HIV in Canada: A primer for service providers
Effective treatment of people living with HIV
- Treatment of people living with HIV that reduces the viral load to undetectable levels is a highly effective strategy to reduce the risk of the sexual transmission of HIV.
- Treatment works by reducing the amount of virus that the HIV negative partner is exposed to, which reduces the chances of HIV finding its way into the body.
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.
There are several factors necessary for maximizing its effectiveness:
- 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.
In people living with HIV, successful antiretroviral treatment (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. 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.
The first study to conclusively show that ART has a prevention benefit was the randomized-controlled trial known as HPTN 052. 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. 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. 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 052 support the findings from three previously conducted observational studies among heterosexual serodiscordant couples that ART substantially reduces the risk of HIV transmission.
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). 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.
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.
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.
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. In fact, in two studies, ART was less than 10% effective. 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%. 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. 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, 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.
The prevention benefits of treatment in individuals may translate to a reduction of HIV transmissions at a population level. The idea is that if enough people living with HIV are on successful treatment, the average amount of the virus circulating in the community (also known as community viral load) should be reduced. This reduction in average community viral load may result in fewer transmissions. There are several barriers that prevent people living with HIV from being on successful treatment. The series of steps and services that an HIV-positive person must be engaged in to be on successful treatment (HIV testing, linkage to care, retention in care, initiation of treatment, treatment adherence) is also known as the HIV treatment cascade. The concept of an HIV treatment cascade has emerged as a way to identify gaps in this continuum of services.
HIV viral load, HIV treatment and sexual HIV transmission – CATIE fact sheet
Treatment and viral load: what do we know about their effect on HIV transmission? – Prevention in Focus
Expert Consensus Viral Load and Risk of HIV Transmission: Summary – Institut national de santé publique du Québec
Antiretroviral Treatment as Prevention (TasP) of HIV and TB – World Health Organization (WHO)
- 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 antiretroviral 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.