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, 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.
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
- 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.1
BMI=body mass index; IQR=interquartile range.
In a clinical trial
APRETUDE delivered superior efficacy with significantly lower
incidence of HIV-1 infection vs a daily oral PrEP (TDF/FTC)
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

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
Incidence of HIV-1 infection by BMI
BMI=body mass index.
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
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
References:
- 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
- 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 - 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
- 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
- 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:
- 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
- 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
- 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
- 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
- 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
CBTWCNT230016