Clinical trial NCT06138600: 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
Official title: 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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: HIV Infections
Keywords: Pre-Exposure Prophylaxis (PrEP)
Long Acting Injectable
Cabotegravir
Lead sponsor: University of Witwatersrand, South Africa
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare
First posted: 2023-11-18
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Adult (≥18 and ≤ 35 years old) male or female willing to access PrEP at the same pharmacy for up to 2 years
Primary purpose: PREVENTION

Brief summary: This is a mixed methods study employing a convergence model triangulation design. Participants in the study will be sexually active young adults starting Pre-exposure Prophylaxis at private pharmacies, who will be offered either Cabotegravir Long-Acting Injectable, oral Pre-exposure Prophylaxis (TDF/FTC\[3TC\]), or Pre-exposure Prophylaxis 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 Pre-exposure Prophylaxis choices. Those choosing oral Pre-exposure Prophylaxis will be seen 3 monthly from V2 onwards, but those choosing Cabotegravir Long-Acting Injectable will be seen 2 monthly from V2. A maximum of 9 visits is possible.

Detailed description: 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 Pre-exposure Prophylaxis initiation. Pre-exposure Prophylaxis will be initiated and monitored according to these and the Pharmacist-Initiated Management of Antiretroviral Therapy guidelines. Pre-exposure Prophylaxis, through these programs, will be offered free of charge. The study is designed to be as "real-world" as possible. Adaptations to routine Pre-exposure Prophylaxis guidelines have been made to accommodate visit-based HIV testing (based on the injectable regimens, which require more frequent access to the clinic). Participant reimbursement will therefore be for the baseline, mid and end-of-study interviews in participants consenting to these interviews. The maximum amount of time a participant in the study can be on either Cabotegravir Long-Acting Injectable or oral Pre-exposure Prophylaxis, or a combination, or, indeed, on neither drug, is therefore 15 months (and an additional three months on oral Pre-exposure Prophylaxis during the transition, as standard of care).

The Investigator anticipates that participants will favour Cabotegravir Long-Acting Injectable, but also anticipates that there may be interesting patterns of use when they learn that they may defer access to Cabotegravir Long-Acting Injectable or oral Pre-exposure Prophylaxis. Participants may favour Pre-exposure Prophylaxis, as they may prefer three monthly visits over the two monthly injection requirements. The Investigator may see participants initially choosing oral Pre-exposure Prophylaxis, and then moving to Cabotegravir Long-Acting Injectable, or even vice versa. The Investigator is unclear on what men may favour versus women. The Investigator will endeavor 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 Pre-exposure Prophylaxis eligibility is the risk profile of the participants taking up Pre-exposure Prophylaxis, a key issue when assessing cost-effectiveness. Finally, the investigator is not excluding women or men who defer Pre-exposure Prophylaxis 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.

Eligibility criteria: Inclusion Criteria:

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Each participant must meet all of the following criteria to be enrolled in this study:

1. Adult male or female (≥18 and ≤ 35 years old)
2. Is self-reported sexually active
3. HIV negative at the time of study enrolment (as determined by a rapid blood test for HIV 1)
4. Body weight ≥ 35 kilograms.
5. Creatinine clearance ≥ 60 mL/min.
6. Willingness to sign informed consent.

Exclusion Criteria:

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Participants meeting the following criteria will be excluded from participating in the study:

1. Symptoms of HIV seroconversion (see Table 1).
2. 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.
3. 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.
4. Known hypersensitivity to or specific contraindications to the use of TDF or FTC/3TC or CABLA.
5. Hep B surface antigen positive or known active Hep B infection.
6. 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:

   1. tuberculosis therapy (i.e., rifampicin, rifapentine, rifabutin)
   2. anticoagulation agents;
   3. anti-convulsants (e.g. carbamazepine, oxcarbazepine, phenobarbital, phenytoin);
   4. herbal products (e.g. St John's Wort).
7. Concurrent use of PrEP from a different medical provider, other than the study site
8. 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.
9. 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.

Primary outcomes:
measure: To describe acceptability of CAB-LA (Long-Acting Cabotegravir) PrEP, amongst different PrEP modalities, including PrEP deferment, in eligible men and women.
timeFrame: 15 Months
measure: To describe acceptability of CAB-LA (Long-Acting Cabotegravir) PrEP, amongst different PrEP modalities, including PrEP deferment, in eligible men and women.
timeFrame: 12 Months
Secondary outcomes:
measure: To describe feasibility of CAB-LA (Long-Acting Cabotegravir) PrEP implementation, amongst different PrEP modalities, including PrEP deferment, in eligible men and women.
timeFrame: 15 Months
measure: To describe feasibility of CAB-LA (Long-Acting Cabotegravir) PrEP implementation, amongst different PrEP modalities, including PrEP deferment, in eligible men and women.
timeFrame: 12 Months
measure: To describe the association of socio-demographic factors, reported sexual behaviour, PrEP knowledge and previous PrEP use on PrEP choice.
timeFrame: 15 Months
measure: To describe the association of socio-demographic factors, reported sexual behaviour, PrEP knowledge and previous PrEP use on PrEP choice.
timeFrame: 12 Months
measure: To describe the uptake, persistence and patterns of transition on each form of PrEP.
timeFrame: 15 Months
measure: To describe a risk profile of those taking up both PrEP regimens, as well as those deferring PrEP.
timeFrame: 15 Months
measure: To describe a risk profile of those taking up both PrEP regimens, as well as those deferring PrEP.
timeFrame: 15 Months
measure: 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.
timeFrame: 15 Months
measure: 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.
timeFrame: 15 Months
measure: To describe participant willingness-to-pay for PrEP services at the end of the study.
timeFrame: 15 Months
Other outcomes:
measure: To describe patient reported and clinical significant adverse events of CAB LA (Long-Acting Cabotegravir) and oral PrEP(TDF/FTC[3TC]) over 15 months
timeFrame: 15 Months
measure: To describe patient reported and clinical significant adverse events of CAB LA (Long-Acting Cabotegravir) and oral PrEP(TDF/FTC[3TC]) over 15 months
timeFrame: 15 Months
measure: To describe patient reported and clinical significant adverse events of CAB LA (Long-Acting Cabotegravir) and oral PrEP(TDF/FTC[3TC]) over 15 months
timeFrame: 15 Months
measure: Viral integrase inhibitor resistance mutations in participants who seroconvert while on CAB-LA (Long-Acting Cabotegravir) PrEP will be documented.
timeFrame: 15 Months
measure: Viral integrase inhibitor resistance mutations in participants who seroconvert while on CAB-LA (Long-Acting Cabotegravir) PrEP will be documented.
timeFrame: 15 Months
Locations:
city: Johannesburg
country: South Africa
facility: Ezintsha, a division of Wits Health Consortium
state: Gauteng
Study officials:
affiliation: Ezintsha, a division of Wits Health Consortium
name: Francois WD Venter, MBBCh
role: STUDY_DIRECTOR
affiliation: Ezintsha, a division of Wits Health Consortium
name: Simiso M Sokhela, MBBCh
role: PRINCIPAL_INVESTIGATOR
affiliation: Ezintsha, a division of Wits Health Consortium
name: Nonkululeko M Mashabane, BPharm
role: STUDY_CHAIR
References: