Why can HIV still be transmitted even when the viral load is undetectable with antiretroviral therapy (ART)?

HIV Transmission with Undetectable Viral Load

The premise of your question contains an important misconception: when HIV viral load is truly and consistently undetectable on antiretroviral therapy (ART), HIV is NOT transmitted sexually—this is the scientifically proven "Undetectable = Untransmittable" (U=U) concept. 1

However, the older guidelines you may be referencing reflect outdated understanding from the early 2000s, before we had definitive proof of U=U.

Why Historical Guidelines Were Cautious

The 2003 CDC guidelines stated that clinicians should assume all patients receiving therapy, even those with undetectable plasma HIV levels, can still transmit HIV 1. This conservative stance was based on several concerns:

• HIV can be detected in genital compartments (semen, rectal secretions, female genital secretions, and pharynx) even when plasma viral load is undetectable 1
• Adherence variability means viral suppression depends on consistent medication taking, and treatment interruptions lead to viral load rebound and increased transmission risk 1
• Compartmentalization of HIV in different body fluids meant that plasma viral load didn't always reflect genital tract viral load 1

The Modern Evidence: U=U is Real

Current 2020 guidelines from the International Antiviral Society-USA Panel definitively state that immediate or early ART treatment eliminates sexual transmission once viral load is undetectable for 6 months and remains undetectable 1. This represents a paradigm shift based on:

• Large prospective studies proving zero HIV transmissions from virally suppressed individuals
• Understanding that sustained undetectable viral load (typically defined as <200 copies/mL in transmission studies) prevents sexual transmission 2

Critical Distinctions: When Transmission Risk Exists

Transmission risk remains in specific scenarios:

1. Imperfect Adherence

• Nonadherence to ART is associated with younger age, Black race/ethnicity, public health insurance, lower CD4 counts, more complex regimens, and binge drinking 3
• Even PWH with undetectable viral loads who have poor adherence are at risk for future viremia and potential transmission during breakthrough episodes 4
• Low drug concentrations despite viral suppression predict future viremia, particularly in Black individuals, those with BMI >30 kg/m², and those reporting <100% adherence 4

2. Treatment Interruptions

• Any scheduled or unscheduled treatment interruption will likely cause viral load rebound and increased transmission risk 1

3. Definition of "Undetectable"

• Most U=U studies used a threshold of <200 copies/mL, not the more sensitive assays with lower limits of 20-50 copies/mL 2
• Viral loads between 50-200 copies/mL ("low-level viremia") have been associated with future virologic failure, though no transmission has been documented at these levels 2

4. Non-Sexual Transmission Routes

• U=U applies only to sexual transmission
• For injection drug use, the only certain prevention is abstaining from injection or not sharing equipment (syringes, needles, cookers, cottons, water) 1
• Neither ART nor post-exposure prophylaxis is a reliable substitute for avoiding HIV exposure through injection equipment 1

How This Differs from Hepatitis

Your comparison to hepatitis is astute. The key differences:

• Hepatitis B can be transmitted even with undetectable viral loads because HBV integrates into hepatocyte DNA and can exist in covalently closed circular DNA (cccDNA) form that persists despite antiviral therapy
• HIV does not have the same reservoir dynamics in genital secretions when plasma viremia is durably suppressed
• The compartmentalization concern from 2003 1 has been disproven by large transmission studies showing zero transmissions with sustained viral suppression

Clinical Bottom Line

For patients with HIV on ART:

• Sustained undetectable viral load (<200 copies/mL for ≥6 months) eliminates sexual transmission risk 1
• Monitor viral load every 3 months until suppressed for 1 year, then every 6 months 5
• Address adherence barriers aggressively, particularly in high-risk groups (younger patients, those with substance use, complex regimens) 3, 4
• Condoms remain recommended to prevent other STIs, not HIV transmission when virally suppressed 1
• For injection drug users, equipment sharing remains a transmission risk regardless of viral suppression 1

The evolution from the 2003 guidelines 1 to current 2020 recommendations 1 reflects one of the most important advances in HIV prevention: proof that treatment is prevention when viral suppression is achieved and maintained.