This article first appeared on the CATIE website here.

Une version française est disponible ici. 

Summary

HIV viral load is the amount of HIV (or number of virus) in the bodily fluids of someone living with HIV. It is measured in the blood as part of routine clinical care. A higher viral load is associated with a higher risk of HIV transmission. Research shows that successful HIV treatment can reduce the viral load to “undetectable” levels and this can reduce the risk of HIV transmission. However, HIV transmission may be possible when the viral load is undetectable because there is still virus present in the blood and other bodily fluids. The risk of HIV transmission when taking antiretroviral treatment may increase if sexually transmitted infections (STIs) are present, doses of medications are missed, or drug resistance develops. This risk may also be higher for anal sex than for vaginal sex.

What is viral load and how is it affected by HIV treatment?

HIV viral load is the number of copies of HIV in the bodily fluids of someone living with HIV. It is measured as the number of copies of the virus in one millilitre of fluid (copies/ml). Viral load is measured in the blood and is used to monitor the progression of HIV infection and the success of HIV treatment. It is not commonly measured in other bodily fluids, such as semen, vaginal fluid or rectal fluid.

HIV treatment consists of a combination of at least three drugs that are normally taken daily. The goal of HIV treatment is to reduce the production (also called replication) of HIV, raise levels of CD4 T-cells, and slow disease progression. HIV treatment is also called highly active antiretroviral treatment (HAART) or antiretroviral therapy (ART).

With successful HIV treatment, the viral load can become very low or “undetectable” in the blood and other bodily fluids.

What is a “normal” viral load?

There is no such thing as a “normal” viral load. The viral load in the bodily fluids can change as a result of several factors, such as the stage of HIV infection and HIV treatment.

During the first few weeks after becoming infected with HIV, the viral load in the blood and other bodily fluids is very high. This stage of HIV infection is known as the acute infection stage and at this time the viral load can reach levels higher than 1 million copies/ml.

The acute HIV infection stage only lasts for a few weeks and then the chronic stage of HIV infection begins. During the chronic stage, the viral load begins to decrease and – after a few months – the viral load stabilizes at a lower level.

If HIV treatment is started, the viral load can be reduced to “undetectable” levels in the bodily fluids within a few months. However, if doses of medications are missed or HIV develops resistance to treatment, then the viral load will increase.What does it mean to have an “undetectable” blood viral load?

“Undetectable” means that the number of virus in the blood is below the limit that viral load tests can detect. Viral load tests used in Canada cannot detect HIV in the blood if there are less than 40–50 copies/ml. Therefore, an undetectable viral load means the amount of virus in the blood is too low to detect, it does not mean that there is no virus present.

Is the viral load in the blood associated with a person’s risk of transmitting HIV?

Research shows that a lower amount of virus in the blood is usually associated with a lower risk of transmitting HIV to others, and a higher viral load is associated with a higher risk.

The amount of virus in the blood is usually correlated with the viral load in the semen, vaginal fluid, and rectal fluid (the fluids commonly involved in the sexual transmission of HIV). This means that when the viral load in the blood decreases, it generally also decreases in the other fluids.

However, the viral load in the different bodily fluids is never exactly the same. For example, the viral load in the semen, vaginal fluid or rectal fluid can sometimes be higher than the viral load in the blood.

Does HIV treatment reduce the risk of sexual transmission of HIV?

Successful antiretroviral treatment can lower the viral load in the blood and other bodily fluids to undetectable levels and this can reduce the risk of sexual HIV transmission.

A randomized controlled study known as HPTN 052 found that HIV treatment reduced the risk of HIV transmission between serodiscordant heterosexual couples by 96% (equivalent to a 26-fold reduction in risk). A serodiscordant couple is where one partner is HIV-positive and the other is HIV-negative.

Couples in the HPTN 052 study were mostly heterosexual, mostly reported 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. Therefore, this study demonstrated the effectiveness of treatment in reducing the risk of HIV transmission through vaginal sex when pills are taken regularly, drug resistance is monitored, and STIs are managed. Antiretroviral treatment may be much less effective than 96% when these conditions are not met.

No studies have been completed among populations who mostly have anal sex, such as some gay men or other men who have sex with men (MSM). However, a working group meeting hosted by the World Health Organization in 2011 concluded that “there is reason to believe that early initiation of ART for HIV prevention will benefit MSM, transgender women, and others who have anal intercourse, although the magnitude of the effect may be different from that observed in serodiscordant heterosexual couples.” In other words, HIV treatment reduces the risk of HIV transmission for gay men and other MSM, but it may or may not be as effective as for heterosexual couples in the HPTN 052 study.

There are ongoing studies that are trying to get a better idea of how well HIV treatment can reduce the risk of HIV transmission among gay men and other MSM.

Is HIV transmission possible when the viral load in the blood is undetectable?

Although the risk of sexual HIV transmission is reduced when the viral load is undetectable, the risk of HIV transmission may not be eliminated.

Many people who have an undetectable viral load in the blood also have an undetectable viral load in other bodily fluids. However, undetectable does not mean that there is no virus, only that the amount of virus is below the limits that tests can detect. Therefore, HIV transmission may still be possible because there is still virus present.

Also, it is possible for people who have an undetectable viral load in the blood to sometimes have detectable (although lowered) levels of virus in their other bodily fluids. A higher level of HIV in the semen, vaginal fluid, and rectal fluid may increase the risk of transmission when the blood viral load is undetectable. However, it is unclear how often this happens and how significant it is in terms of HIV transmission. Research shows it may be more common if a person has an STI, but can also happen in the absence of STIs.

What is the risk of HIV transmission when the blood viral load is undetectable?

