U = U: The evidence is in. Spreading the word that undetectable = untransmissable is the next crucial step

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By Murray Penner of Prevention Access Campaign

Undetectable = Untransmittable, or U=U, is a clear, effective, simple way to convey the fact that a person living with HIV who is on antiretroviral therapy and whose virus is suppressed cannot transmit HIV to sexual partners. In 2016, Prevention Access Campaign, a health equity initiative with the goal of ending the HIV/AIDS pandemic as well as HIV-related stigma, launched a campaign to promote the value of HIV treatment as prevention by disseminating the U=U message among affected communities through the efforts of medical providers, health agencies, advocacy organizations, and activists. Treatment for HIV not only improves the social, sexual, and reproductive lives of people with HIV, but is also a powerful tool in the HIV prevention toolkit. The U=U campaign is a crucial strategy for maximizing the public health benefits of treatment as preventio

Today, an overwhelming body of scientific evidence has established that there is no risk of sexual transmission of HIV when the partner living with HIV has an undetectable viral load, validating the U=U message.

HPTN 052 Shows Treatment is Prevention

With preliminary results released in 2011, the randomized HPTN 052 study led by Dr. Myron Cohen found that early initiation of antiretroviral treatment was associated with a 93% lower risk of linked partner HIV acquisition compared to delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22), leading to the trial being unblinded and all participants who were living with HIV being offered antiretroviral treatment. The study enrolled 1,763 couples with mixed HIV status from nine countries. Of the participants, 78 seroconverted during the study; of these, 46 were virologically linked to the HIV-positive partner, 26 were not linked, and 6 could not be traced. Among the 46 linked cases, three (3) were in the early treatment group, versus 43 in the delayed treatment group. Most importantly, according to final data released in 2016, no linked transmissions were observed when the treated partner’s viral load was stably suppressed by antiretroviral treatment.

PARTNER Finds Zero Transmission Within Couples When Virus Suppressed by Antiretrovial Treatment 

From September 2010 to May 2014  the study found no sexual transmission of HIV among mixed HIV status couples when the index partner was virologically suppressed. The study enrolled 1,166 HIV mixed status couples (both heterosexual couples and gay male couples) from 14 European countries. All couples reported condomless sex, and the index partner was virally suppressed. During a median follow-up of 1.3 years per couple, a total of 11 HIV-negative partners acquired HIV during the study period, but none of the transmissions were phylogenetically linked (i.e., the newly diagnosed partner did not acquire HIV from the enrolled index partner), making the within-couple transmission rate zero.

With 16,889 Acts of Condomless Sex, Zero Transmission from Partner with ART-Suppressed Virus, Opposites Attract Further Validates U=U 

This study found no sexual transmission of HIV among mixed status couples when the index partner was virologically suppressed. The study recruited a total of 358 gay male mixed HIV status couples from Australia, Rio de Janeiro, and Bangkok. The final analysis focused only on 343 couples who attended at least one follow-up visit. Based on a median per couple follow-up of 1.7 years, the study found no instances of linked HIV transmission. About 57 percent of the index partners reported anal sex with an outside partner at any time during follow-up. The study included a total of 16,889 acts of condomless anal sex. While there were three new HIV transmissions, none was linked to the index partner.

2019 PARTNER 2 Results Underscore Partner Findings

This extension of the original PARTNER study aimed to provide more definitive estimates of the risk of HIV transmission in gay male mixed HIV status couples than that provided by the first phase. At a median follow-up of two years, the study found no sexual transmission of HIV among 782 serodiscordant gay male couples when the index partner was virologically suppressed. Of 777 HIV-negative partners, 288 (37%) reported condomless sex with other partners. While 15 new HIV acquisitions occurred during follow-up, none were phylogenetically linked to the index partner.

In 2019, treatment as prevention—the medical strategy based on U=U message—was embraced by the US Department of Health and Human Services Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV and endorsed by the U.S. Centers for Disease Control and Prevention.

