Acceptability and Feasibility of Injectable Cabotegravir Pre-exposure Prophylaxis (PrEP) Versus Oral PrEP in Routine Care up to 15 Months in Private Pharmacies in South Africa

Study Overview
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Brief Summary
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This is a mixed methods study employing a convergence model triangulation design. Participants in the study will be sexually active young adults starting PrEP at private pharmacies, who will be offered either CAB-LA, oral PrEP (TDF/FTC[3TC]), or PrEP deferment at each of their regular visits, with the option to switch between options for up to 15 months, with a final exit interview following the transition to standard-of-care. The number of study visits will vary, depending on participant PrEP choices. Those choosing oral PrEP, will be seen 3 monthly from V2 onwards, but those choosing CAB-LA, will be seen 2 monthly from V2. A maximum of 9 visits is possible.

Detailed Description
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In the ATLAS study participants were asked, after they had transitioned back to conventional oral antiretroviral therapy, whether they preferred injectable or oral treatment. Their feedback on their preference overwhelming favoured injectables9. Women and men will be recruited from existing Ezintsha programs operating within the pharmacies, using current government criteria for PrEP initiation. PrEP will be initiated and monitored according to these and the PIMART guidelines. PrEP, through these programs, will be offered free of charge. The study is designed to be as real-world as possible. Adaptations to routine PrEP guidelines have been made to accommodate visit-based HIV testing (based on the injectable regimens, which require more frequent access to the clinic). Participant re-imbursement will therefore be for the baseline, midand end-of-study interviews in participants consenting to these interviews. The maximum amount of time a participant on the study can be on either CAB- LA or oral PrEP, or a combination, or, indeed, on neither drug, is therefore 15 months (and an additional three months on oral PrEP during the transition, as standard of care). The Investigator anticipate that participants will favour CAB- LA, but also anticipate that there may be interesting patterns of use when they learn that they may defer access to CAB- LA or oral PrEP. Participants may favour PrEP, as they may prefer three monthly visits over the two monthly injection requirements. The Investigator may see participants initially choosing oral PrEP, and then moving to CAB- LA, or even vice versa. The Investigator is unclear on what men may favour versus women. The Investigator will endeavour to recruit at least 20 men in the study, appreciating that not much is known about this group in the sub-Saharan Africa context. One of the most important analyses that will flow from information collected when assessing for PrEP eligibility is the risk profile of the participants taking up PrEP, a key issue when assessing cost effectiveness. Finally, the investigator is not excluding women or men who defer PrEP initially. These various combinations will provide interesting quantitative, but more importantly, qualitative data on preferences, and on how services may be improved to accommodate participants' choices.

Official Title
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Acceptability and Feasibility of Injectable Cabotegravir Pre-exposure Prophylaxis (PrEP) Versus Oral PrEP in Routine Care up to 15 Months in Private Pharmacies in South Africa

