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 Clinical Trial

HPTN 084 (N=3224) was a randomized, double-blind, active-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 in adult cisgender women.1 See details below.

TDF/FTC=tenofovir disoproxil fumarate/emtricitabine.

HPTN 084 Trial Design

Trial design and primary endpoint1


Primary endpoint:
Incidence of HIV-1 infection

Selected inclusion criteria1:

  • Cisgender women, 18 to 45 years old
  • HIV-1 negative at screening and enrollment
  • At high risk of sexually acquiring HIV-1 infection
  • Negative pregnancy test
  • Use of long-acting contraception

Selected exclusion criteria:

  • History of liver disease1,2
  • Pregnant or currently breastfeeding1

*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 084 selected baseline characteristics1

chart
chart

 

  • At baseline, >99% of participants were non-white cisgender women and ~50% were <25 years of age 

All participants were assigned female sex at birth; 2 identified as transgender male; 3 identified as male. 
BMI=body mass index; IQR=interquartile range.

HPTN 084 Efficacy

In a clinical trial

APRETUDE delivered superior efficacy with significantly lower 

incidence of HIV-1 infection vs a daily oral PrEP (TDF/FTC)
 

90%
CABENUVA efficacy data

Resistance

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

§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.

 

CI=confidence interval; INSTI=integrase strand transfer inhibitor; NRTI=nucleoside/nucleotide reverse transcriptase inhibitor; PrEP=pre-exposure prophylaxis; TDF/FTC=tenofovir disoproxil fumarate/emtricitabine.

 

Cumulative incidence of HIV-1 infections in HPTN 084

Cumulative events are the overall number of HIV infections in each arm over time.​ 4

HPTN 084 Efficacy Subgroups

Based on an analysis of prespecified subgroups and populations

APRETUDE demonstrated a consistent protective benefit across age and BMI groups vs a daily oral PrEP (TDF/FTC)

Incidence of HIV-1 infection by age

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

Incidence of HIV-1 infection by BMI

BMI=body mass index.

HPTN 084 Resistance Profile

Resistance mutations3

 
  • No resistance-associated mutations (RAMs) were detected in participants receiving APRETUDE3 
  • Of the infections in the APRETUDE arm, no major INSTI RAMs were detected3
  • Of the incident infections in the TDF/FTC arm, NRTI RAMs were detected in 1 of the participants3

 

HPTN 084 Adherence Subset

Based on an analysis of tenofovir concentrations in dried blood spots from a randomly selected subset of 405 participants in the TDF/FTC arm (secondary endpoint)1,4

82% 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.
CDC guidelines recommend cisgender women taking daily oral PrEP be 100% adherent, meaning 7 days a week.​ 5
CDC guidelines recommend cisgender women taking daily oral PrEP be 100% adherent, meaning 7 days a week.​ 5
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.
CDC=Centers for Disease Control and Prevention; fmol=femtomole.

References:

  1. Delany-Moretlwe S, Hughes JP, Bock P, et al; HPTN 084 study group. 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
  2. Evaluating the safety and efficacy of long-acting injectable cabotegravir compared to daily oral TDF/FTC for pre-exposure prophylaxis in HIV-uninfected women. ClinicalTrials.gov identifier: NCT03164564. Published May 23, 2017. Updated November 3, 2021. Accessed March 3, 2023. https://clinicaltrials.gov/ct2/
    show/NCT03164564
  3. Eshleman SH, Fogel JM, Piwowar-Manning E, et al. Characterization of HIV infections in women who received injectable cabotegravir or tenofovir disoproxil fumarate/emtricitabine for HIV prevention: HPTN 084. J Infect Dis. 2022;225(10):1741-1749. doi:10.1093/infdis/jiab57
  4. HIV Prevention Trials Network. HPTN 084: A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) for Pre-Exposure Prophylaxis in HIV-Uninfected Women (protocol version 3.0; August 12, 2021). March 3, 2023. https://www.hptn.org/
    research/studies/
    hptn084#views-field-field-
    public-files
  5. 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

 

References:

  1. Delany-Moretlwe S, Hughes JP, Bock P, et al; HPTN 084 study group. 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
  2. Evaluating the safety and efficacy of long-acting injectable cabotegravir compared to daily oral TDF/FTC for pre-exposure prophylaxis in HIV-uninfected women. ClinicalTrials.gov identifier: NCT03164564. Published May 23, 2017. Updated November 3, 2021. Accessed March 3, 2023. https://clinicaltrials.gov/ct2/show/NCT03164564
  3. Eshleman SH, Fogel JM, Piwowar-Manning E, et al. Characterization of HIV infections in women who received injectable cabotegravir or tenofovir disoproxil fumarate/emtricitabine for HIV prevention: HPTN 084. J Infect Dis. 2022;225(10):1741-1749. doi:10.1093/infdis/jiab57
  4. HIV Prevention Trials Network. HPTN 084: A Phase 3 Double Blind Safety and Efficacy Study of Long-Acting Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC) for Pre-Exposure Prophylaxis in HIV-Uninfected Women (protocol version 3.0; August 12, 2021). March 3, 2023. https://www.hptn.org/research/studies/hptn084#views-field-field-public-files
  5. 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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