Table of Contents
A new idea came to the forefront in 2006 at the International AIDS Conference held in Toronto. Since then, this idea has received increasing attention around the world. Treating people living with HIV may reduce the sexual transmission of HIV on a population level
. We are familiar with the idea that if someone uses a condom for sex they can protect themselves and others from getting HIV -- this is something an individual is able to do to protect themselves and others. But "treatment as prevention" moves away from the focus on individual
prevention efforts toward an approach that focuses on reducing the number of new HIV infections in an entire community or population
. So what does all of this really mean?
What Is Treatment as Prevention?
We know that treatment for HIV can effectively reduce the amount of virus in the blood of someone living with HIV (often to levels that cannot be detected by current viral load tests). For many people this reduction in the amount of virus may reduce infectivity (their ability to transmit the virus). However, we also know that treatment does not eliminate the virus from the body which means that the risk of transmission from one person to another is only potentially
reduced and not eliminated. This is why treatment as prevention does not work on an individual level -- the reduction in risk of transmission is not enough to replace conventional methods of prevention, such as practicing safer sex or using clean needles.
However, treatment as prevention may work on a population level. The idea is that if enough people living with HIV are diagnosed and successfully treated, then the result should be a reduction in the average amount of the virus circulating in the community. This reduction in average viral load, over many different exposures to HIV within a population, may result in the occurrence of fewer transmissions. The reduced HIV transmission rate is an effect that only happens when large groups of people living with HIV are successfully treated. This is why experts only envision treatment as prevention as a population-level approach, which would be undertaken in combination with conventional prevention programs.
How Do We Know If Treatment as Prevention Will Work?
We don't really know for certain if treatment of a large group of people and the resulting reduction in average viral load will result in a meaningful and reliable reduction in HIV transmission. However, four types of evidence suggest that it might work at a population level:
- studies on mother-to-child (vertical) transmission;
- studies of serodiscordant couples;
- ecological studies;
- modelling studies.
We are now able to dramatically reduce the transmission of HIV from an HIV-positive mother to her child.1 Treating the expectant mother with antiretroviral therapy reduces the mother's viral load, thus potentially reducing the risk of transmission because the fetus is exposed to less virus in utero and during birth. However, the fetus also receives antiretroviral therapy while in the womb (as antiviral drugs penetrate the placenta) and the child may also receive antiviral drugs post birth. These forms of pre- and post-exposure prophylaxis may also play a role in the reduction of vertical transmission from mother to child.
The success of reducing the risk of mother-to-child transmission through the use of antiretroviral treatment provides proof of concept (not concrete evidence) that antiretroviral therapy may be able to reduce the risk of sexual transmission.
Observational Studies of Serodiscordant Couples
Observational research investigates the outcome of something that is naturally occurring. The researcher does not assign a person to either treatment or no treatment -- it is something that has happened naturally.
Observational studies investigating the number of HIV transmissions in serodiscordant couples (where one partner is HIV-positive and the other is HIV-negative) where the HIV-positive individual is receiving highly active antiretroviral therapy (HAART), provide some evidence to support the theory that treatment may reduce but not eliminate HIV transmissions.
A recent systematic review compiled the data from five studies that examined HIV transmission in serodiscordant heterosexual couples where the HIV-positive individual was receiving treatment. When all the data were combined, the results showed that heterosexual HIV transmissions were reduced by 92%: from 5.64 transmissions per 100 person-years in people not on HAART to 0.46 transmissions per 100 person-years in people on HAART.2
However, caution should be used when making conclusions based on these data. First, the studies are only observational and therefore you can't rule out that the effect (reduction in HIV transmissions) was due to something other than treatment. For example, people who choose to start treatment may also be the type of people who are more likely to use a condom -- if this is true then it may be the condom use that explains the reduction in HIV transmission rather than the treatment itself.
Second, there are relatively few studies that have looked for HIV seroconversions in serodiscordant couples. Due to the relatively small amount of data it is difficult to accurately assess the potential reduction in HIV risk. Finally, there were no studies that included gay men and other men who have sex with men. This means we can't say what the potential effect may be in these populations.