Although we know having an undetectable blood viral load can greatly reduce the risk of HIV transmission, it is unclear exactly what this risk is reduced to.

In the research conducted so far, there have been no recorded HIV transmissions among heterosexual couples where the HIV-positive partner is on treatment and their blood viral load is undetectable. However, this does not mean the risk through condomless sex is zero. All of the couples studied to date have also reported using condoms often. This makes it difficult to determine the risk of HIV transmission when no condom is used.

Although there have been no studies among gay men and other MSM, there has been one report of HIV transmission occurring between two men when the HIV-positive partner had an undetectable viral load.

Also, the risk of HIV transmission when the viral load is undetectable may not be the same for all types of sex. This risk may be higher for anal sex than for vaginal sex, particularly if the HIV-negative partner is the receptive partner (bottom) during anal sex. This is because receptive anal sex generally carries a higher baseline HIV risk than other types of sex.

There are ongoing studies following serodiscordant heterosexual and same-sex couples who are taking HIV treatment, have an undetectable viral load, and do not always use condoms. These studies will provide a better understanding of the risk of HIV transmission when the viral load is undetectable and no condom is used.

What does this all mean for people who want to use HIV treatment to prevent HIV transmission?

There are no simple answers on viral load, HIV treatment and their relationship to HIV transmission and prevention. However, there are key messages for those who want to use HIV treatment to reduce their risk of HIV transmission:

• Check to make sure the blood viral load is undetectable before starting this approach and get frequent viral load tests to ensure it remains undetectable while using this strategy. It is generally recommended that the viral load be undetectable for 6 months before using this approach.
• Take pills exactly as prescribed. Adherence to treatment is critical to keep the viral load undetectable in the blood and prevent the development of drug resistance.
• Get tested regularly for STIs (including, syphilis, gonorrhea, chlamydia, and herpes). STIs can increase the risk an HIV-positive person transmits HIV and an HIV-negative person becomes infected with HIV. If either partner has an STI, start treatment immediately and try to avoid condomless sex during this time.
• Ask your doctor about vaccinations for hepatitis A, hepatitis B, and human papilloma virus (HPV).
• Using other HIV prevention strategies as much as possible – particularly condoms and lube – will help reduce the overall risk of HIV transmission.

References

Wawer MJ, Gray RH, Sewankambo NK et al. Rates of HIV-1 Transmission per Coital Act, by Stage of HIV-1 Infection, in Rakai, Uganda. Journal of Infectious Diseases. 2005 May 1;191(9):1403 –1409.

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, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. New England Journal of Medicine. 2011 Aug 11;365(6):493–505.

World Health Organization. WHO and U.S. NIH Working Group Meeting on Treatment for HIV Prevention among MSM: What Additional Evidence is Required. Geneva; 2011 Nov.

Sheth PM, Kovacs C, Kemal KS et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS. 2009 Sep 24;23(15):2050–4.

Stürmer M, Doerr HW, Berger A, Gute P. Is transmission of HIV-1 in non-viraemic serodiscordant couples possible? Antiviral Therapy. 2008;13(5):729–32.

Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nature Reviews Microbiology. 2004 Jan;2(1):33–42.

Loutfy MR, Wu W, Letchumanan M et al. Systematic Review of HIV Transmission between Heterosexual Serodiscordant Couples where the HIV-Positive Partner Is Fully Suppressed on Antiretroviral Therapy. PLoS ONE. 2013 Feb 13;8(2):e55747.

This article first appeared on the CATIE website here.  

Une version française est disponible ici.  

The importance of HIV testing, knowledge of HIV status and early diagnosis of HIV infection cannot be overstated, particularly given recent advancements in our understanding of HIV treatment and prevention. 

People who are aware of their HIV-positive status can access care and support services and initiate treatment when they are ready. Advances in treatment mean that people with HIV can live almost as long and as healthy as people who are uninfected. To get the most out of treatment, research suggests it may need to be started soon after becoming infected with the virus. Currently, however, many people in Canada are not learning about their HIV status until late in their disease, when they start to develop symptoms or opportunistic infections. At this point, antiretroviral treatment can help improve their health but not as effectively as when treatment is started earlier. 

Knowledge of HIV status is also important for the prevention of HIV transmission. Generally, once people become aware of their HIV infection, they take measures to reduce their risk of HIV transmission. Also, once diagnosed, treatment can be initiated and this can further help reduce the risk of HIV transmission. Research suggests that the majority of HIV transmissions may originate from people who are unaware of their HIV status. 

For those who test negative, testing represents an important opportunity to provide HIV prevention information and counselling. 

According to 2011 estimates from the Public Health Agency of Canada (PHAC), approximately 25% of people living with HIV in Canada were unaware of their HIV status. Therefore, undiagnosed HIV infection represents a major public health challenge and is undermining HIV treatment and prevention in Canada. 

Barriers to testing 

There are several barriers to increasing the uptake of HIV testing and reducing the proportion of people who are undiagnosed in Canada. According to a synthesis of the evidence conducted by the European Center for Disease Prevention and Control and published in 2010, these barriers include: 

• inability to accurately assess levels of risk for exposure to HIV by some clients and providers
• lack of comfort discussing HIV testing and lack of knowledge about HIV among clients and providers
• provider time constraints for risk assessments and pre- and post-test counselling
• cumbersome consent procedures
• fear of stigma and discrimination associated with risk behaviors and/or testing HIV positive 

PHAC guidelines and recommendations 

PHAC recently released an HIV Screening and Testing Guide that “seeks to reduce the number of undiagnosed HIV infections in Canada by offering a framework for care providers to explore options that will enhance their ability to provide HIV testing, as well as to better tailor their testing approaches to meet the specific needs of their practice and clients.” 

