HIV Infections
Conditions
Keywords
Pre-Exposure Prophylaxis, PrEP
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
The purpose of this study is to 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. This study will enroll healthy, HIV-uninfected adolescents assigned male at birth, including men who have sex with men (MSM), transgender women (TGW), and gender non-conforming people. The 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 may be provided the opportunity to enroll in a local open label study of CAB, if available. Participants will attend about 18 study visits throughout the study. Visits may include physical examinations, blood collection, urine collection, rectal and oral pharyngeal swab collection, risk reduction and adherence counseling, and behavioral or acceptability assessments.
Interventions
DRUGTenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet
300 mg/200 mg fixed-dose combination tablets
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
No minimum to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Assigned male at birth (includes MSM, TGW, and gender non-conforming people) * At enrollment, aged below 18 years * At enrollment, body weight ≥ 35 kg (77 lbs.) * Willing to provide informed consent for the study * Self-reported sexual activity with a male in the past 12 months * 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 cells/mm3 * Hemoglobin ≥ 11g/dL * Calculated creatinine clearance ≥ 60 mL/minute using modified Schwartz equation (≤ grade 2) * Alanine aminotransferase (ALT) \< 2.0 times the upper limit of normal (ULN) 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 * Willing to undergo all required study procedures * If currently on pre-exposure prophylaxis (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.
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 which would, in the opinion of the site investigator, would hinder 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 * Surgically-placed or injected buttock implants or fillers, per self-report. Contact the CMC for guidance regarding questions about individual cases * 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 the 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Endpoint: Proportion 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, whichever comes first. | 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: Proportion 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, whichever comes first. | 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 1. Participant refused further participation 2. Participant is unwilling or unable to comply with required study procedures 3. Participant refused further study product use 4. Participant unable to adhere to visit schedule |
| Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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, whichever comes first. | Definition of completing all scheduled injections for participants who are confirmed HIV positive or discontinue product due to the following reasons: * Death * Early study closure * HBV infection During Step 2: Both enrolled and injection populations: completed all injections whose target window closed prior to death/seroconversion/product discontinuation date |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Receiving One or More Injections Who Experience Grade 2 or Higher Clinical AEs and Laboratory Abnormalities From Initial Injection to 36 Weeks Later. | Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first. | Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities from the first injection visit to approximately 36 weeks later regardless of whether participants received all 5 injections. |
| Proportion of Injection Visits That Occurred On-time. | Measured through participant's last step 2 injection. | Number and percentage of injections given, using the number of injections expected as the denominator. while the 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). Those who have been terminated, are HIV infected, or have permanently discontinued study products at the time of visit will be excluded from the number of expected injections. |
| Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Measured from the participant's first injection visit up to 8 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. |
| Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Measured through participant's first oral visit up to the last Step 2 injection visit. | Counts of episodes of anal intercourse without a condom will be summarized (mean and sd) at enrollment and each regular Step 1 and Step 2 follow-up visit (W4, W5, W9, W17, W25, W33). |
| 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 (Number of Sexual Partners) During the Study Period | Measured through participant's first oral visit up to last Step 2 injection visit. | Counts of sexual partners will be summarized (mean and sd) at enrollment and each regular Step 1 and Step 2 follow-up visit (W4, W5, W9, W17, W25, W33). |
| Measure Study Product Concentrations in Enrolled Participants With HPTN Laboratory Center (LC) Confirmed HIV Infection Throughout Study. | Measured through seroconverter's first Oral visit up through end of study participation (step1, 2, 3) | For infections occurring prior to (or on the first day of) Step 3, we will include visit level plasma CAB concentrations, for individual seroconverters. For infections occurring after the start of Step 3, we will include visit level plasma CAB concentrations as well as concentrations of TFV and TFV-DP (if applicable). |
| Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and LaboratoryAbnormalities 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, whichever comes first. | 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
United States
Participant flow
Recruitment details
The study will be targeted towards at-risk, sexually active adolescent populations of MSM in the US. Enrollment will occur over approximately 18 months.
Pre-assignment details
A total of 9 participants were eligible and enrolled. The Study has 3 steps, Oral CAB, Injection CAB LA and the Follow-up of Injection CAB with use of TDF/FTC, Truvada® for daily use or continued CAB injections for 48 weeks. One participant terminated before the end of Step 2 Withdrawal by Subject. Of the 8 remaining participants, one participant Scheduled exit visit/end of study prior to the start of Step 3. Within Step 3, one participant switched from TDF/FTC to Injection CAB LA.
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 may be offered the opportunity to join an open label CAB study instead, if such a study is being implemented in their area at the time.
Cabotegravir (CAB) tablet: 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.
Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet: 300 mg/200 mg fixed-dose combination tablets | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Cabotegravir Long Acting Injection Phase | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Cabotegravir Long Acting |
|---|---|
| Age, Continuous | 16.4 years STANDARD_DEVIATION 0.7 |
| Age, Customized 12-15 years old | 1 Participants |
| Age, Customized 16-17 years old | 8 Participants |
| Age Standardized BMI z-score Classification Normal | 6 Participants |
| Age Standardized BMI z-score Classification Obese | 2 Participants |
| Age Standardized BMI z-score Classification Overweight | 1 Participants |
| Age Standardized BMI z-score Classification Severe thinness | 0 Participants |
| Age Standardized BMI z-score Classification Thinness | 0 Participants |
| Do you have a regular place or home where you stay and store your things? No | 0 Participants |
| Do you have a regular place or home where you stay and store your things? Yes | 9 Participants |
| In the past 6 months, how frequently did you worry that your household would not have enough food? Never worried | 8 Participants |
| In the past 6 months, how frequently did you worry that your household would not have enough food? Often worried | 1 Participants |
| In the past 6 months, how frequently did you worry that your household would not have enough food? Sometimes worried | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Sex/Gender, Customized Female | 1 Participants |
| Sex/Gender, Customized Gender Nonconforming/Gender Variant | 1 Participants |
| Sex/Gender, Customized Male | 6 Participants |
| Sex/Gender, Customized Self-Identify | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 | 0 / 6 | 0 / 3 |
| other Total, other adverse events | 8 / 9 | 9 / 9 | 5 / 6 | 3 / 3 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 | 1 / 6 | 0 / 3 |
Outcome results
Primary
Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future.
Definition of completing all scheduled injections for participants who are confirmed HIV positive or discontinue product due to the following reasons: * Death * Early study closure * HBV infection During Step 2: Both enrolled and injection populations: completed all injections whose target window closed prior to death/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, whichever comes first.
Population: Includes all enrolled participants and all enrolled participants who receive at least one injection of CAB LA.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants Who Receive at Least One Injection Whom Would Consider Using CAB LA for HIV Prevention in the Future. | Participant who received at least one injection among all enrolled participants | 9 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 | 6 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 the end of Step 2 | 4 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 HIV: Prefer not using a product | 0 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 HIV: Prefer not to answer | 0 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 HIV: Condoms only | 1 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 HIV: Oral PrEP pills only | 0 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 HIV: Injectable PrEP only | 0 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 HIV: Condoms and oral PrEP pills together | 1 Participants |
| Cabotegravir Long Acting | Acceptability Endpoint: Proportion of Participants Who Complete All Scheduled Injections and Proportion of Participants 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 HIV: Condoms and injectable PrEP together | 4 Participants |
95% CI: [22.3, 95.7]
Primary
Safety Endpoint: Proportion 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, whichever comes first.
Population: Includes enrolled participants who receive at least one injection of CAB LA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cabotegravir Long Acting | Safety Endpoint: Proportion 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. | 8 Participants |
95% CI: [51.8, 99.7]
Primary
Tolerability Endpoint: Proportion 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 1. Participant refused further participation 2. Participant is unwilling or unable to comply with required study procedures 3. Participant refused further study product use 4. 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, whichever comes first.
Population: Includes all enrolled participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | Tolerability Endpoint: Proportion 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 received at least 1 injection of CAB LA | 9 Participants |
| Cabotegravir Long Acting | Tolerability Endpoint: Proportion 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) or above ISR | 3 Participants |
| Cabotegravir Long Acting | Tolerability Endpoint: Proportion 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 reported any injection site reaction (ISR) | 5 Participants |
| Cabotegravir Long Acting | Tolerability Endpoint: Proportion 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 Procedure | 1 Participants |
| Cabotegravir Long Acting | Tolerability Endpoint: Proportion 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 completed all scheduled injections | 8 Participants |
95% CI: [0.3, 48.3]
Secondary
Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period
Counts of episodes of anal intercourse without a condom will be summarized (mean and sd) at enrollment and each regular Step 1 and Step 2 follow-up visit (W4, W5, W9, W17, W25, W33).