Ecological studies examine the association between two different variables at a population level. In this instance ecological studies look at the association between the availability of HAART and HIV incidence in a defined area. In Taiwan, after free HAART was made available to people living with HIV, there was a 53% decrease in the number of new HIV-positive tests.3 In San Francisco, after HAART became available there was an estimated decline of 60% in HIV infections in gay men.4 In British Columbia (B.C.), after the introduction of free HAART, there was an estimated 50% reduction in new HIV infections.5
It is important to keep in mind that ecological studies, while useful, may not tell the whole story. For example, it is possible that in some or all of these situations, other prevention efforts that may have occurred at or around the same time may have contributed to any decrease found in HIV transmission rates.
A modelling study is a hypothetical description of what could happen if a change is made in a population or community. Modelling studies have attempted to explain the relationship between the effect of HAART and viral load on HIV transmission. A model developed by researchers in B.C. suggests that, at a population level, HAART may reduce the risk of HIV transmission. The model predicted that, with increasing numbers of people receiving HAART, there will be fewer transmissions within the population. However, the model suggests that at least 75% of people who are clinically eligible for treatment would have to receive treatment for there to be a substantial reduction in HIV transmission.6
It is important to remember that models are only our best guess as to what might happen. They provide no proof that in the real world this will happen.
Randomized Control Trials
Randomized controlled trials (RCTs) are the most rigorous form of scientific study. They are the best way to determine whether a cause-effect relationship exists between treatment and outcome. This is because everyone has the same chance of being assigned to a treatment group or a control group and no one knows which group they are in. This means we can be pretty sure that any difference found is due to the intervention or treatment and not because of differences between the groups.
RCTs are considered to be the "gold standard" in evidence. Unfortunately, there are no results from RCTs available that assess whether treatment reduces HIV transmissions at a population level. There are a few trials in development but the results will not be available for years.
Why Doesn't Treatment as Prevention Work on an Individual Level?
"Viral load" is a measure of the amount of the virus in the body of someone living with HIV. When someone is successfully treated for HIV with HAART, the blood viral load test reads as "undetectable." However, this does not mean that the virus is not present; rather, the level of virus in the blood is very low -- too low for the test to find it. However, since there is still virus in the body there is still a chance that with every sexual act the individual could transmit HIV to their partner.
While a blood viral load test result of "undetectable" means there is a very low level of virus in the blood at the time the test was taken, there are a few things about viral load and testing that underline the complexity of this issue:
- First, people who are successfully treated with HAART can experience unexplained temporary increases in viral load. These are known as "blips." Because blips only last for a short time (usually less than three weeks)7-9 they may be missed by routine blood viral load tests (which often take place every three months). In other words, the person with HIV may not know when and if they are experiencing a blip.
- Second, the blood viral load test is the only routine test for viral load in Canada. However, sexual transmission of HIV occurs through exposure to other fluids -- seminal, anal or vaginal fluids. There is research showing that HIV can be detected in the genital fluids of some people who have undetectable viral load in the blood.10-17 Therefore, someone might have an undetectable viral load in blood but not in their genital secretions -- which may affect the risk of sexual transmission. However, even if the amount of the virus is similar in blood and genital fluids, it is important to remember that an undetectable reading doesn't mean the virus is gone.
- Finally, sexually transmitted infections (STIs) have also been implicated in causing increases in viral load in genital fluids, which could affect one's ability to transmit the virus.18-19 Compounding this issue is that some STIs can be asymptomatic; meaning those with STIs and their partners may not know they have one and therefore may not be aware that they could be prone to increases in viral load.
These factors mean that an individual can never be exactly sure if their viral load is undetectable in all parts of their body. This does not mean that viral load tests are inaccurate; rather, it implies that blood viral load tests do not tell the entire story.
It is important to understand that an individual with an undetectable viral load can still transmit HIV. There has been at least one case reported of an HIV transmission in a serodiscordant couple, where the HIV-positive individual was on HAART and had an undetectable blood viral load.20
Furthermore, a modelling study predicted a persistent risk for HIV transmission on an individual level.21 The purpose of this model was to estimate the total number of HIV transmissions in serodiscordant couples where the HIV-positive person was successfully treated with HAART. In a population of 10,000 serodiscordant couples over 10 years, it was estimated that HIV transmissions might still take place as follows:
- 215 transmissions from an HIV-positive woman to an HIV-negative man;
- 425 transmissions from an HIV-positive man to an HIV-negative woman;
- 3,524 transmissions from an HIV-positive man to an HIV-negative man.21
While there is some evidence that treatment as prevention may have an impact on HIV transmission at the level of the population, it will not eliminate all HIV transmissions. For service providers who are working to prevent individual HIV transmissions, this is clearly very important. This information provides a rationale for the need to continue with existing prevention efforts such as condom promotion and distribution.
