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HIV Viral Load and Transmissibility

Three drug combinations of antiretroviral medications for the treatment of HIV were introduced in 1996. These therapeutic regimens substantially decreased viral loads in a high percentage of patients, often below the level of detection in plasma. Many patients experienced sustained, undetectable viral loads for extended periods of time. In 2008, Switzerland declared that individuals with HIV who did not have any other sexually transmitted infection and achieved and maintained an undetectable viral load for at least 6 months, did not transmit HIV sexually. This was the first declaration of the U = U concept, meaning that Undetectable equals Untransmittable. Subsequent studies have confirmed and extended this finding. A systematic review of 12 recent clinical studies concluded that there is negligible risk (0.00 transmissions/100 person-years, 95% CI, 0.00-0.28) of HIV sexual transmission among HIV-discordant partners when the partner with HIV adheres to ART and maintains a suppressed viral load (<200 HIV-1 RNA copies/mL) measured routinely every 4 to 6 months.

The validity of the U=U concept depends on achieving and maintaining an undetectable viral load. To achieve this goal, several principles must be followed:

  • Antiretroviral therapy (ART) must be taken as prescribed
  • Undetectable viral load may take up to 6 months of ART to achieve.
  • Once achieved, continued adherence to ART therapy is required.
  • Viral load testing should be performed every 3 to 4 months after plasma HIV-1 RNA level becomes undetectable (<200 copies/mL).
  • Viral load testing can be extended to every 6 months if viral suppression and stable immunologic status are maintained for >2 years
  • Stopping therapy negates the validity of assuming U = U.

The Panel on Antiretroviral Guidelines for Adults and Adolescents recommends the following schedule for viral load testing for individuals with HIV in the United States:

  • At entry into care
  • Upon initiation of ART or at the time of treatment regimen modification
  • Two to 8 weeks after ART initiation or modification
  • Repeated testing every 4 to 8 weeks until HIV-1 RNA viral load is suppressed to less than 200 HIV-1 RNA copies/mL
  • Repeated testing every 3 to 4 months.
  • Repeated testing every 6 months for individuals who are adherent to treatment with consistently suppressed viral load and stable immunologic status for more than 2 years

Stopping ART represents a significant challenge to successful implementation of U = U. When ART is stopped, viral rebound usually occurs within 2 to 3 weeks to levels associated with increased risk of HIV transmission.


Eisinger RW, Dieffenbach, Fauci AS, HIV Viral Load and Transmissibility of HIV Infection: Undetectable Equals Untransmittable. JAMA, published online Jan 10, 2019. doi:10.1001/jama.2018.21167

DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. October 25, 2018.

LeMessurier J, Traversy G, Varsaneux O, et al. Risk of sexual transmission of human immunodeficiency virus with antiretroviral therapy, suppressed viral load and condom use: a systematic review. CMAJ. 2018;190(46):E1350-E1360. doi:10.1503/cmaj.180311

Hamlyn E, Ewings FM, Porter K, et al; INSIGHT SMART and SPARTAC Investigators. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection.PLoS One. 2012;7(8):e43754. doi:10.1371/journal.pone.0043754

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