The U=U message:

  • Supports reduced stigma and discrimination toward people living with HIV, including self-stigma that occurs when people internalize negative public attitudes and suffer negative consequences such as diminished sense of self-worth, poor health outcomes, and reduced quality of life;
  • Promotes demand for HIV testing services and supports early treatment initiation;
  • Provides social, emotional, and practical support to establish and maintain good treatment adherence;
  • Helps people with HIV, members of affected communities, and stakeholders understand the importance of viral suppression to maintaining the long-term health of people living with HIV.

Lancet Issues a Call to Action on Ending the HIV Epidemic in the United States

The Lancet special issue on HIV in the United States in 2021 concludes with a “Call to Action” by Dr. Chris Beyrer outlining the measures needed for Ending the HIV Epidemic initiative to succeed. Among the many items addressed in the call to action, U=U has a critical role to play. Ensuring that those living with HIV have the treatment and services they need to achieve and maintain an undetectable viral load not only saves lives, but also prevents new transmissions.

The call to action states:

  • A national culturally competent effort is needed to raise awareness of U=U as a promising approach to reduce HIV stigma, which has a powerful potentiating role in both acquisition risks and treatment challenges.
  • Health-care professionals need to inform patients living with and affected by HIV about U=U to improve, first and foremost, personal health, as well as public health; sharing this information might greatly improve the social and emotional wellbeing of people living with HIV, reduce HIV stigma, reduce anxiety associated with HIV testing, and help motivate treatment uptake, treatment adherence, and engagement in care.
  • Advocates should be equipped to use the so-called public health argument from U=U in advocacy to increase access and remove barriers to quality health care; ensuring people with HIV have the treatment and services they need to achieve and maintain an undetectable viral load not only saves lives, but also is an effective way to prevent new transmissions.
  • Providers should advocate for use of the concept of undetectable equals untransmittable (U=U) in messaging and support all patients to remain virally suppressed.

Recent research supports the value of the U=U message as part of a comprehensive HIV treatment and prevention outreach and education strategy.

Positive Perspectives Survey Shows Benefit of Health Care Provider U=U Discussion

Based on data from the 25-country 2019 Positive Perspectives Survey of people living with HIV on antiretroviral therapy (n=2389) led by Chinyere Okoli, found overall, 66.5% reported ever discussing U=U with their health care provider. Compared with those unaware of U=U, those reporting U=U discussions with their health care provider had lower odds of suboptimal adherence (AOR=0.59, 95% CI 0.44 to 0.78) and higher odds of self-reported viral suppression (AOR=2.34, 95% CI 1.72 to 3.20), optimal sexual health (AOR=1.48, 95% CI 1.14 to 1.92) and consistent disclosure of HIV status to prospective sexual partners (AOR=2.99, 95% CI 1.42 to 6.28). While exposure to U=U information from non-health care provider sources was beneficial, the observed associations were greatest among those who reported discussions with health care providers.

U=U Messaging Increases Uptake of HIV Testing Among Men in South Africa

A team led by Dr. Philip Smith of University of Cape Town, South Africa compared testing rates following standard of care days when peer promoters told men about the availability of HIV testing at the mobile clinic to outcomes on intervention days, when peer promoters delivered U=U messages. Peer promoters delivered 1048 invitations over 12 days. In the standard of care group, 68 (13%) of 544 men invited tested for HIV (3, 4.4% HIV-positive). In the U=U group, 112 (22%) of 504 men invited tested for HIV (7, 6.3% HIV-positive). Men in the U=U group had greater odds of testing for HIV (adjusted odds ratio=1.59, 95% CI=0.98-2.57).

2020 Findings Show U=U Messaging Reduces Burden of Stigma for Men Living with HIV

An analysis of an online survey among 30,361 adolescent and adult (aged 13-99) sexual minority men living with HIV, led by H. Jonathon Rendina across the United States found that 80% of those surveyed reported that U = U was beneficial for their self-image and societal HIV stigma, 58.6% reported it made them feel “much better” about their own HIV status, and 40.6% reporting it had the potential to make HIV stigma “much better.”

