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

NCT ID: NCT02720094

Last Updated: 2025-10-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

4570 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-19

Study Completion Date

2025-03-31

Brief Summary

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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).

Detailed Description

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The purpose of this study is to 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).

This study will enroll HIV-uninfected MSM and TGW at risk for acquiring HIV infection. Participants will be followed for a total of 4 years.

This study will take place in three steps. Participants will be randomly assigned to one of two arms:

Arm A:

Step 1: Participants will receive daily oral CAB tablets and daily oral TDF/FTC placebo tablets for 5 weeks.

Step 2: Participants will receive an intramuscular (IM) injection of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily oral TDF/FTC placebo tablets to Week 153.

Arm B:

Step 1: Participants will receive daily oral TDF/FTC tablets and daily oral CAB placebo tablets for 5 weeks.

Step 2: Participants will receive daily oral TDF/FTC tablets and an IM injection of placebo at two time points 4 weeks apart and every 8 weeks thereafter to Week 153.

In Step 3, all participants (Arms A and B) will receive daily oral TDF/FTC tablets starting at Week 153 (last day of Step 2)/Day 0 (first day of Step 3) and continue for 48 weeks.

Participants will attend up to 47 study visits throughout the study. Visits may include physical examinations, blood collection, urine collection, an electrocardiogram (ECG), and rectal swab collection. Some participants may have a bone mineral density-energy x-ray absorptimetry (DXA) scan at select visits.

All participants will be transitioned to locally available HIV prevention services, including services for PrEP, if available, at the end of their participation in the study.

HPTN 083-01 is a sub-study of HPTN 083. The purpose of this study is to evaluate the safety, tolerability, and acceptability of CAB LA for the prevention of HIV among adolescent males. Participants will receive oral CAB for 5 weeks, followed by 29 weeks on CAB LA, then quarterly visits for 48 weeks after final injection. All participants who have received at least one injection will be followed for 48 weeks after their last injection. Total study duration per participant will be approximately 21 months.

HPTN 083-02 is a qualitative sub-study of participants enrolled in HPTN 083. The purpose of this study is to explore potential barriers, facilitators, and potentially modifiable issues related to adherence to clinic visits in the context of injectable PrEP; to learn about preferences and decision making regarding the use of oral versus injectable PrEP, or other biomedical prevention products; and to gather explanatory qualitative data regarding participants' experiences in HPTN 083 to better interpret study results and guide next prevention strategies. Participants in this sub-study will complete one individual semi-structured qualitative interview.

Conditions

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HIV Infections

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Arm A

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.

Group Type EXPERIMENTAL

Cabotegravir Oral Tablet

Intervention Type DRUG

30 mg tablet

TDF/FTC tablets

Intervention Type DRUG

300 mg/200 mg fixed-dose combination tablets

Placebo for TDF/FTC tablets

Intervention Type DRUG

CAB LA

Intervention Type 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

Arm B

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.

Group Type EXPERIMENTAL

TDF/FTC tablets

Intervention Type DRUG

300 mg/200 mg fixed-dose combination tablets

Placebo for cabotegravir oral tablet

Intervention Type DRUG

Placebo for CAB LA

Intervention Type DRUG

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

Interventions

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Cabotegravir Oral Tablet

30 mg tablet

Intervention Type DRUG

TDF/FTC tablets

300 mg/200 mg fixed-dose combination tablets

Intervention Type DRUG

Placebo for TDF/FTC tablets

Intervention Type DRUG

Placebo for cabotegravir oral tablet

Intervention Type DRUG

CAB LA

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

Intervention Type DRUG

Placebo for CAB LA

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

Intervention Type DRUG

Other Intervention Names

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Oral cabotegravir Truvada Placebo for Truvada Placebo for oral cabotegravir Long acting cabotegravir Injectable cabotegravir Placebo for long acting cabotegravir

Eligibility Criteria

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Inclusion Criteria

* 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)

* Although not protocol exclusionary, sites should carefully consider the advisability of enrolling participants with calculated creatinine clearance between 60-70 mL/min, as limited changes in creatinine clearance during study conduct will lead to protocol-mandated product holds and may alter the risk-benefit considerations of study participation
* Alanine aminotransferase (ALT) less than 2 times the upper limit of normal (ULN)
* Total bilirubin less than or equal to 2.5 times ULN
* Hepatitis B virus (HBV) surface antigen (HBsAg) negative
* Hepatitis C virus (HCV) Ab negative
* No Grade 3 or higher laboratory abnormalities on any laboratory tests obtained at screening, including tests obtained as part of a panel of tests ordered to obtain the protocol-required laboratory test results.
* No medical condition that, in the opinion of the study investigator, would interfere with the conduct of the study (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
* Willing to undergo all required study procedures