What Are the Main Components of a "Treatment as Prevention" Program?
Increasing the Number of People Who Know They Are HIV-Positive
In Canada, it is estimated that 26% of people living with HIV don't know they have HIV.22 This means that approximately 16,900 people in Canada are unaware they have HIV because they haven't been tested (or tested recently enough to know they are now HIV-positive).
Increasing the number of people who know they have HIV is important for several reasons. First, research has shown that when people know they are HIV-positive they are more likely to take steps to protect their partners than when they are unaware.23-25 Therefore, increasing the number of people who know they are infected should lead to a reduction in HIV risk behaviours.
Second, and most importantly for treatment as prevention, increasing testing and thus the number of people who know they are HIV-positive should result in more people accessing care and treatment.
Increasing the Number of People With HIV Receiving Treatment
In order for treatment as prevention to work we need to increase the number of people on treatment. This can be done by increasing the number of people who access care and treatment and increasing the number of people who are clinically eligible for HAART.
In the mid 1990s anti-HIV treatments, called highly active antiretroviral therapy (HAART) became available for people living with HIV. HAART has been shown to significantly reduce the risk of illness and death as result of HIV.26-31
But not everyone needs to be on treatment. The CD4+ count is the main indicator used to determine when someone should start treatment (clinical eligibility). In the past, there was a trend towards delaying the start of HIV treatment until the CD4+ cell count fell quite low, below 200 copies/ mm3.
However, recent research shows that starting treatment at higher CD4+ counts reduces the occurrences of illness and death.32-34 The reason for this is that HIV can cause chronic inflammation, which, over prolonged periods of time, can damage the body. HAART may reduce the level of inflammation caused by HIV, slowing or perhaps even stopping the damage.
Based on this new research, current treatment guidelines now recommend that all people living with HIV should start HAART before their CD4+ count falls below 350 cells/mm3 and in certain circumstances they should start at even higher CD4+ counts.35 In short, the clinical guidelines now suggest that getting on treatment to reduce viral load, even in people with relatively high CD4+ counts, is often the best for the health of people living with HIV. These new guidelines should result in more people living with HIV getting on treatment.
Access to Treatment
However, clinical guidelines do not tell the entire story. Research conducted in 2006 found that only 50% of those who were clinically eligible for HAART in B.C. were receiving therapy.6 Research in B.C. also shows that particular groups, especially those who are stigmatized and marginalized, are less likely to access treatment even though HAART is available at no cost to all people living with HIV in the province.36 The groups less likely to access treatment include young men who have sex with men, Aboriginal peoples, the homeless, the poor, the mentally ill and people who inject drugs.36
It is important that barriers such as stigma and discrimination are addressed in order to increase the number of clinically eligible individuals accessing care and receiving HAART.
Community-based AIDS service organizations (ASOs) in Canada have been at the forefront of HIV prevention since HIV emerged in our communities. The work that has been done has been integral to prevention efforts in Canada. With the advent of potential new approaches to HIV prevention, such as treatment as prevention, there may be exciting changes to community-based programming and expansion of the knowledge necessary to prevent HIV transmission within a more complex HIV prevention arena.
Due to the complexity and less than perfect nature of the science involved in treatment as prevention, service providers need to be aware of what the science is saying. We know that currently there is uncertainty regarding the impact of treatment as prevention at a population level. However, at an individual level this approach does not provide a level of protection that would allow individuals to forego conventional prevention approaches.
However, some have misinterpreted the science surrounding this approach and have concluded that people living with HIV can forego condom use. This may be compounded by the increasing media attention being paid to the potential role of treatment as prevention, which may also be misinformed. The risk is that if enough people stop conventional forms of HIV prevention (such as condom use) because they think it is safe to do so, any benefits that might have been gained by this approach could be offset and even overridden, resulting in increasing HIV transmission rates.
Talking about risk and assessing risk may become more complicated as a result of this new prevention approach. Service providers will need to be ready to answer a new battery of questions about HIV prevention from people within their community.
