Bob Leahy: Thanks for talking to us. James, we're hearing a lot about treatment as prevention lately, particularly since HPTN052 and then the 2012 International AIDS Conference in Washington. But for those who haven’t been following, can you give a quick outline of the science behind treatment as prevention and why it holds promise at the population level?
James Wilton: We can think of treatment as prevention in two ways: as a prevention strategy for individuals and as a public health strategy to reduce HIV transmissions (or HIV incidence) in a population. These two types of “treatment as prevention” are related but also have important differences. Each type raises its own issues and concerns, so it’s important to know the differences between the two and not use them interchangeably.
At the individual level, the term “treatment as prevention” refers to the use of antiretroviral treatment by a person living with HIV to reduce their personal risk of HIV transmission. Research shows that treatment can reduce HIV replication in the body and lower the amount of virus, or viral load, in the blood and other bodily fluids to undetectable levels. Since viral load is an important factor that determines whether an exposure leads to HIV infection, being on treatment and having an undetectable viral load can reduce the risk of HIV transmission. A study known as HPTN 052 has shown that treatment can reduce the risk of HIV transmission by up to 96% for people living with HIV in heterosexual serodiscordant relationships.
As a public health approach, the goal of “treatment as prevention” is to reduce the number of new HIV transmissions in a population by increasing the proportion of people living with HIV who are on successful antiretroviral treatment. Since we know that treatment can reduce an individual’s viral load and risk of HIV transmission, this strategy may be able to reduce the overall viral load circulating in a population (also known as community viral load) and help control the spread of HIV. Some research shows that rates of new HIV transmissions have been reduced in populations where the proportion of people living with HIV on treatment has increased and the community viral load has decreased.
But then you and others have suggested, probably quite rightly, that the reductions in HIV transmission rates we’ve seen in studies like HPTN 052 – the 96% for instance, albeit in mostly heterosexual couples - may not be played out in the real world. Why would that be?
The results from the HPTN 052 study confirmed that “treatment as prevention” can work at the individual level. It told us that a person living with HIV (who is in a heterosexual relationship and mostly having vaginal sex) can reduce their personal risk of passing HIV to their partner by up to 96% by starting antiretroviral treatment.
However, this reduction in HIV transmission risk was achieved under the “ideal” conditions of a clinical trial. In clinical trials, participants are commonly provided with high levels of support services. Couples in the HPTN 052 study were provided with ongoing adherence support, viral load tests to monitor drug resistance, and STI testing and treatment. All of these services helped ensure the success of treatment at reducing the risk of HIV transmission.
Will heterosexual serodiscordant couples experience the same reduction in HIV transmission risk in the “real world”? Possibly, but it’s pretty safe to assume that it will depend on whether the couples have access to the same services as in the HPTN 052 study and how often they used them. For example, a recent “real world” study of heterosexual serodiscordant couples in China found that treatment only reduced transmission rates by 26%. It’s clear that treatment will be less than 96% effective at reducing HIV transmission risk if pills are not taken regularly, drug resistance develops, or STIs aren’t managed.
Furthermore, the HPTN 052 study did not tell us how well “treatment as prevention” will work as a public health strategy. Remember, this study enrolled a group of HIV-positive people who already knew their HIV status, were in care, and had access to treatment. This isn’t the case for many HIV-positive people outside of a clinical trial. In a “real world” population of people living with HIV, some don’t know their HIV status, have not or cannot access care, have not remained in care, or have not or cannot access treatment. These types of barriers will limit the number of people who have an undetectable viral load and, therefore, the success of a “treatment as prevention” strategy.
The HIV treatment cascade (or HIV care cascade) is a recently coined term for the continuum of steps and services required for a person living with HIV to achieve an undetectable viral load. These include knowledge of HIV status through testing and diagnosis, linkage to care, support to remain in care, support to access antiretroviral treatment, initiation of treatment, and support to adhere to treatment. Gaps or “leaks” in this cascade mean that, in general, only a relatively small proportion of people living with HIV in a population have an undetectable viral load.
For example, in the United States it is estimated that only 28% of people living with HIV have an undetectable viral load because people “leak” out at different points in this cascade. There are no accurate estimates for Canada, but preliminary data suggest that we may have a similar situation here. According to the Public Health Agency of Canada, 26% of people living with HIV do not know they are HIV-positive and therefore can’t access care and treatment services. We are only just beginning to look at where we are falling short in other parts of the treatment cascade in different regions and populations in Canada.
