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APRETUDE DEMONSTRATED SUPERIOR EFFICACY VS DAILY ORAL TDF/FTC ACROSS DIVERSE POPULATIONS IN TWO LARGE CLINICAL TRIALS[1-3]

HIV Prevention Trials Network (HPTN) 083 and HPTN 084 were randomised, double-blind, double-dummy, active-controlled, non-inferiority trials evaluating the efficacy and safety of APRETUDE compared with daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV-1 prevention.[1–3]

The study populations were cisgender men and transgender women who have sex with men (HPTN 083, N=4,566) and cisgender women (HPTN 084, N=3,224), and the primary efficacy endpoint was the rate of incident HIV-1 infection.[1–3]

HPTN 083 trial design[1–3]

Those in the APRETUDE arm had a 69% reduction in the risk of HIV-1 acquisition vs daily oral TDF/FTC (0.37 vs 1.22 per 100 person-years, HR [95% CI]: 0.31 [0.16–0.58], p=0.0003)*[1,13]

Adapted from Landovitz RJ et al. 2021.[2]

The blinded phase was stopped early by a Data Safety Monitoring Board for successfully meeting the specified objectives on 14 May 2020 for HPTN 083 and 5 November 2020 for HPTN 084.[4]

All study visits included an HIV rapid test, a laboratory-based HIV antigen and antibody test, assessment of adverse events, collection of plasma samples, and counselling on adherence and HIV risk reduction.[2,3]

HPTN trial populations included those disproportionately impacted by HIV-1[1–3,6–8]

HPTN 083 selected baseline characteristics[2]

0%
Men who have sex with men (n=3,992/4,566)
0%
Transgender women who have sex with men (n=570/4,566)
0%
18–29 years (n=3,080/4,566)
0%
30–39 years (n=1,048/4,566)
0%
Black or mixed ethnicity

APRETUDE demonstrated superior efficacy in reducing the risk of HIV-1 acquisition vs daily oral TDF/FTC[1–3,5–9]

Cisgender men and transgender women who have sex with men

Those in the APRETUDE arm had a 69% reduction in the risk of HIV-1 acquisition vs daily oral TDF/FTC (0.37 vs 1.22 per 100 person-years, HR [95% CI]: 0.31 [0.16–0.58], p=0.0003)*,[1,14]

Adapted from Summary of Product Characteristics and Data on File REF-244320

* Following the primary analysis of HPTN 083, extended retrospective virologic testing was performed to better characterise the timing of HIV-1 infections. As a result, one of the 13 incident infections in participants receiving APRETUDE was determined to be a prevalent infection. The original HR (95% CI) from the primary analysis is 0.34 (0.18–0.62).[1]

Few individuals developed resistance mutations with APRETUDE and daily oral TDF/FTC in HPTN 083†[1-2,9]

  • In the blinded phase of HPTN 083, integrase strand transfer inhibitor (INSTI) resistance-associated mutations (RAMs) were observed in <1% of participants in the APRETUDE arm (n=4/2,281). In the TDF/FTC arm, four participants had nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations (n=4/2,285)[1]
  • All participants who acquired breakthrough INSTI resistance were able to be suppressed using standard antiretroviral regimens (where data were available)[11]

APRETUDE was the preferred choice of pre-exposure prophylaxis (PrEP) regimen over daily oral TDF/FTC in participants entering the open-label extension (OLE) of HPTN 083[12]

Most participants chose APRETUDE over daily oral TDF/FTC as their preferred PrEP option to complete the study with.§,[12]

56.8% (2,592/4,566) of participants entered the HPTN 083 OLE phase and were offered a choice of CAB LA or TDF/FTC for HIV PrEP (n=2592)‡,[13]

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* Following the primary analysis of HPTN 083, extended retrospective virologic testing was performed to better characterise the timing of HIV-1 infections. As a result, one of the 13 incident infections in participants receiving APRETUDE was determined to be a prevalent infection. The original HR (95% CI) from the primary analysis is 0.34 (0.18–0.62).[1]

** Following the primary analysis of HPTN 084, extended retrospective virologic testing was performed to better characterise the timing of HIV-1 infections. As a result, one of the four incident infections in participants receiving APRETUDE was determined to be a prevalent infection. The original HR (95% CI) from the primary analysis is 0.12 (0.05–0.31).[1]

† From data collected during the blinded phase of HPTN 083 up to and including 14 May 2020.[2]

‡ From data collected during the blinded phase of HPTN 084 up to and including 5 November 2020.[3,7]

§ At a planned interim review, an independent data safety and monitoring board recommended the study be unblinded. The protocol was amended as an OLE in which participants were offered the choice to complete the study with open-label APRETUDE or daily oral TDF/FTC. 2,592/4,566 (56.8%) participants entered the HPTN 083 OLE phase and were offered a choice of CAB LA or daily TDF/FTC for HIV PrEP[13]

CI, confidence interval; HIV-1, human immunodeficiency virus type 1; HPTN, HIV Prevention Trials Network; HR, hazard ratio; INSTI, integrase strand transfer inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; OLE, open-label extension; PrEP, pre-exposure prophylaxis; RAM, resistance-associated mutation; TDF/FTC, tenofovir disoproxil fumarate/emtricitabine; US, United States.

References:

  1. Apretude (cabotegravir). Summary of Product Characteristics (SmPC)
  2. Landovitz RJ et al. N Engl J Med. 2021;385(7):1581–1592.
  3. Delany-Moretlwe S et al. Lancet. 2022;399(10337):1779–1789.
  4. The HIV Prevention Trials Network. HPTN 083. Available at: https://www.hptn.org/research/studies/hptn083. Accessed: April 2024.
  5. The HIV Prevention Trials Network. HPTN 084 Study Demonstrates Superiority of CAB LA to Oral TDF/FTC for the Prevention of HIV. Available at: https://www.hptn.org/news-and-events/press-releases/hptn-084-study-demonstrates-superiority-of-cab-la-to-oral-tdfftc-for. Accessed: April 2024.
  6. Clinical Trials Arena. APRETUDE (cabotegravir) for the Treatment of HIV-1 Pre-Exposure Prevention (PrEP). Available at: https://www.clinicaltrialsarena.com/projects/APRETUDE-cabotegravir-hiv-1-prep/. Accessed: April 2024.
  7. Mascolini M. Presentation at the 24th International AIDS Conference. 29 July–2 August 2022. Montreal, Canada.
  8. Scott H et al. Presentation at the 30th Conference on Retroviruses and Opportunistic Infections (CROI). 19–22 February 2023. Seattle, Washington, USA.
  9. Landovitz RJ et al. Poster presented at HIV Glasgow. 23–26 October 2022. Virtual and Glasgow, Scotland. O21.
  10. Marzinke MA et al. J Infect Dis. 2021;224:1581–1592.
  11. Marzinke MA et al. Antimicrob Agents Chemother. 2023;67(4):e0005323.
  12. Delany-Moretlwe S et al. Presented at IAS 2023. 23-26 July. Brisbane, Australia. 5998.
  13. Clement ME, et al. AIDS 2024, the 25th International AIDS Conference, 22 – 26 July, Munich, Germany & Virtual. Abstract 1341
  14. Data on File, REF-244320

PM-GB-CBT-WCNT-240003 November 2024

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