What is the most suitable HIV prevention regimen for a patient with high-risk bisexual behavior and multiple medications for diabetes?

HIV Prevention for High-Risk Bisexual Male Patient

For this 48-year-old male with high-risk bisexual behavior, injectable cabotegravir (Apretude) 600 mg IM is the appropriate HIV prevention regimen, administered as two initial injections 4 weeks apart, followed by injections every 8 weeks (not monthly for 2 months as stated in the plan). 1

Correcting the Dosing Schedule

The proposed plan contains a critical dosing error. The correct FDA-approved dosing schedule for cabotegravir long-acting injectable PrEP is:

• Initial dosing: 600 mg IM for the first two injections, separated by 4 weeks 1
• Maintenance dosing: 600 mg IM every 8 weeks thereafter 1
• The plan stating "monthly for 2 months then every 2 months" is incorrect and does not align with FDA labeling 2

Why Injectable Cabotegravir is Appropriate for This Patient

Cabotegravir LA demonstrated superior efficacy compared to daily oral TDF/FTC in preventing HIV acquisition in men who have sex with men and transgender women, with an 66% relative risk reduction (hazard ratio 0.34) 3. This makes it an excellent choice for this high-risk patient population.

Patient-Specific Advantages:

• Eliminates daily oral adherence concerns: The patient is already on multiple medications for diabetes, and adding another daily oral medication increases pill burden and potential adherence challenges 1
• Patient preference for injectable route: The patient explicitly prefers IM administration, which aligns with the cabotegravir formulation 2
• High-risk behavior profile: History of chlamydia and multiple sexual encounters despite reported consistent condom use indicates ongoing risk that warrants highly effective PrEP 1

Pre-Initiation Requirements (Critical Safety Steps)

Before administering the first cabotegravir injection, the following tests are mandatory:

• Combined HIV antibody and antigen testing to confirm HIV-negative status 1, 4
• HIV RNA testing if any clinical suspicion of acute infection exists (recent exposure <1 month or acute symptoms) 2
• Serum creatinine and estimated creatinine clearance 1, 4
• Hepatitis B surface antigen (HBsAg) 1, 4
• Hepatitis C antibody 1, 4
• STI screening: Gonorrhea and chlamydia testing by NAAT (genital and extragenital sites) 1, 4
• Baseline liver function tests (AST/ALT) 1

Critical Pitfall to Avoid:

Never initiate cabotegravir if HIV status is uncertain or if acute HIV infection is suspected, as monotherapy with cabotegravir alone can lead to rapid development of integrase resistance mutations (particularly Q148R and E138A/K substitutions) 2. If HIV infection is diagnosed after cabotegravir exposure, transition immediately to a complete treatment regimen using a protease inhibitor or NNRTI-based regimen, not an INSTI-based regimen 1.

Monitoring Schedule During Cabotegravir PrEP

At Each Injection Visit (Every 8 Weeks After Initial Phase):

• Rapid point-of-care HIV testing on the day of injection prior to administration 1
• Combined antibody/antigen test sent to laboratory (but do not delay injection for results) 1

Every 4 Months (Every Second Injection):

• STI screening (gonorrhea, chlamydia, syphilis) 1

Every 6 Months:

• Liver enzyme monitoring (AST/ALT) 1
• Renal function assessment (creatinine clearance) 4

Managing Missed or Delayed Injections

This is a common clinical scenario requiring specific guidance:

• If injection is <8 weeks late: Resume as soon as possible after confirming HIV-negative status 1
• If injection is ≥8 weeks late from due date: Restart the initial dosing schedule (two injections 4 weeks apart) before returning to the 8-week maintenance interval 1
• During any dosing interruption: Consider bridging with daily oral TDF/FTC if the patient remains at risk 1

Special Considerations for This Patient

Diabetes and Polypharmacy:

• Review all diabetes medications for potential drug interactions: Cabotegravir has minimal drug-drug interactions compared to boosted regimens, making it suitable for patients on multiple medications 5
• No dose adjustments needed for renal impairment unless creatinine clearance is severely compromised 2

Hepatitis B Considerations:

• If HBsAg-positive: Cabotegravir does not treat hepatitis B. If PrEP is discontinued, the patient will need alternative hepatitis B therapy or close monitoring for hepatitis flares 4

Injection Site Reactions (Most Common Adverse Effect)

Injection site reactions occur in approximately 81-92% of cabotegravir recipients, but rarely lead to discontinuation 6, 7, 3. Management strategies include:

• Aggressive management with topical and systemic analgesics 1
• Hot or cold packs 1
• Reassurance that reactions are typically Grade 1-2 (mild to moderate) and decrease over time 7

Only 4% of participants discontinued due to injection intolerance in clinical trials, and most participants (75-79%) reported satisfaction and willingness to continue 6.

Monitoring for Hepatotoxicity and Depression

• Hepatotoxicity has been reported with cabotegravir: Monitor liver enzymes every 6 months and discontinue if hepatotoxicity is confirmed 2
• Depressive disorders reported in clinical trials: Screen for mood changes, depression, and suicidal ideation at each visit 2

If HIV Infection Occurs Despite PrEP

In the event of HIV acquisition while receiving cabotegravir PrEP:

• Obtain genotypic resistance testing including integrase mutations 1
• Initiate treatment with a dolutegravir-, bictegravir-, or ritonavir-boosted darunavir-based regimen (not raltegravir or elvitegravir, as cross-resistance is common) 1
• Expect potential INSTI resistance mutations (E138A+Q148R or G140A+Q148R), which confer cross-resistance to raltegravir and elvitegravir but retain susceptibility to dolutegravir and bictegravir 2, 3

Cost and Coverage Considerations

The plan mentions concerns about CPT code J0739 with costs exceeding $5000. Cabotegravir LA (Apretude) is expensive, typically exceeding $3,000 per injection, but patient assistance programs and insurance coverage pathways exist. Work with pharmacy and insurance to secure prior authorization, emphasizing the superior efficacy compared to oral PrEP and the patient's specific clinical circumstances (polypharmacy, preference for injectable route, high-risk behavior) 8.