CATIE statement on the use of antiretroviral treatment (ART) to maintain an undetectable viral load to prevent the sexual transmission of HIV
Over the past several years the HIV prevention toolbox has expanded significantly. This is due to a rapid growth in our knowledge of effective approaches that help prevent the transmission of HIV. However, to maximize the impact on the HIV epidemic, we must effectively increase awareness, uptake and proper use of these approaches.
The CATIE statements summarize the best available evidence on the effectiveness of three approaches to help prevent the sexual transmission of HIV. These statements were developed to help service providers in Canada adapt their programs and incorporate this evidence into their messaging.
There are three highly effective strategies to reduce the risk of the sexual transmission of HIV:
- The consistent and correct use of antiretroviral treatment (ART) by people living with HIV to maintain an undetectable viral load
- The consistent and correct use of oral Truvada as pre-exposure prophylaxis (PrEP)
- The consistent and correct use of condoms
When any highly effective strategy is used consistently and correctly as part of a comprehensive plan for sexual health, the risk for HIV transmission ranges from very low to negligible.
The following statement focuses on the use of antiretroviral treatment (ART) by people living with HIV to maintain an undetectable viral load. A simple key message is followed by recommendations for service providers and a list of available tools and resources. A review of the evidence is also provided that service providers can use for more specific discussions around risk according to clients’ needs. Please consult the companion statements for more information on the other two highly effective strategies.
The consistent and correct use of antiretroviral treatment (ART) by people living with HIV to maintain an undetectable viral load is a highly effective strategy to reduce the risk of the sexual transmission of HIV. When this strategy is used consistently and correctly as part of a comprehensive plan for sexual health, the risk for HIV transmission is negligible.
For more information, please see the evidence review at the end of this statement.
Recommendations for service providers
In addition to improving the health of people living with HIV, it is now clear that ART also has important HIV prevention benefits when it is used to maintain an undetectable viral load. People working in HIV have an important role to play in promoting this approach as a highly effective prevention strategy.
Below are recommendations on how you might better integrate the use of ART for prevention into your programming.
1. Improve awareness of the use of ART to maintain an undetectable viral load as a highly effective HIV prevention strategy, including the factors that are important for maximizing its effectiveness. Any educational and counselling activities provided for clients (both HIV positive and HIV negative, but particularly for those in serodiscordant relationships) should include information on the prevention benefit of ART and how to use it correctly.
Education and counselling activities should also include discussion of other prevention strategies such as, but not limited to, condoms and pre-exposure prophylaxis (PrEP). Encourage clients to choose the combination of strategies that will work most effectively for them.
It is important that clients – whether people living with HIV or those at risk for HIV – be given information and offered counselling about the use of ART to maintain an undetectable viral load as a highly effective strategy to prevent the sexual transmission of HIV. This should include the factors necessary for maximizing its effectiveness. Emphasize that:
- Adherence to ART is essential for this prevention approach to be effective. The achievement and maintenance of an undetectable viral load (defined as less than 40 or 50 copies of the virus per millilitre of blood) is dependent on the consistent daily use of antiretroviral therapy.
- Achievement of an undetectable viral load after starting ART is critical to the effectiveness of this approach. It may take six months or more to achieve an undetectable viral load. A viral load test is the only way to know if the viral load has reached undetectable levels.
- Maintenance of a sustained undetectable viral load is necessary for this approach to be effective. Regular viral load testing is the only way to monitor for a sustained undetectable viral load.
- Regular clinic visits are required. Clinic visits will include the provision of regular care, including viral load monitoring.
When discussing with a client the use of ART to maintain an undetectable viral load, it is important to recognize that each client has the right to decide whether or not to take ART based on their own assessment of what is best for their health and well-being.
You can also lead or support efforts to improve awareness of the use of ART to maintain an undetectable viral load as a prevention approach among a range of service providers in your area including doctors, nurses, pharmacists and non-clinical staff at community-based organizations.
2. Facilitate and support appropriate uptake of the use of ART to maintain an undetectable viral load as a prevention strategy. Several treatment guidelines now recommend the offer of ART to all people living with HIV, regardless of their CD4 count. This recommendation is based on the health benefits of starting ART early for people living with HIV, although an important secondary benefit is the reduced risk of HIV transmission. If your client is HIV positive, you should help the client link to HIV care if they are not already in care. The client’s decision to start ART should be well-informed. ART requires a life-long commitment to daily pill-taking and regular visits with a healthcare provider. Facilitating informed decision-making for clients may require provision of services that support the doctor–patient relationship.
