Injectable Cabotegravir Compared to TDF/FTC For PrEP in HIV-Uninfected Men and Transgender Women Who Have Sex With Men

NCT02720094 | Completed Phase 2 Results DMC

• 2 other identifiers: HPTN 08320725
• Study Type: interventional
• Target: 4,570
• Locations: 7 countries
• Sites: 43

Brief Summary

This study will evaluate the safety and efficacy of the injectable drug cabotegravir (CAB LA), for pre-exposure prophylaxis (PrEP) in HIV-uninfected cisgender men and transgender women who have sex with men (MSM and TGW).

Conditions

HIV Infections

Keywords

Pre-Exposure Prophylaxis; PrEP

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Documented Incident HIV Infections During Steps 1 and 2

  All HIV infections included in this analysis have been reviewed and confirmed by an independent, blinded Endpoint Adjudication Committee (EAC).

  HIV tests at enrollment, weeks 2, 4, 5, every injection visit (every 8 weeks) and every safety visit (2 weeks after each injection visit). Analyzed through week 153 or the date of DSMB decision to unblind all participants, whichever is earliest.

• Number of Participants Experiencing Grade 2 or Higher Clinical and Laboratory Adverse Events

  The primary safety endpoint analyses included Grade 2 or higher clinical and laboratory AEs during Steps 1 and 2.

  Treatment emergent AE* measured with onset date through participant's last study visit, or the date of DSMB decision to unblind all participants, whichever is earliest. Assessed at each visit (injections visits q 8 weeks and safety visits q 8 weeks).

Secondary Outcomes (13)

• Number of Participants With Documented Incident HIV Infections in Step 2

  HIV tests at enrollment, weeks 2, 4, 5, every injection visit (every 8 weeks) and every safety visit (2 weeks after each injection visit). Analyzed through week 153 or the date of DSMB decision to unblind all participants, whichever is earliest.

• Changes From Baseline in Creatinine and Creatinine Clearance Levels

  Reported week 57 (injection visit #8) and week 105 (injection visit #14)

• Number of Participants With Grade 3 or 4 Liver-related Adverse Events (AEs)

  Treatment emergent AE measured with onset date through participant's last study visit, or the date of DSMB decision to unblind all participants, whichever is first. Assessed at each visit. (Injection visits q 8 weeks and safety visits q 8 weeks)

• Incidence of Resistance Mutations to Study Products (Including But Not Limited to K65R, M184V/I, Q148R) Among Seroconverters

  Measured from date of detection of infection, up to 4 years after study entry, with timing/intervals as determined by the HPTN laboratory center

• Changes in Weight From Baseline

  Reported through the week 153 injection, or the date of DSMB decision to unblind all participants, whichever is earliest. Collected at each injection visit (every 8 weeks).

Study Arms (2)

Arm A

EXPERIMENTAL

In Step 1, participants will receive daily oral CAB and daily oral TDF/FTC placebo for 5 weeks. In Step 2, participants will receive CAB LA and daily oral TDF/FTC placebo to Week 153. In Step 3, participants will receive daily oral TDF/FTC starting at Week 153 and for 48 weeks.

Drug: Cabotegravir Oral Tablet; Drug: TDF/FTC tablets; Drug: Placebo for TDF/FTC tablets; Drug: CAB LA

Arm B

EXPERIMENTAL

In Step 1, participants will receive daily oral TDF/FTC and daily oral CAB placebo for 5 weeks. In Step 2, participants will receive daily oral TDF/FTC and placebo for CAB LA to Week 153. In Step 3, participants will receive daily oral TDF/FTC starting at Week 153 and for 48 weeks.

