention

Long-Acting Injectable Antiretroviral Agents for HIV Treatment and Prevention

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

Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

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