Wednesday 29 June, 2016 13.00 EDT
Treatment as prevention: do the individual prevention benefits translate to the population level?
Antiretroviral treatment can dramatically improve the long-term health of someone living with HIV. It can also reduce their risk of onward HIV transmission. Therefore, efforts to increase the number of HIV-positive people who are on treatment may – as a secondary benefit to improving health – help curb the number of new HIV infections in Canada and around the world. The idea that treatment may be able to prevent HIV transmission at the population level and have an impact on the HIV epidemic is commonly referred to as “treatment as prevention.” This has led to the concept of a “test and treat” or “seek, test and treat” strategy: a public health approach with the goal of maximizing the prevention benefits of treatment by increasing treatment coverage and decreasing community viral load.
Treatment provides prevention benefits at the individual level by reducing viral load
Antiretroviral treatment (ART) can reduce the viral load in the blood, semen, vaginal fluid and rectal fluid to very low levels (undetectable by current viral load tests) and this can reduce an individual’s risk of HIV transmission. This was demonstrated in a randomized controlled study known as HPTN 052 where treatment reduced the risk of HIV transmission by 96% among heterosexual serodiscordant couples.1 However, it is important to point out that couples in this study reported mostly having vaginal sex and were provided with regular adherence counselling, viral load tests, testing and treatment for sexually transmitted infections (STIs), and prevention counselling and free condoms. All of these may have helped maximize the prevention benefit of treatment.
While it’s unclear if the same reduction in risk applies to other populations – such as couples who do not receive these ongoing services, people in casual relationships, gay men and other men who have sex with men (MSM), and people who use injection drugs – it is generally thought that ART reduces HIV risk to some extent.2
[UPDATE: In March 2014, a preliminary analysis of an ongoing study (the PARTNER study) reported the first direct evidence that ART can significantly reduce HIV risk for gay men and other MSM.]
Prevention benefits at a population level?
Since treatment has prevention benefits at the individual level, it makes sense to think it may also have prevention benefits at the population level. In other words, increasing the number of HIV-positive people on treatment could lower the total amount of virus circulating in a community (also known as community viral load) and lead to a reduction in the number of new HIV infections.
So what evidence do we have? As HIV testing and treatment have become more accessible over the past decade, the number of HIV-positive people on treatment has been steadily increasing in most parts of the world. Whether the prevention benefits of treatment have already translated to the population level (prior to the implementation of any specific “seek, test and treat” strategies) can be explored by looking at whether increases in treatment coverage – and subsequent decreases in community viral load – have coincided with a reduction in new HIV diagnoses or estimated number of new HIV infections (also known as HIV incidence).
However, the evidence available so far is observational and has its limitations. Even if it is found that the number of HIV diagnoses (or HIV incidence) decreased in a population as more people accessed HIV treatment (a positive finding), it is difficult to know exactly why this happened. For example, a decrease in HIV diagnoses may have been the direct result of increased treatment coverage or it may have been the result of other HIV prevention interventions that were implemented at the same time.
Conversely, if it is found that HIV diagnoses stayed the same or increased as treatment coverage increased (a null finding), it is also difficult to know why this happened. For example, this may mean that treatment did not have prevention benefits or, on the other hand, it is possible that treatment did prevent transmissions but improvements in HIV testing services led to the identification of more cases of HIV and made it appear that treatment did not have an effect.
Furthermore, community viral load may not be a good indicator of overall infectiousness in a population. This is because community viral load is generally calculated using the viral load measurements of people living with HIV who are diagnosed and in care. Therefore, this measure does not include those who are undiagnosed or not in care and, as a result, may not reflect the viral load among all HIV-positive people in a community.
Because of these limitations, the evidence available so far should be viewed cautiously.
Below is a summary of the evidence of whether treatment has had a prevention impact in different populations.
Heterosexual populations in low-to-middle income countries
Globally, several countries have experienced decreases in estimated HIV incidence as treatment coverage has increased, suggesting treatment may be having a prevention impact.3 According to UNAIDS, HIV incidence decreased by more than 25% in 39 countries – the majority of which were low-to-middle income, in sub-Saharan Africa, and have generalized heterosexual epidemics – between 2001 and 2011. During the same time period, treatment coverage increased dramatically in many of these countries. For example, treatment coverage in sub-Saharan Africa increased by more than 100-fold. Although other HIV prevention efforts were also dramatically scaled up during this time, some experts think increased treatment coverage may have contributed to the decrease in new HIV infections.4
Furthermore, a recent study of a group of over 16,000 HIV-negative individuals in a rural area in South Africa found that for every 1% increase in ART coverage among people living with HIV, the risk of HIV infection decreased by 1.4%.Furthermore, an HIV-negative person living in a community with treatment coverage of 30–40% was on average 38% less likely to become infected than if they were living in a community with coverage less than 10%.5
People who use injection drugs in British Columbia
“Treatment as prevention” may be occurring among people who use injection drugs in British Columbia. Between 1996 and 2009, the number of people with HIV on ART in B.C. increased from 837 to 5413 (a 550% increase) and – in the same time period – the number of new HIV diagnoses fell from 702 to 338 per year (a 50% decrease).6 However, HIV diagnoses only decreased among people who use injection drugs and not among non-injection drug using populations. In a separate Vancouver-based study, decreased community viral load was associated with reduced estimated HIV incidence among a group of HIV-negative drug users.7
Even though reductions were observed among injection drug users in these studies, some experts have noted that other services for this population were improved during this time and may have contributed to this decrease.8 For example, the Vancouver-based supervised injection site known as Insite opened its doors in 2003.