Time frame: Measured through participant's first oral visit up to the last Step 2 injection visit.
Population: Includes all enrolled participants:~For each visits: analysis population includes participants with non-missing value.~For the difference between 2 visits: analysis population only includes participants with non-missing values for both visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Enrollment | 1 Episodes of condomless anal intercourse | Standard Deviation 1.3 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 4 | 1 Episodes of condomless anal intercourse | Standard Deviation 2.3 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 4: Change from previous visit | 0 Episodes of condomless anal intercourse | Standard Deviation 1.1 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 4: Change from baseline | 0 Episodes of condomless anal intercourse | Standard Deviation 1.1 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 5 | 0 Episodes of condomless anal intercourse | Standard Deviation 0.7 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 5: Change from previous visit | -1 Episodes of condomless anal intercourse | Standard Deviation 1.8 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 5: Change from baseline | 0 Episodes of condomless anal intercourse | Standard Deviation 0.7 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 9 | 0 Episodes of condomless anal intercourse | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 9: Change from previous visit | 0 Episodes of condomless anal intercourse | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 9: Change from baseline | -1 Episodes of condomless anal intercourse | Standard Deviation 1.1 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 17 | 0 Episodes of condomless anal intercourse | Standard Deviation 1.1 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 17: Change from previous visit | 0 Episodes of condomless anal intercourse | Standard Deviation 0.8 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 17: Change from baseline | 0 Episodes of condomless anal intercourse | Standard Deviation 0.5 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 25 | 0 Episodes of condomless anal intercourse | Standard Deviation 0.7 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 25: Change from previous visit | 0 Episodes of condomless anal intercourse | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 25: Change from baseline | 0 Episodes of condomless anal intercourse | Standard Deviation 0.7 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 33 | 0 Episodes of condomless anal intercourse | Standard Deviation 0 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 33: Change from previous visit | 0 Episodes of condomless anal intercourse | Standard Deviation 0.8 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Episodes of Anal Intercourse Without a Condom) During the Study Period | Week 33: Change from baseline | -1 Episodes of condomless anal intercourse | Standard Deviation 1.5 |
Secondary
Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period
Counts of sexual partners will be summarized (mean and sd) at enrollment and each regular Step 1 and Step 2 follow-up visit (W4, W5, W9, W17, W25, W33).
Time frame: Measured through participant's first oral visit up to last Step 2 injection visit.
Population: Includes all enrolled participants:~For each visits: analysis population includes participants with non-missing value.~For the difference between 2 visits: analysis population only includes participants with non-missing values for both visits. .
| 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 | Week 5 | 0 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 | Week 4: Change from previous visit | 0 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 | Week 4: Change from baseline | 0 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 | Week 5: Change from previous visit | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 5: Change from baseline | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 9 | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| 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 0.7 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 9: Change from baseline | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 17 | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| 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 0 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 17: Change from baseline | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 25 | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| 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 | 0 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 | Week 25: Change from baseline | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 33 | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| 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 | 0 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 | Week 33: Change from baseline | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Enrollment | 0 Number of Sexual Partners | Standard Deviation 0.4 |
| Cabotegravir Long Acting | Change From Enrollment of Self-reported Sexual Behavior (Number of Sexual Partners) During the Study Period | Week 4 | 0 Number of Sexual Partners | Standard Deviation 0.5 |
Secondary
Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and LaboratoryAbnormalities 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, whichever comes first.