These guidelines include the following recommendations to address the barriers listed above and to improve HIV testing in Canada. 

The offer of an HIV test should be made part of periodic routine medical care.The guide acknowledges that targeted testing among populations at highest risk of HIV infection needs to continue but should be complemented with a less targeted testing approach among populations that may be perceived as being lower risk. Research shows that many people at risk for HIV infection (including those who are later diagnosed with HIV) are not requesting, or being offered, an HIV test despite multiple interactions with the health system, likely because of perceived low risk of HIV infection on the part of the client and provider. These interactions represent “missed opportunities” for HIV testing and potential diagnosis of HIV infection. 

Therefore, a major recommendation in the guide is that providers take a more active approach and routinely offer HIV testing to clients—whether or not they have asked for a test. Routinely offering HIV testing to patients will help overcome some of the barriers to testing. Also, it may help normalize HIV testing and further reduce stigma and discrimination associated with HIV. 

To reduce the fear often associated with an HIV diagnosis, which can be a barrier to testing, the guide recommends that care providers emphasize the benefits of treatment and that HIV is now considered a chronic manageable condition. 

Simplify risk assessments. 

The guide acknowledges pre-test risk assessments as a potential barrier to HIV testing. Therefore, it states that instead of providing an in-depth comprehensive HIV behavioural risk assessment prior to offering an HIV test, a more brief assessment is sufficient. This assessment should ensure that clients understand the following: 

• how HIV is transmitted
• the advantages and disadvantages of HIV testing
• how to interpret the results 

After the brief assessment, a client should simply be asked if they want an HIV test. This approach allows the client to assess their own risk without feeling compelled to provide sensitive personal information. This helps to overcome any discomfort the tester and/or client may feel in discussing these issues, which can sometimes be a barrier to testing.  

HIV testing must remain voluntary and based on informed consent. 

The guide states that verbal consent prior to HIV testing is sufficient and written consent prior is not necessary. 

Use a flexible approach to pre- and post-test counselling. 

The guide encourages care providers to use a flexible approach and tailor the extent of pre- and post-test counselling to each client’s unique needs and situation. While providing extended counselling is preferred, the guide acknowledges that this may be a barrier for both the provider and client, particularly due to time and resource constraints. More specifically, the guide states that shorter counselling may be more appropriate for certain testers, such as pregnant women in labour, well-informed patients and repeat testers. The provision of print, video, mobile and web-based resources can help streamline the pre-test process and inform decisions with regards to HIV testing.

 Offer couples testing. 

The guide stresses the importance of testing together for those in an ongoing sexual relationship with a regular partner as it allows: 

• a common understanding of the risks associated with HIV transmission
• a shared understanding of each other’s HIV status
• an opportunity to make decisions about prevention, treatment and care together 

Research studies suggest that couples who test and learn their status together are more likely to adopt preventive measures than those who test alone. 

Integrate HIV testing services. 

The guide encourages the integration of HIV testing into other services, particularly those that test for infections that can be transmitted the same way as HIV and/or negatively impact the health of people living with HIV. 

These services include the following: 

• clinical services for tuberculosis (TB), sexually transmitted infections (STIs) and hepatitis C
• antenatal care services
• sexual Health and family planning services
• drug and alcohol treatment services
• newcomer and travel health clinics
• mental illness treatment and psychiatric services
• cancer or oncology clinics 

Integrating HIV testing into these other services provides additional opportunities to test for HIV and identify undiagnosed individuals. 

While positive results should always be provided in person (preferably by the initial care provider), alternate approaches can be used to provide negative results. 

Ideally, negative test results should be provided in person, however, the guide acknowledges that this can be challenging to do for all individuals. Therefore, providers can use a previously agreed upon alternative for those who are unlikely to return for their test results. These alternative approaches may include a secure telephone call, letter or email. The guide emphasizes that effort should be made to ensure that the information is provided confidentially. 

It is important that clients are not informed that only HIV-positive results will be provided in person. This may create anxiety when a person is asked to return to get their results in person. 

Discuss the window period with those who test HIV negative. 

If someone is “in the window period,” there is a chance that even though they may have been infected with HIV, the test won’t be able to detect the infection and will give a negative result. The window period differs for each type of HIV test and also depends on each individual. To ensure that a person was not in the window period at the time the test was performed, the guide recommends that follow-up testing be performed at three weeks and three months following the most recent possible exposure. However, the guide states that additional HIV testing during the window period, particularly following a “high-risk” exposure, may help identify infection earlier. 

Discuss frequency of retesting with those who test HIV negative. 

The guide recommends that individuals involved in “high-risk practices” be screened for HIV at least once a year. Since many variables determine an individual’s potential risk of HIV infection, the guide does not recommend an exact frequency of HIV testing for different levels of risk. However, when considering the need for retesting, the guide recommends that care providers consider factors such as populations at increased risk for HIV exposure, characteristics of partners and local epidemiology. 

Provide information and referrals—regardless of test results—and link newly diagnosed individuals to care. 

HIV testing is an important opportunity to educate individuals at risk of acquiring HIV and those who are newly diagnosed and link them to additional services. For example, all people tested for HIV—regardless of their results—should be provided with information and linked to services to help them reduce their risk of acquiring or transmitting HIV. Therefore, in preparation for HIV testing, the guide suggests that providers contact care and support organizations to obtain referral resources to provide to clients. 

Research shows that people living with HIV who are linked to and engaged in care have better health outcomes than those who are not. Therefore, newly diagnosed individuals should be referred to an infectious disease specialist who treats HIV. Also, effort should be made to complete baseline testing for CD4 count, viral load, drug resistance and co-infections (hepatitis B and C, STIs, TB) as soon after diagnosis as possible. 

