Evaluating the Safety and Efficacy of Long-Acting Injectable Cabotegravir Compared to Daily Oral TDF/FTC for Pre-Exposure Prophylaxis in HIV-Uninfected Women

NCT03164564 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 2 other identifiers: HPTN 08438070
• Study Type: interventional
• Target: 3,224
• Locations: 7 countries
• Sites: 20

Brief Summary

This study will evaluate the safety and efficacy of the long-acting injectable agent cabotegravir (CAB LA) compared to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in HIV-uninfected women.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (2)

• Number of Pariicipants With Documented Incident HIV Infections

  The number of participants with an incident HIV infection that is confirmed by the HPTN Laboratory Center and Endpoint Adjudication Committee.

  HIV tests at enrollment, weeks 2, 4, and 5, then every 4 weeks through week 25, then every 8 weeks. Analyzed through week 185 or the date of DSMB decision to unblind all participants, whichever is earliest.

• Number of Participants Who Experienced Grade 2 or Higher Clinical and Laboratory Adverse Events (AEs) in Steps 1 and 2

  AEs will be summarized using MedDRA System Organ Class and preferred terms.

  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)

Study Arms (2)

Arm A: CAB + Placebo TDF/FTC + CAB LA

EXPERIMENTAL

During Step 1, participants will receive daily oral CAB and oral TDF/FTC placebo for 5 weeks. In Step 2, participants will receive injections of CAB LA at two time points 4 weeks apart and every 8 weeks thereafter and daily oral TDF/FTC placebo beginning at Week 5. In Step 3, participants will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.

Drug: Oral CAB; Drug: Oral TDF/FTC; Drug: Placebo for oral TDF/FTC; Drug: CAB LA

Arm B: TDF/FTC + Placebo CAB + Placebo CAB LA

ACTIVE COMPARATOR

During Step 1, participants will receive daily TDF/FTC and oral CAB placebo for 5 weeks. In Step 2, participants will receive daily TDF/FTC and placebo for CAB LA injections at two times points 4 weeks apart and every 8 weeks thereafter beginning at Week 5. In Step 3, participants will receive daily TDF/FTC for up to 48 weeks, starting no later than 8 weeks after the last injection.

Drug: Oral TDF/FTC; Drug: Placebo for oral CAB; Drug: Placebo for CAB LA

Interventions

Oral CAB DRUG

CAB 30 mg tablet

Also known as: Cabotegravir

Arm A: CAB + Placebo TDF/FTC + CAB LA

Oral TDF/FTC DRUG

TDF/FTC 300 mg/200 mg fixed dose combination tablet

Also known as: Tenofovir disoproxil fumarate/emtricitabine, Truvada

Arm A: CAB + Placebo TDF/FTC + CAB LA; Arm B: TDF/FTC + Placebo CAB + Placebo CAB LA

Placebo for oral CAB DRUG

Placebo tablets

Arm B: TDF/FTC + Placebo CAB + Placebo CAB LA

Placebo for oral TDF/FTC DRUG

Placebo tablets

Arm A: CAB + Placebo TDF/FTC + CAB LA

CAB LA DRUG

600 mg administered as one 3 mL (600 mg) intramuscular injection in the gluteal muscle

Also known as: Cabotegravir long-acting injectable

Arm A: CAB + Placebo TDF/FTC + CAB LA

Placebo for CAB LA DRUG

Administered as one 3 mL intramuscular injection in the gluteal muscle

Arm B: TDF/FTC + Placebo CAB + Placebo CAB LA

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Born female
• years at the time of screening
• Willing and able to provide informed consent
• Willing and able to undergo all required study procedures
• Non-reactive HIV test results at Screening and Enrollment. Note: HIV-uninfected, based on HIV test results obtained at Screening and just prior to randomization at the Enrollment visit. All HIV test results from the Screening visit must be obtained and must all be negative/non-reactive. This includes testing for acute HIV infection, which must be performed within 14 days of Enrollment. In addition, at least one HIV test result using blood drawn at the Enrollment visit must be obtained prior to randomization into the study and must be negative/non-reactive. Individuals who have one or more reactive or positive HIV test result(s) will not be enrolled, even if subsequent confirmatory testing indicates that they are not HIV-infected (see SSP Manual). Those with any enrollment HIV test result positive will proceed through the HIV algorithm per the SSP but will not be able to receive study product regardless of subsequent test results.
• Sexually active (i.e., vaginal intercourse on a minimum of two separate days in the 30 days prior to Screening)
• Score of greater than or equal to 5 using a modified VOICE risk score
• No plans to re-locate or travel away from the site for greater than or equal to 8 consecutive weeks during study participation
• Creatinine clearance of greater than or equal to 60 mL/min (using Cockcroft-Gault equation) (use sex at birth for calculation)
• Hepatitis B virus (HBV) surface antigen (HBsAg) negative and accepts vaccination
• Alanine aminotransferase (ALT) less than 2 x upper limit of normal (ULN) and total bilirubin (Tbili) less than or equal to 2.5 x ULN
• HCV antibody negative
• If of reproductive potential (defined as pre-menopausal women who have not had a sterilization procedure per self-report, such as hysterectomy, bilateral oophorectomy, tubal ligation or salpingectomy), must have a negative beta human chorionic gonadotropin (βHCG) pregnancy test (sensitivity of less than or equal to 25 mIU/mL) performed (and results known) on the same day as and before initiating the protocol-specified study product(s) at Enrollment.
• Have documented evidence of surgical sterilization, OR documented evidence of no uterus (e.g., hysterectomy), OR must agree to use a reliable form of long acting contraception, during the trial and for 52 weeks after stopping the long acting injectable, or 30 days after stopping oral study product, from the list below:
• Intrauterine device (IUD) or intrauterine system (IUS) that meets less than 1% failure rate as stated in the product label