Exclusion Criteria

* 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.)
* Past or current participation in HIV vaccine trial. An exception will be made for participants that can provide documentation of receipt of placebo (not active arm). Note: Past participation in a monoclonal antibody study is not exclusionary, effective as of Version 1.0 of HPTN 083.
* 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
* Inflammatory skin conditions that compromise the safety of intramuscular (IM) injections, per the discretion of the Investigator of Record. Mild skin conditions may not be exclusionary at the discretion of the Investigator of Record (IoR) or designee in consultation with the CMC
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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ViiV Healthcare

INDUSTRY

Sponsor Role collaborator

Gilead Sciences

INDUSTRY

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Raphael J. Landovitz, MD, MSc

Role: STUDY_CHAIR

University of California, Los Angeles

Locations

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Alabama CRS

Birmingham, Alabama, United States

Site Status

UCLA Vine Street Clinic CRS

Los Angeles, California, United States

Site Status

UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

East Bay AIDS Center (EBAC) CRS

Oakland, California, United States

Site Status

Bridge HIV CRS

San Francisco, California, United States

Site Status

Children's Hospital Colorado CRS

Aurora, Colorado, United States

Site Status

George Washington Univ. CRS

Washington D.C., District of Columbia, United States

Site Status

The Ponce de Leon Center CRS

Atlanta, Georgia, United States

Site Status

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, United States

Site Status

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

Chicago, Illinois, United States

Site Status

UIC Project WISH CRS

Chicago, Illinois, United States

Site Status

New Orleans Adolescent Trials Unit CRS

New Orleans, Louisiana, United States

Site Status

Johns Hopkins University CRS

Baltimore, Maryland, United States

Site Status

Fenway Health (FH) CRS

Boston, Massachusetts, United States

Site Status

Washington University Therapeutics (WT) CRS

St Louis, Missouri, United States

Site Status

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, United States

Site Status

Weill Cornell Chelsea CRS

New York, New York, United States

Site Status

Harlem Prevention Center CRS

New York, New York, United States

Site Status

New York Blood Center CRS

New York, New York, United States

Site Status

Bronx Prevention Research Center CRS

The Bronx, New York, United States

Site Status

Chapel Hill CRS

Chapel Hill, North Carolina, United States

Site Status

Greensboro CRS

Greensboro, North Carolina, United States

Site Status

Cincinnati Clinical Research Site

Cincinnati, Ohio, United States

Site Status

Ohio State University CRS

Columbus, Ohio, United States

Site Status

Penn Prevention CRS

Philadelphia, Pennsylvania, United States

Site Status

St. Jude Children's Research Hospital CRS

Memphis, Tennessee, United States

Site Status

Houston AIDS Research Team CRS

Houston, Texas, United States

Site Status

Hospital General de Agudos JM Ramos Mejía CRS

Ciudad de Buenos Aires, Buenos Aires, Argentina

Site Status

Fundacion Huesped CRS

Buenos Aires, , Argentina

Site Status

Hospital Nossa Senhora da Conceicao CRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Centro de Referencia e Treinamento DST/AIDS CRS

São Paulo, São Paulo, Brazil

Site Status

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS

Rio de Janeiro, , Brazil

Site Status

Centro de Pesquisas Clínicas IC-HCFMUSP CRS

São Paulo, , Brazil

Site Status

ACSA CRS

Iquitos, Maynas, Peru

Site Status

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

Bellavista, Provincia Constitucional del Callao, Peru

Site Status

Via Libre CRS

Lima, , Peru

Site Status

Barranco CRS

Lima, , Peru

Site Status

San Miguel CRS

Lima, , Peru

Site Status

Groote Schuur HIV CRS

Cape Town, Western Cape, South Africa

Site Status

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

Pathum Wan, Bangkok, Thailand

Site Status

Silom Community Clinic CRS

Bangkok, Changwat Nonthaburi, Thailand

Site Status

CMU HIV Prevention CRS

Chiang Mai, , Thailand

Site Status

Yen Hoa Health Clinic CRS

Hanoi, , Vietnam

Site Status

Countries

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United States Argentina Brazil Peru South Africa Thailand Vietnam

References

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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 Jul 1:ciaf221. doi: 10.1093/cid/ciaf221. Online ahead of print.

Reference Type DERIVED
PMID: 40590452 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38783534 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38709006 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37952550 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37783219 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34379922 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32497490 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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20725

Identifier Type: REGISTRY

Identifier Source: secondary_id

HPTN 083

Identifier Type: -

Identifier Source: org_study_id

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