Integration of Treatment and Prevention Programming
There have long been two silos in HIV -- treatment and prevention -- with little mixing between the two parts. However, treatment as prevention combines the two halves and necessitates a more holistic approach to HIV and HIV programming. It pushes treatment into the prevention realm, requiring programmers to figure out how traditional treatment-focussed programming could be utilized or adapted to enhance the success of treatment as prevention in reducing HIV infections in the community.
As we know, in order for treatment as prevention to work, we need to increase access to testing, care and treatment. Historically these are areas outside the prevention realm that are now essential to ensuring the optimal success of this potential new approach. Depending on the availability of local services, community-based organizations may have to create new programming or enhance existing programming to ensure optimal access to testing, care and treatment. Examples of such activities are HIV testing campaigns; rapid point-of-care testing; outreach to bring more people into contact with testing services; programs aimed at linking HIV-positive people with care providers; treatment counselling; treatment support programs; and adherence counselling, to name a few.
Combination Approach to Prevention in Community Programming
Combination prevention is now seen as the way forward to preventing HIV transmission. This approach utilizes a strategic combination of HIV prevention approaches to try to ensure that everyone in need has access to prevention messaging and programming when they need it. This means that program planners, with the knowledge of their communities, determine the best-case mix of programming to ensure that the fewest number of people fall through the holes in the safety net they have created by layering many different types of prevention programs.
Since we are introducing another approach to prevention, one that we know is not a magic bullet, it is very important that treatment as prevention be envisioned as yet another potential component to HIV prevention. Program planners will have to figure out how their prevention approaches fit together with treatment as prevention to ensure the best level of protection for people at risk living in their community.
Protecting the Rights of People Living With HIV
Community-based agencies must continue to be vigilant around the rights of people living with or at risk for HIV. Since the theory of treatment as prevention promotes that the more people who know they have HIV and are on treatment, the better off we are in terms of prevention, there is fear that this could affect the individual rights of people to make their own decisions. Therefore, the community has an important role to play in ensuring that the human rights of people at risk for or living with HIV are safeguarded independent of the potential public health benefits of this approach.
In terms of testing, voluntary testing must remain the mainstay of testing within Canada. Any attempt to increase testing rates in Canada should not violate this central ideology. In terms of treatment, the choice to begin HIV treatment must rest solely with the individual living with HIV, and treatment must only be offered when medically necessary. While there may be a public health benefit to having all people on HAART in Canada, this benefit should never remove the choice to start therapy from the individual. Furthermore, treatment guidelines should always be made with the interests of the individual as paramount.
Impact on Services
In addition to programming aimed at increasing testing and treatment, community agencies may have additional demands on them for other services. As discussed, research has found that some marginalized people are not currently accessing treatment. However, many of these people are not well positioned to start treatment due to competing priorities in their life, such as poverty, drug use and homelessness. To better position marginalized people for treatment, an array of issues may have to be addressed, including education, housing, mental health, addictions and many more before treatment issues can be addressed. These issues may place additional burden on community agencies.
The cost of increasing the number of people on therapy could have a large financial impact. There is some concern that this increasing cost could lead to prevention dollars being diverted to finance treatment costs (since treatment is now seen as a form of prevention). The community must fight to ensure that funding agencies do not divert dollars in this manner.
It should be noted that preliminary work in this area estimates that there will be substantial financial benefits in the long-run due to a reduction in new HIV transmissions.12 Policy-makers need to envision a short-term increase in costs for long-term cost savings and keep this in mind when allocating resources.
What Is Happening on the Ground?
In April 2009 at the Canadian Association of HIV Researchers (CAHR) conference in Vancouver, Gordon Campbell, the premier of B.C., announced that his government was committed to implementing several pilot projects in the province to test programming that will bring more people into treatment.
This announcement followed more than a year of meetings between the Ministry of Health Services and stakeholders to discuss new treatment programs. An independent consulting group was hired to review the evidence and to create a macro plan detailing what it would take to make these programs a reality. While these plans are not yet available publicly, it appears that these programs will be comprehensive, attempting to address the competing priorities in hard-to-reach populations. The programs will be piloted in the Downtown Eastside of Vancouver and in northern B.C.
To Wrap Up ...
