U=U: THE SCIENCE BEHIND ZERO HIV TRANSMISSION WITH UNDETECTABLE VIRAL LOADS

Background

“Undetectable=Untransmittable” (U=U) is a groundbreaking public health campaign that emerged from a growing body of scientific evidence showing that people living with HIV who achieve and maintain an undetectable viral load through antiretroviral therapy (ART) cannot sexually transmit the virus to others. The concept has significantly impacted HIV prevention, stigma reduction, and the lives of people living with HIV.

Through funding from USAID and PEPFAR, Project Last Mile leverages private sector expertise in strategic marketing to educate and motivate people living with HIV towards achieving viral suppression. Project Last Mile’s support for national efforts for U=U includes developing a toolkit for in-clinic use and training health workers. 

Below are outlined some of the key studies that underpin the science behind zero HIV transmission with undetectable viral loads.

Key studies
1) HPTN 052 study (2011)

The HIV Prevention Trials Network (HPTN) 052 study was a landmark clinical trial that provided the first substantial evidence supporting U=U. This study enrolled 1,763 serodiscordant couples (one partner living with HIV and the other not across Africa, Asia, and the Americas.

It demonstrated that early initiation of ART in the HIV-positive partner reduced HIV transmission by 96% compared to delayed treatment.

Reference: Cohen, Myron S., et al. “Prevention of HIV-1 infection with early antiretroviral therapy.” New England journal of medicine 365.6 (2011): 493-505.

2) PARTNER 1 study (2016)

The PARTNER 1 study provided more robust evidence supporting U=U. It followed 888 serodiscordant couples (548 heterosexual and 340 gay male couples) across 14 European countries.

Despite over 58,000 condomless sex acts, there were zero cases of HIV transmission when the HIV-positive partner maintained an undetectable viral load.

Reference: Rodger, Alison J., et al. “Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy.” Jama 316.2 (2016): 171-181.

3) PARTNER 2 study (2019)

Following up on the initial PARTNER study, PARTNER 2 focused exclusively on gay male couples, providing additional data to confirm U=U.

This study included over 77,000 condomless sex acts and found zero transmissions from HIV-positive partners with undetectable viral loads.

Reference: Rodger, Alison J., et al. “Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study.” The Lancet 393.10189 (2019): 2428-2438.

4) Opposites attract study (2017)

This study focused on serodiscordant gay male couples in Australia, Thailand, and Brazil.

Over 16,000 condomless sex acts were reported, and there were zero HIV transmissions when the HIV-positive partner had an undetectable viral load.

Reference: Grulich, Bavinton, et al. (2017). HIV transmission in male serodiscordant couples in Australia, Thailand and Brazil. AIDS, 31(12), 1703-1710.

Conclusion

These studies collectively provide strong evidence that effective ART resulting in an undetectable viral load prevents the sexual transmission of HIV. The U=U message has been endorsed by leading health organizations, including the U.S. Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), and has played a crucial role in changing public
perceptions about HIV, reducing stigma, and promoting the health and well-being of people living with HIV.