Gay men and other MSM in high-income countries
“Treatment as prevention” does not appear to be happening among many populations of gay men and other MSM. In most high-income countries, estimated HIV incidence among MSM is remaining stable or continuing to increase despite increases in treatment coverage and decreases in community viral load.9,10
For example, in England and Wales, treatment uptake among diagnosed MSM in care rose from 69% in 2001 to 80% in 2010 and an estimated 53% of all MSM living with HIV in 2010 had an undetectable viral load.11,12 However, the annual number of new HIV diagnoses remained unchanged during this time period. Treatment coverage levels among MSM in France and Australia are similar to those in the UK but the number of new HIV diagnoses are continuing to increase in these countries.13,14 While the number of new HIV infections does not appear to be decreasing, experts think HIV incidence among MSM in many high-income countries would be higher if not for increased treatment coverage.15,16,17,18
An exception is the experience of San Francisco, where increased treatment coverage and decreased community viral load has been associated with a reduction in new HIV diagnoses.19 Between 2004 and 2008 the proportion of diagnosed HIV-positive MSM in care with an undetectable viral load increased from 45% to 78% (resulting in a decline in community viral load) and the number of new HIV diagnoses decreased from 798 to 434 (a 54% decrease). A more recent study – extending this time period to 2011 – supports the idea that “treatment as prevention” is occurring among gay men in this city.20
Increased treatment coverage has not reduced HIV incidence in Washington, D.C. Between 2004 and 2008, the proportion of diagnosed HIV-positive individuals in care with an undetectable viral load increased from 15% to 58%, the community viral load decreased, but the annual number of new HIV diagnoses did not change.21
In Southern Alberta, treatment coverage among people living with HIV in care increased from 62% to 81% between 2001 and 2010, while the proportion of people with a viral load of less than 200 copies/ml increased from 49% to 72%. Despite the large increase in treatment coverage and viral suppression, community viral load surprisingly remained stable and the number of new HIV diagnoses increased.22
Factors limiting treatment coverage and its prevention benefits
While the evidence above provides some indication of a relationship between increased treatment coverage, decreased community viral load and HIV prevention, the null findings – particularly among gay men and other MSM – suggest levels of treatment coverage in some populations may be insufficient to reduce HIV incidence. In fact, modelling studies suggest treatment coverage may need to exceed a certain threshold before its prevention benefits are observed.23 Therefore, efforts to further increase the proportion of people on successful treatment may improve HIV prevention efforts.
However, several factors are limiting treatment coverage among populations of people living with HIV. These include 1) the large proportion of people living with HIV who are undiagnosed, 2) poor engagement in HIV care, and 3) recommendations in treatment guidelines.
While treatment coverage has been increasing among HIV-positive people who are diagnosed and know their HIV status, the proportion of people with HIV who are undiagnosed has remained relatively stable in many parts of the world and this is limiting treatment coverage. For example, the Public Health Agency of Canada estimates that approximately 25% of people with HIV in Canada do not know their status (this proportion has not changed significantly over the last decade).24 Unfortunately, undiagnosed individuals cannot benefit from care and treatment, and research suggests they may contribute to the majority of HIV transmissions in a population.25
Poor engagement in HIV care is another barrier to increasing treatment coverage. Diagnosed individuals who are not engaged in HIV care cannot start treatment when they are ready to do so. Also, care is important to support adherence to medications so that treatment can successfully reduce the viral load to undetectable levels. Unfortunately, research suggests many people are not being linked to care after diagnosis and not remaining in care once linked.26
The number of people on treatment is also influenced by how soon an HIV-positive individual is eligible to start treatment once diagnosed and in care. Although many factors determine when someone is offered – and starts – treatment, an important one is eligibility recommendations in treatment guidelines. Coincidentally, as we have learned more about the prevention benefits of early treatment, we have also learned more about the importance of early treatment for the health of people living with HIV.27 As a result, over the last several years, guidelines have moved toward recommending increasingly earlier treatment.
