HIV Infections
Conditions
Brief summary
This study will establish the minimum safety, tolerability and acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an adolescent population, potentially transforming the field of HIV prevention for young people.
Detailed description
This study will enroll sexually-active, healthy, HIV-uninfected adolescents assigned female sex at birth. Total participant commitment for the entire study is approximately 1.5 years. This study will take place in three steps. In Step 1, participants will receive daily oral CAB tablets for 5 weeks. In Step 2, participants will receive a series of five intramuscular (IM) injections of CAB LA, administered at 8-week intervals after a 4-week loading dose (injections at Weeks 5, 9, 17, 25 & 33). A safety visit will follow each injection to ascertain safety data, including injection site reactions. In Step 3, all participants who have received at least one injection will be followed quarterly (every 3 months) for 48 weeks after their last injection. Participants will receive oral TDF/FTC for daily use for 48 weeks or join and open-label extension CAB study in their area, if available. Participants will attend about 18 study visits throughout the study. Visits may include physical examinations, blood collection, urine collection, vaginal swab collection, risk reduction and adherence counseling, and behavioral or acceptability assessments.
Interventions
30 mg tablets
DRUGCAB 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
DRUGOral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
300 mg/200 mg fixed-dose combination tablets
Sponsors
ViiV Healthcare
Bill and Melinda Gates Foundation
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Assigned female at birth * At enrollment, below 18 years of age * At enrollment, body weight ≥ 35 kg (77 lbs.) * Willing and able to provide informed assent/consent for the study and/or able to obtain written parental/guardian informed consent * Self-reported sexual activity with a male (oral, anal or vaginal) in the past 12 months * Willing and able to undergo all study procedures * In general, good health, as evidenced by the following laboratory values: * Non-reactive / negative HIV test results\*\*, * Absolute neutrophil count \> 799 cells/mm3, * Platelet count ≥ 100,000/mm3, * Hemoglobin ≥ 11g/dL, * Calculated creatinine clearance ≥ 60 mL/minute using the modified Schwartz equation, * Alanine aminotransferase (ALT) \< 2.0 times the upper limit of normal (ULN) (≤ grade 1) and total bilirubin (Tbili) ≤ 2.5 x ULN, * Hepatitis B virus (HBV) surface antigen (HBsAg) negative) and accepts vaccination, * Hepatitis C virus (HCV) Antibody negative * Must have a negative beta human chorionic gonadotropin (βHCG) pregnancy test (sensitivity of ≤ 25 mIU/mL) performed (and results known) on the same day as Enrollment and before initiating study product * Must agree to use a reliable form of long acting contraception, during the trial and for 48 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 \<1% failure rate as stated in the product label * Hormone-based contraceptive that meets \<1% failure rate when used consistently and correctly as stated in the product label (implants or injectables only; this excludes combined oral contraception) * If currently on PrEP from a non-study source, willing to stop said PrEP prior to enrollment and agree to switch to oral CAB for the lead-in period and CAB LA injections. * HIV-uninfected, based on HIV test results obtained at Screening and 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. 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).
Exclusion criteria
* Co-enrollment in any other HIV interventional research study or other concurrent studies which may interfere with this study (as provided by self-report or other available documentation) * Past or current participation in HIV vaccine trial with exception for participants who can provide documentation of receipt of placebo * Exclusively had sex with biological females in lifetime * In the last 6 months (at the time of screening): * active or planned use of any substance use which would, in the opinion of the site investigator, interfere with study participation (including herbal remedies), as described in the Investigator's Brochure (IB) or listed in the Study Specific Procedures (SSP), and/ or Protocol Section 4.4, * Known history of 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 * Tattoo or other dermatological condition overlying the buttock region that 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) * Known history of clinically significant bleeding * A history of seizure disorder, per self-report * Medical, social or other condition that, in the opinion of the site investigator, would interfere with the conduct of the study or safety of the participant (e.g., provided by self-report, or found upon medical history and examination or in available medical records) * Plans to move out of the geographic area within the next 18 months or otherwise unable to participate in study visits, according to the site investigator * Pregnant or currently breastfeeding at the time of screening or intends to become pregnant and/or breastfeed while on study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41 | 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. |
| 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. | Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41 | 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 |
| 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. | Measured through participant's first injection visit up to, 8 weeks after the last Step 2 injection visit or week 41 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percent of Injection Visits That Occurred On-time | Measured through participant's last study visit, up to approximately 1.5 years after study entry. | 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). |
| Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Measured through participant's study visit, up to Week 48 from enrollment. | 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. |
| Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit | Measured through participant's first Oral visit up to, 10 weeks after the last Step 2 injection visit or week 41 | 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. |
| Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study | 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. |
| Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period | Measured through participant's last study visit, up to approximately 1.5 years after study entry. | 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 episodes of vaginal sex without a condom) using a poisson model and binary outcomes (any episodes of anal sex without a condom) using a logistic model. |
| Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit. | Measured through weeks 5, 6, 9, 10, 17, 18, 25, 26, 33, 34, 41 (33 +8) | 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. |
| 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 | Measured through participant's first Oral visit up to, 8 weeks after the last Step 2 injection visit or week 41 | 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) |
Countries
South Africa, Uganda, Zimbabwe
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Cabotegravir Long Acting 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 | 55 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| CAB LA Oral Phase | Adverse Event | 1 |
| CAB LA Oral Phase | Withdrawal by Subject | 1 |
| Step 3 | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Cabotegravir Long Acting |
|---|---|
| Age, Continuous | 16.0 Years STANDARD_DEVIATION 1.1 |
| Age, Customized 12-15 years old | 15 Participants |
| Age, Customized 16-17 years old | 40 Participants |
| Number of Participants per BMI Category as Determined by Age-Standardized Z-score Normal | 38 Participants |
| Number of Participants per BMI Category as Determined by Age-Standardized Z-score Obese | 2 Participants |
| Number of Participants per BMI Category as Determined by Age-Standardized Z-score Overweight | 14 Participants |
| Number of Participants per BMI Category as Determined by Age-Standardized Z-score Severe thinness | 0 Participants |
| Number of Participants per BMI Category as Determined by Age-Standardized Z-score Thinness | 1 Participants |
| Race/Ethnicity, Customized Black | 35 Participants |
| Race/Ethnicity, Customized Shona | 20 Participants |
| Region of Enrollment South Africa | 18 participants |
| Region of Enrollment Uganda | 17 participants |
| Region of Enrollment Zimbabwe | 20 participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 0 Participants |
| Sexual Orientation: Straight/Heterosexual | 55 Participants |
| Weight <50 kg | 15 Participants |
| Weight >=50 kg | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 55 | 0 / 53 | 0 / 48 |
| other Total, other adverse events | 48 / 55 | 52 / 53 | 29 / 48 |
| serious Total, serious adverse events | 0 / 55 | 2 / 53 | 0 / 48 |
Outcome results
Primary
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.
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
Time frame: 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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
95% CI: [47, 74.7]
Primary
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.
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cabotegravir Long Acting | 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
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 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
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
95% CI: [0, 6.7]
Secondary
Change From Enrollment of Self-reported Sexual Behavior (Increased Episodes of Vaginal or Anal Sex Without a Condom) During the Study Period
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 episodes of vaginal sex without a condom) using a poisson model and binary outcomes (any episodes of anal sex without a condom) using a logistic model.
Time frame: Measured through participant's last study visit, up to approximately 1.5 years after study entry.
Population: Includes enrolled female adolescents.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
Comparison: 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 episodes of vaginal sex without a condom) using a poisson model.p-value: 0.009395% CI: [-1.03, -0.14]poisson model
Comparison: 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 binary outcomes (any episodes of anal sex without a condom) using a logistic model.p-value: 0.825995% CI: [-3.06, 2.44]Regression, Logistic
Secondary
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period
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.
Time frame: Measured through participant's study visit, up to Week 48 from enrollment.
Population: Includes enrolled female adolescents.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
Comparison: 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.p-value: 0.109395% CI: [-0.61, 0.06]poisson model
Secondary
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 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)
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
95% CI: [84.3, 98.8]
Secondary
Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit | <4x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit | >8x PA-IC90: Injection 1 | 34 Participants |
| Cabotegravir Long Acting | Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit | >8x PA-IC90: Injection 2 | 50 Participants |
| Cabotegravir Long Acting | Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit | >8x PA-IC90: Injection 3 | 53 Participants |
| Cabotegravir Long Acting | Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit | >8x PA-IC90: Injection 4 | 52 Participants |
| Cabotegravir Long Acting | Count of Participants Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) at Each Injection Visit | >8x PA-IC90: Injection 5 | 48 Participants |
Secondary
Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study
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.
Time frame: Measured through participant's last study visit, up to approximately 1.5 years after study entry.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study | Total Participants HIV-positive at Enrollment | 0 Participants |
| Cabotegravir Long Acting | Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study | Number of participants infected | 0 Participants |
| Cabotegravir Long Acting | Evaluate Rates of HIV Drug Resistance Among Participants Who Acquire HIV Infection During the Study | Number of drug resistance cases | 0 Participants |
95% CI: [0, 10.8]
Secondary
Measurement of Pharmacokinetic Parameters, Mean and Associated Deviations of Drug Concentrations at Each Injection Visit.
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
| Cabotegravir Long Acting | 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 |
Secondary
Number and Percent of Injection Visits That Occurred On-time
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).
Time frame: Measured through participant's last study visit, up to approximately 1.5 years after study entry.
Population: Participants with at least one Injection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cabotegravir Long Acting | Number and Percent of Injection Visits That Occurred On-time | Number of Injections Given | 263 Number of Injections |
| Cabotegravir Long Acting | Number and Percent of Injection Visits That Occurred On-time | Number of Injections given On-time | 228 Number of Injections |
95% CI: [93.3, 100]