Trial Outcomes & Findings for Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Females (NCT NCT04824131)

Last Updated: 2024-12-03

Results Overview

Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities (reported as adverse events) from the first injection visit to 8 weeks after the last Step 2 injection visit or week 41, whichever comes first.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

55 participants

Primary outcome timeframe

Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41

Results posted on

2024-12-03

Participant Flow

The study target population is sexually-active, healthy female adolescents aged below 18 years. The study target is to enroll more than 50 participants with at least 50 participants receiving at least one injection. Participant recruitment will take approximately 12 months.

A total of 55 participants were eligible and enrolled. The Study has 3 steps, Oral CAB, Injection CAB LA and the Follow-up of Injection CAB levels with use of TDF/FTC, Truvada® for daily use for 48 weeks. Two participants terminated before Step 2 "Refused participation" and "Adverse Event" so 53 participants received CAB LA injection. Finally out of 53 in Step 3 two further terminated due to " Refused Participation".

Participant milestones

Participant milestones
Measure	Cabotegravir Long Acting Oral cabotegravir (30mg tablet) Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC): 300 mg/200 mg fixed-dose combination tablets
CAB LA Oral Phase STARTED	55
CAB LA Oral Phase COMPLETED	53
CAB LA Oral Phase NOT COMPLETED	2
CAB LA Injection Phase STARTED	53
CAB LA Injection Phase COMPLETED	53
CAB LA Injection Phase NOT COMPLETED	0
Step 3 STARTED	53
Step 3 CAB Open-Label Extension	49
Step 3 Tenofovir/Emtricitabine"	0
Step 3 COMPLETED	51
Step 3 NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cabotegravir Long Acting Oral cabotegravir (30mg tablet) Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC): 300 mg/200 mg fixed-dose combination tablets
CAB LA Oral Phase Adverse Event	1
CAB LA Oral Phase Withdrawal by Subject	1
Step 3 Withdrawal by Subject	2

Baseline Characteristics

Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Females

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cabotegravir Long Acting n=55 Participants In Step 1, participants will receive one CAB tablet orally every day for 5 weeks. In Step 2, participants will receive an intramuscular (IM) injection of CAB LA at Weeks 5, 9, 17, 25, and 33. In Step 3, participants will receive a TDF/FTC tablet orally every day for 48 weeks or join an open-label extension CAB study in their area, if available. Oral cabotegravir (CAB): 30 mg tablets 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 Oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC): 300 mg/200 mg fixed-dose combination tablets
Age, Continuous	16.0 Years STANDARD_DEVIATION 1.1 • n=5 Participants
Age, Customized 12-15 years old	15 Participants n=5 Participants
Age, Customized 16-17 years old	40 Participants n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Black	35 Participants n=5 Participants
Race/Ethnicity, Customized Shona	20 Participants n=5 Participants
Region of Enrollment Uganda	17 participants n=5 Participants
Region of Enrollment South Africa	18 participants n=5 Participants
Region of Enrollment Zimbabwe	20 participants n=5 Participants
Sexual Orientation: Straight/Heterosexual	55 Participants n=5 Participants
Weight <50 kg	15 Participants n=5 Participants
Weight >=50 kg	40 Participants n=5 Participants
Number of Participants per BMI Category as Determined by Age-Standardized Z-score Obese	2 Participants n=5 Participants
Number of Participants per BMI Category as Determined by Age-Standardized Z-score Overweight	14 Participants n=5 Participants
Number of Participants per BMI Category as Determined by Age-Standardized Z-score Normal	38 Participants n=5 Participants
Number of Participants per BMI Category as Determined by Age-Standardized Z-score Thinness	1 Participants n=5 Participants
Number of Participants per BMI Category as Determined by Age-Standardized Z-score Severe thinness	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41

Population: Includes enrolled female adolescent participants who receive at least one injection of CAB LA.

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=53 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Count and Percentage of Participants Experiencing Any Grade 2 or Higher Clinical Adverse Events (AEs) and Laboratory Abnormalities Among Participants Who Receive at Least One Injection of CAB LA.	50 Participants

PRIMARY outcome

Timeframe: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41

Population: Includes enrolled female adolescents who receive at least one injection of CAB LA.

