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 084 (N=3224) was a randomized, double-blind, placebo-controlled superiority trial conducted in 20 sites around sub-Saharan Africa to evaluate the safety and efficacy of APRETUDE compared with daily oral TDF/FTC for HIV-1 prevention exclusively in cisgender women.^1,2 See details below.

FTC=emtricitabine; TDF=tenofovir disoproxil fumarate.

HPTN 084: Trial Design

The first and only long-acting, injectable PrEP study exclusively in cisgender women¹

Selected inclusion criteria²:

Cisgender women, 18-45 years old
HIV-1 negative at screening and enrollment
At high risk of sexually acquiring HIV-1 infection
Negative pregnancy test (if of reproductive potential)
Use of long-acting contraception (if not sterile or with history of hysterectomy)

Selected exclusion criteria²:

History of liver disease
Pregnant or currently breastfeeding

Trial Design and Primary Endpoint^1,2

*Optional oral lead-in, if used, should be taken for approximately 1 month (at least 28 days).¹

Primary endpoint:

Incidence of HIV-1 infections¹

The blinded phase of the trial was stopped early based on efficacy results at the first preplanned interim analysis²

HPTN 084: Selected Baseline Characteristics

Selected Baseline Characteristics^1,2

IQR=interquartile range.

HPTN 084: Efficacy

In a clinical trial¹

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

Significantly Lower Incidence of HIV-1 Infection vs a Daily Oral PrEP

Hazard ratio (95% CI): 0.10 (0.04-0.27); P<0.0001. APRETUDE incidence rate 0.15/100 person-years vs 1.85/100 person-years for TDF/FTC.

^†An initial analysis showed 4 incident infections in the APRETUDE arm (hazard ratio [95% CI]: 0.12 [0.05-0.31]). Retrospective testing showed 1 of the 4 to be a prevalent infection, resulting in 3 incident infections.¹

Resistance

Of the infections in the APRETUDE arm, no major INSTI resistance-associated mutations were detected¹
Of the incident infections in the TDF/FTC arm, NRTI resistance-associated mutations were detected in 1 of the participants³

Incident infections were infections which occurred over time among subjects uninfected at enrollment.

Prevalent infections were infections present (but unrecognized/undiagnosed) at enrollment subsequently identified on retrospective testing.

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

In a clinical trial¹

APRETUDE delivered superior efficacy with significantly lower incidence of HIV-1 infection vs a daily oral PrEP

Cumulative Incidence of HIV-1 Infections in HPTN 084

Subgroup Analysis

Based on an analysis of prespecified subgroups and populations¹

APRETUDE demonstrated a consistent protective benefit across age and BMI groups vs a daily oral PrEP

Incidence of HIV-1 Infection by Age

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

Incidence of HIV-1 Infection by BMI

BMI=body mass index.

HPTN 084: Resistance Profile

Resistance mutations

No resistance-associated mutations were detected in participants receiving APRETUDE
Of the prevalent infections in the APRETUDE arm, there were no major INSTI resistance-associated mutations detected³
Of the prevalent infections in the TDF/FTC arm, there were no major NRTI resistance-associated mutations detected³

HPTN 084: Adherence Subset Analysis

Based on an analysis of TFV plasma levels in a subset of the TDF/FTC arm²

Plasma levels revealed that some participants did not achieve recommended levels of tenofovir

Detectable Levels of Tenofovir²

Figure shows the proportion of a randomly selected subset of participants (n=375) in the TDF/FTC arm with drug concentrations measured in plasma that reflects use of tenofovir over the previous 1 to 2 weeks.²

Centers for Disease Control and Prevention guidelines recommend cisgender women taking daily oral PrEP be 100% adherent, meaning 7 days a week⁴

TFV=tenofovir.; W=week.

TFV=tenofovir; W=week.

Continue the Efficacy Story

References:

APRETUDE [package insert]. Research Triangle Park, NC: ViiV Healthcare; 2021.
Delany-Moretlwe S; HPTN 084 Study Team. Long acting injectable cabotegravir is safe and effective in preventing HIV infection in cisgender women: results from HPTN 084. Presented at: HIV R4P Virtual Conference; January 27, 2021. Abstract LB1479.
Marzinke MA, Delany-Moretlwe S, Agyei Y; HPTN 084 Study Team. Long-acting injectable PrEP in women: laboratory analysis of HIV infections in HPTN 084. Poster presented at: 11th International AIDS Society Conference on HIV Science; July 18-21, 2021. Virtual
Centers for Disease Control and Prevention. Preexposure Prophylaxis for the Prevention of HIV Infection in the United States: 2021 Update. December 2021. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf

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IMPORTANT SAFETY INFORMATION

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

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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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Trademarks are owned by or licensed to the

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CBTWCNT220014 September 2022 Produced in USA.

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