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Cabotegravir Injection [Apretude]
* Drug: Tenofovir disoproxil fumarate / emtricitabine (or lamivudine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Each participant must meet all of the following criteria to be enrolled in this study: Adult male or female (≥18 and ≤ 35 years old) Is self-reported sexually active HIV negative at the time of study enrolment (as determined by a rapid blood test for HIV 1) Body weight ≥ 35 kilograms. Creatinine clearance ≥ 60 mL/min. Willingness to sign informed consent. Exclusion Criteria: - Participants meeting the following criteria will be excluded from participating in the study: Symptoms of HIV seroconversion (see Table 1). Pregnant (participant must have a negative beta human chorionic gonadotrophin (b-hCG) urine test at screening) or lactating women, or women intending to become pregnant or breastfeed during the study. Is in good health, with no surgical or medical condition which may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the safety of the volunteer or the objectives of the study or impair their ability to comply with the dosing schedule and/or protocol evaluations. The Investigator should make this determination in consideration of the volunteer's medical history. This including, but not limited to, the following: a. History of severe hepatic impairment, history of liver cirrhosis with or without viral hepatitis co-infection. b. Unstable or poorly controlled seizure disorder. c. History of coagulopathies, or current or anticipated need for chronic anticoagulation. d. Presence of a tattoo or other dermatological condition overlying the gluteus region which would realistically obstruct administration of an intramuscular injection. Known hypersensitivity to or specific contraindications to the use of TDF or FTC/3TC or CABLA. Hep B surface antigen positive or known active Hep B infection. Is receiving or has received the following agents within 28 days prior to screening, and cannot discontinue their use for the duration of the study: tuberculosis therapy (i.e., rifampicin, rifapentine, rifabutin) anticoagulation agents; anti-convulsants (e.g. carbamazepine, oxcarbazepine, phenobarbital, phenytoin); herbal products (e.g. St John's Wort). Concurrent use of PrEP from a different medical provider, other than the study site Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results. Inability or unwillingness to be followed up for the study period, including plans to move out the study geographical area in the next 12 months or otherwise unable to participate in the study visits as determined by the PI.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Adult (≥18 and ≤ 35 years old) male or female willing to access PrEP at the same pharmacy for up to 2 years
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cabotegravir Long Acting Injectable<br>Investigational Product: Cabotegravir Dosage Formulation: 600 mg suspension for injection Route of Administration: Intra-muscular injection Dosing Instructions: 1 vial (600 mg) injected monthly for the initial visit (Month 1 and 2), then every 2 months thereafter (from Month 2 onwards) | Drug: Cabotegravir Injection [Apretude]<br>* White to slightly pink free flowing suspension suspension for injection contained in a brown coloured vial. Each vial is for single use and does not require dilution prior to administration.<br>* Other names: Apretude;|
| Active Comparator: Tenofovir disoproxil fumarate + Emtricitabine/Lamivudine (TDF/FTC[3TC])<br>Investigational Product: Tenofovir disoproxil fumarate / emtricitabine (or lamivudine) Dosage Formulation: 300 mg / 200 mg (300mg) fixed dose combination tablet Route of Administration: Oral Dosing Instructions: 1 tablet (300/200/ TDF/FTC) daily or (300/300/TDF/3TC) daily | Drug: Tenofovir disoproxil fumarate / emtricitabine (or lamivudine)<br>* TDF/FTC is currently available as standard of care for PrEP in the public sector as per the department of health guidelines.<br>* Other names: Tenemine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe acceptability of CAB-LA (Long-Acting Cabotegravir) PrEP, amongst different PrEP modalities, including PrEP deferment, in eligible men and women. | Acceptability of CAB-LA (Long-Acting Cabotegravir) as determined by qualitative and quantitative assessment using piloted and validated semi-structured questionnaires for acceptability. (Quantitative data will be expressed as ratios) | 15 Months | 
| To describe acceptability of CAB-LA (Long-Acting Cabotegravir) PrEP, amongst different PrEP modalities, including PrEP deferment, in eligible men and women. | Acceptability of Intervention Measure (AIM)/ Intervention Appropriateness Measure/ (IAM), at 12 months and end of study. (Expressed as ratios where applicable) | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To describe feasibility of CAB-LA (Long-Acting Cabotegravir) PrEP implementation, amongst different PrEP modalities, including PrEP deferment, in eligible men and women. | Feasibility of CAB-LA (Long-Acting Cabotegravir) as determined by qualitative and quantitative assessment using piloted or validated semi-structured questionnaires and on feasibility conducted with participants and healthcare workers. | 15 Months | 
| To describe feasibility of CAB-LA (Long-Acting Cabotegravir) PrEP implementation, amongst different PrEP modalities, including PrEP deferment, in eligible men and women. | Feasibility of Intervention Measure (FIM) completed by healthcare workers at exit and participants at 12 months and end of study. | 12 Months | 
| To describe the association of socio-demographic factors, reported sexual behaviour, PrEP knowledge and previous PrEP use on PrEP choice. | Tests of association between PrEP choice and selected predictor variables. | 15 Months | 
| To describe the association of socio-demographic factors, reported sexual behaviour, PrEP knowledge and previous PrEP use on PrEP choice. | Proportion of individuals who are using each type of PrEP collected at study start, month 12 and end of study. | 12 Months | 
| To describe the uptake, persistence and patterns of transition on each form of PrEP. | Attending all study visits/retention extracted from participant EDC (Electronic Data Capture) visit forms. | 15 Months | 
| To describe a risk profile of those taking up both PrEP regimens, as well as those deferring PrEP. | Willingness to take CAB-LA (Long-Acting Cabotegravir) for the entire study duration extracted from participant EDC forms | 15 Months | 
| To describe a risk profile of those taking up both PrEP regimens, as well as those deferring PrEP. | Willingness to take CAB-LA post study stop collected at end of study using semi-structured interviews. | 15 Months | 
| To describe operational suggestions from the participants regarding how health services could be improved regarding better/more comfortable/faster/cheaper/other add-on sexual reproductive services. | Extent to which the study staff could easily administer CAB-LA (Long-Acting Cabotegravir). | 15 Months | 
| To describe the provider experiences and perceptions of CAB-LA (Long-Acting Cabotegravir) PrEP implementation, amongst different PrEP modalities, including PrEP deferment, in eligible men and women. | Healthcare worker perspectives on maintenance, demand creation and service delivery post study completion collected during a focus group discussion conducted at the end of the study. | 15 Months | 
| To describe participant willingness-to-pay for PrEP services at the end of the study. | Willingness to pay for CAB-LA (Long-Acting Cabotegravir) collected at the end of the study using semi-structured interviews. | 15 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pre-Exposure Prophylaxis (PrEP), Long Acting Injectable, Cabotegravir