Universal Treatment Needed to Achieve HIV Prevention Goals

In 2020, researchers at the U.S. Centers for Disease Control and Prevention led by Stephanie L. Sansom PhD compared the current funding allocation for HIV testing, prevention and treatment with (1) a limited-reach scenario with expanded efforts to serve eligible persons and (2) an unlimited-reach scenario in which all eligible persons could be served. Using the current allocation of resources and scaling up the number of HIV-positive individuals who receive treatment, the study found that the limited-reach scenario reduces new HIV diagnoses by 69%, and the unlimited reach scenario by 94%. The study concluded that optimal allocation of funds for HIV prevention and treatment can achieve substantial reductions in new transmissions. Achieving reductions of more than 90% under current funding will require that virtually all HIV-positive individuals receive sustained treatment.

Prevention Access Campaign — Disseminating the Message of U=U

Prevention Access Campaign (PAC) provides technical assistance for communities and activists to integrate U=U in public health communications, clinical, and advocacy work based on best practices learned from the extensive U=U community. PAC facilitates the sharing of resources among the global U=U community, including social marketing and communications materials, advocacy strategies, and research. Contact PAC to find out how PAC can help you advocate for U=U in your clinical setting, educational program, community-based organization, or government health agency.

Murray C. Penner is the U.S. executive director of Prevention Access Campaign – U=U. He also currently serves as board president of the AIDS Activists Coalition and a board member of Harbor Path, Inc. He previously held the executive director and deputy executive director roles at the National Alliance of State and Territorial AIDS Directors (NASTAD). Mr. Penner also served as planning coordinator for the Fort Worth, Texas, Ryan White planning body; administrator with the Fort Worth Metropolitan and Greater Oklahoma City YMCAs; and community-elected co-chair of the regional HIV prevention community planning group in north central Texas.

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References

[DHHS 2018; CDC 2019] In 2019, The New York State Department of Health AIDS Institute published guidelines for implementing the U=U message in clinical settings, as did the Australasian Society of HIV, Viral Hepatitis and Sexual Health Medicine. [NYDOHAI 2020; ASHM 2020]

[DHHS 2018]Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services.

[CDC 2019]Centers for Disease Control and Preventions. Effectiveness of Prevention Strategies to Reduce the Risk of Acquiring or Transmitting HIV. Page last reviewed: November 12, 2019. https://www.cdc.gov/hiv/risk/estimates/preventionstrategies.html

[NYDOHAI 2020] New York State Department of Health AIDS Institute. U=U Guidance for Implementation in Clinical Settings. June 2019; updated December 2020.

[ASHM 2020] The Australasian Society of HIV, Viral Hepatitis and Sexual Health Medicine (2020). U=U ASHM Guidance for Healthcare Professionals (3rd Edition) Allan. B (Ed.) October 2020.

[Calabrese 2019] Calabrese SK, Mayer KH. Providers should discuss U=U with all patients living with HIV. Lancet HIV. 2019;6(4):e211-e213. https://pubmed.ncbi.nlm.nih.gov/30772420/

[Montaner 2006] Montaner JS, Hogg R, Wood E, et al. The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet. 2006;368:531-536. https://pubmed.ncbi.nlm.nih.gov/16890841/

[Cohen 2007]Cohen MS, Gay C, Kashuba AD, et al. Narrative review: antiretroviral therapy to prevent the sexual transmission of HIV-1. Ann Intern Med. 2007; 146:591-601 https://pubmed.ncbi.nlm.nih.gov/17438318/

[Cohen 2016] Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral Therapy for the Prevention of HIV-1 Transmission. N Engl J Med. 2016;375(9):830-839. https://pubmed.ncbi.nlm.nih.gov/27424812/

[Rodger 2016] Rodger AJ, Cambiano V, Bruun T, 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. 2016;316(2):171-81. https://pubmed.ncbi.nlm.nih.gov/27404185/

