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, 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 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 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 Characteristics1,2

chart
chart

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

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

90%
CABENUVA efficacy data

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.

Incidence of HIV-1 Infection

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

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

Based on the efficacy results at a planned interim analysis, it was determined that the prespecified criteria for stopping the blinded portion of the trial had been met

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
chart

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

adherance
chart

 

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:

  1. APRETUDE [package insert]. Research Triangle Park, NC: ViiV Healthcare; 2021.
  2. 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.
  3. 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
  4. 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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