Drug: TDF/FTC tablets; Drug: Placebo for cabotegravir oral tablet; Drug: Placebo for CAB LA

Interventions

Cabotegravir Oral Tablet DRUG

30 mg tablet

Also known as: Oral cabotegravir

Arm A

TDF/FTC tablets DRUG

300 mg/200 mg fixed-dose combination tablets

Also known as: Truvada

Arm A; Arm B

Placebo for cabotegravir oral tablet DRUG

Also known as: Placebo for oral cabotegravir

Arm B

CAB LA DRUG

Administered as one 3 mL (600 mg) IM injection in the gluteal muscle at two time points 4 weeks apart and every 8 weeks thereafter

Also known as: Long acting cabotegravir, Injectable cabotegravir

Arm A

Placebo for CAB LA DRUG

Administered as one 3 mL IM injection in the gluteal muscle at two time points 4 weeks apart and every 8 weeks thereafter

Also known as: Placebo for long acting cabotegravir

Arm B

Placebo for TDF/FTC tablets DRUG

Also known as: Placebo for Truvada

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MSM and TGW, 18 years or older at the time of screening (male at birth)
• Willing to provide informed consent for the study
• At high risk for sexually acquiring HIV infection based on self-report of at least one of the following:
• Any condomless receptive anal intercourse in the 6 months prior to enrollment (condomless anal intercourse within a monogamous HIV seronegative concordant relationship does not meet this criterion)
• More than five partners in the 6 months prior to enrollment (regardless of condom use and HIV serostatus, as reported by the enrollee)
• Any stimulant drug use in the 6 months prior to enrollment
• Rectal or urethral gonorrhea or chlamydia or incident syphilis in the 6 months prior to enrollment
• SexPro score of less than or equal to 16 (U.S. sites only)
• In general good health, as evidenced by the following laboratory values, which must be from specimens obtained within 45 days prior to study enrollment:
• Non-reactive / negative HIV test results. More information on this criterion can be found in the protocol.
• Hemoglobin greater than 11 g/dL,
• Absolute neutrophil count greater than 750 cells/mm\^3
• Platelet count greater than or equal to 100,000/mm\^3
• Calculated creatinine clearance greater than or equal to 60 mL/minute using the Cockcroft-Gault equation (use sex at birth for calculation)
• Alanine aminotransferase (ALT) less than 2 times the upper limit of normal (ULN)

You may not qualify if:

• One or more reactive or positive HIV test result at Screening or Enrollment, even if HIV infection is not confirmed
• Active or recent use of any illicit intravenous drugs ("recent" defined as in the 90 days prior to enrollment)
• Co-enrollment in any other interventional research study or other concurrent studies that may interfere with this study (as provided by self-report or other available documentation. Exceptions may be made if appropriate after consultation with the CMC.)
• Clinically significant cardiovascular disease, as defined by history/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease
• Has a tattoo or other dermatological condition overlying the buttock region which in the opinion of the IoR or designee, in consultation with the CMC, may interfere with interpretation of injection site reactions
• Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy)
• Coagulopathy (primary or iatrogenic) which would contraindicate IM injection (concomitant anticoagulant or anti-platelet therapy use should be discussed with the CMC)
• Active or planned use of prohibited medications as described in the Investigator's Brochure or listed in the Study Specific Procedures (SSP) Manual (provided by self-report, or obtained from medical history or medical records). In particular, future use of TDF/FTC at any point during the study.
• Known or suspected allergy to study product components (active or placebo), including egg or soy products (egg and soy products are contained in Intralipid)
• Surgically-placed or injected buttock implants or fillers, per self-report. Contact the CMC for guidance regarding questions about individual cases.
• Alcohol or substance use that, in the opinion of the study investigator, would jeopardize the safety of the participant on study (e.g., provided by self-report, or found upon medical history and examination or in available medical records).
• History of seizure disorder, per self-report
• QTc interval (B or F) greater than 500 msec

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• ViiV Healthcare: collaborator
• Gilead Sciences: collaborator

Study Sites (43)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

UCLA Vine Street Clinic CRS

Los Angeles, California, 90024, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035, United States

Location

East Bay AIDS Center (EBAC) CRS

Oakland, California, 94609, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado CRS

Aurora, Colorado, 80045, United States

Location

George Washington Univ. CRS

Washington D.C., District of Columbia, 20037-1894, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Adolescent & Young Adult Research at The CORE Center (AYAR at CORE)