Treatment as prevention is a new potential approach to help curb the growth of the HIV epidemic. If we take a step back, away from the science and all the questions about whether and how much it will work -- bringing more people into care is essential regardless of any prevention benefit. Despite access to care and treatment in Canada, people are being diagnosed with HIV infection late and some are dying without ever receiving treatment. Any programming to bring people into treatment is long overdue and imperative to ensure that marginalized communities receive the same benefits of health care as the rest of the population.
|Statement on ART as Prevention|
In October 2009, international HIV/AIDS advocacy organizations wrote a statement directed at participants of an upcoming treatment as prevention Consultation hosted by the World Health Organization that was held in November. This statement outlines support for treatment as prevention but highlights factors that should be integral to any planning and implementation of research projects related to treatment as prevention.
Read the full statement here.
Laurel Challacombe holds a Masters degree in Epidemiology and is currently Manager of Research and Evaluation at CATIE. Laurel has worked in the field of HIV for over 10 years and has held a variety of positions in both provincial and regional organizations, working in research and knowledge transfer and exchange.
- Volmink J, Siegfried N, van der Merwe L, Brocklehurst P. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003510. DOI: 10.1002/14651858.CD003510.pub2
- Attia S, Egger M, Muller M, Zwahlen M, Low N. Sexual transmission of HIV according to viral load and antiretroviral therapy: Systematic review and meta-analysis. AIDS. 2009. 23:1397-1404.
- Fang CT, Jsu HM, Twu SJ, et al. Decreased HIV transmission after a policy of providing free access to highly active antiretroviral therapy in Taiwan. Journal of Infectious Diseases. 2004.190:879-885
- Porco TC, Martin JN, Page-Shafer KA, et al. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy. AIDS. 2004. 18:81-88.
- Montaner JSG, Hogg R, Wood E, Kerr T, Tyndall M, Levy AR, Harrigan PR. The case for expanding access to highly active antiretroviral therapy to curb the growth of the HIV epidemic. Lancet. 2006. 368:531-536.
- Lima VD, Johnston K, Hogg RS, Levy AR, Harrigan R, Anema A, et al. Expanded Access to Highly Active Antiretroviral Therapy: A Potentially Powerful Strategy to Curb the Growth of the HIV Epidemic. The Journal of Infectious Disease. 2008.198:59-67.
- Di Mascio M, Markowitz M, Louie M, et al. Viral blip dynamics during highly active antiretroviral therapy. The Journal of Virology.2003. 77:12165-12172.
- Nettles RWE, Kieffer TL, Kwon P, et al. Intermittent HIV-1 Viremia (blips) and drug resistance in patients receiving HAART. Journal of the American Medical Association. 2005. 293:817-829.
- van Sighem A, Zhang S, Reiss P, et al. Immunologic, virologic, and clinical consequences of episodes of transient viremia during suppressive combination antiretroviral therapy. Journal of Acquired Immune Deficiency Syndrome. 2008. 48:104-108.
- Zhang H, Dornadula G, Beumont M, et al. Human immunodeficiency virus type 1 on the semen of men receiving highly active antiretroviral therapy. New England Journal of Medicine. 1998. 339:1803-1809.
- Fiore, JR, Suligoi B, Saracino A, et al. Correlates of HIV-1 shedding in cervicovaginal secretions and effects of antiretroviral therapies. AIDS. 2003. 17(15):2169-2176.
- Barroso PF, Harrison LH, de Fatima Melo M, et al. Adherence to antiretroviral therapy and persistence of HIV RNA in semen. JAIDS. 2003. 32:435-440.
- Neely MN, Benning L, Xu J, et al. Cervical shedding of HIV-1 RNA among women with low levels of viremia while receiving highly active antiretroviral therapy. JAIDS 2007. 44(1):38-42.
- Cu-Uvin S, Caliendo AM, Reinert S, et al. Effect of highly active antiretroviral therapy on cervicovaginal HIV-1 RNA. AIDS. 2000. 14:415-421.
- Cu-Uvin S, Snyder B, Harwell JI, et al. Association between paired plasma and cervicovaginal lavage fluid HIV-1 levels during 36 months. Journal of Acquired Immune Deficiency Syndrome. 2006. 42:584-557.