Number and percent of participants who receive at least 1 injection and who discontinue receiving injections prior to the full course of injections due to intolerability of injection or burden of study procedures. Reasons for intolerability may include: 1. Injection site reaction 2. Burden of study procedure i. Participant refused further participation ii. Participant is unwilling or unable to comply with required study procedures iii. Participant refused further study product use iv. Participant unable to adhere to visit schedule

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=53 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Tolerability Endpoint: Percentage of Participants Who Receive at Least 1 Injection and Who Discontinue Receiving Injections Prior to the Full Course of Injections Due to Intolerability of Injection, Frequency of Injections or Burden of Study Procedures. Number of participants who have reported any grade 2 (moderate) and above ISR	3 Participants
Tolerability Endpoint: Percentage of Participants Who Receive at Least 1 Injection and Who Discontinue Receiving Injections Prior to the Full Course of Injections Due to Intolerability of Injection, Frequency of Injections or Burden of Study Procedures. Participants who Discontinued Early due to Intolerability of Injection or Burden of Study Procedures	0 Participants
Tolerability Endpoint: Percentage of Participants Who Receive at Least 1 Injection and Who Discontinue Receiving Injections Prior to the Full Course of Injections Due to Intolerability of Injection, Frequency of Injections or Burden of Study Procedures. Enrolled Participants who Completed all Scheduled Injections	53 Participants
Tolerability Endpoint: Percentage of Participants Who Receive at Least 1 Injection and Who Discontinue Receiving Injections Prior to the Full Course of Injections Due to Intolerability of Injection, Frequency of Injections or Burden of Study Procedures. Number of participants who have reported any injection site reaction (ISR)	14 Participants

PRIMARY outcome

Timeframe: Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41

Population: Includes enrolled female adolescents who receive at least one injection of CAB LA and who Completed All Scheduled Injections

Number and percent of participants who complete all scheduled injections: Defined as completing all scheduled injections for participants who are confirmed pregnant, confirmed HIV seroconverted, or discontinue product due to the following reasons: * Death * Early study closure * HBV infection During Step 1: Enrolled population: completed all 0 of 0 scheduled injections Injection population: not applicable, did not receive injection During Step 2: Both enrolled and injection: completed all injections whose target window closed prior to pregnancy/seroconversion/product discontinuation date

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=52 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. If you wanted to protect yourself from getting HIV: Oral PrEP pills only	1 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. Participants with Acceptability Endpoint at the end of Step 2	52 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. Participants who received at least one injection and preferred injectable PrEP at end of Step 2	32 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. If you wanted to protect yourself from getting HIV: Prefer not using a product	1 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. If you wanted to protect yourself from getting HIV: Condoms only	7 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. If you wanted to protect yourself from getting HIV: Injectable PrEP only	12 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. If you wanted to protect yourself from getting HIV: Condoms and oral PrEP pills together	8 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. If you wanted to protect yourself from getting HIV: Condoms and injectable PrEP together	20 Participants
Acceptability Endpoint: Count and Percentage of Participants Who Complete All Scheduled Injections and Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. If you wanted to protect yourself from getting HIV: Prefer not to answer	3 Participants

SECONDARY outcome

Timeframe: Measured through participant's first Oral visit up to, 10 weeks after the last Step 2 injection visit or week 41

Population: Includes enrolled female adolescents who receive at least one injection of CAB LA.

CAB drug concentrations will be measured in plasma to generate CAB-LA concentration-time profiles among study participants. Measurements will occur at study visits during the injection phase of the study as well as during the pharmacologic "tail" phase. Count of participants for injection visits in which a participant remains above the 1x (0.166 mcg/mL), 4x (0.664 mcg/mL) and 8x (1.33 mcg/mL) PA-IC90. Concentrations above the 3 PA-IC90 are associated with rectal protection in a non-human primate study, and concentrations above the 8x PA-IC90 are expected to be associated with protection in humans.

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=53 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit <4x PA-IC90	0 Participants
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit 4x PA-IC90 - <8x PA-IC90: Injection 1	19 Participants
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit 4x PA-IC90 - <8x PA-IC90: Injection 2	3 Participants
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit >8x PA-IC90: Injection 1	34 Participants
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit >8x PA-IC90: Injection 2	50 Participants
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit >8x PA-IC90: Injection 3	53 Participants
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit >8x PA-IC90: Injection 4	52 Participants
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit >8x PA-IC90: Injection 5	48 Participants

SECONDARY outcome

Timeframe: Measured through weeks 5, 6, 9, 10, 17, 18, 25, 26, 33, 34, 41 (33 +8)

Population: All study participants who have received at least one injection of CAB-LA

CAB drug concentrations will be measured throughout the study, and the study team will characterize variability in concentrations at each visit by determining mean concentrations, as well as associated deviations.