For those who test HIV positive, develop a partner notification plan and discuss public health importance of disclosure. 

Previous and current partners of newly diagnosed individuals represent a population at high risk of HIV infection. Therefore, notifying previous/current partners and encouraging them to get tested may help identify undiagnosed HIV infections. The guide encourages care providers to develop partner notification plans with newly diagnosed individuals. Also, care providers should inform clients that positive test results will be shared with Public Health, which can help with partner notification while maintaining the client’s anonymity and privacy. 

Voluntary disclosure of HIV status to partners has several potential benefits. For example, it may motivate partners to seek testing and/or adopt measures to prevent HIV transmission. Also, it provides an opportunity for the HIV-positive person to receive social support, develop risk-reduction strategies with partners and prevent co-infections. Therefore, the guide states that care providers should emphasize the importance of voluntary disclosure of HIV status to those who are newly diagnosed. 

Conclusion 

PHAC’s new HIV Screening and Testing Guide contains a series of recommendations to increase the uptake of HIV testing, reduce the proportion of people who are unaware of their HIV infection and diagnose people as early as possible after HIV infection. These goals are critical for improving the health of people living with HIV and for preventing HIV transmissions in Canada. One way the guide seeks to meet these goals is by normalizing HIV testing and making the offer of such testing a routine part of medical care. More nuanced and detailed information can be found in the full guide. 

It is important to note that PHAC’s guide is only meant to complement existing efforts and “does not supersede any provincial/territorial legislative, regulatory, policy and practice requirements or professional guidelines that govern and inform the practice of care providers in their respective jurisdictions. Care providers should comply with local Public Health regulations with conducting HIV testing.” 

- James Wilton 

Resources  

HIV Screening and Testing Guide – Public Health Agency of Canada 

WHO guidelines encourage couples HIV testing and counselling and use of antiretroviral treatment for prevention – Prevention in Focus  

Recently infected individuals: a priority for HIV prevention – Prevention in Focus  

Detecting HIV earlier: Advances in HIV testing – Prevention in Focus  

A rapid approach to community-based HIV testing – Prevention in Focus  

How do you know if you have HIV? – Managing your health  

References  

Johnson LF et al. Life expectancies of South African adults starting antiretroviral treatment: collaborative analysis of cohort studies. PLoS Medicine, 10:4. E1001418. 

May M et al. Life expectancy of HIV-1-positive individuals approaches normal, conditional on response to antiretroviral therapy: UK collaborative HIV cohort study. Eleventh International Congress on Drug Therapy in HIV Infection, Glasgow, abstract O133, 2012. 

Van Sighem AI, Gras LAJ, Reiss P, Brinkman K, De Wolf F. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS. 2010 Jun 19;24(10):1527–35. 

Nakagawa F, Lodwick RK, Smith CJ, Smith R, Cambiano V, Lundgren JD, et al. Projected life expectancy of people with HIV according to timing of diagnosis. AIDS. 2012 Jan;26(3):335–43. 

Nakagawa F, May M, Phillips A. Life expectancy living with HIV: recent estimates and future implications. Curr. Opin. Infect. Dis. 2013 Feb;26(1):17–25. 

Siegfried N, Uthman OA, Rutherford GW. Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults. Cochrane Database of Systematic Reviews. 2010 Mar 17;(3):CD008272. 

Althoff KN, Gange SJ, Klein MB et al. Late presentation for human immunodeficiency virus care in the United States and Canada. Clinical Infectious Diseases. 2010 Jun;50(11):1512–20. 

Fisher, M. (2008). Late diagnosis of HIV infection: major consequences and missed opportunities. Current Opinion in Infectious Diseases. 21(1):1-3.

 Marks G, Crepaz N, Senterfitt JW, Janssen RS. Meta-analysis of high-risk sexual behavior in persons aware and unaware they are infected with HIV in the United States: implications for HIV prevention programs. Journal of Acquired Immune Deficiency Syndromes. 2005 Aug 1;39(4):446–53. 

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. 

Government of Canada Public Health Agency of Canada (2010). HIV/AIDS Epi Updates. Available from: www.phac-aspc.gc.ca/aids-sida/publication/epi/2010/2-eng.php 

European Centre for Disease Prevention and Control. HIV testing: Increasing uptake and effectiveness in the European Union. Stockholm: ECDC; 2010. 

Government of Canada Public Health Agency of Canada (2013). HIV screening and testing guide. Available from http://www.catie.ca/sites/default/files/EN_HIV-Screening-Guide-2013.pdf 

El-Bassel N, Gilbert L, Witte S et al. Couple-based HIV prevention in the United States: advantages, gaps, and future directions. Journal of Acquired Immune Deficiency Syndromes. 2010 Dec;55 Suppl2:S98–S101.

This article first appeared on the CATIE website here.

Une version française est disponible ici. 

What is the STOP HIV AIDS Project?

“We can prevent the late diagnosis of HIV/AIDS.”

One of the key markers of success for the Vancouver STOP Project is the expansion of opportunities for HIV testing and early diagnosis for all people in Vancouver. To reach specific populations disproportionately affected by HIV, including gay men, people who use injection drugs, sex workers, refugees, immigrants and Aboriginal people, the Vancouver STOP Project expanded the number of settings that now routinely offer HIV testing to clients – either with standard blood- draw tests or rapid, point-of-care tests. In many of these sites, HIV testing was not previously available or testing rates were low. Access to testing has been expanded in primary healthcare centres, mental health and addictions services, supportive housing, in the justice system and in other settings.

