APRETUDE OFFERED MORE POWERFUL HIV PROTECTION

VS TRUVADA in HPTN 083 cisgender men and transgender women

HPTN=HIV Prevention Trials Network.

Trial design and primary endpoint
Noninferiority trial included the prespecified ability to test for superiority of APRETUDE over TRUVADA^1-3

Primary endpoint: Incidence of HIV-1 infection

Selected inclusion criteria¹:

Cisgender men and transgender women who have sex with men and are at high risk of sexually acquiring HIV-1 infection

Age ≥18

HIV-1 negative at screening and enrollment

Selected exclusion criteria¹:

Active or recent (90 days prior to enrollment) illicit intravenuous drug use

Current or chronic history of liver disease⁴

Surgically placed or injected buttock implants or fillers

*Oral lead-in up to 5 weeks. Study arms included: TRUVADA (300-mg TDF/200-mg FTC) tablet once daily and oral APRETUDE placebo once daily; oral APRETUDE (30-mg) tablet once daily and TRUVADA placebo once daily.

^†Optional oral lead-in, if used, should be taken for at least 28 days.

TDF/FTC=tenofovir disoproxil fumarate/emtricitabine.

Select baseline characteristics¹

^‡The APRETUDE Prescribing Information indicates n=2281 for the APRETUDE arm and n=2285 for the TRUVADA arm.

IQR=interquartile range.

SUPERIOR HIV PROTECTION VS TRUVADA IN HPTN 083

Fewer HIV-1 acquisitions

69% reduction in the risk of acquiring HIV-1 with APRETUDE (0.37/100 person-years) vs TRUVADA (1.22/100 person-years) (HR [95% CI]: 0.31 [0.16-0.58]; P=0.0003)

CI=confidence interval; HR=hazard ratio.

Don’t patients deserve to know that APRETUDE offered more powerful HIV protection vs TRUVADA?

THE APRETUDE CLINICAL TRIALS WERE STOPPED EARLY DUE TO HIGH EFFICACY VS TRUVADA^1,5,6

The independent Data and Safety Monitoring Board recommended the study sponsor stop the blinded phase of the trials and share the results^6,7

According to protocol amendments, study participants were given a choice between either open-label APRETUDE or TRUVADA following the unblinded phase^7,8

Choose the powerful HIV protection of APRETUDE for your patients

See HPTN 083 safety data

CONSISTENT PROTECTION ACROSS DIVERSE PATIENT GROUPS IN HPTN 083

The results from these prespecified subgroup analyses were consistent with the overall protective effect of APRETUDE

RESISTANCE DATA

Of the prevalent infections, 1 INSTI-associated mutation was detected in the APRETUDE arm and 2 NRTI-associated mutations were detected in the TRUVADA arm¹⁰

HIV-1 RNA testing may allow for earlier detection of HIV, potentially reducing the risk of resistance while on PrEP¹¹

^§R263K (n=1), E138A+Q148R (n=1), G140A+Q148R (n=1), L74I+E138E/K+G140G/S+Q148R+E157Q (n=1).

^||M184l (n=1), M184V (n=2), K65R (n=1).

INSTI=integrase strand transfer inhibitor; NRTI=nucleoside/nucleotide reverse transcriptase inhibitor; RAM=resistance-associated mutation.

Review data from HPTN 084, the trial in cisgender women.

See the data

View expert discussion from colleagues

Watch Dr Theo Hodge discuss the efficacy and safety of APRETUDE.

View all videos

Real HCP compensated by ViiV Healthcare.

Video still of Dr Hodge, an African American male physician

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References:

Landovitz RJ, Donnell D, Clement ME, et al. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med. 2021;385(7):595-608. doi:10.1056/NEJMoa2101016
Clement ME, Zhe W, Fichtenbaum C, et al. Pre-exposure prophylaxis product choice in US participants in HPTN 083. Poster Presented at: Conference on Retroviruses and Opportunistic Infections; February 19-22, 2023; Seattle, WA. Accessed March 1, 2024. https://www.croiconference.org/abstract/pre-exposure-prophylaxis-product-choice-in-us-participants-in-hptn-083
Delany-Moretlwe S, Hanscom B, Angira F, et al. Initial PrEP product choice: results from the HPTN 084 open-label extension. Abstract presented at: lAS 2023; July 26, 2023; Brisbane, Australia. Accessed March 1, 2024. https://www.hptn.org/sites/default/files/inline-files/220725%20IAS%202023%20product%20choice%20revised.pdf
Safety and efficacy study of injectable cabotegravir compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC), for pre-exposure prophylaxis in HIV-uninfected cisgender men and transgender women who have sex with men. Clinical Trials.gov. November 2023. Accessed January 26, 2024. https://clinicaltrials.gov/study/NCT02720094
Delany-Moretlwe S, Hughes JP, Bock P, et al. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet. 2022;399(10337):1779-1789. doi:10.1016/S0140-6736(22)00538-4
HPTN 084 Study Demonstrates Superiority of CAB LA to Oral TDF/FTC for the Prevention of HIV in cisgender women in sub-Saharan Africa. HIV Prevention Trials Network. Accessed January 26, 2024. https://www.hptn.org/sites/default/files/inline-files/HPTN%20084%20DSMB%20FAQ_V1.0_8Nov2020_0.pdf
Global HIV prevention study to stop early after ViiV Healthcare’s long-acting injectable formulation of cabotegravir dosed every two months shows higher efficacy than daily oral prep. News release. ViiV; May 18, 2020. Accessed October 12, 2023. https://viivhealthcare.com/en-us/media-center/news/press-releases/2020/may/global-hiv-prevention-study-to-stop-early-after-viiv-healthcares
HIV Prevention Trials Network. HPTN 084: A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women (protocol version 5.0; October 6, 2023). Accessed February 29, 2024. https://www.hptn.org/research/studies/hptn084
Data on file, ViiV Healthcare.
Marzinke MA, Grinsztejn B, Fogel JM, et al. Characterization of human immunodeficiency virus (HIV) infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083. J Infect Dis. 2021;224(9):1581-1592. doi:10.1093/infdis/jiab152
Eshleman S, Fogel JM, Halvas EK, et al. CAB-LA PrEP: Early detection of HIV infection may reduce INSTI resistance risk. Abstract presented at: Conference on Retroviruses and Opportunistic Infections; February 12-16, 2022; Virtual. Accessed March 1, 2024. https://www.croiconference.org/abstract/cab-la-prep-early-detection-of-hiv-infection-may-reduce-insti-resistance-risk

INDICATION

APRETUDE is indicated for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection in adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition. Individuals must have a negative HIV-1 test prior to initiating APRETUDE (with or without an oral lead-in with oral cabotegravir) for HIV-1 PrEP.

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION

INDICATION

IMPORTANT SAFETY INFORMATION

BOXED WARNING: RISK OF DRUG RESISTANCE WITH USE OF APRETUDE FOR HIV-1 PRE-EXPOSURE PROPHYLAXIS (PrEP) IN UNDIAGNOSED HIV-1 INFECTION

Individuals must be tested for HIV-1 infection prior to initiating APRETUDE or oral cabotegravir, and with each subsequent injection of APRETUDE, using a test approved or cleared by the FDA for the diagnosis of acute or primary HIV-1 infection. Drug-resistant HIV-1 variants have been identified with use of APRETUDE by individuals with undiagnosed HIV-1 infection. Do not initiate APRETUDE for HIV-1 PrEP unless negative infection status is confirmed. Individuals who acquire HIV-1 while receiving APRETUDE for PrEP must transition to a complete HIV-1 treatment regimen.

CONTRAINDICATIONS

Do not use APRETUDE in individuals:
- with unknown or positive HIV-1 status
- with previous hypersensitivity reaction to cabotegravir
- receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifampin, and rifapentine

WARNINGS AND PRECAUTIONS
Comprehensive Management to Reduce the Risk of HIV-1 Infection:

Use APRETUDE as part of a comprehensive prevention strategy, including adherence to the administration schedule and safer sex practices, including condoms, to reduce the risk of sexually transmitted infections (STIs). APRETUDE is not always effective in preventing HIV-1 acquisition. Risk for HIV-1 acquisition includes, but is not limited to, condomless sex, past or current STIs, self-identified HIV risk, having sexual partners of unknown HIV-1 viremic status, or sexual activity in a high prevalence area or network. Inform, counsel, and support individuals on the use of other prevention measures (e.g., consistent and correct condom use; knowledge of partner[s] HIV-1 status, including viral suppression status; regular testing for STIs)
Use APRETUDE only in individuals confirmed to be HIV-1 negative. HIV-1 resistance substitutions may emerge in individuals with undiagnosed HIV-1 infection who are taking only APRETUDE, because APRETUDE alone does not constitute a complete regimen for HIV-1 treatment. Prior to initiating APRETUDE, ask seronegative individuals about recent (in past month) potential exposure events and evaluate for current or recent signs or symptoms consistent with acute HIV-1 infection (e.g., fever, fatigue, myalgia, skin rash). If recent (<1 month) exposures to HIV-1 are suspected or clinical symptoms consistent with acute HIV-1 infection are present, use a test approved or cleared by the FDA as an aid in the diagnosis of acute HIV-1 infection
When using APRETUDE, HIV-1 testing should be repeated prior to each injection and upon diagnosis of any other STIs
Additional HIV testing to determine HIV status is needed if an HIV-1 test indicates possible HIV-1 infection or if symptoms consistent with acute HIV-1 infection develop following an exposure event. If HIV-1 infection is confirmed, then transition the individual to a complete HIV-1 treatment
Counsel individuals without HIV-1 to strictly adhere to the recommended dosing and testing schedule for APRETUDE

Potential Risk of Resistance with APRETUDE:

There is a potential risk of developing resistance to APRETUDE if an individual acquires HIV-1 either before, while taking, or following discontinuation of APRETUDE. To minimize this risk, it is essential to clinically reassess individuals for risk of HIV-1 acquisition and to test before each injection to confirm HIV-1–negative status. Individuals who are confirmed to have HIV-1 infection must transition to a complete HIV-1 treatment. If individuals at continuing risk of HIV-1 acquisition discontinue APRETUDE, alternative forms of PrEP should be considered and initiated within 2 months of the final injection of APRETUDE

Long-Acting Properties and Potential Associated Risks with APRETUDE:

Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to 12 months or longer). Take the prolonged-release characteristics of cabotegravir into consideration and carefully select individuals who agree to the required every-2-month injection dosing schedule because non-adherence or missed doses could lead to HIV-1 acquisition and development of resistance

Hypersensitivity Reactions:

Serious or severe hypersensitivity reactions have been reported in association with other integrase inhibitors and could occur with APRETUDE
Discontinue APRETUDE immediately if signs or symptoms of hypersensitivity reactions develop. Clinical status, including liver transaminases, should be monitored and appropriate therapy initiated

Hepatotoxicity:

Hepatotoxicity has been reported in a limited number of individuals receiving cabotegravir with or without known pre-existing hepatic disease or identifiable risk factors
Clinical and laboratory monitoring should be considered and APRETUDE should be discontinued if hepatotoxicity is suspected and individuals managed as clinically indicated

Depressive Disorders:

Depressive disorders (including depression, depressed mood, major depression, persistent depressive disorder, suicidal ideation or attempt) have been reported with APRETUDE
Promptly evaluate patients with depressive symptoms

Risk of Reduced Drug Concentration of APRETUDE Due to Drug Interactions:

The concomitant use of APRETUDE and other drugs may result in reduced drug concentration of APRETUDE
Refer to the full Prescribing Information for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during use of, and after discontinuation of APRETUDE; review concomitant medications during use of APRETUDE

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥1%, all grades) with APRETUDE were injection site reactions, diarrhea, headache, pyrexia, fatigue, sleep disorders, nausea, dizziness, flatulence, abdominal pain, vomiting, myalgia, rash, decreased appetite, somnolence, back pain, and upper respiratory tract infection.

DRUG INTERACTIONS

Refer to the full Prescribing Information for important drug interactions with APRETUDE
Drugs that induce UGT1A1 may significantly decrease the plasma concentrations of cabotegravir

USE IN SPECIFIC POPULATIONS

Lactation: Assess the benefit-risk of using APRETUDE to the infant while breastfeeding due to the potential for adverse reactions and residual concentrations in the systemic circulation for up to 12 months or longer after discontinuation
Pediatrics: Not recommended in individuals weighing less than 35 kg

Please see full Prescribing Information, including Boxed Warning, for APRETUDE.

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PMUS-CBTWCNT240070 October 2024

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