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=53 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 5	7.4 mcg/mL Standard Deviation 7.2
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 5	5.8 mcg/mL Standard Deviation 4.5
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 6	4.4 mcg/mL Standard Deviation 2.7
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 6	1.7 mcg/mL Standard Deviation 1.0
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 9	3.3 mcg/mL Standard Deviation 1.7
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 9	2.1 mcg/mL Standard Deviation 1.6
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 10	5.1 mcg/mL Standard Deviation 2.1
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 10	3.1 mcg/mL Standard Deviation 1.5
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 17	3.2 mcg/mL Standard Deviation 0.9
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 17	2.9 mcg/mL Standard Deviation 1.2
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 18	4.5 mcg/mL Standard Deviation 1.3
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 18	3.9 mcg/mL Standard Deviation 1.6
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 25	3.5 mcg/mL Standard Deviation 1.1
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 25	3.1 mcg/mL Standard Deviation 1.1
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 26	5.0 mcg/mL Standard Deviation 1.9
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 26	3.8 mcg/mL Standard Deviation 1.2
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 33	3.8 mcg/mL Standard Deviation 1.3
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 33	3.3 mcg/mL Standard Deviation 1.1
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 34	4.5 mcg/mL Standard Deviation 1.4
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 34	4.2 mcg/mL Standard Deviation 1.4
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. <50 Kg: Week 42	3.7 mcg/mL Standard Deviation 1.0
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. >=50 Kg: Week 42	3.2 mcg/mL Standard Deviation 1.0

SECONDARY outcome

Timeframe: Measured through participant's first Oral visit up to, 8 weeks after the last Step 2 injection visit or week 41

Population: Includes enrolled female adolescents.

Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities from: 1. enrollment to week 5 (oral phase (step 1), including interim visits). 2. enrollment to 8 weeks following the last injection received (aggregate over oral + injection phases (step 1-step 2) including interim visits)

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=55 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and Laboratory Abnormalities in the Oral Phase and the Aggregate Oral and Injection Phases Number of Participants with Grade 2 or Higher AEs in Oral Phase	31 Participants
Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and Laboratory Abnormalities in the Oral Phase and the Aggregate Oral and Injection Phases Number of Participants with Grade 2 or above AEs during Injection Phase	50 Participants
Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and Laboratory Abnormalities in the Oral Phase and the Aggregate Oral and Injection Phases Number of Participants with Grade 2 or Higher AEs in Oral and Injection Phase	51 Participants

SECONDARY outcome

Timeframe: Measured through participant's last study visit, up to approximately 1.5 years after study entry.

Population: Participants with at least one Injection

Number and percent of injection visits (up to 5 per participant) that occur "on-time", using the number of injections given as the denominator. This will be presented along with the total number and percent of injections given, among all intended injections (i.e. 5 injections per participant).

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=263 Number of Injections Expected Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Number and Percent of Injection Visits That Occurred "On-time" Number of Injections Given	263 Number of Injections
Number and Percent of Injection Visits That Occurred "On-time" Number of Injections given On-time	228 Number of Injections

SECONDARY outcome

Timeframe: Measured through participant's study visit, up to Week 48 from enrollment.

Population: Includes enrolled female adolescents.

We will use generalized estimating equations (GEE) with robust variance to model change in self-reported sexual behavior from enrollment (W0) to follow up visits (W4, W5, W9, W17, W25, W33, W+12, W+24, W+36, W+48), with an indicator variable for all on-study visits (i.e. enrollment visit = 0) to measure change in the outcome behavior. We will model count outcomes (number of sexual partners) using a poisson model.