The small Targeted Testing Team identified, collaborated with, trained and supported 88 sites to introduce the routine offer of HIV testing as part of their complement of services. In some settings, such as primary healthcare centres where clinicians were already accustomed to ordering blood work and delivering difficult diagnoses, the change has been relatively smooth. In other venues, such as dental clinics and mental health and addictions services where HIV testing has traditionally not been offered, in part due to significant structural barriers, it’s been more challenging.

Across all sites, ongoing and responsive support has been critical to the success of this project. Nurse educators from the Targeted Testing Team return to sites every few months to offer additional support and to help reduce barriers to embedding testing in health services. Importantly, they also provide updates on each site’s testing trends, which demonstrates to the staff how many tests they have done, the number of new diagnoses and possibly, what impact the initiative is having in Vancouver.

According to Misty Bath, a former nurse educator on the team, the team works hard to ensure that clinicians know there is support for them when one of their patients is diagnosed with HIV. When a person tests positive for HIV, clinicians can draw on the expertise of the STOP Outreach Team or Vancouver Coastal Health Communicable Disease Control to offer specialized diagnosis and linkage to care services.

In addition to supporting others to offer expanded testing opportunities, the Targeted Testing Team hosts HIV testing events at universities, and staffs micro-clinics in bathhouses and a mobile outreach van that travels to outdoor sex venues frequented by gay men and other men who have sex with men.

The team has made significant inroads in normalizing HIV testing both among clinicians and among the people for whom they provide care. According to Bath, “There’s still a lot that we can do to sustain improvements in testing.” As part of this drive, the team is currently working closely with First Nation communities located within Vancouver Coastal Health to increase the availability of testing for Aboriginal people closer to home.

What is the program

The targeted testing initiative is a new project developed and led by the Vancouver STOP Project. It aims to ensure that people who are at high risk for HIV have easy access to testing and, for those who test HIV-positive, that they are diagnosed early and linked to appropriate care and support. It accomplishes this through the implementation of the routine offer of HIV testing at sites that have never offered testing and at sites that had not been optimally offering testing, but that are frequented by people who are at high risk for HIV. Some sites offer standard blood-draw test while others offer a blended standard and rapid test, both with pre-and post-test counselling.

In the last two years, through this initiative, access to testing has been expanded in 88 sites, including primary healthcare centres, abortion and youth clinics, mental health and addictions services, the justice system, supportive housing, First Nation communities within Vancouver Coastal Health’s region, and in bathhouses and at outdoor sex venues frequented by gay men. For many of these sites, the implementation of HIV testing was a significant change to their practice. Managing and supporting this change was, therefore, an important component of successful implementation.  

This initiative is led by a group of nurse educators and a program manager known as the Targeted Testing Team. This group is a smaller part of the STOP Outreach Team, an interdisciplinary clinical team responsible for improving engagement and linkage to care for people with some of the most complex barriers to care. For more information on this, please see the Programming Connection case study on the STOP Outreach Team.

The team successfully expanded access to HIV testing and diagnosis in in three ways. The team:

 1. provides training and support to clinicians and service providers whose clientele is drawn from high prevalence populations

 2. offers regular workshops on rapid testing and the introduction of routine testing for clinicians wanting to build their skills

 3. provides HIV testing clinics in non-traditional outreach settings such as bathhouses and outdoor sex venues

To read more go here. 

This article first appeared on the website of Pacific AIDS Network here.  Republished with permisision of the author. Folllow PAN on twitter at @PAN_CBR

I didn’t attend AIDS 2012 in Washington last July, but I do remember that when others came back they were all abuzz about the concept of the treatment cascade as possibly the next “big thing” in the way that we conceptualize HIV prevention and treatment. Now, many months later, and numerous references to the treatment cascade in meetings, policy documents, articles, and other HIV-discourse hubs later, I have to give my AIDS 2012-attending friends and colleagues pats on the back because I think they were right.

This example of an HIV cascade of prevention and care appears in the 2012 document “From Hope To Health,” which lays out the BC government’s framework for the provincial expansion of the STOP HIV/AIDS program.

While the meme of “AIDS free generation” also took hold at AIDS2012, it’s purpose was mainly to offer hope and buoy a movement, while the treatment cascade seems to be a model that is transforming how we approach HIV treatment and work to identify gaps in the continuum of care (from prevention, to testing, to care and treatment) so that fewer individuals are lost along the way.

Roughly defined, the HIV treatment cascade (or the cascade in care) is a way of calculating what proportion of HIV in a country or community is on anti-retroviral treatment and is virally suppressed – meaning no detectable virus in the blood – and how many people “fall off” the cascade at each step. Below are some interesting and key documents to look at in order to build an understanding of this concept.

From Hope to Health: Towards an AIDS-free Generation – On December 1, 2012, the British Columbia Ministry of Health released a guidance document for the province’s expansion of the Seek and Treat for Optimal Prevention (STOP) project across the province. What was notable in the document was the inclusion of a figure illustrating a “treatment and care cascade for BC” (see image above), which was expanded from the traditional cascade model to also include “number of people at risk for HIV but not infected” as the starting point. It will be very interesting to see how the model is implemented. 

The HIV treatment cascade – patching the leaks to improve HIV prevention – This comprehensive article written by James Wilton and Logan Broeckaert at CATIE is excellent in that translates the treatment cascade by explaining each “step” of the cascade and provides real-world examples of interventions and services that are used to help stop the leaks in the cascade. Wilton and Broechaert also address a concern regarding human rights that arises when using models such as this, which may reduce people to numbers and risk the goal (ie of low viral load in a population) seeming more important than individual agency. They say, “It’s critical that human rights are respected and that people living with or at risk of HIV are empowered to make decisions about testing and treatment that are right for them.”

