PrEP Breakthrough risks

I've used PrEP on and off over the years, and got curious about how breakthrough infections might (at least in theory) happen. I spent a few hours searching and asking an AI questions, and here are the things that bottoms might not realize are reducing the effectiveness of their PrEP meds. This list focuses on the biological and mechanical drivers of HIV transmission. Within the "chasing" and "gifting" subcultures, these factors are often combined to create the highest possible "viral challenge" to a PrEP regimen.

Baseline transmission rates

In clinical research, "average" receptive anal sex (bottoming) without a condom involves an HIV-positive partner with a detectable but chronic viral load (typically in the tens of thousands, not millions).

Baseline Transmission Risk: 1.4% per act (approximately 1 in 72).

PrEP Effectiveness (Baseline): 99% reduction in risk, resulting in a 0.014% chance per act (approximately 1 in 7,000).

Ranked Risk Factors for PrEP Breakthrough

Ordered from the most significant biological "multiplier" to the lowest. The "baseline risk multiplier" is in parentheses for each action.

• Acute Phase Viral Load (Partner): An insertive partner who was infected 2–4 weeks ago has a viral load in the millions. This is the #1 driver of breakthrough. (20-26x)
• Transmitted Drug Resistance (TDR): If the partner’s virus is already resistant to the drugs in Truvada/Descovy (mutations like M184V or K65R), PrEP effectiveness drops toward 0%. (10-50x)
• Rectal Trauma (Mechanical Shearing): Visible or microscopic tearing caused by large girth, "hard" thrusting, or aggressive dilation. This provides the "bloodstream shortcut." (3-8x)
• Multiple HIV+ Partners (Serial Exposure): Engaging in a "train" or "pozzing party." This is a numbers game; each new ejaculation is a fresh "roll of the dice" against the medication. (Each partner increases risk by 1%)
• Post-Sex "Sealing" (Butt Plug): Inserting a plug immediately after sex to prevent ejaculate leakage and force deeper absorption through pressure. (2-3x)
• Active Rectal STIs (Syphilis/Gonorrhea/Chlamydia): STIs recruit a massive number of HIV "target cells" to the surface of the tissue and cause "leaky" inflammation. (3-5x)
• Drug Use (Crystal Meth/PNP): Specifically because meth causes vasoconstriction followed by intense inflammation, and it often leads to longer, more vigorous sex sessions that cause significantly more tissue damage. (3-5x)
• Deep Sigmoid Deposition: Utilizing a long penis (8"+) or positions like "Legs on Shoulders" to deposit semen past the rectum and into the more vascular sigmoid colon. (1.5-2x)
• Short Refractory Period (The "Double Load"): A top who can ejaculate again within 30 minutes. This introduces a second massive viral challenge before the body has even begun to process or expel the first. (1.5-2x)
• Deep Saline Douching: Stripping the protective mucus layer and causing osmotic stress to the cells, making them more permeable. (2x)
• Popper Use (Alkyl Nitrites): While poppers relax the sphincter (reducing some tear risk), they are vasodilators. They increase blood flow to the rectal tissues, which may theoretically speed up the systemic absorption of the virus once it crosses the membrane. (1.5-2x)

Highly Multiplicative Combinations

This table highlights how certain actions, when combined, create a risk that is greater than the sum of its parts—even with an "average" partner (Viral load ~100k, 6-7" inch penis). PrEP's approximate effectiveness is in parentheses.

• Crystal Meth + "Legs on Shoulders" - Meth reduces pain perception and increases stamina, leading to much more aggressive, prolonged "piston" trauma in the deepest part of the tract. (95-97%)
• Deep Douching + Multiple Partners - The mucus "shield" is gone. Each subsequent partner is depositing virus onto raw, exposed tissue that is increasingly inflamed by repeated friction. (96-98%)
• Popper Use + Post-Sex Plug - Poppers dilate the blood vessels (making them "wider" and more receptive) while the plug provides the pressure to force the virus into those vessels. (98-99%)
• Short Refractory Period + Sigmoid Depth - The first load acts as a "lubricant" and "buffer" that allows the second load to be pushed even deeper and stay in contact with the tissue longer. (85-90%)
• Meth (Slamming/Injection) + "Legs up" Missionary - Injecting meth causes systemic inflammation and affects the gut's immune environment, making the receptive partner’s T-cells more "activated" and easier for HIV to infect. (95-97%)
• "Dry" Sex + Aggressive Dilation - Using toys to stretch the area and then having sex with minimal lube creates "micro-fissures" that act as direct conduits to the bloodstream. (94-97%)

Even "normal" play can have a meaningful reduction in the overall protection PrEP provides.

Action Added - Cumulative Multiplier - Breakthrough Probability (on PrEP)

• Baseline (Standard sex) - 1x - 0.014% (1 in 7,000)
• + Deep Douching - 2.8x - 0.04% (1 in 2,500)
• + Toy Dilation - 5.6x - 0.08% (1 in 1,250)
• + Legs on Shoulders - 11.2x - 0.15% (1 in 660)
• + Poppers - 16.8x - 0.23% (1 in 430)
• + Cum again (2 loads in a session) - 25.2x - 0.35% (1 in 285)

If you take that, and add a top who's got a bigger than average (6") dick, you're looking at:

• 7" length / 4.9" girth - 45.4x - 0.64% (1 in 156)
• 8" length / 5.2" girth - 81.7x - 1.14% (1 in 88)
• 9" length / 5.5" girth - 147.0x - 2.06% (1 in 48)

Even an average sized top (or a little bigger than average) who takes their time before they bust their load can cause a much higher risk of a breakthrough, especially if he "plugs you up" to use the first load as lube for the second round:

• Baseline (~5 minutes of thrusting):
  • First load - 16.8x  - 0.23% (1 in 430)
  • Second load - 25.2x - 0.35% (1 in 285)
  • Plugged for 20 minutes after each load - 2.5x - 0.88% (1 in 114)
  • 7" top - 2.2x - 1.94% (1 in 52)
• 10 minutes of thrusting
  • First load - 21.8x  - 0.30% (1 in 330)
  • Second load - 32.8x - 0.46% (1 in 217)
  • Plugged for 20 minutes after each load - 2.5x - 1.15% (1 in 87)
  • 7" top - 2.2x - 2.53% (1 in 40)
• 20 minutes of thrusting
  • First load - 37.0x  - 0.51% (1 in 196)
  • Second load - 55.4x - 0.78% (1 in 128)
  • Plugged for 20 minutes after each load - 2.5x - 1.95% (1 in 51)
  • 7" top - 2.2x - 4.29% (1 in 23)

• 30 minutes of thrusting
  • First load - 62.4x  - 0.87% (1 in 115)
  • Second load - 93.6x - 1.31% (1 in 76)
  • Plugged for 20 minutes after each load - 2.5x - 3.28% (1 in 30)
  • 7" top - 2.2x - 7.22% (1 in 14)

• 45 minutes of thrusting (a true marathon top)
  • First load - 137.2x  - 1.92% (1 in 52)
  • Second load - 205.8x- 2.88% (1 in 35)
  • Plugged for 20 minutes after each load - 2.5x - 7.20% (1 in 14)
  • 7" top - 2.2x - 7.20% (1 in 6)