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=55 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 5	2 Number of Sexual Partners Standard Deviation 3.1
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 5: Change from previous visit	0 Number of Sexual Partners Standard Deviation 4.0
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 5: Change from baseline	-1 Number of Sexual Partners Standard Deviation 4.8
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 9	2 Number of Sexual Partners Standard Deviation 4.8
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 9: Change from previous visit	0 Number of Sexual Partners Standard Deviation 2.4
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 9: Change from baseline	-1 Number of Sexual Partners Standard Deviation 4.1
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 17	2 Number of Sexual Partners Standard Deviation 5.0
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 17: Change from previous visit	0 Number of Sexual Partners Standard Deviation 1.1
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 17: Change from baseline	-1 Number of Sexual Partners Standard Deviation 4.3
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 25	3.1 Number of Sexual Partners Standard Deviation 6.3
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 25: Change from previous visit	1 Number of Sexual Partners Standard Deviation 5.1
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 25: Change from baseline	0 Number of Sexual Partners Standard Deviation 3.1
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 33	2 Number of Sexual Partners Standard Deviation 4.4
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 33: Change from previous visit	-1 Number of Sexual Partners Standard Deviation 3.9
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 33: Change from baseline	-1 Number of Sexual Partners Standard Deviation 4.2
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 12	3 Number of Sexual Partners Standard Deviation 5.8
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 12: Change from previous visit	0 Number of Sexual Partners Standard Deviation 7.7
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 12: Change from baseline	-1 Number of Sexual Partners Standard Deviation 8.9
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 24: Change from baseline	2 Number of Sexual Partners Standard Deviation 7.4
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 36	6 Number of Sexual Partners Standard Deviation 14.3
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 36: Change from previous visit	-1 Number of Sexual Partners Standard Deviation 2.6
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 36: Change from baseline	2 Number of Sexual Partners Standard Deviation 7.8
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 48	1 Number of Sexual Partners Standard Deviation 0
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Enrollment	3 Number of Sexual Partners Standard Deviation 6.0
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 4	2 Number of Sexual Partners Standard Deviation 5.2
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 4: Change from previous visit	-1 Number of Sexual Partners Standard Deviation 5.5
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Week 4: Change from baseline	-1 Number of Sexual Partners Standard Deviation 5.5
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 24	6 Number of Sexual Partners Standard Deviation 13.1
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 24: Change from previous visit	3 Number of Sexual Partners Standard Deviation 12.1
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 48: Change from previous visit	1 Number of Sexual Partners Standard Deviation 0.7
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period Step 3 - week + 48: Change from baseline	1 Number of Sexual Partners Standard Deviation 0.7

SECONDARY outcome

Timeframe: Measured through participant's last study visit, up to approximately 1.5 years after study entry.

Population: Includes enrolled female adolescents.

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=55 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 9: Change from baseline	-1 Number of Episodes Standard Deviation 2.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 4: Change from previous visit	1 Number of Episodes Standard Deviation 11.3
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 4: Change from baseline	1 Number of Episodes Standard Deviation 11.3
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 5: Change from previous visit	0 Number of Episodes Standard Deviation 2.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 5: Change from baseline	1 Number of Episodes Standard Deviation 9.7
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 9	0 Number of Episodes Standard Deviation 0.5
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 9: Change from previous visit	-2 Number of Episodes Standard Deviation 9.9
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 17	1 Number of Episodes Standard Deviation 1.9
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 17: Change from previous visit	1 Number of Episodes Standard Deviation 1.9
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 17: Change from baseline	-1 Number of Episodes Standard Deviation 1.6
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 25	2 Number of Episodes Standard Deviation 12.8
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 25: Change from previous visit	2 Number of Episodes Standard Deviation 13.3
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 25: Change from baseline	1 Number of Episodes Standard Deviation 12.8
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 33	1 Number of Episodes Standard Deviation 1.3
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 33: Change from previous visit	-2 Number of Episodes Standard Deviation 13.5
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 33: Change from baseline	-1 Number of Episodes Standard Deviation 2.3
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 12	1 Number of Episodes Standard Deviation 2.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 12: Change from previous visit	0 Number of Episodes Standard Deviation 2.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 12: Change from baseline	0 Number of Episodes Standard Deviation 3.4
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 24	0 Number of Episodes Standard Deviation 0.7
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 24: Change from previous visit	-1 Number of Episodes Standard Deviation 2.8
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 36	2 Number of Episodes Standard Deviation 4.4
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 36: Change from previous visit	2 Number of Episodes Standard Deviation 4.9
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 36: Change from baseline	1 Number of Episodes Standard Deviation 3.8
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 48	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Enrollment	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 4: Change from baseline	0 Number of Episodes Standard Deviation 0.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 5	0 Number of Episodes Standard Deviation 0.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 5: Change from previous visit	0 Number of Episodes Standard Deviation 0.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 5: Change from baseline	0 Number of Episodes Standard Deviation 0.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 9	0 Number of Episodes Standard Deviation 0.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 9: Change from previous visit	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 9: Change from baseline	0 Number of Episodes Standard Deviation 0.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 17	0 Number of Episodes Standard Deviation 1.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 17: Change from previous visit	0 Number of Episodes Standard Deviation 1.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 17: Change from baseline	0 Number of Episodes Standard Deviation 1.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 25	0 Number of Episodes Standard Deviation 0.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 25: Change from previous visit	0 Number of Episodes Standard Deviation 1.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 25: Change from baseline	0 Number of Episodes Standard Deviation 0.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 33	0 Number of Episodes Standard Deviation 0.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 33: Change from previous visit	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 33: Change from baseline	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 12	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 12: Change from baseline	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 24	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 24: Change from previous visit	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 24: Change from baseline	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 36	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 36: Change from previous visit	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 36: Change from baseline	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 48	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 48: Change from previous visit	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Enrollment	1 Number of Episodes Standard Deviation 2.1
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 4	2 Number of Episodes Standard Deviation 11.5
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Week 5	2 Number of Episodes Standard Deviation 9.8
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 24: Change from baseline	-1 Number of Episodes Standard Deviation 1.9
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 48: Change from previous visit	-1 Number of Episodes Standard Deviation 0.7
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Vaginal Sex without a Condom: Step 3 - week + 48: Change from baseline	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 4	0 Number of Episodes Standard Deviation 0.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Week 4: Change from previous visit	0 Number of Episodes Standard Deviation 0.2
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 12: Change from previous visit	0 Number of Episodes Standard Deviation 0.0
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period Anal Sex without a Condom: Step 3 - week + 48: Change from baseline	0 Number of Episodes Standard Deviation 0.0