Support clients who are using ART with education about its consistent and correct use to maintain an undetectable viral load as a prevention strategy. You may have to deliver, or link clients to, interventions to support medication adherence and continued engagement in medical care. Encourage clients who, in addition to the benefit to their own health, decide to use ART to maintain an undetectable viral load for prevention to have regular viral load testing. They should also discuss their viral load test results with their partner(s) on an ongoing basis (if possible).
Encourage and support clients to communicate openly with their sex partner(s). Clients may need support to disclose their HIV status to a sex partner. Important discussion topics may also include whether there are sexual partners outside the relationship, and the results of viral load monitoring and sexually transmitted infection (STI) tests. Educating HIV-negative clients about HIV viral load and what it means to be undetectable may give them a better understanding of the concept of treatment as prevention.
3. Encourage a comprehensive plan for sexual health. Discuss how the use of ART to maintain an undetectable viral load fits into a comprehensive plan for sexual health. When used consistently and correctly, the use of ART to maintain an undetectable viral load is a highly effective strategy to reduce the risk of the sexual transmission of HIV. However, there are still rare circumstances in which HIV transmission can occur within the context of a serodiscordant relationship when the positive partner is on ART. There is a risk of HIV transmission just after starting ART before an undetectable viral load is reached. There is also a risk of HIV transmission due to virological failure. Virological failure occurs when ART fails to maintain the positive partner’s viral load at undetectable levels. This can be due to poor treatment adherence, drug resistance, and drug toxicity. However, the main risk for HIV transmission within non-monogamous serodiscordant relationships in which the HIV-positive partner is on successful ART (and has an undetectable viral load) comes from sexual partners outside the relationship.
It’s important that clients understand these risks and the options available to them so they can make an informed decision about using ART as part of a comprehensive sexual health plan to further minimize the risk for HIV transmission over the long term. A comprehensive sexual health plan also helps to protect against STIs because ART does not provide any protection against STIs.
4. Address underlying risk of HIV transmission. HIV prevention counselling offers an opportunity to engage individuals at risk for acquiring or transmitting HIV in additional services. You can help your clients address the underlying factors that may increase their risk for acquiring and transmitting HIV, such as depression or alcohol and other substance use; reinforce safer sex strategies; and facilitate the increased use of all appropriate prevention strategies. You may find that risk-reduction counselling alone is not enough. You may need to provide – or link clients to – appropriate and relevant support services.
5. Offer comprehensive couples-based counselling. For couples, you may want to offer to counsel both partners in the relationship at the same time (couples-based counselling) as this may be more effective than counselling partners individually. Couples-based counselling can create a supportive space where clients can come to a consensual agreement on how to reduce their risk of HIV transmission, develop ways to support each other in using HIV prevention strategies consistently and correctly, and discuss potentially sensitive issues relevant to HIV prevention. Be prepared to discuss issues such as what a couple wants from sex and the type of sex they enjoy most; the desire for pleasure, intimacy, conception, and monogamy or non-monogamy; and disclosure of sex outside the relationship. This counselling can also support non-monogamous clients to develop strategies or agreements to reduce the risk of acquiring HIV or STIs from outside partners, such as the consistent and correct use of condoms for sex outside the relationship.
6. Incorporate information about the use of ART to maintain an undetectable viral load as prevention into all prevention programming to increase its impact. In-person counselling is one way to convey information about ART as a highly effective prevention strategy. However, this information can be integrated into a variety of other communication channels, such as print publications, websites and campaigns to increase its reach and impact.
Tools and Resources
Treatment and viral load: what do we know about their effect on HIV transmission? – Prevention in Focus
Insight into HIV transmission risk when the viral load is undetectable and no condom is used (overview of the PARTNER study) – CATIE News
Couples HIV testing and counselling – Prevention in Focus
Guidelines, position papers and consensus statements
Canadian Consensus Statement on the health and prevention benefits of HIV antiretroviral medications and HIV testing – CTAC, CATIE, positivelite.com
Risk of sexual transmission of HIV from a person with HIV who has an undetectable viral load: Messaging primer – Prevention Access Campaign
Community Consensus Statement on access to HIV treatment and its use for prevention – AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC, NAM/aidsmap
Expert Consensus: Viral Load and Risk of HIV Transmission – Institut National de Santé Publique du Quebec (INSPQ)
Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations – World Health Organization (WHO)
In people living with HIV, successful ART can reduce the amount of virus (viral load) in the blood and other bodily fluids to undetectable levels, usually within a few months of starting treatment. In Canada, an undetectable viral load is usually defined as fewer than 40 or 50 copies of the virus per millilitre of blood.