Chicago, Illinois, 60612, United States

Location

UIC Project WISH CRS

Chicago, Illinois, 60612, United States

Location

New Orleans Adolescent Trials Unit CRS

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21205, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Harlem Prevention Center CRS

New York, New York, 10027, United States

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

Bronx Prevention Research Center CRS

The Bronx, New York, 10451, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Greensboro CRS

Greensboro, North Carolina, 27401, United States

Location

Cincinnati Clinical Research Site

Cincinnati, Ohio, 45219, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, 38105-3678, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77030, United States

Location

Hospital General de Agudos JM Ramos Mejía CRS

Ciudad de Buenos Aires, Buenos Aires, C1221ADC, Argentina

Location

Fundacion Huesped CRS

Buenos Aires, C1202ABB, Argentina

Location

Hospital Nossa Senhora da Conceicao CRS

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Centro de Referencia e Treinamento DST/AIDS CRS

São Paulo, São Paulo, 04121-000, Brazil

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, 21040-360, Brazil

Location

Centro de Pesquisas Clínicas IC-HCFMUSP CRS

São Paulo, 05403-010, Brazil

Location

ACSA CRS

Iquitos, Maynas, 1, Peru

Location

CITBM - UNIDEC, Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS

Bellavista, Provincia Constitucional del Callao, 15081, Peru

Location

Via Libre CRS

Lima, 15001, Peru

Location

Barranco CRS

Lima, 15063, Peru

Location

San Miguel CRS

Lima, 32 - 15088, Peru

Location

Groote Schuur HIV CRS

Cape Town, Western Cape, 7925, South Africa

Location

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS

Pathum Wan, Bangkok, 10330, Thailand

Location

Silom Community Clinic CRS

Bangkok, Changwat Nonthaburi, 11000, Thailand

Location

CMU HIV Prevention CRS

Chiang Mai, 50202, Thailand

Location

Yen Hoa Health Clinic CRS

Hanoi, 100000, Vietnam

Location

Related Publications (7)

• Brown TT, Arao RF, Warsi M, Phanuphak N, Vasconcelos R, Oyedele T, Sullivan PA, Hanscom B, Rooney JF, Rinehart AR, McCauley M, Grinsztejn B, Landovitz RJ. Bone Changes With Long-Acting Cabotegravir or Tenofovir Disoproxil Fumarate/Emtricitabine for HIV Prevention in Cisgender Men and Transgender Women: HPTN 083. Clin Infect Dis. 2025 Dec 24;81(5):983-986. doi: 10.1093/cid/ciaf221.

  PMID: 40590452 DERIVED

• Psaros C, Goodman GR, Lee JS, Rice W, Kelley CF, Oyedele T, Coelho LE, Phanuphak N, Singh Y, Middelkoop K, Griffith S, McCauley M, Rooney J, Rinehart AR, Clark J, Go V, Sugarman J, Fields SD, Adeyeye A, Grinsztejn B, Landovitz RJ, Safren SA; HPTN 083-02 Study Team. HPTN 083-02: factors influencing adherence to injectable PrEP and retention in an injectable PrEP study. J Int AIDS Soc. 2024 May;27(5):e26252. doi: 10.1002/jia2.26252.

  PMID: 38783534 DERIVED

• Han K, Patel P, McCallister S, Rinehart AR, Gandhi Y, Spreen W, Landovitz RJ, Delany-Moretlwe S, Marzinke MA, McKeon T, Budnik P, van Wyk J, Ford SL. Long-acting cabotegravir pharmacokinetics with and without oral lead-in for HIV PrEP. Antimicrob Agents Chemother. 2024 Jun 5;68(6):e0147523. doi: 10.1128/aac.01475-23. Epub 2024 May 6.

