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 Clinical Trial

HPTN 083 (N=4566) was a randomized, double-blind, placebo-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.1,2 See details below.

FTC=emtricitabine; TDF=tenofovir disoproxil fumarate.

HPTN 083: Trial Design

APRETUDE was studied in cisgender men and transgender women who have sex with men

Selected inclusion criteria:

  • HIV-1 negative at screening and enrollment1
  • Age ≥182
  • At high risk of sexually acquiring HIV-1 infection2

Selected exclusion criteria:

  • Active or recent (90 days prior to enrollment) illicit intravenous drug use2
  • Current or chronic history of liver disease3
  • Surgically placed or injected buttock implants or fillers2

Trial Design and Primary Endpoint1,2

chart
chart

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

Primary endpoint:

  • Incidence of HIV-1 infection1,2
  • Safety: Grade ≥2 clinical and laboratory events

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

HPTN 083: Selected Baseline Characteristics

Selected Baseline Characteristics2

baseline chart
FLAIR TRIAL DESIGN1-3

The APRETUDE Prescribing Information indicates n=2281 for the APRETUDE arm and n=2285 for the TDF/FTC arm.1

The APRETUDE Prescribing Information indicates n=2281 for the APRETUDE arm and n=2285 for the TDF/FTC arm.1

  • Participants in the US were inclusive of the Black/African American and Latinx communities of men and transgender women who have sex with men, who comprise the greatest percentage of new HIV diagnoses4

IQR=interquartile range.

HPTN 083: Efficacy

In a clinical study1

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

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

chart
CABENUVA efficacy data

Hazard ratio (95% CI): 0.31 (0.16-0.58); P=0.0003. APRETUDE incidence rate 0.37/100 person-years vs 1.22/100 person-years for TDF/FTC.

 

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.1

Resistance

  • Of the incident and prevalent infections in the APRETUDE arm, INSTI resistance-associated mutations (RAMs) were detected in 4 and 1 participants, respectively1,5
  • Of the incident and prevalent infections in the TDF/FTC arm, NRTI RAMs were detected in 4 and 2 participants, respectively5

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.

Incidence of HIV-1 Infection

In a clinical study1

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 083

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

Based on the efficacy results at the first preplanned interim analysis, it was determined that the prespecified criteria for stopping the blinded portion of the trial had been met2

Subgroup Analysis

Based on an analysis of prespecified subgroups and populations1

A consistent benefit was seen across all subgroups studied with APRETUDE vs a daily oral PrEP2

Incidence of HIV-1 Infection in Prespecified Subgroups

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

§Cisgender MSM and transgender women who have sex with men.

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

MSM=men who have sex with men; PY=patient-years; TGW=transgender women.

HPTN 083: Resistance Profile

Resistance mutations

confirmed virologic
resistance
  • Resistance developed in <1% of participants in HPTN 0831
  • Of the prevalent infections in the APRETUDE arm, INSTI resistance-associated mutations (RAMs) were detected in virus from 1 participant (E138K+Q148K)
  • Of the prevalent infections in the TDF/FTC arm, NRTI RAMs were detected in viruses from 2 participants [M184I (n=1); M184V/I (n=1)]

HPTN 083: Adherence Subset Analysis

Based on an exploratory analysis of dried blood spots in a subset of the TDF/FTC arm

Overall, on average, ~30% of participants did not achieve the minimum levels of tenofovir recommended

 

Figures show the proportion of a randomly selected subset of participants in the TDF/FTC arm (n=390) with drug concentrations measured in dried blood spots reflecting the average tenofovir use over the previous 1 to 2 months.5

Proportion of Participants With 4-7 TDF/FTC Doses/Week5

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

fmol=femtomole; W=week.

 

Figure shows the proportion of a randomly selected subset of participants in the TDF/FTC arm (n=390) with drug concentrations measured in dried blood spots reflecting the average tenofovir use over the previous 1 to 2 months.5

  • Individuals should strictly adhere to the recommended dosing schedule for prescribed PrEP1

fmol=femtomole.; W=week.

Continue the Efficacy Story

References:

  1. APRETUDE [package insert]. Research Triangle Park, NC: ViiV Healthcare; 2021.
  2. Landovitz RJ, Donnell D, Clement C, et al; for the HPTN 083 Study Team. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med. 2021;385:595-608. doi:10.1056/NEJMoa2101016
  3. 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. ClinicalTrials.gov identifier: NCT02720094. Published March 25, 2016. Updated August 4, 2020. Accessed August 6, 2021. https://clinicaltrials.gov/ct2/show/record/NCT02720094
  4. Centers for Disease Control and Prevention website. HIV Surveillance Report, 2019. Vol 32. May 2021. https://www.cdc.gov/hiv /library/reports/hiv-surveillance/vol-32/index.html
  5. 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:jiab152. doi:10.1093/infdis/jiab152

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