We now know that the amount of HIV in the fluid of someone living with HIV is an important predictor of HIV transmission to an HIV-negative person after a sexual exposure. Research shows that a lower blood viral load is associated with a reduced risk of sexual HIV transmission.1 When the viral load in the blood decreases, it also decreases in the sexual fluids (semen, vaginal fluid and rectal fluid) that are commonly involved in the sexual transmission of HIV.2
The first study to conclusively show that ART has a prevention benefit was the randomized-controlled trial known as HPTN 052.3 In this trial, interim results showed that treatment reduces the risk of HIV transmission by 96% among heterosexual serodiscordant couples who have mostly vaginal sex. In the final analysis of HPTN 052, 78 HIV-negative partners became infected with HIV during the entire study.4,5 Genetic analysis of the virus from the previously HIV-negative partners showed that 26 of the 78 (33%) were infected by a sexual partner outside of the primary relationship, and 46 (59%) came from the HIV-positive partner with whom they enrolled in the study. Of the 46 HIV infections that originated from the HIV-positive partner that was enrolled in the study, only eight occurred when the partner was on ART.4,5 However, despite being on ART the viral load of the HIV-positive partner was likely detectable in all eight cases. Four infections occurred within the first three months of the HIV-positive partner starting ART and four occurred in couples who had experienced virological failure (when the viral load returns to detectable levels). The results of HPTN 0524,5 support the findings from three previously conducted observational studies among heterosexual serodiscordant couples that ART substantially reduces the risk of HIV transmission.6–8
Results from a large observational study known as PARTNER showed that an undetectable viral load dramatically reduces the risk of HIV transmission for both heterosexual and same-sex male couples in the absence of other forms of HIV prevention (condoms, PrEP or PEP).9,10 Overall, there were a large number of unprotected sex acts (no condoms, PrEP or PEP) when the viral load was undetectable – approximately 22,000 among gay couples and 36,000 among heterosexual couples enrolled in the study. By the end of the study, 11 of the HIV-negative partners had become infected with HIV (10 gay men and one heterosexual person). Genetic analysis of the virus from the previously HIV-negative partners showed that all 11 were infected by a sex partner outside of the relationship, and not by the HIV-positive partner with whom they enrolled in the study. This meant that there were no HIV transmissions between the couples enrolled in the study, despite the large number of unprotected sex acts between them.10
A preliminary analysis of an observational study similar to PARTNER, called Opposites Attract, also found no HIV transmission among serodiscordant same-sex male couples when the viral load was undetectable despite over 5,000 condomless anal sex acts.11
Although these results are extremely promising and all point towards negligible risk, it is not possible to conclude the risk for HIV transmission is zero when the HIV-positive partner is undetectable. The PARTNER and Opposites Attract studies are continuing to follow same-sex male serodiscordant couples to increase confidence in the results for anal sex.
While there have been no HIV transmissions between serodiscordant couples enrolled in PARTNER and Opposites Attract when the HIV-positive partner had an undetectable viral load, there is one suspected case in the literature in which HIV transmission may have occurred when the HIV-positive partner had an undetectable viral load at the time of transmission.12
All study participants in the HPTN 052, PARTNER and Opposites Attract studies were in stable serodiscordant relationships and engaged in ongoing healthcare services, including adherence counselling and regular medical care to monitor viral load. Partners in all three studies were also tested and treated for STIs on an ongoing basis and received prevention counselling, including free condoms. The risk reduction provided by ART may be lower for couples who do not receive similar appropriate supports. For example, in several observational studies of stable heterosexual serodiscordant couples where study investigators did not provide these additional services and supports, ART was not as effective at reducing the risk of HIV transmission.13 In fact, in two studies, ART was less than 10% effective.14,15 This is likely because many participants in these studies were not adherent to their medications.