[Bavinton 2019] Bavinton BR, Prestage GP, Jin F, et al. Strategies used by gay male HIV serodiscordant couples to reduce the risk of HIV transmission from anal intercourse in three countries. J Int AIDS Soc. 2019;22(4):e25277. https://pubmed.ncbi.nlm.nih.gov/30983155/

[Okoli 2010] Okoli C, Van de Velde N, Richman B, et al. Undetectable equals untransmittable (U = U): awareness and associations with health outcomes among people living with HIV in 25 countries. Sex Transm Infect. 2021;97(1):18-26. https://pubmed.ncbi.nlm.nih.gov/32732335/

[Smith 2021] Smith P,  Buttenheim A, Schmucker L, et al. Undetectable=untransmittable (U=U) messaging increases uptake of HIV testing among men: Results from a pilot cluster randomized trial. Preprint. https://www.medrxiv.org/content/10.1101/2020.11.23.20236695v1

[Rendina 2020] Rendina HJ, Talan AJ, Cienfuegos-Szalay J, Carter JA, Shalhav O. Treatment Is More Than Prevention: Perceived Personal and Social Benefits of Undetectable = Untransmittable Messaging Among Sexual Minority Men Living with HIV. AIDS Patient Care STDS. 2020;34(10):444-451. https://pubmed.ncbi.nlm.nih.gov/33064015/

[Calabrese 2021] Calabrese SK, Mayer KH, Marcus JL. Prioritising pleasure and correcting misinformation in the era of U=U. Lancet HIV. 2021;8(3):e175-e180.https://pubmed.ncbi.nlm.nih.gov/33662266/

[Beyrer 2021] Beyrer C, Adimora AA, Hodder SL, et al. Call to action: how can the US Ending the HIV Epidemic initiative succeed? [published online ahead of print, 2021 Feb 18]. Lancet. 2021;S0140-6736(21)00390-1. https://pubmed.ncbi.nlm.nih.gov/33617770/

[Sansom 2021] Sansom SL, Hicks KA, Carrico J, et al. Optimal Allocation of Societal HIV Prevention Resources to Reduce HIV Incidence in the United States. Am J Public Health. 2021;111(1):150-158. https://pubmed.ncbi.nlm.nih.gov/33211582/

One thought on “U = U: The evidence is in. Spreading the word that undetectable = untransmissable is the next crucial step

  1. RG

    Murray,

    Nice article. Wanted to amplify your message and provide some historical perspective.

    The data supporting the role of treatment as prevention was available in 2001 (Quinn et al) and treatment as prevention was later proposed by Montaner as an important means of preventing illness, death and transmission (Lancet 2006). The Swiss Statement in 2008 brought the importance of suppression to the fore and was supported by Attia et al’s metanalysis showing 92% reduction in risk (2009). The UNAIDS 90-90-90 targets focusing on achieving increased access to successful treatment (73% of people living with HIV suppressed) were released in 2014 (nearly 15 years later) and then WHO finally changed its recommendation to test and treat in 2015. Now the world is catching up from the disastrous WHO’s “test and wait until severely ill” strategy that delayed access to treatment primarily in the South–over 12M people still do not have access to successful treatment with hundreds of thousands of them living in the US. U=U builds on this science and is a powerful force to improve access to treatment.

    Billions have been spent on the HIV response, but in many settings the resources have not resulted in ART coverage above 60-70% of people living with HIV with suppression rates only in the 50-60% range–this is clearly inadequate, leaving millions of people to die from lack of access to treatment. Matching resources with treatment coverage and its positive impact will be critical to ensure the end of the pandemic. Too often they are not examined together, robbing the community at risk of the ability to understand how their taxes are being deployed to fight HIV.

    Using the accepted global targets like 90-90-90 and 95-95-95 has helped other countries in Europe and Africa and beyond to reach improved access to successful treatment. See recent articles and report for the global rankings. The US could consider this strategy as it could help people working on HIV to focus on catching up with many other countries in terms of delivering minimal care to people living with HIV.

    U=U is the right thing to do and it is never to late to get it done–keep going!

    Reply

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