In June and July, CATIE is presenting four webinars that focus on new developments in HIV and hepatitis C (HCV) research, integrated approaches to HIV treatment and prevention, and the integration of HIV, HCV and other sexually transmitted and blood-borne infections in frontline work. 

These webinars are designed as a good orientation to the issues that will be discussed at the CATIE Forum: New Science, New Directions in HIV & HCV, September18-19, and CATIE recommends that all those planning to attend the Forum, or follow it via live-streaming, sign up for all four webinars.

These webinars will be of interest to many healthcare providers, community-based and public health workers, and program planners, so we encourage anyone who works in HIV and HCV frontline work to join us.

Register now to attend the CATIE Forum Webinars

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Durant les mois de juin et juillet, CATIE présente quatre webinaires qui font le point sur les nouveaux développements en recherche sur le VIH et le VHC, les approches intégrées du traitement et de la prévention du VIH, ainsi que l’intégration du VIH, du VHC et des autres infections transmissibles sexuellement et par le sang dans la pratique de première ligne.

Ces webinaires ont pour but d’orienter les sujets qui seront discutés lors du Colloque de CATIE : Nouvelle science, Nouvelles orientations en matière de VIH et de VHC, qui se déroulera les 18 et 19 septembre; CATIE recommande à toutes les personnes qui ont l’intention d’assister au Colloque, ou de le suivre par l’entremise des webémissions en direct de s’inscrire à chacun des quatre webinaires.

Ces webinaires intéresseront de nombreux fournisseurs de soins de santé, des professionnels de la santé publique et communautaire et des responsables de l’élaboration de programmes;  nous incitons donc à se joindre à nous toute personne qui travaille dans la pratique de première ligne du VIH et du VHC.

Inscrivez-vous maintenant pour participer au webinaires du Colloque de CATIE.

 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 recent article by Sean Hosein first appeared on the CATIE website here.

Une version française est disponible ici.

It has been 32 years since AIDS was first recognized and 30 years since the cause—a virus we now call HIV—was first isolated. In that time enormous advances have been made: There are tests that can detect HIV and treatment (commonly called ART or HAART) has transformed HIV into a chronic illness. Furthermore, the power of ART is so profound that a young HIV-positive adult who begins treatment shortly after diagnosis today, who takes his/her medicines every day exactly as directed and who has no or limited co-existing health conditions is expected to live for several decades.

Although ART has helped to transform HIV into a chronic illness—particularly in high-income countries such as Canada, Australia and the U.S. and regions such as Western Europe—there are still issues. This treatment must be taken at least once a day, every day, for the rest of a person’s life. Such high levels of adherence may be difficult to sustain for many years. Furthermore, medicines to treat HIV, particularly the newest and most tolerable drugs, are relatively expensive. As the vast majority of HIV-positive people live in low- and middle-income countries, some researchers have wondered whether it is possible to provide care and treatment for all HIV-positive people in those places. At present, not every HIV-positive person in those countries can access care and treatment. Thus, a cure would be very desirable for many reasons.

Know your co-receptors

HIV needs at least two receptors to enter and infect a cell. The first receptor is CD4+, which is found on many immune system cells. HIV usually then needs one of two other co-receptors, either CCR5 or CXCR4.

Some strains of HIV prefer to use CCR5, others CXCR4, and still others use both co-receptors.

Back to the cure

Since the late 1980s, researchers have attempted to cure HIV infection. However, in the first two decades of the AIDS epidemic, such efforts were largely dangerous and unsuccessful.

Then, in 2008, a major development occurred. Doctors in Berlin appeared to have cured an HIV-positive man, who was suffering from leukemia, of both cancer and HIV. The “Berlin patient” had been taking ART for several years prior to his cancer treatment and received chemotherapy, radiation and transplants of stem cells. What was unique in this case was that the donor of the stem cells had a rare mutation (called a delta-32 mutation by researchers) that resulted in his cells having no CCR5 co-receptors. This made the cells somewhat resistant to HIV infection. After intensive chemotherapy and radiation, ART was withheld and the stem cells were transplanted and took hold in his bone marrow, helping to create his new immune system. However, the man’s new immune system attacked parts of his body, a complication called GvHD (graft vs. host disease), and doctors had to prescribe a mix of powerful immune-suppressing drugs to manage this complication. His cancer returned and he had to undergo intensive chemotherapy again as well as another stem cell transplant.