You may not qualify if:

• One or more reactive HIV test results at Screening or Enrollment, even if HIV infection is not confirmed
• Pregnant or currently breastfeeding, or intends to become pregnant and/or breastfeed during the study
• Co-enrollment in any other HIV interventional research study (provided by self-report or other available documentation), with one exception: IMPAACT 2026 (co-enrollment in IMPAACT 2026 is permitted for participants who become pregnant)
• Current or past enrollment in an HIV vaccine or broadly neutralizing antibody trial
• 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)
• History of seizure disorder, per self-report
• 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 may interfere with interpretation of injection site reactions (ISRs)
• Coagulopathy (primary or iatrogenic) which would contraindicate IM injection
• Active or planned use of prohibited medications as described in the Investigator Brochure (IB) or listed in the Study Specific Procedures Manual (SSP) (provided by self-report, or obtained from medical history or medical records)
• Known or suspected allergy to study product components (active or placebo), including egg or soy products (egg and soy products are contained in Intralipid)
• If potentially able to conceive, unwilling to adhere to long acting contraception (IUD/IUS, injection, or implant) with a less than 1% failure rate when used consistently and correctly as stated in the product package insert/ manufacturer's guidelines

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (20)

Gaborone CRS

Gaborone, South-East District, Botswana

Location

Eswatini Prevention Center CRS

Mbabane, Eswatini

Location

Kisumu Crs

Kisumu, Nyanza, 40100, Kenya

Location

Malawi CRS

Lilongwe, Central Region, Malawi

Location

Blantyre CRS

Blantyre, Malawi

Location

Soweto HPTN CRS

Johannesburg, Gauteng, 1862, South Africa

Location

Ward 21 CRS

Johannesburg, Gauteng, 2001, South Africa

Location

Botha's Hill CRS

Durban, KwaZulu-Natal, 3660, South Africa

Location

Isipingo CRS

Isipingo, KwaZulu-Natal, 4110, South Africa

Location

Verulam CRS

Verulam, KwaZulu-Natal, 4340, South Africa

Location

Desmond Tutu TB Centre - Stellenbosch University (DTTC-SU) CRS

Cape Town, Western Cape, 7505, South Africa

Location

Emavundleni CRS

Cape Town, Western Cape, 7750, South Africa

Location

UVRI-IAVI HIV Vaccine Program LTD. CRS

Entebbe, Uganda

Location

Baylor-Uganda CRS

Kampala, Uganda

Location

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS

Kampala, Uganda

Location

Zengeza CRS

Chitungwiza, Mashonaland East Province, Zimbabwe

Location

Seke South CRS

Chitungwiza, Zimbabwe

Location

St Mary's CRS

Chitungwiza, Zimbabwe

Location

Milton Park CRS

Harare, Zimbabwe

Location

Spilhaus CRS

Harare, Zimbabwe

Location

Related Publications (3)

• Marzinke MA, Han K, Hanscom B, Guo X, Piwowar-Manning E, Hendrix CW, Rose S, Spooner E, Mathew C, Innes S, Sekabira R, Mutambanengwe M, Rooney JF, Rinehart AR, Adeyeye A, Cohen MS, Hosseinipour M, Ford SL, Delany-Moretlwe S. Pharmacologic evaluation of delayed long-acting cabotegravir administration among cisgender women in HPTN 084. Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0099424. doi: 10.1128/aac.00994-24. Epub 2024 Sep 23.

  PMID: 39311597 DERIVED

• Delany-Moretlwe S, Hughes JP, Bock P, Ouma SG, Hunidzarira P, Kalonji D, Kayange N, Makhema J, Mandima P, Mathew C, Spooner E, Mpendo J, Mukwekwerere P, Mgodi N, Ntege PN, Nair G, Nakabiito C, Nuwagaba-Biribonwoha H, Panchia R, Singh N, Siziba B, Farrior J, Rose S, Anderson PL, Eshleman SH, Marzinke MA, Hendrix CW, Beigel-Orme S, Hosek S, Tolley E, Sista N, Adeyeye A, Rooney JF, Rinehart A, Spreen WR, Smith K, Hanscom B, Cohen MS, Hosseinipour MC; 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 May 7;399(10337):1779-1789. doi: 10.1016/S0140-6736(22)00538-4. Epub 2022 Apr 1.

  PMID: 35378077 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; Tenofovir; Emtricitabine; 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)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-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

• Sinead Delany-Moretlwe, PhD, DTM&H

  Wits Reproductive Health and HIV Institute CRS (WRHI CRS)

  STUDY CHAIR

• Mina Hosseinipour, MD, MPH

  University of North Carolina (UNC) Project-Malawi, Tidziwe Centre

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: May 22, 2017
• First Posted: May 23, 2017
• Study Start: November 7, 2017
• Primary Completion: November 5, 2020
• Study Completion (Estimated): October 17, 2026
• Last Updated: October 9, 2025
• Results First Posted: March 28, 2023

Record last verified: 2025-09

Locations

ES (1); KE (1); ZA (7); BO (1); UG (3); ZI (5); MA (2)