OK, so let’s look at what treatment as prevention looks like in practice. Aren’t we doing it already? You’ve said in the past a treatment as prevention strategy is really about doing a better job at what we should already be doing. That implies performance gaps. Can you be specific as to where we’re falling short right now?
Yes, to some extent, we are doing it already. Although we didn’t know it at the time, potent combination antiretroviral treatment (commonly called ART or HAART) began preventing HIV transmission when people first started taking it in 1996. Since then we have gained a much better understanding of the role earlier treatment can play in preventing HIV transmissions and improving the health outcomes of people living with HIV. As a result, we have begun to think about how we might do things differently; for example, by taking a more proactive approach to engaging people living with HIV in testing, care and support, and treatment services.
There are a number of things we need to be doing a better job at. We need to improve access to different types of testing, rethink our testing strategies and develop more innovative ways of linking people who test positive to care and support services. Once a person is in care, we need to do a better job of supporting them to stay in care and linking them to appropriate services. Education and counseling needs to include information on the health and prevention benefits (and risks) of earlier treatment. Finally, people who want to start treatment need to have access to the medications and then be supported in their adherence (ability to take their medications every day, exactly as directed). Achieving improvements in engagement will also require new partnerships to be formed so we can bridge the divide between clinic and community. For example, peer navigation programs deploy peers from the community into clinical settings to help people living with HIV navigate their way through the healthcare system after diagnosis.
Improving engagement of people living with HIV in healthcare and social services is something we should be doing anyways, regardless of the role treatment plays in prevention. I don’t like the term “treatment as prevention” because it suggests that the sole reason for taking this pro-active approach is to prevent new HIV transmissions, when we know that it also has the potential to improve the health of people living with HIV.
We are beginning to see changes around the world and also in Canada. The STOP program in British Columbia has been the most publicized initiative, but there are many other programs and interventions being implemented across the country which are doing some really good things to engage people living with HIV in testing, care and support, and treatment services. These all have the potential to improve health of people living with HIV and prevent new HIV transmissions.
I see that. But, James, we are not really any closer to knowing what the reduction in infections though ART might be in gay and bi men, right? There have been a lot of suggestions that treatment as prevention hasn’t worked in gay/bi communities, but some have also suggested that there is no reason to assume that the reduction in transmission risk through correctly talking ART will be all that much less than the 96% recorded in the heterosexual cohort, at least in a trial setting, in some circumstances. Dr. Rupert Kaul said to me last month “Although we don’t have specific data about anal sex from the studies to date, my best guess is that if you are an HIV uninfected man who only practices insertive anal sex (studies say that is about 10% or less of gay men) then if your partner goes on antiretovirals this will have the same protective benefit for you as was seen in the HPTN 052 study.” Do you agree?
At the individual level, there is no reason to think that successful treatment won’t also reduce the risk of HIV transmission for gay and bi men (and others who engage in anal sex). However, it is still not clear if this reduction will be as great as it was for heterosexual couples in the HPTN 052 study (who were mostly engaging in vaginal sex). Fortunately there are some ongoing studies that are trying to answer this question, such as the Opposites Attract study in Australia and the PARTNER and START trials in Europe.
As I mentioned in my previous interview for PositiveLite.com, even if the reduction in risk is the same for gay and bi men, the risk of HIV transmission while on treatment may still be higher for anal sex than for vaginal sex. For example, when not on treatment, research suggests that the risk of HIV transmission through receptive anal sex is up to 20-times higher than vaginal sex. What does this mean for the risk of HIV transmission when the viral load is undetectable? Does a higher HIV transmission risk when not on treatment mean that the risk will also be higher when on treatment? We don’t know and ongoing studies are trying to answer these questions. As for insertive anal sex, most studies suggest the HIV transmission risk when not on treatment is in the same ballpark as for vaginal sex.
While we wait for gaps in the research to be filled, experts are trying to develop a consensus on the research that is available. For example, the British HIV Association (BHIVA) recently released a position statement on the use of antiretroviral therapy to reduce HIV transmission.