- Kalichman SC, Di Berto G, Eaton L. Human immunodeficiency virus viral loads in blood plasma and semen: Review and implications of empirical findings. Sexually Transmitted Diseases. 2007. 35(1):55-60.
- Lorello G, la Porte C, Pilon R, Zhang G, Karnauchow T, MacPherson P. Discordance in HIV-1 viral loads and antiretroviral drug concentrations comparing semen and blood plasma. HIV Medicine. 2009. 10:548-554.
- Cohen M, Galvin S. The role of sexually transmitted diseases in HIV transmission. Nature Reviews Microbiology. 2004. 2:39-41.
- Cohen MS, Hoffman IF, Royce RA, et al, for the AIDSCAP Malawi Research Group. Reduction of concentration of HIV-1 in semen after the treatment of urethritis: Implications for prevention of sexual transmission of HIV-1. Lancet. 1997. 349;1868-1873.
- Sturmer M, Doerr HW, Berger A, Bute P. Is transmission of HIV-1 in non-viraemic serodiscordant couples possible? Antiviral Therapy. 2008. 13:729-732.
- Wilson DP, Law MG, Grulich AE, Cooper DA, Kaldor JM. Relation between HIV viral load and infectiousness: A model-based analysis. Lancet 2008. 372:314-320.
- Agence de la santé publique du Canada. Sommaire -- Estimations de la Prévalence et de l'Incidence du VIH au Canada, 2008. Division de la surveillance et de l'évaluation des risques, Centre de la lutte contre les maladies transmissibles et les infections, Agence de la santé publique du Canada, 2009.
- Hays RB, Paul J, Ekstrand M, et al. Actual versus perceived HIV status, sexual behavioral and predictors of unprotected sex among young gay and bisexual men who identify as HIV-negative, HIV-positive and untested. AIDS. 1997. 11:1495-1502.
- Higgins DL, Galavotti C, O'Reilly KR, et al. Evidence of the effects of HIV antibody counseling and testing on risk behaviour. JAMA. 1991. 266:2419-2429.
- Wenger NS, Kusseling FS, Beck K, et al. Sexual behaviour of individuals infected with the human immunodeficiency virus: the need for intervention. Archives of Internal Medicine. 1994. 154:1849-1854
- Miiro G, Todd J, Mpendo J, Watera C, Munderi P, Nakubulwa S, et al. Reduced morbidity and mortality in the first year after initiating highly active anti-retroviral therapy (HAART) among Ugandan adults. Tropical Medicine & International Health. 2009. 14 (5):556-563.
- Palella F, Chmiel J, Deloria-Knoll M, Moorman A, Holmberg S. Continued low mortality and morbidity, and HAART utilization among HIV-infected patients in the HIV outpatient study (HOPS). Conf Retroviruses Opportunistic Infect. Feb 4-8, 2001. 8:122 (Abstract no. 268B).
- Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. New England Journal of Medicine. 1998. 338:853-860.
- Emini EA. Protease inhibitors. In: Program and abstracts of the 3rd Conference on Retroviruses and Opportunistic Infections. January 28-February 1, 1996; Washington, DC. Abstract L1.
- Carpenter CCJ, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1996: recommendations of an international panel. Journal of the American Medical Association. 1996. 276:146-154.
- Hammer SM. Clinical practice. Management of newly diagnosed HIV infection. New England Journal of Medicine. 2005. 353:1702-1710.
- Kitahata MM, Gange SJ, Abraham AG, Merriman B, Saag MS, Justice AC et al. Effect of Early versus Deferred Antiretroviral Therapy for HIV on Survival. New England Journal of Medicine. 2009. 360:1815-1826.
- When To Start Consortium. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1 infected patients: a collaborative analysis of 18 cohort studies. The Lancet. 2009. 373:1352-1363.
- Strategies for Management of Antiretroviral Therapy (SMART) Study Group, Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. Journal of Infectious Disease 2008. 197:1084-1086.
- Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. November 3, 2008. [Accessed 1 August 2009.]
- Montaner JSG. Treatment as Prevention: Expansion of Highly Active Anti Retroviral Therapy Coverage -- A Powerful New Tool to Reduce New HIV Infections at a Population Level. 18th Annual Canadian Conference on HIV/AIDS Research. Clinical Sciences Plenary. Vancouver, B.C., Canada. April 23-26, 2009.