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, 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

baseline chart
FLAIR TRIAL DESIGN1-3
  • 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)

chart
CABENUVA efficacy data

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

confirmed virologic
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 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
4 or more doses per week are anticipated to provide high levels of protection against HIV-1 acquisition for MSM.​ 6
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.
fmol=femtomole.

References:

  1. 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 
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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:

  1. 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 
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

CBTWCNT230016