At the population level, we still have a lot to learn about how “treatment as prevention” may impact the spread of HIV among gay men. Studies show that HIV transmission rates among some populations of gay men is remaining stable or increasing even though the proportion of people on treatment is increasing. It’s not entirely clear why this is. Some researchers think that recent increases in risk behavior and STI prevalence among some gay men may be offsetting the prevention benefit of antiretroviral treatment. Many researchers also think the majority of HIV transmissions are happening among people who are not aware they have HIV, which suggests that better testing programs are needed. Moving forward we need to make sure that we don’t look at HIV in isolation and re-evaluate how well we are doing at STI testing, prevention and treatment work and at meeting the sexual health needs of gay men.
One aspect of treatment as prevention is that people are offered treatment immediately on diagnosis, irrespective of their CD4 count. This is certainly in line with US treatment guidelines and in fact is a practice followed to some extent north of the border. How universal is this in Canada and if not universal, why not?
Recently, the major treatment guidelines in the United States, produced by the Department of Health and Human Services (DHHS) and the United States International Antiviral Society (IAS-USA), changed to recommend offering treatment regardless of CD4 count. In Canada, only British Columbia and Quebec have developed treatment guidelines. The guidelines in British Columbia recommend treatment for anyone with a CD4 count below 500 and say treatment should be considered for patients with a CD4 count higher than 500 in certain other situations, such as specific other health conditions or if there is a heightened risk of HIV transmission (that is, if they are in a serodiscordant relationship). Quebec’s guidelines recommend that people with a CD4 count below 350 start therapy. For people with a CD4 count over 350, Quebec’s guidelines say that the decision to recommend treatment should be individualized and based on clinical factors, such as hep C co-infection, how high the viral load is and how fast the CD4 count is declining.
Treatment guidelines area a set of important recommendations that are intended to help doctors provide effective care to people living with HIV. While guidelines often influence doctor’s decisions, they are not rules that must be followed. Ultimately the conversation about starting treatment is one that happens between a doctor and their patient and it will depend on many factors. The recommendation to offer treatment immediately is based on the need to get the discussion started as soon as possible and ensure people living with HIV have the information needed to make an informed choice. Offering treatment is not the same as telling a person to start treatment. The doctor and the person living with HIV will need to consider readiness to start treatment, for example, as well as the benefits and risks of early treatment.
Which brings me to my next question. Treatment as prevention advocates argue that the benefit is not only in reducing infectiousness but in improving health outcomes for people starting ART early. Are there in fact better outcomes when people start treatment early? And what are they?
The treatment guidelines I just mentioned discuss the evidence for their recommendations.
More and more research is showing that even early on in the course of HIV infection the virus can begin to cause long-lasting and permanent changes to certain organs and the way the immune system works. Research is also showing that uncontrolled HIV replication causes ongoing inflammation which may lead to premature aging of the immune system and accelerated development of age-related conditions such as cardiovascular disease. As we have learned more about the damage uncontrolled HIV replication causes to the body, and the ability of antiretroviral treatment to control HIV replication and partially reverse damage to the immune system and organs, guidelines have moved to recommend earlier and earlier initiation of treatment.
There is evidence that starting treatment before CD4 counts fall below 500 may be beneficial to people living with HIV and there is strong evidence for starting treatment before CD4 counts fall below 350. Although we don’t have definitive evidence that initiating treatment at CD4 counts of higher than 500 improves health outcomes, we do know starting treatment at any CD4 count can raise CD4 levels and slow further declines. Many of us are eagerly anticipating the results of the START study, a large (4,000+ participants) randomized controlled study that will provide a definitive answer to this unanswered question. Results are expected within the next couple years.
I suppose you could argue too that the recent Supreme Court decision that suggested disclosure is required unless condoms and a “low” viral load are present is another argument for going on treatment at the outset of one’s journey with HIV - to avoid ending up in court. Of course whether that’s the kind of coercion we want to see is another matter.
Anyway, let’s talk about one of the objections to starting treatment on diagnosis. We hear a lot about the necessity for informed consent, but surely that can be stipulated and the tools provide to make that happen. I mean we use those tools – consent forms, for instance – in clinical trials all the time, no?
It’s important that people living with HIV have constructive and meaningful discussions with their healthcare provider before they make the decision to start treatment. These discussions need to explore their readiness to start treatment, the risks and benefits of initiating treatment and what the evidence does, and does not, tell us. Ultimately the decision needs to rest with the person living with HIV.
