For HIV-1–negative, at-risk adults and adolescents weighing at least 35 kg for PrEP to reduce the risk of sexually acquired HIV-1. See full Indication.

HPTN 083 (N=4566) was a randomized, double-blind, active-controlled noninferiority trial conducted in 43 sites around the world to evaluate the safety and efficacy of APRETUDE compared with daily oral TDF/FTC for HIV-1 prevention in adult cisgender men and transgender women who have sex with men. The trial included the prespecified ability to test for superiority of APRETUDE over TDF/FTC.¹ See details below.

TDF/FTC=tenofovir disoproxil fumarate/emtricitabine.

HPTN 083 Trial Design

Trial design and primary endpoint¹

Primary endpoint: Incidence of HIV-1 infection¹

Selected inclusion criteria:

HIV-1 negative at screening and enrollment
Age ≥18¹
At high risk of sexually acquiring HIV-1 infection¹

Selected exclusion criteria:

Active or recent (90 days prior to enrollment) illicit intravenous drug use¹
Current or chronic history of liver disease²
Surgically placed or injected buttock implants or fillers¹

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

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

HPTN 083 selected baseline characteristics¹

Participants in the US were inclusive of the Black/African American and Latino communities of men and transgender women who have sex with men, who constitute the greatest percentage of new HIV diagnoses³

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

IQR=interquartile range.

HPTN 083 Efficacy

In a clinical study

APRETUDE delivered superior efficacy with significantly lower incidence of HIV-1 infection vs a daily oral PrEP (TDF/FTC)

Resistance

Of the incident and prevalent infections in the APRETUDE arm, INSTI resistance-associated mutations (RAMs) were detected in 4 and 1 participant(s), respectively⁴
Of the TDF/FTC incident and prevalent infections, NRTI RAMs were detected in 4 and 2 participants, respectively⁴

^§An initial analysis showed 13 incident infections in the APRETUDE arm (hazard ratio [95% CI]: 0.34 [0.18-0.62]). Retrospective testing showed 1 of the 13 to be a prevalent infection, resulting in 12 incident infections.

CI=confidence interval; INSTI=integrase strand transfer inhibitor; NRTI=nucleoside/nucleotide reverse transcriptase inhibitor;

PrEP=pre-exposure prophylaxis.

Cumulative incidence of HIV-1 infections in HPTN 083

Cumulative events are the overall number of HIV infections in each arm over time. ⁵

HPTN 083 Efficacy Subgroups

Based on an analysis of prespecified subgroups and populations

A consistent protective benefit was seen across all subgroups studied with APRETUDE vs a daily oral PrEP (TDF/FTC)

Pooled analysis of incidence of injection site reactions from Week 4 to Week 48

The results from these prespecified subgroup analyses were consistent with the overall protective effect¹

^||Cisgender MSM and transgender women who have sex with men.

MSM=men who have sex with men;
PY=person-year.

HPTN 083 Resistance Profile

Resistance mutations

Of the incident and prevalent infections in the APRETUDE arm, INSTI resistance-associated mutations (RAMs) were detected in 4 and 1 participant(s), respectively⁴
Of the incident and prevalent infections in the TDF/FTC arm, NRTI RAMs were detected in 4 and 2 participants, respectively⁴

HPTN 083 Adherence Subset

Based on an analysis of tenofovir concentrations in dried blood spots from a randomly selected subset of 390 participants in the TDF/FTC arm (tertiary endpoint)⁵

28% of participants appeared to take ≤4 TDF/FTC doses per week¹

Over the 153-week study period ¹

Figure shows the proportion of participants with drug concentrations measured in dried blood spots reflecting ≤4 doses/week (<700 fmol/punch) or 4-7 doses/week (≥700 fmol/punch) tenofovir use over the previous 1 to 2 months. ¹

Individuals should strictly adhere to the recommended dosing schedule for prescribed PrEP.

4 or more doses per week are anticipated to provide high levels of protection against HIV-1 acquisition for MSM. ⁶

Individuals should strictly adhere to the recommended dosing schedule for prescribed PrEP.

fmol=femtomole.

References:

Landovitz RJ, Donnell D, Clement ME, et al; HPTN 083 Study Team. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med. 2021;385(7):595-608. doi:10.1056/NEJMoa2101016
Injectable cabotegravir compared to TDF/FTC for PrEP in HIV-uninfected men and transgender women who have sex with men. ClinicalTrials.gov identifier: NCT02720094. Published March 25, 2016. Updated September 23, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/record/NCT02720094
Centers for Disease Control and Prevention. HIV Surveillance Report, 2020. Vol 33. May 2022. Updated May 24, 2022. Accessed March 3, 2023. https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-33/index.html
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
HIV Prevention Trials Network. HPTN 083: A Phase 2b/3 Double Blind 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 (protocol version 4.0; February 10, 2021). Accessed March 3, 2023. https://www.hptn.org/research/studies/hptn083#views-field-field-public-files
Centers for Disease Control and Prevention. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States: 2021 Update. December 2021. Accessed May 1, 2023. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf

References:

Landovitz RJ, Donnell D, Clement ME, et al; HPTN 083 Study Team. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med. 2021;385(7):595-608. doi:10.1056/NEJMoa2101016
Injectable cabotegravir compared to TDF/FTC for PrEP in HIV-uninfected men and transgender women who have sex with men. ClinicalTrials.gov identifier: NCT02720094. Published March 25, 2016. Updated September 23, 2022. Accessed December 8, 2022. https://clinicaltrials.gov/ct2/show/record/NCT02720094
Centers for Disease Control and Prevention. HIV Surveillance Report, 2020. Vol 33. May 2022. Updated May 24, 2022. Accessed March 3, 2023. https://www.cdc.gov/hiv/library/reports/hiv-surveillance/vol-33/index.html
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
HIV Prevention Trials Network. HPTN 083: A Phase 2b/3 Double Blind 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 (protocol version 4.0; February 10, 2021). Accessed March 3, 2023. https://www.hptn.org/research/studies/hptn083#views-field-field-public-files
Centers for Disease Control and Prevention. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States: 2021 Update. December 2021. Accessed May 1, 2023. https://www.cdc.gov/hiv/pdf
/risk/prep/cdc-hiv-prep-
guidelines-2021.pdf

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ARROW

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 become infected with 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 HIV-1 uninfected individuals 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

INDICATION

APRETUDE is indicated in at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. 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.

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

CBTWCNT230020

To report SUSPECTED ADVERSE REACTIONS, contact ViiV Healthcare at
1-877-844-8872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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CBTWCNT230014 April 2023 Produced in USA.

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