What are the key aspects of Pre-Exposure Prophylaxis (PrEP) and other main Human Immunodeficiency Virus (HIV) medications, including their mechanisms, indications, and side effects?

From the Guidelines

PrEP is recommended for individuals at risk for HIV infection, with tenofovir disoproxil fumarate/emtricitabine once daily being the recommended oral PrEP regimen 1. The key aspects of Pre-Exposure Prophylaxis (PrEP) and other main Human Immunodeficiency Virus (HIV) medications include their mechanisms, indications, and side effects.

Mechanisms and Indications

• PrEP is a medication strategy for HIV prevention that involves taking antiretroviral drugs before potential exposure to HIV.
• The main PrEP options include Truvada (emtricitabine/tenofovir disoproxil fumarate) and Descovy (emtricitabine/tenofovir alafenamide), typically taken as one pill daily.
• For HIV treatment, the standard approach is antiretroviral therapy (ART) using a combination of medications from different drug classes.
• Common regimens include integrase strand transfer inhibitors (like Biktarvy, Triumeq, or Dovato) combined with nucleoside reverse transcriptase inhibitors.
• These medications work by preventing HIV from replicating in different ways - blocking viral entry into cells, inhibiting viral DNA production, or preventing viral integration into host DNA.

Side Effects and Monitoring

• Side effects vary by medication but may include nausea, headache, fatigue, and kidney or bone density issues with some drugs.
• Regular medical monitoring is essential for both PrEP users and HIV treatment patients to assess effectiveness, manage side effects, and monitor organ function.
• HIV medications must be taken consistently to maintain effectiveness, as poor adherence can lead to viral resistance.
• Initiation of PrEP is recommended as soon as feasible for individuals who have chosen to use it 1.
• PrEP is highly effective when taken as prescribed, reducing HIV infection risk by about 99%, while modern HIV treatments can reduce viral loads to undetectable levels, preventing transmission and allowing people with HIV to live normal, healthy lives.

Special Considerations

• For men who have sex with men (MSM), a double dose (2 pills) of tenofovir disoproxil fumarate/emtricitabine is recommended on the first day 1.
• For MSM with or at risk for kidney dysfunction, osteopenia, or osteoporosis, daily tenofovir alafenamide/emtricitabine is recommended 1.
• Oral PrEP dosing using the 2-1-1 (or on-demand) method is recommended only for MSM 1.
• Injectable cabotegravir every 8 weeks is recommended (pending approval by regulatory agencies and availability) as PrEP for cisgender men and transgender women who have sex with men 1.

From the Research

Mechanisms of Pre-Exposure Prophylaxis (PrEP)

• PrEP medications, such as emtricitabine/tenofovir disoproxil fumarate (TDF) and emtricitabine/tenofovir alafenamide (TAF), work by preventing the HIV virus from replicating in the body 2, 3.
• The combination antiretroviral regimen, TDF/emtricitabine, has been shown to prevent HIV transmission when taken as a single pill once daily 2.

Indications for PrEP

• PrEP is indicated for individuals at high risk of acquiring HIV, including men who have sex with men, high-risk heterosexuals, and injection drug users who share injection equipment 2, 4.
• The Centers for Disease Control and Prevention (CDC) recommends that people at high risk for HIV acquisition be offered PrEP 5.

Efficacy of PrEP

• The efficacy of daily TDF/emtricitabine exceeds 90% but is highly correlated with degree of adherence 2.
• On-demand PrEP has been shown to be a valid alternative to daily PrEP for men who have sex with men (MSM), providing greater choice in HIV prevention 6.

Side Effects of PrEP

• TDF/emtricitabine is safe and well-tolerated, with only 2% of people discontinuing PrEP due to adverse effects 2.
• Common side effects of PrEP include renal dysfunction and bone mineral density loss 4.
• On-demand PrEP has been associated with a low incidence of treatment-related adverse events, including nausea, vomiting, and diarrhea 6.

Resistance to PrEP

• Resistance to TDF/emtricitabine when used for PrEP is rare (<0.1%) and usually occurs when PrEP is inadvertently prescribed to individuals with undiagnosed acute HIV infection 2.
• The development of drug resistance in the event of seroconversion is a concern with PrEP use 4.

Future of PrEP

• Several investigational drugs are in the pipeline for PrEP against HIV infection, including integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) 5.
• Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition 5.