Science Validates Undetectable = Untransmittable HIV Prevention Message

People living with HIV whose virus is completely, durably suppressed by treatment will not sexually transmit the virus to an HIV-negative partner, according to NIAID Director Anthony S Fauci, M.D. The success of this HIV prevention strategy is contingent on achieving and maintaining an undetectable viral load—the amount of HIV genetic material in the blood—by taking medication to treat HIV daily as directed.

Dr. Fauci delivered these remarks at the July 22 U=U 2018: Celebrate, Activate and Implement! meeting held prior to the 22nd International AIDS Conference (AIDS 2018) in Amsterdam.

Over the past two years, a grassroots movement has emerged to promote the value of HIV treatment as prevention through the “Undetectable = Untransmittable” campaign, also known as U=U. In his keynote lecture titled “U=U: Science and Policy,” Dr. Fauci traced the science behind the U=U message from early observational studies to more recent, large clinical trials.

For nearly two decades, scientists have recognized that viral load is a key determinant of HIV transmission, Dr. Fauci explained. Studies conducted before the availability of effective treatment for HIV, known as antiretroviral therapy (ART), revealed that higher viral loads correlate with higher rates of both sexual and perinatal, or mother-to-child, transmission of HIV.

The advent of triple-drug ART in 1996 marked a turning point in treatment for HIV, transforming what was once a largely fatal infection into a manageable chronic condition. Observational studies conducted in the late 1990s and early 2000s suggested that viral loads lowered by ART were associated with reduced risk of HIV transmission, Dr. Fauci noted. Some of this research focused on perinatal HIV transmission, while other studies investigated sexual transmission in couples in which one partner was living with HIV and the other was not. In addition, epidemiological studies have shown that as the number of people in a community who are virally suppressed rises, the number of new HIV infections falls.

Findings from the breakthrough NIH-funded HPTN 052 clinical trial a decade-long study involving more than 1,600 heterosexual couples, offered clear-cut evidence that ART that consistently suppresses HIV also prevents sexual transmission of the virus. In 2011, the HPTN 052 investigators reported that starting ART when the immune system is relatively healthy, as opposed to delaying therapy until the immune system has been weakened by the virus, dramatically reduces the risk of sexually transmitting HIV. The protective effect of starting ART early was sustained over four additional years of follow-up. Importantly, when viral loads were measured, no HIV transmissions were observed when ART consistently, durably suppressed the virus in the partner living with HIV. 

Two additional studies, PARTNER and Opposites Attract, reinforced the conclusion that HIV is not transmitted sexually when the partner living with HIV has a sustained undetectable viral load. These studies also extended the finding to male-male couples, tracking a combined 34,911 condom less anal sex acts. Findings from a follow-on study, called PARTNER 2, involving an additional 880 male-male couples are scheduled to be presented at AIDS 2018.

Dr. Fauci emphasized that achieving and maintaining an undetectable viral load are essential for the U=U HIV prevention strategy to be effective. He also acknowledged some of the issues that people living with HIV may face, such as the challenge of adhering to daily ART for life. Even when viral load is undetectable, HIV is still present in the body, and the virus rebounds to detectable levels if treatment is stopped. Dr. Fauci noted that some people with an undetectable viral load may have detectable HIV genetic material in other bodily fluids, such as semen, but there is no scientific evidence that such material is associated with HIVtransmission.

Dr. Fauci concluded that the body of scientific evidence to-date has established that there is effectively no risk of sexual transmission of HIV when the partner living with HIV has a durably undetectable viral load, validating the U=U message of HIV treatment as prevention.