While all of this evidence strongly supports the ability of ART to substantially reduce the risk of HIV transmissions, this is contingent on the achievement and maintenance of an undetectable viral load. Achieving an undetectable viral load can take time – up to six months or more. HPTN 052 conducted an analysis to determine how long it takes to achieve an undetectable viral load. In HIV-positive participants on ART the cumulative percentage of participants who achieved an undetectable viral load by three, six, nine and 12 months were 76%, 87%, 90%, and 91%.5 Maintenance of an undetectable viral load over time is also critical; however, virological failure can occur (when the viral load returns to detectable levels). Virological failure happens when ART fails to maintain a person’s viral load at undetectable levels due to poor treatment adherence, drug resistance, or drug toxicity. People experiencing virological failure are not aware of this until their next viral load test. This time period between viral load tests provides an opportunity for the transmission of HIV if virological failure has occurred. A change in therapy or adherence support may be required to suppress the viral load if virological failure does occur.
Several studies show that STIs can increase the risk of HIV transmission, but these studies did not measure the viral load of the HIV-positive partner.16 Evidence from the PARTNER study suggests that STIs may not impact transmission in the context of an undetectable viral load – having an STI was not associated with HIV transmission in this study. However, regular STI testing and treatment should be part of any comprehensive sexual health plan.
Based on studies where participants were in stable serodiscordant relationships, we conclude that the consistent and correct use of ART to maintain an undetectable viral load, when combined with a comprehensive sexual health plan, is a highly effective strategy to reduce the risk of the sexual transmission of HIV.
- Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. New England Journal of Medicine. 2000 Mar 30;342(13):921–929.
- Baeten JM, Kahle E, Lingappa JR, et al. Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Science Translational Medicine. 2011 Apr 6;3(77):77ra29.
- Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine. 2011 Aug 11;365(6):493–505.
- Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. New England Journal of Medicine. 2016;375:830–9. Available from: http://www.nejm.org/doi/pdf/10.1056/NEJMoa1600693
- Eshleman SH, Hudelson SE, Redd AD, et al. Treatment as Prevention: Characterization of partner infections in the HIV Prevention Trials Network 052 trial. Journal of Acquired Immune Deficieny Syndromes. 2016 Aug 16. [in press]
- Reynolds S, Makumbi F, Nakigozi G, et al. HIV-1 transmission among HIV-1 discordant couples before and after the introduction of antiretroviral therapy. AIDS. 2011;25:473–477.
- Melo MG, Santos BR, Lira RD, et al. Sexual Transmission of HIV-1 among serodiscordant couples in Porto Alegre, Southern Brazil. Sexually Transmitted Diseases. 2008;35:912–915.
- Donnell D, Baeten J, Kiarie J, et al. Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis. Lancet. 2010;6736(10):2092–2098.
- Rodger A et al. HIV transmission risk through condomless sex if HIV+ partner on suppressive ART: PARTNER study. In: Program and abstracts of the 21st Conference on Retroviruses and Opportunistic Infections, March 3 to 6th, 2014, Boston, U.S., abstract 153LB.
- 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. Journal of the American Medical Association. 2016;316(2):171–81. Available from: http://jama.jamanetwork.com/article.aspx?articleid=2533066
- Grulich AE, Bavinton BR, Jin F, et al. HIV transmission in male serodiscordant couples in Australia, Thailand and Brazil. 22nd Conference on Retroviruses and Opportunistic Infections, Seattle, USA , 2015. Late breaker poster 1019 LB.
- Sturmer M et al. Is transmission of HIV-1 in non-viraemic serodiscordant couples possible? Antiretroviral Therapy. 2008;13:729-32.
- Anglemyer A, Rutherford GW, Horvath T, et al. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples. Cochrane Database Systematic Reviews. 2013;4:CD009153.
- Lu Wang, Zeng Ge, Jing Luo, et al. HIV transmission risk among serodiscordant couples: A retrospective study of former plasma donors in Henan, China. Journal of Acquired Immune Deficieny Syndromes. 2010;55:232–238. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058178/
- Birungi J, Min JE, Muldoon KA et al. Lack of effectiveness of aantiretroviral therapy in preventing HIV infection in serodiscordant couples in Uganda: An observational study. Plos One. 2015 July 14: 10(7):e0132182.
- Ward H, Rönn M. The contribution of STIs to the sexual transmission of HIV. Current Opinion in HIV and AIDS. 2010 Jul;5(4):305–10.