Undetectable Equals Untransmittable: A Game Changer for HIV Prevention (2024)

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In February 2019, the US government launched “Ending the HIV Epidemic: A Plan for America” (1). This 10-year initiative plans to reduce new human immunodeficiency virus (HIV) infections in the United States to <3000 per year by 2030, with a focus on high-burden areas. To put that goal into perspective, the United States saw 38 739 new cases of HIV in 2017, and the number of new cases each year has remained relatively steady since 2012 (1).

The “Ending the HIV Epidemic: A Plan for America” initiative is feasible because HIV prevention and treatment medications have proven both efficacious and effective. Individuals who are HIV-negative can be prescribed pre-exposure prophylaxis (PrEP), a single pill consisting of 2 antiretroviral drugs. Taken once each day, PrEP is 99% effective in preventing HIV transmission (1). Likewise, individuals who are HIV-positive can receive antiretroviral therapy (ART), which can reduce viral loads to undetectable levels.

Endorsed by the CDC, the concept that undetectable equals untransmittable (U=U) stems from a variety of clinical studies that demonstrate HIV-positive individuals who have consistently maintained undetectable viral loads for at least 6 months with ART cannot transmit HIV to others (2,). In 2016, the first phase of a prospective observational study, Partners of People on ART — A New Evaluation of the Risks (PARTNER1), found no HIV transmissions among a cohort of 888 heterosexual and gay serodifferent partners (3,). However, because of the lack of couple-years among gay couples, the 95% CI upper limit of HIV transmission rate among serodifferent gay couples was almost double that of serodifferent heterosexual couples. These findings made HIV healthcare providers cautious in promoting U=U among men who have sex with men (MSM). In a recently published article, Rodger et al. performed the second phase of the PARTNER study (PARTNER2), which focused solely on serodifferent gay male couples (4). Between September 15, 2010, and July 31, 2017, serodifferent gay male couples from 75 clinical sites in 14 European countries enrolled in the study. At the end of follow-up on April 30, 2018, there were 1593 eligible couple-years of follow-up from 782 couples. Couple-years were considered eligible if condomless sex was reported, there was no use of PrEP or postexposure prophylaxis (PEP) by the HIV-negative partner, and the HIV-positive partner had a suppressed viral load (plasma HIV-1 RNA <200 copies/mL) within the past year. During eligible follow-up, 15 of the initial HIV-negative partners seroconverted. However, after genetic testing of the viruses, it was determined that there were no within-couple phylogenetically linked transmissions. Therefore, this study concluded that there is a transmission rate of 0% for condomless anal sex when the HIV-positive partner on ART has a viral load of <200 copies/mL (95% CI upper limit, 0.23 per 100 couple-years).

The PARTNER2 study confirmed the results produced by both the PARTNER1 study mentioned earlier and the Opposites Attract study (5). The Opposites Attract study was a multisite observational cohort study published in 2018. It had similar methodology to the PARTNER2 study but recruited serodifferent gay male couples in Australia, Brazil, and Thailand. The Opposites Attract study also saw similar results, with no phylogenetically linked HIV transmissions when the HIV-positive partner had a viral load of <200 copies/mL. However, like the PARTNER1 study of gay couples, the Opposites Attract study had the same issue of a broad confidence interval given too few eligible couple-years during follow-up.

The PARTNER2 study confirms with more certainty that there is effectively no risk of HIV transmission through anal sex when the viral load of the HIV-positive individual is undetectable, as is the case for vagin*l sex. This finding has major implications for clinical practice. First, it is the responsibility of all HIV-specialized and non–HIV-specialized medical providers to educate the public about U=U. More education will reduce the stigma about HIV in the US population and may motivate more individuals to be tested for HIV. It can also empower and encourage HIV-positive individuals to adhere to their ART regimens to achieve and maintain undetectable status. The outcome of the PARTNER2 study also emphasizes the importance of the “test and treat” model. Same-day or rapid ART initiation after a positive HIV test result is vital to linking the individual to care and helping that person start the journey to an undetectable viral load. Just as important, providers must link HIV-positive individuals to other services to address mental health, adherence support, drug use, housing, and other social determinants of health support to help sustain undetectable viral loads. Finally, it is important for practitioners to continue to promote the use of condoms during sex, even if the HIV-positive partner has an undetectable viral load. Given the scientific backing of U=U, the potential exists for individuals to discontinue condom use and thus increase the incidence of sexually transmitted infections. The importance of condoms must be included in education about U=U.

HIV in the United States is on the cusp of elimination because of effective prevention and treatment options. The concept of U=U continues to be supported by research studies. The recent PARTNER2 study further validated that risk of HIV transmission through condomless sex among MSM and anal sex with suppressed viral loads is effectively zero. The results of the PARTNER2 study are exciting and make the notion of ending the epidemic a possible reality. It is now important for the medical and public health community to educate everyone about the concept of U=U, to implement the test and treat model so HIV-positive individuals can be linked with care to achieve and maintain undetectable status, and to continue promoting the use of condoms.

Nonstandard abbreviations

HIV, human immunodeficiency virus; PrEP, pre-exposure prophylaxis; ART, antiretroviral therapy; U=U, undetectable equals untransmittable; MSM, men who have sex with men; PEP, postexposure prophylaxis.

Author Contributions

All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved.

Authors’ Disclosures or Potential Conflicts of Interest

Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest:

Employment or Leadership

None declared.

Consultant or Advisory Role: R.R. Patel, Gilead Sciences, Inc., ViiV Healthcare Limited.

Stock Ownership: None declared.

Honoraria: R.R. Patel received honoraria for consulting for Gilead Sciences, Inc. and Viiv Healthcare Limited.

Research Funding: None declared.

Expert Testimony: None declared.

Patents: None declared.

References

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