Wednesday 29 June, 2016 13.00 EDT
CATIE statement on the use of antiretroviral treatment (ART) and 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 daily oral Truvada as pre-exposure prophylaxis (PrEP)
- The consistent and correct use of condoms
Highly effective strategies can reduce the risk of HIV transmission by 90% or more.
The following statement focuses on 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 a highly effective strategy is used consistently and correctly as part of a comprehensive plan for sexual health, it is rare for HIV to be transmitted.
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. People working in HIV have an important role to pay in promoting ART and an undetectable viral load as a highly effective prevention strategy.
Below are recommendations on how you might better integrate ART for prevention into your practice.
1. Improve awareness of ART and an undetectable viral load as a highly effective HIV prevention strategy, including the factors 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 the education provided includes information on how to maximize the HIV prevention benefit of ART and an undetectable viral load. This requires:
- an HIV-positive individual to have a sustained undetectable blood viral load (defined as less than 40 or 50 copies per ml of blood)
- both sexual partners to have no untreated sexually transmitted infections (STIs).
If these biological conditions are not met, the effectiveness of this strategy may be less.
Remind clients there are behavioural and contextual factors that are important to ensure that the above biological criteria are met. This includes:
- high adherence to medications
- regular care for the HIV-positive person to monitor viral load and, if needed, receive adherence support
- STI testing and (if necessary) treatment for all sex partners. STI testing may need to occur on a regular basis (every three to six months) if sex is also taking place outside the relationship.
Your clients should know that ART and an undetectable viral load for prevention can be much less effective against HIV transmission when doses of ART are missed. Your clients should know that it is important for them to attend regular medical appointments while on ART.
You can also lead or support efforts to improve awareness of ART and an undetectable viral load for prevention 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 and use of ART and an undetectable viral load as a prevention strategy. Several treatment guidelines recommend the offer of ART to all people living with HIV, regardless of their CD4 count. These recommendations are based on the health benefits of starting ART early, although an important secondary benefit is a 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 decision to start ART should be well-informed and not coerced. ART may cause side effects and toxicities, and 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 and an undetectable viral load as a prevention strategy with advice and education about the consistent and correct use of this strategy. You may have to deliver, or link clients to, interventions to support medication adherence and continued engagement in medical care. Encourage clients who decide to use ART for prevention to have regular viral load testing and discuss their viral load test results with their partner(s) on an ongoing basis (if possible). Any clients who have not disclosed their HIV status to a sex partner may need support in doing so.
Encourage and support clients to communicate openly with their sex partner(s). Important discussion topics related to the effectiveness of ART as prevention include relationship status, whether there are sexual partners outside the relationship (to inform the development of strategies to avoid introducing STIs from outside partners), and viral load and STI test results. 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 and encourage them to talk to HIV-positive partners about their viral load and their adherence to medication.
3. Encourage a comprehensive plan for sexual health. Discuss how ART and an undetectable viral load fits into a comprehensive plan for sexual health. When used consistently and correctly, ART and an undetectable viral load is a highly effective strategy to reduce the risk of sexual transmission of HIV. However, it does not eliminate the risk. We know that adherence to daily medications can be an issue for some people and this can decrease the effectiveness of ART as prevention. We also know that virological failure can occur, which means that the treatment stops suppressing the viral load. This can provide a window of opportunity for HIV transmission to occur before the elevated viral load is picked up on viral load testing. We also know that while the risk for HIV transmission is quite low from a single exposure, the risk for HIV transmission increases over multiple exposures to HIV. This means that the more someone participates in a behaviour that poses a risk for HIV transmission the greater their risk of getting HIV. Finally, we know that ART as prevention does not protect against STIs. It’s important that clients know these risks so they can make an informed decision about combining ART as prevention with other risk-reduction strategies to help minimize their HIV and STI risk over the long term.
