Antiretroviral Therapy Adherence Crucial for Undetectable Equals Untransmittable Method in HIV

The concept that individuals living with HIV who achieve and maintain an undetectable viral load cannot sexually transmit the virus to others has widespread implications for the prevention and treatment of HIV, according to a commentary published in JAMA.

However, this concept, called HIV Undetectable=Untransmittable (U=U), has only been widely validated by clinical evidence in recent years.

In the JAMA report, officials from the National Institutes of Health’s National Institute of Allergy and Infectious Diseases speak to the clinical studies that support U=U and discuss its implications. The authors noted that the validity of the U=U concept relies on achieving and maintaining an undetectable viral load, pointing to the importance of adherence to antiretroviral therapy (ART).

“To enhance the overall success of the U=U concept, it is important to implement programs that help patients remain in care and address challenges in their lives that result in stopping therapy,” the authors wrote.

The first evidence of U=U was observed in a 2011 study conducted by the HIV Prevention Trials Network. The study compared the effect of early versus delayed initiation of ART in the partner with HIV among 1763 HIV-discordant couples, according to the study. The results showed a 96.4% reduction in HIV transmission in the early ART group compared with the delayed group. After 5 years of follow-up, the protective effect of early ART persisted, with no linked transmission when viral load was durably suppressed by ART.

Further studies continued to confirm and build on these findings, including the PARTNER 1 and PARTNER 2 studies. In the PARTNER 1 study, 1166 HIV-discordant couples were examined for risk of transmission when 1 partner with HIV was receiving ART and had achieved and maintained viral suppression. The researchers reported no linked HIV transmissions after approximately 58,000 condomless sexual acts.

In addition, the PARTNER 2 study showed no cases of HIV transmission between HIV-discordant men who have sex with men, despite approximately 77,000 condomless sexual acts.

According to the authors, achieving an undetectable viral load can take up to 6 months of ART, but continued adherence is necessary to prevent viral rebound. Because viral rebound can occur within 2 to 3 weeks of stopping ART, ensuring that therapy is taken as prescribed is essential to the successful implementation of U=U.

Guidelines from the Department of Health and Human Services recommend viral load testing every 3 to 4 months after the plasma HIV-1 RNA level reaches undetectable. If viral suppression and stable immunologic status are maintained for more than 2 years, viral load testing can be extended to every 6 months thereafter, the authors wrote.

Furthermore, U=U has broad implications for the treatment and prevention of HIV from a scientific and public health perspective.

“The U=U concept provides incentives for individuals with HIV to seek, initiate, and adhere to ART,” the authors concluded. “In addition, it adds incentives to effort to control and ultimately end the HIV/AIDS pandemic because treatment as prevention is a critical tool in preventing the spread of HIV infection.”

Reference

RW Eisinger, CW Dieffenbach, AS Fauci. HIV viral load and transmissibility of HIV infection: undetectable equals untransmittable. Journal of the American Medical Association. 2019. Doi: 10.1001/jama.2018.21167.