The Berlin patient survived all of these interventions and recurrent cancer. He has not needed to resume ART and sophisticated tests have revealed that either he has no HIV or he has extremely low levels of this virus deep within his body from time to time.

Why the cure?

Researchers are divided about why the Berlin patient was apparently cured. Research teams have proposed different possible reasons for his apparent cure, as follows:

• the intensive bouts of chemotherapy and radiation
• the bone marrow transplant from a donor with a delta-32 mutation
• the intensive stimulation of his immune system arising from GvHD
• the use of transplant medicines, which dampen inflammation and reduce HIV’s ability to infect cells

It is likely that more than one of these factors played a role in his recovery from HIV.

Excitement

The apparent cure of the Berlin patient has excited the imaginations of many researchers and doctors around the world. Clinical trials are underway, mostly in the U.S and Western Europe, assessing different methods for attempting to cure HIV infection. Eventually some of these trials will occur in Canada.

Caution needed

Some of the attempts at a cure, such as genetic therapy, have been relatively safe. However, in attempting to replicate the success of the Berlin patient, other HIV-positive people have died. This is not surprising, as intense chemotherapy and radiation with or without transplant drugs are very debilitating.

Researchers at Harvard University have attempted a variation of the protocol used with the Berlin patient. Although two HIV-positive patients with cancer have volunteered for this experiment and have survived for several years, they remain weak, both physically and immunologically. A major difference between these patients and the Berlin patient is that they have not stopped taking ART. Due to their poor state of health, their doctors have been reluctant to withhold ART, so it is not yet clear if they have been cured.

These experiments with stem cell transplants and chemotherapy and subsequent transplant drugs are dangerous and will not be done on a large scale because among HIV-negative cancer patients such procedures carry a death rate of about 15%. No one is certain about the death rate for HIV-positive people, but it is likely to be at least as high.

Much caution with intense monitoring and hospitalizations will be needed for attempts at a cure. This will particularly be the case as researchers use multiple methods on the same person to attempt a cure.

Still, researchers should be praised for showing imagination and embracing cure research. Such encouragement is necessary because many of the complex ways that HIV interacts with the immune system are not fully understood. Therefore, much research on monkeys infected with SIV (simian immunodeficiency virus), mice transplanted with human immune systems, and HIV-positive people will be needed to gain such an understanding.

The journey toward a cure will not be easy and many challenges lie ahead. Some of the challenges are known, others may only become known as experiments proceed. As with any great scientific endeavour, there will be setbacks. This means that research funding agencies and the public need to be patient. The initial wave of cure research experiments over the next five years should be viewed as exploratory and their results preliminary. This research will seek to answer important scientific questions that can then be used to build a foundation as researchers work toward a cure.

To assist researchers in developing new ideas for cure research, Canada’s premier scientific agency, the Canadian Institutes for Health Research (CIHR), will be seeking proposals from research teams across the country. These proposals will be reviewed by scientists and the most promising proposal(s) funded for five years.

Resources

Hints of a cure—the future of stem cell transplants and HIV – CATIE News

Gene therapy for HIV—outcomes from a recent experiment – CATIE News

Attempts at a cure – TreatmentUpdate

—Sean R. Hosein

REFERENCES:

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 2. Katlama C, Deeks SG, Autran B, et al. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet. 2013; in press.

 3. Samson M, Libert F, Doranz BJ, et al. Resistance to HIV-1 infection in Caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature. 1996 Aug 22;382(6593):722-5.

 4. Moore JP, Kitchen SG, Pugach P, et al. The CCR5 and CXCR4 co-receptors—central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection. AIDS Research and Human Retroviruses. 2004 Jan;20(1):111-26.

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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.