SECONDARY outcome

Timeframe: Measured through participant's last study visit, up to approximately 1.5 years after study entry.

Data from steps 1, 2, and 3 will be included. The number of cases of drug resistance will be summarized. All cases of drug resistance among incident HIV infections will be described.

Outcome measures

Outcome measures
Measure	Cabotegravir Long Acting n=55 Participants Injectable cabotegravir 3 mL (600 mg) intramuscular (IM) injection
Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study Total Participants HIV-positive at Enrollment	0 Participants
Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study Number of participants infected	0 Participants
Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study Number of drug resistance cases	0 Participants

Adverse Events

Step 1 - CAB LA Oral Phase

Serious events: 0 serious events

Other events: 48 other events

Deaths: 0 deaths

Step 2 - CAB LA Injection Phase

Serious events: 2 serious events

Other events: 52 other events

Deaths: 0 deaths

Step 3 - Follow up

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Step 1 - CAB LA Oral Phase n=55 participants at risk A 5-week oral CAB 30mg QD safety lead-in	Step 2 - CAB LA Injection Phase n=53 participants at risk A series of 5 intramuscular (IM) injections of 3 mL (600 mg) cabotegravir administered at 8-week intervals after a 4-week loading dose (injections at weeks 5, 9, 17, 25 \& 33)	Step 3 - Follow up n=48 participants at risk A blood draw visit, the +8 Week Visit, will follow the last injection to monitor CAB drug levels, with additional blood collection at the +24, +36, and +48 Week Visits. All participants who have received at least one injection will be followed for 48 weeks after their last injection. Waning levels of cabotegravir (the PK tail) will be covered with locally sourced oral Tenofovir/emtricitabine (Trade name: TDF/FTC, Truvada®) for daily use for 48 weeks.
Psychiatric disorders Suicide attempt	0.00% 0/55 • Measured through participant's first Oral visit up to, follow-up 48 weeks Step 3 SAE, NON SAE \& Mortality are summarized by Steps (Oral, Injection \& Follow-up).	1.9% 1/53 • Number of events 1 • Measured through participant's first Oral visit up to, follow-up 48 weeks Step 3 SAE, NON SAE \& Mortality are summarized by Steps (Oral, Injection \& Follow-up).	0.00% 0/48 • Measured through participant's first Oral visit up to, follow-up 48 weeks Step 3 SAE, NON SAE \& Mortality are summarized by Steps (Oral, Injection \& Follow-up).
Reproductive system and breast disorders Ovarian cyst	0.00% 0/55 • Measured through participant's first Oral visit up to, follow-up 48 weeks Step 3 SAE, NON SAE \& Mortality are summarized by Steps (Oral, Injection \& Follow-up).	1.9% 1/53 • Number of events 1 • Measured through participant's first Oral visit up to, follow-up 48 weeks Step 3 SAE, NON SAE \& Mortality are summarized by Steps (Oral, Injection \& Follow-up).	0.00% 0/48 • Measured through participant's first Oral visit up to, follow-up 48 weeks Step 3 SAE, NON SAE \& Mortality are summarized by Steps (Oral, Injection \& Follow-up).

Other adverse events

Additional Information

HPTN Statistical Manager

HPTN Statistical & Data Management Center

Phone: 1206-667-4004

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place