  PMID: 38709006 DERIVED

• Landovitz RJ, Hanscom BS, Clement ME, Tran HV, Kallas EG, Magnus M, Sued O, Sanchez J, Scott H, Eron JJ, Del Rio C, Fields SD, Marzinke MA, Eshleman SH, Donnell D, Spinelli MA, Kofron RM, Berman R, Piwowar-Manning EM, Richardson PA, Sullivan PA, Lucas JP, Anderson PL, Hendrix CW, Adeyeye A, Rooney JF, Rinehart AR, Cohen MS, McCauley M, Grinsztejn B; HPTN 083 Study Team. Efficacy and safety of long-acting cabotegravir compared with daily oral tenofovir disoproxil fumarate plus emtricitabine to prevent HIV infection in cisgender men and transgender women who have sex with men 1 year after study unblinding: a secondary analysis of the phase 2b and 3 HPTN 083 randomised controlled trial. Lancet HIV. 2023 Dec;10(12):e767-e778. doi: 10.1016/S2352-3018(23)00261-8. Epub 2023 Nov 9.

  PMID: 37952550 DERIVED

• Marzinke MA, Hanscom B, Wang Z, Safren SA, Psaros C, Donnell D, Richardson PA, Sullivan P, Eshleman SH, Jennings A, Feliciano KG, Jalil E, Coutinho C, Cardozo N, Maia B, Khan T, Singh Y, Middelkoop K, Franks J, Valencia J, Sanchez N, Lucas J, Rooney JF, Rinehart AR, Ford S, Adeyeye A, Cohen MS, McCauley M, Landovitz RJ, Grinsztejn B; HPTN 083 study group. Efficacy, safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir for HIV pre-exposure prophylaxis in transgender women: a secondary analysis of the HPTN 083 trial. Lancet HIV. 2023 Nov;10(11):e703-e712. doi: 10.1016/S2352-3018(23)00200-X. Epub 2023 Sep 29.

  PMID: 37783219 DERIVED

• Landovitz RJ, Donnell D, Clement ME, Hanscom B, Cottle L, Coelho L, Cabello R, Chariyalertsak S, Dunne EF, Frank I, Gallardo-Cartagena JA, Gaur AH, Gonzales P, Tran HV, Hinojosa JC, Kallas EG, Kelley CF, Losso MH, Madruga JV, Middelkoop K, Phanuphak N, Santos B, Sued O, Valencia Huamani J, Overton ET, Swaminathan S, Del Rio C, Gulick RM, Richardson P, Sullivan P, Piwowar-Manning E, Marzinke M, Hendrix C, Li M, Wang Z, Marrazzo J, Daar E, Asmelash A, Brown TT, Anderson P, Eshleman SH, Bryan M, Blanchette C, Lucas J, Psaros C, Safren S, Sugarman J, Scott H, Eron JJ, Fields SD, Sista ND, Gomez-Feliciano K, Jennings A, Kofron RM, Holtz TH, Shin K, Rooney JF, Smith KY, Spreen W, Margolis D, Rinehart A, Adeyeye A, Cohen MS, McCauley M, Grinsztejn B; HPTN 083 Study Team. Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women. N Engl J Med. 2021 Aug 12;385(7):595-608. doi: 10.1056/NEJMoa2101016.

  PMID: 34379922 DERIVED

• Scarsi KK. Chasing the cabotegravir tail: implications for prevention. Lancet HIV. 2020 Jul;7(7):e451-e453. doi: 10.1016/S2352-3018(20)30165-X. Epub 2020 Jun 1. No abstract available.

  PMID: 32497490 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

cabotegravir; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: HPTN Statistical Manager
• Organization: HPTN Statistical & Data Management Center

HPTN-Data-Access@scharp.org

206-667-4004

Study Officials

• Raphael J. Landovitz, MD, MSc

  University of California, Los Angeles

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2016
• First Posted: March 25, 2016
• Study Start: December 19, 2016
• Primary Completion: May 14, 2020
• Study Completion: March 31, 2025
• Last Updated: March 19, 2026
• Results First Posted: November 24, 2023

Record last verified: 2026-03

Locations

PE (5); TH (3); VN (1); US (27); ZA (1); AR (2); BR (4)