Grappling with the HIV Treatment Cascade – In this PositiveLite.com article (originally published aidsmap.com), Gus Cairns looks at reports from the USA and Europe in terms of the proportion of individuals that are virally suppressed. This piece is interesting because it indicates that – although that the treatment cascade is a model that allows us to conceptualize the proportion of a population that has been tested and is retained in care – it is not a simple task to obtain actual numbers for each step. As PositiveLite.com editors suggest, without reliable data on the actual numbers, more research is certainly needed to confirm the extent of treatment penetration and to monitor future treatment as prevention initiatives.

North American Housing and HIV/AIDS Research Summit VII: Closing the Housing Gap in the HIV Treatment Cascade – This upcoming conference, to be held in Montreal in late September 2013, is a great example of the where the concept of treatment cascade is going next. As the title of the conference suggests, there is certainly a need to query how the social determinants of health, such as housing, inequitable distribution of resources, gender, food security, etc., can impact how many people are “lost” at each step of the cascade. The Summit will explore the potential of housing strategies to improve HIV treatment effectiveness in various jurisdictions. I believe that this is the tip of the iceberg in how we will be seeing various segments of the HIV service and research community engage with this concept.

Questions? Feedback? Get in touch!

Andrea Langlois (above) is the Community-Based Research Manager, Pacific AIDS Network. She is on twitter at @PAN_CBR.

This article by Sean Hosein first appeared on the CATIE website here  

Une version française est disponible ici. 

In high-income countries such as Canada, Australia and the U.S. and in regions such as Western Europe, huge advances have been made in the treatment of HIV disease. Researchers increasingly expect that a young person who is diagnosed today and who initiates potent combination anti-HIV therapy (commonly called ART or HAART) and who has minimal co-existing health conditions should have several additional decades of life expectancy.

The combinations of therapies available for the initial treatment of HIV are plentiful. Furthermore, pill taking has been simplified by the availability of the co-formulation of several drugs into one pill, creating an entire regimen in a single tablet. Such single-tablet regimens need only be taken once daily. However, things were not always this way.

A look at the past

Initial treatment for HIV infection, when it became available in the late 1980s, consisted of a single drug—the nuke (nucleoside reverse transcriptase inhibitor) AZT (zidovudine, Retrovir)—given at high doses and taken every four hours. Such a regimen frequently caused headache, nausea, vomiting and damaged the bone marrow.

In the early 1990s, other anti-HIV drugs in the same class became available, including the following nukes:

• ddC (zalcitabine, Hivid)
• ddI (didanosine, Videx)
• d4T (stavudine, Zerit) 

These three drugs, commonly called d-drugs, initially appeared to be better tolerated but soon showed their own side effects, such as peripheral neuropathy (painful nerves in the hands, feet and legs). ddC is no longer manufactured and treatment guidelines in high-income countries now discourage the use of d4T and ddI.

In 1996, a new class of anti-HIV drugs became available—protease inhibitors (PIs). When used in combination with nukes, the results were dramatic. For the first time in the history of the AIDS pandemic, people showed sustained recovery from AIDS-related infections.

However, shortly after HAART became available, reports emerged of a strange syndrome of changes in body shape sometimes associated with the loss of the fatty layer just under the skin. This loss of fat, called lipoatrophy, affected all parts of the body but its effect on the face could become most distressing.

Initially, because PIs were the latest class of anti-HIV therapy, they were suspected as the culprits. However, a few years later, researchers began to realize that exposure to d4T and, to a lesser extent, AZT, was linked to lipoatrophy. Today, drugs such as d4T and AZT are generally not recommended as first-line therapy in high-income countries.

Nukes today

In the current era, nukes remain the backbone of many regimens. Nukes commonly used today include the following combinations:

• abacavir + 3TC – sold as a fixed-dose formulation called Kivexa (or Epzicom) and also found in Trizivir
• tenofovir + FTC – sold as a fixed-dose formulation called Truvada and also found in other combinations such as Atripla, Complera and Stribild 

A lingering sense of caution

Decisions about starting therapy for HIV infection have always been challenging; both doctors and their patients have weighed the risks and benefits, as well as a person’s ability to take HIV medicines exactly as directed for many years. In the current era, with safer, simpler therapies and more results from clinical trials, the risk–benefit ratio has swung strongly in favour of very early initiation of therapy. The most recent version of the U.S. Department of Health and Human Services’ (DHHS) HIV/AIDS Treatment Guidelines recommends early therapy for all HIV-positive people, for two reasons, as follows:

• At the level of the individual, early treatment can help preserve the immune system and improve health.
• From a public health point of view, treating more HIV-positive people reduces the amount of HIV in their blood, other tissues, and genital fluids. The result is decreased sexual infectiousness. As a result of this reduced infectiousness, at the level of a large urban area or region, widespread use of ART can help to reduce new cases of HIV transmission. This approach of treating people to reduce their infectiousness is called TasP—treatment as prevention. 

Despite the general tolerability and safety of Kivexa and Truvada, some HIV-positive people and their doctors remain somewhat wary of nukes in general, given their checkered history, and wonder about the potential of these drugs for causing new, unknown side effects. This latter concern is increased as HIV-positive people age and need to take multiple medications, heightening the potential for drug interactions and side effects.

Emerging research suggests the possibility that nukes can affect the energy-producing parts of cells (mitochondria). However, nuke combinations commonly used in the initiation of therapy today have not been proven to cause mitochondrial damage that is directly linked to the ill health of ART users.