For example, in 2009 the World Health Organization guidelines raised the eligibility threshold for starting treatment from 200 to 350 CD4 cells and their new guidelines – released in 2013 – increases this threshold to 500 CD4 cells. Furthermore, several major treatment guidelines in the United States – which previously recommended treatment initiation when the CD4 count dropped below 500 cells – now recommend that treatment be offered as soon as a person is diagnosed with HIV, regardless of their CD4 count. These guidelines include those produced by the Department of Public Health in San Francisco (revised in 2010), the Department of Health and Human Services (revised in 2012), and the International Antiviral Society-USA (revised in 2012).
Therefore, the evidence available so far cannot answer the question of what the potential prevention benefit of treatment might be if the proportion of undiagnosed people was much smaller, engagement in HIV care (including support for adherence) was improved, and more people were on therapy due to new treatment guidelines.
Seek, test and treat – maximizing the prevention benefits
Promisingly, modelling studies suggest the impact of treatment on HIV incidence could be significantly improved by increasing rates of HIV testing, offering treatment earlier and improving linkage to care, retention in care and treatment adherence.28,29,30,31 The impact in these models varies from moderate to dramatic (depending on the assumptions used) and it is clear that treatment alone will not be able to end the epidemic.
These modelling studies – and the other evidence described above – have led to the concept of a “test and treat” or “seek, test and treat” strategy. This strategy involves proactive efforts to increase the proportion of people who are on successful treatment by improving engagement in HIV testing, care and support, and treatment services (also known as the treatment cascade). These efforts not only have the potential to prevent HIV transmissions, but also improve the health of people living with HIV.
However, several questions currently remain unanswered with regards to “seek, test and treat” approaches and the use of treatment as a public health HIV prevention strategy. For example, is it feasible to significantly decrease the proportion of people who are undiagnosed and increase the proportion who are on successful treatment? What is needed to do this and how much can it reduce HIV incidence? There are also unanswered questions regarding the acceptability, sustainability and affordability of this approach.
Several large coordinated “seek, test and treat” initiatives are ongoing to answer these questions, although they have yet to be fully evaluated. These include:
Between 2010 and 2013, a pilot project called the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP) Project funded more than three dozen initiatives in Vancouver and Prince George. One of the aims of the overall project was to reduce the number of new HIV infections by taking an active public health approach to finding people living with HIV (either newly diagnosed or lost to care), bringing them into HIV treatment programs, and supporting them to stay on treatment.
While STOP is sometimes referred to as “seek and treat,” it also addresses individual and community needs across the full continuum of care, including prevention, engagement, and linkage to care and support. It has done this by expanding opportunities for everyone to get tested for HIV through routine offers of testing in hospitals and family practice and by offering testing in locations that cater to people at ongoing or higher risk for HIV infection; by improving the system of linkage to care and treatment, both for HIV and mental health and addictions, through the STOP Outreach Team and the Peer Navigation Program; and by providing expanded opportunity to receive HIV primary care and adherence support in community settings.
Evaluation of the pilot project is ongoing. Results so far show that the number of patients engaged in care has increased by 39% since the beginning of STOP. The mean community viral load has also declined.32 In April 2013, the Government of British Columbia announced it was funding the province-wide roll out of the STOP Project.
San Francisco’s HIV/AIDS Strategy (2010–2014) is a system-wide approach to HIV prevention, treatment, care and support. The goals of the strategy are to optimize the health outcomes of people living with HIV and reduce the number of new HIV transmission by suppressing community viral load. The strategy integrates public health services, primary care, and the services of community-based HIV/AIDS service organizations – and includes a research component – in order to reduce the cracks through which people seeking services may fall. The strategy, set to be completed in 2014, has not yet been evaluated.
In order to improve health outcomes for people living with HIV and reduce the number of new infections, San Francisco rolled out a city-wide approach. This approach is based on early diagnosis, engagement, linkage to care, and treatment adherence support. It includes promoting routine testing in medical settings and updating testing protocols and policies in community-based settings (counselling is no longer a prerequisite to get an HIV test and populations at increased risk are encouraged to test every three to six months). It also includes providing intensive prevention interventions to people at elevated risk for HIV infection and providing appropriate services for, and a universal offer of treatment to, those already living with HIV.
What can frontline organizations do?
Treatment has an important role to play in strengthening HIV prevention efforts and should be considered an important component of a comprehensive approach to HIV prevention. However, it will not be able to end the epidemic alone. Community-based organizations will continue to play an important role in the implementation of other biomedical, behavioural and structural HIV prevention strategies, such as the provision of condoms and education, risk-reduction counselling, post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), stable housing, and mental health services.
Frontline organizations should also think about the role they can play in maximizing the prevention benefit of treatment and ensuring individual rights are respected. This may include tools to support informed decision making, treatment readiness, and the doctor–patient relationship; use of innovative approaches to reaching the undiagnosed, improving engagement in care, and supporting adherence; and efforts to improve STI prevention and treatment (as untreated STIs in either partner may offset the prevention benefit of treatment).
Community consensus statement on the use of antiretroviral therapy in preventing HIV transmission – European AIDS Treatment Group, NAM
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