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 ART 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
Community consensus statement on the use of antiretroviral therapy in preventing HIV transmission – NAM/Aidsmap.com and European AIDS Treatment Group (EATG)
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)
Position statement on the use of antiretroviral therapy to reduce HIV transmission – The British HIV Association (BHIVA) and the Expert Advisory Group on AIDS (EAGA)
The PARTNER study: A conversation with James Wilton – PositiveLite.com
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 whether infection is transmitted 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), which are those 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 show us that treatment reduces the risk of HIV transmission by 96% among heterosexual serodiscordant couples who have mostly vaginal sex. These results supported findings from three previously conducted observational studies among heterosexual serodiscordant couples suggesting a reduction in HIV risk of 90% or more.4–6
After HPTN 052, preliminary results from an observational study known as PARTNER confirmed that ART can also dramatically reduce the risk of HIV transmission through anal sex.7 The PARTNER study is a large observational study following heterosexual and serodiscordant male couples. In the preliminary analysis, couples reported more than 44,000 condomless vaginal and anal sex acts when the viral load was undetectable. No HIV transmissions occurred. Another preliminary analysis of an observational study similar to PARTNER, called Opposites Attract, also found no HIV transmission among serodiscordant gay couples when the viral load was undetectable despite over 5,000 condomless anal sex acts.8
Although these results are promising, it does not mean the risk of HIV transmission when undetectable is zero. The PARTNER and Opposites Attract studies are continuing to follow couples to increase confidence in their results. We also know that there are two suspected cases in which HIV transmission has occurred when the HIV-positive partner had an undetectable viral load at the time of transmission.9,10
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.11 In fact, in two studies, ART was less than 10% effective.12,13 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 reduce HIV transmissions, this is contingent on the maintenance of a suppressed viral load. However, we know that virological failure can occur, which provides a window of opportunity for the transmission of HIV. Virological failure happens when ART fails to suppress HIV and maintain a person’s viral load at undetectable levels. A change in therapy is required to suppress the viral load again. This is a concern because people are not aware they are experiencing virological failure until their next viral load test. This time period between viral load tests provides an opportunity for the transmission of HIV if a virological failure has occurred. We know that four documented transmissions occurred in HPTN 052 due to virological failure.14
There are two other ways viral load can fluctuate, but it is unclear if these have any role in increasing the risk for HIV transmission. First, people can experience temporary small increases in viral load called ‘blips.’ Second, people who have an undetectable viral load in their blood can sometimes have detectable but lowered levels of virus in their sexual fluids.15–19 However, evidence tells us this doesn’t happen very often and may be more common in people with an STI.20–22
The impact of STIs on HIV transmission when the viral load is undetectable is not entirely clear. 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.20 Some participants in the HPTN 052 and PARTNER studies had STIs, yet no HIV transmissions occurred, suggesting the impact of STIs may not be significant. However, regular STI testing provided by study investigators ensured that STIs were detected and treated early, thereby minimizing their potential impact on HIV transmission.
Based on studies where participants were in stable serodiscordant relationships, we conclude that the consistent and correct use of ART, when combined with a comprehensive sexual health plan that includes regular STI testing and treatment and ongoing adherence and risk-reduction counselling, 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.
- 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. HIV Transmission risk through condomless sex if HIV+ partner on suppressive ART: Partner study. Oral presentation at: 21st Conference on Retroviruses and Opportunistic Infections, Boston, USA, 2014. Available from: http://www.croiwebcasts.org/console/player/22072 [Accessed July 14, 2015]
- 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.
- Fisher M et al. Determinants of HIV-1 Transmission in men who have sex with men: a combined clinical, epidemiological and phylogenetic approach. AIDS. 2010;24(11): 1739-47.
- 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.
- Eshleman SH, Hudelson SE, OU SS, et al. Treatment as prevention: characterization of partner infections in the HIV Prevention Trials Network 052 trial. In: Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 19-22 July 2015, Vancouver, Canada. Abstract MOAC0106LB.
- Cu-Uvin S, DeLong AK, Venkatesh KK, et al. Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2010 Oct 23;24(16):2489–97.
- Sheth PM, Kovacs C, Kemal KS, et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS. 2009 Sep 24;23(15):2050–2054.
- Politch JA, Mayer KH, Welles SL, et al. Highly active antiretroviral therapy does not completely suppress HIV in semen of sexually active HIV-infected men who have sex with men. AIDS. 2012 Jul 31;26(12):1535–1543.
- Marcelin A-G, Tubiana R, Lambert-Niclot S, et al. Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. AIDS. 2008 Aug 20;22(13):1677–1679.
- Lampinen TM, Critchlow CW, Kuypers JM, et al. Association of antiretroviral therapy with detection of HIV-1 RNA and DNA in the anorectal mucosa of homosexual men. AIDS. 2000 Mar 31;14(5):F69–F75.
- 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.
- Kiviat NB, Critchlow CW, Hawes SE, et al. Determinants of human immunodeficiency virus DNA and RNA shedding in the anal-rectal canal of homosexual men. Journal of Infectious Diseases. 1998 Mar;177(3):571–578.
- Atashili J, Poole C, Ndumbe PM, et al. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. AIDS. 2008 Jul 31;22(12):1493–1501.