Aging and HIV

Some researchers have found hints of apparently accelerated aging in some HIV-positive people. Specifically, some organ-systems, such as the brain, heart, blood vessels and bones, appear to have aged more quickly than they should.

The cause of this apparent aging is not clear.

If premature or accelerated aging does exist in HIV infection, there may be several potential causes affecting different people, including the following:

• long-term exposure to specific proteins produced by HIV-infected cells
• higher-than-normal levels of inflammation, which accompanies chronic viral infections such as HIV
• substance use
• tobacco smoking
• co-infection with other germs, such as members of the herpes virus family—CMV (cytomegalovirus) and EBV (Epstein-Barr virus) 

The immune system and aging

Several research teams have found that, if left untreated, HIV infection does prematurely age the immune system. HIV appears to cause this by repeatedly activating the immune system and producing inflammation. This virus also appears to cause complex and poorly understood changes to the immune system shortly after it enters the body.

ART greatly reduces HIV-related inflammation but cannot entirely eliminate it. Prolonged exposure to higher-than-normal levels of inflammation is associated with many chronic illnesses and it is possible that such inflammation over the long-term may play a role in reports of accelerated aging seen in some HIV-positive people in studies. However, it is important to bear in mind that exposure to unhealthy behaviours—particularly tobacco smoking—also causes inflammation. Separating all the possible drivers of accelerated aging in HIV-positive people will not be easy and will require many studies, some of them quite expensive and daunting in their complexity.

Much caution needed

A research team in Australia has been exploring the theory that nukes somehow contribute to the apparent acceleration in aging in HIV-positive people. Their work, conducted in complex laboratory experiments on cells from HIV-negative and HIV-positive people suggests the possibility that the drug tenofovir (Viread) may accelerate the aging of the immune system. However, we urge our readers to treat this finding with a great deal of caution, if only because the results from the Australian experiments are not definitive. Furthermore, due to built-in limitations of their study’s design (it is cross-sectional in nature), questions remain about the significance of their findings. Next up, we will explore some of the issues related to the Australian study.

—Sean R. Hosein

REFERENCES:

 1. Boasso A, Royle CM, Doumazos S, et al. Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis. Blood. 2011 Nov 10;118(19):5152-62.

 2. Herbeuval JP, Nilsson J, Boasso A, et al. HAART reduces death ligand but not death receptors in lymphoid tissue of HIV-infected patients and simian immunodeficiency virus-infected macaques. AIDS. 2009 Jan 2;23(1):35-40.

 3. Bestilny LJ, Gill MJ, Mody CH, et al. Accelerated replicative senescence of the peripheral immune system induced by HIV infection. AIDS. 2000 May 5;14(7):771-80.

 4. Leeansyah E, Cameron PU, Solomon A, et al. Inhibition of telomerase activity by HIV Nucleos(t)ide Reverse Transcriptase Inhibitors: a potential factor contributing to HIV-associated accelerated ageing. Journal of Infectious Diseases. 2013; in press.

 5. Payne BA, Wilson IJ, Hateley CA, et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nature Genetics. 2011 Jun 26;43(8):806-10.

 6. Helleberg M, Afzal S, Kronborg G, et al. Mortality Attributable to Smoking Among HIV-1-Infected Individuals: A Nationwide, Population-Based Cohort Study. Clinical Infectious Diseases. 2013; in press.

 7. Rasmussen LD, Kessel L, Molander LD, et al. Risk of cataract surgery in HIV-infected individuals: a Danish nationwide population-based cohort study. Clinical Infectious Diseases. 2011 Dec;53(11):1156-63.

 8. Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clinical Infectious Diseases. 2011 Dec;53(11):1120-6.

 9. Pathai S, Lawn SD, Weiss HA, et al. Increased ocular lens density in HIV-infected individuals with low nadir CD4 counts in South Africa: evidence of accelerated aging. Journal of Acquired Immune Deficiency Syndromes. 2013; in press.

 10. Smith RL, de Boer R, Brul S, et al. Premature and accelerated aging: HIV or HAART? Frontiers in Genetics. 2012;3:328.

 11. Carr A, Samaras K, Burton S, et al. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. AIDS. 1998 May 7;12(7):F51-8.

 12. van der Valk M, Gisolf EH, et al. Increased risk of lipodystrophy when nucleoside analogue reverse transcriptase inhibitors are included with protease inhibitors in the treatment of HIV-1 infection. AIDS. 2001 May 4;15(7):847-55.

 13. Cohen S, Janicki-Deverts D, Turner RB, et al. Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. JAMA. 2013 Feb 20;309(7):699-705.

This article by James Wilton originally appeared on the CATIE http://www.catie.ca/en/home  website here. 

Une version française est disponible ici.

The sexual transmission of HIV occurs after an exposure to fluids that contain HIV, such as semen and fluids from the vagina and rectum. Research shows that a higher amount of HIV (viral load) in these fluids increases the risk of HIV transmission and that a lower viral load decreases the risk.1

Treatment, viral load and HIV transmission

The viral load in the blood of a person living with HIV is measured to monitor the success of antiretroviral therapy (also called ART, HAART or cART). Successful HIV treatment can reduce the viral load in the blood (and other bodily fluids) to undetectable levels and thereby reduce the risk of sexual HIV transmission. In fact, a research study known as HPTN 052 found that the risk of HIV transmission among heterosexual serodiscordant couples was 96% lower when the HIV-positive partner was on treatment.2 (In serodiscordant couples, one partner is HIV-positive and the other is HIV-negative.)

Undetectable viral load does not mean that there is no virus, but rather that the amount of HIV in a bodily fluid is below a level that tests can detect. (Tests used in some places, such as Canada, cannot detect HIV if there are less than 40 copies of HIV per ml of blood, while tests used in other parts of the world have higher limits of detection.)