The tools we need are those that support the doctor-patient relationship to ensure informed decision-making and treatment readiness. CATIE has developed several of these tools, such as an HIV treatment talking tool (Your Doc Talk), treatment videos (Starting HIV treatment: Personal Stories), A Practical Guide to HIV Drug Treatment, and workshops. Some of these tools are available at http://www.catie.ca/en/starting-treatment.
I want to explore whether talking about treatment as prevention is dangerous in itself. Could it for instance result in an increase in risk behavior?
I don’t think talking about treatment as prevention is dangerous and the complexities of this approach means we need more discussion, not less. However, we do need to be careful with how we talk about treatment as prevention and make sure that we aren’t giving simple answers to complex questions.
Several concerns have been raised about how “treatment as prevention” is promoted and the potential for increased risk behavior is one of them. At the moment it is just that, a potential concern. However, there is some research showing that people who are aware of the prevention benefits of treatment are less likely to report using condoms. I don’t think anyone is saying that this concern means that we shouldn’t be talking about “treatment as prevention”, just that we need to be careful how we talk about it.
One more question about starting treatment early: we haven’t heard much about concerns for side effects issues if people start treatment earlier than they might otherwise have done. As someone who has suffered from pretty severe peripheral neuropathy from exposure to drugs which later proved to be toxic in the long term and led to irreversible nerve damage in my feet, is there reason to be concerned about side effects emerging in the long term through lengthened exposure to newer HIV drugs tested only over the short term?
Newer antiretroviral drugs are generally more tolerable and safer than older drugs, but some haven’t been available for a long time so we aren’t really sure about their long-term effects. We always need to be vigilant about side effects and this will continue to be an area of ongoing research. This brings us back to informed consent and the information that needs to be discussed with a person living with HIV before they start treatment. For some people this may mean they don’t want to start treatment, for others the benefits of starting treatment may outweigh the potential risks.
I’m liking how CATIE seem to be taking a proactive role in getting people together from across Canada to talk about treatment as prevention Can you talk about how CATIE’s role in this work will look like over the next several years.
CATIE is trying to broaden the discussion and facilitate national dialogue on what a range of new developments mean for HIV treatment and prevention programming and policies in Canada. A lot of the focus recently has been on “treatment as prevention”, but this is only one recent advancement with important implications. There have been several others in HIV testing, prevention, care and support, and treatment and we need to reflect on what all of these mean for our front-line response to the HIV epidemic in Canada.
Historically, treatment and prevention have tended to be viewed as separate silos in terms of programming and policies. However, the new developments in the field really emphasize that this division is artificial and that we need to consider the full continuum of HIV prevention, testing/diagnosis, care/support and treatment as mutually reinforcing elements of an effective response that must be integrated in a comprehensive approach. Also, the prevention and treatment of STIs need to be part of such an approach.
I gather you have already had one meeting - a deliberative dialogue on integrating prevention and treatment, trying to shift towards a Canada-wide consensus on this issue? Did specific outcomes emerge from those discussions?
Last fall we brought together stakeholders from across Canada to discuss the issues raised by recent research, including research on treatment as prevention, and its implications for integrated approaches to HIV treatment and prevention. A meeting report will be available soon on our website. This discussion has helped to inform a number of initiatives CATIE will be undertaking in the next year or so. We will be developing tools for front-line organizations to help them reflect on what this new research might mean for their programming; including a “Planning Roadmap” that provides an integrated framework for program planning and case studies of innovative new programs.
We will also be hosting a national knowledge exchange forum in Toronto on September 17-19, 2013 called “New Science, New Directions in HIV and Hepatitis C”. This forum will bring together front-line workers, program planners, public health workers, people living with HIV and/or hepatitis C, and policy makers from across Canada to share experiences, discuss innovative programs and reflect on what new these new developments mean for our response.
Good work, James, from CATIE and yourself! Thank you for talking to us. Let’s continue this discussion later . I’m particularly interested to hear your views on new prevention technologies . . .
(Watch for part two of this interview where Bob Leahy asks James Wilton about new prevention technologies.)
About James Wilton: James Wilton is the Project Coordinator of the Biomedical Science of HIV Prevention Project at CATIE. James has an undergraduate degree in Microbiology and Immunology from the University of British Columbia.