Population: Includes enrolled participants who began step 1 (oral phase).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cabotegravir Long Acting | Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and LaboratoryAbnormalities in the Oral Phase and the Aggregate Oral and Injection Phases | Number of participants with Grade 2 or Higher AEs in Oral Phase | 3 Participants |
| Cabotegravir Long Acting | Count and Percentage of Participants Experiencing Grade 2 or Higher Clinical AEs and LaboratoryAbnormalities 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 | 8 Participants |
Secondary
Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90)
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 from the participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41
Population: Includes enrolled participants who receive at least one injection of CAB LA.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 1 | >=1x - <4x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 1 | >=4x - <8x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 1 | >=8x PA-IC90 | 8 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 2 | <1x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 2 | >=1x - <4x PA-IC90 | 1 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 2 | >=4x - <8x PA-IC90 | 2 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 2 | >=8x PA-IC90 | 6 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 3 | <1x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 3 | >=1x - <4x PA-IC90 | 1 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 3 | >=4x - <8x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 3 | >=8x PA-IC90 | 7 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 4 | <1x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 4 | >=1x - <4x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 4 | >=4x - <8x PA-IC90 | 2 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 4 | >=8x PA-IC90 | 6 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 5 | <1x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 5 | >=1x - <4x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 5 | >=4x - <8x PA-IC90 | 1 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 5 | >=8x PA-IC90 | 6 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Injection 1 | <1x PA-IC90 | 1 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Step 3 +8 weeks | <1x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Step 3 +8 weeks | >=1x - <4x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Step 3 +8 weeks | >=4x - <8x PA-IC90 | 0 Participants |
| Cabotegravir Long Acting | Count of Participant-study Visits Above the Protein-adjusted Inhibitor Concentration (90%; PA-IC90) | Step 3 +8 weeks | >=8x PA-IC90 | 7 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.
Population: Includes all enrolled participants who seroconverted during the study.
| 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 | Number of 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 resistant cases | 0 Participants |
Secondary
Measure Study Product Concentrations in Enrolled Participants With HPTN Laboratory Center (LC) Confirmed HIV Infection Throughout Study.
For infections occurring prior to (or on the first day of) Step 3, we will include visit level plasma CAB concentrations, for individual seroconverters. For infections occurring after the start of Step 3, we will include visit level plasma CAB concentrations as well as concentrations of TFV and TFV-DP (if applicable).
Time frame: Measured through seroconverter's first Oral visit up through end of study participation (step1, 2, 3)
Population: All enrolled participants who became HIV infected during the study (Step 1, 2 or 3).~Serum concentrations were not collected for this measure because no participants had HPTN Laboratory Center (LC) Confirmed HIV Infection at enrollment or during Steps 1,2, and 3.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Measure Study Product Concentrations in Enrolled Participants With HPTN Laboratory Center (LC) Confirmed HIV Infection Throughout Study. | Number of participants HIV-positive at enrollment | — |
| Unknown | Measure Study Product Concentrations in Enrolled Participants With HPTN Laboratory Center (LC) Confirmed HIV Infection Throughout Study. | Number of participants infected | — |
Secondary
Proportion of Injection Visits That Occurred On-time.
Number and percentage of injections given, using the number of injections expected as the denominator. while the 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). Those who have been terminated, are HIV infected, or have permanently discontinued study products at the time of visit will be excluded from the number of expected injections.
Time frame: Measured through participant's last step 2 injection.
Population: Includes enrolled participants who receive at least one injection of CAB LA.~By the end of step 2, just 1/8 participants missed their last injection but continued with the study and received a step 3 injection. This participant was counted as having 100% of injections completed with 5 injections. For this analysis, through the end of Step 2, technically 1 less injection was given in this case.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cabotegravir Long Acting | Proportion of Injection Visits That Occurred On-time. | Number of injections given | 40 Number of Injections given |
| Cabotegravir Long Acting | Proportion of Injection Visits That Occurred On-time. | Number of injections given on-time | 32 Number of Injections given |
95% CI: [51.8, 99.7]
Secondary
Proportion of Participants Receiving One or More Injections Who Experience Grade 2 or Higher Clinical AEs and Laboratory Abnormalities From Initial Injection to 36 Weeks Later.
Number and percent of participants experiencing any Grade 2 or higher clinical adverse events (AEs) or laboratory abnormalities from the first injection visit to approximately 36 weeks later regardless of whether participants received all 5 injections.
Time frame: Measured through participant's first injection visit up to 8 weeks after the last Step 2 injection visit or Week 41, whichever comes first.
Population: Includes enrolled participants who receive at least one injection of CAB LA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cabotegravir Long Acting | Proportion of Participants Receiving One or More Injections Who Experience Grade 2 or Higher Clinical AEs and Laboratory Abnormalities From Initial Injection to 36 Weeks Later. | 8 Participants |
95% CI: [51.8, 99.7]