Also, not all people living with HIV who take HIV treatment and have an undetectable viral load in the blood also have an undetectable viral load in their other bodily fluids. Research suggests that of those people living with HIV who have an undetectable blood viral load, 5 to 48% can have detectable virus in their semen, vaginal fluid and rectal fluid.3,4,5

Although previous research has demonstrated that treatment can reduce the risk of HIV transmission in heterosexual couples, it is unclear exactly what the HIV transmission risk is when a person’s blood viral load is undetectable. A recent systematic review6 of the literature was conducted by Dr. Mona Loutfy, one of Canada’s leading infectious disease specialists, and colleagues to gain a better understanding of this risk.

Systematic review

The authors searched for published studies that followed serodiscordant heterosexual or same-sex couples over time. The main purpose of the review was to find studies that met the following criteria:

• the HIV-positive partner was on antiretroviral treatment
• the number of HIV infections in the HIV-negative partner was recorded
• if HIV transmission occurred, the HIV-positive partner’s blood viral load was measured close to the time of transmission

The authors identified only three studies that fit all of their criteria. These studies followed a total of 222 heterosexual couples from Brazil, Spain and Uganda.

An additional three studies were identified that fit all of their criteria but did not measure the viral load of the HIV-positive partner near the time of HIV transmission, including the HPTN 052 randomized controlled trial. These studies enrolled a total of 1,304 couples on treatment.

Overall, these six studies contained 2,975 person-years follow up of treated couples. This is the equivalent of following 2,975 couples for one year. The vast majority of these couples were heterosexual and only a small number were same-sex couples (3% of the couples in the HPTN 052 study were same-sex).

Number of HIV transmissions and HIV transmission risk

In the three studies where viral load was measured, no HIV transmissions occurred among couples where the HIV-positive partner was on treatment and the viral load was undetectable.

In the additional three studies, for which viral load was not measured, a total of four transmissions occurred. However, it is not known if the viral load of the HIV-positive partner was detectable or undetectable at the time of transmission. All of these HIV transmissions occurred shortly after the HIV-positive partner started treatment; therefore, the viral load was likely declining but still detectable when transmission occurred.

In these six studies, the definition of undetectable viral load ranged from less than 50 copies per ml to less than 500.

The lack of HIV transmissions in these studies does not mean there is no risk of HIV transmission when the viral load is undetectable. Using data from all six studies (but excluding the four HIV transmissions that occurred in the additional three studies), the authors calculated that when the viral load is undetectable, there may be a 1% risk of HIV transmission per 10 years of relationship and sexual activity.

Limitations of the study findings

There are several factors—other than viral load—that can influence the risk of HIV transmission between serodiscordant couples and may partly explain the lack of HIV transmissions observed in this review. As a result, the authors of the systematic review listed several caveats to their findings, including the lack of data on:

1.Extent of condom use 

Condoms are an effective method of preventing the transmission of HIV and many STIs and couples in these studies may have been using condoms often. For example, in the HPTN 052 study, 96% of the couples reported using condoms every time they had sex. Although people often say they use condoms more than they actually do, condom use may have played an important role in keeping the number of HIV transmissions low in these studies.

2. Same-sex couples and type of sexual intercourse

The vast majority of the couples enrolled in the studies were heterosexual and were (likely) having mostly vaginal sex. Therefore, it is unclear how much these findings apply to same-sex couples and other couples who mostly have anal sex. Some researchers think the risk of HIV transmission when undetectable may be higher for anal sex compared to vaginal sex.

3. Rates of sexually transmitted infections (STIs)

STIs are known to increase the risk of HIV-positive people transmitting HIV and HIV-negative partners becoming infected. STIs may increase the risk of HIV transmission even when a person’s viral load is undetectable. However, most of the studies reviewed did not provide data on STIs other than HIV; therefore, the review could not evaluate their impact.

In general, the risk of having STIs is lower among stable heterosexual couples (particularly those who are monogamous) than among people in casual relationships. Also, in some studies, such as the HPTN 052 study, participants were provided with regular STI testing and treatment which can help to further reduce the rate of STIs. A low number of STIs among couples in these studies may have decreased the risk of HIV transmission.

Conclusion

This systematic review supports previous research showing that treatment can significantly reduce the risk of HIV transmission among heterosexual couples. The authors concluded: “Our findings suggest minimal risk of sexual HIV transmission for heterosexual serodiscordant couples when the HIV-positive partner has full viral suppression on cART with caveats regarding information on sexual intercourse type, STIs, and condom use. These findings have implications when counseling heterosexual serodiscordant couples on sexual and reproductive health.”

Research is ongoing to gain a better understanding of the risk of HIV transmission (a) when the HIV-positive partner’s viral load is undetectable and condoms are not used and (b) in same-sex serodiscordant couples where the HIV-positive partner is taking ART.

RESOURCE:

Understanding Risk: A Conversation

REFERENCES:

 1. 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.

 2. 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.

 3. 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):1677–9.

 4. Sheth PM, Yi TJ, Kovacs C et al. Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy. Mucosal Immunology. 2012 May;5(3):248–57.

 5. Sheth PM, Kovacs C, Kemal KS et al. Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS. 2009 Sep 24;23(15):2050–4.

 6. Loutfy MR, Wu W, Letchumanan M et al. Systematic Review of HIV Transmission between Heterosexual Serodiscordant Couples where the HIV-Positive Partner Is Fully Suppressed on Antiretroviral Therapy. PLoS ONE. 2013 Feb 13;8(2):e55747.