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From Prevention in Focus, Fall 2011 Recently infected individuals: A priority for HIV prevention James Wilton People living with HIV can potentially transmit HIV to others through unprotected sex at any time during their life. However, emerging research suggests that a disproportionate number of HIV transmissions—perhaps more than 12 half—may originate from people during the first few months after they become infected with HIV. , In this article, we explore why recently infected individuals are more likely to transmit HIV to others and how we can help prevent these transmissions from occurring. What’s happening in the body after HIV infection? To understand why recently infected people are more likely to transmit HIV to others, we need to look at what’s going on in the body after HIV infection occurs. After someone becomes infected with HIV, the virus begins to replicate very quickly and the amount of virus in the body and bodily fluids (such as the blood, semen, vaginal fluid and rectal fluid) rises rapidly. In some individuals, this takes its toll on the body and can cause fever, fatigue, night sweats, headache, diarrhea, sore throat and/or a rash. These symptoms generally appear about two weeks after infection occurs.3 Other individuals who become infected notice no symptoms at all during this period. A few weeks after infection, the body’s immune system begins to fight back against the virus. An important part of this immune response includes the production of anti-HIV antibodies—small proteins made by certain immune cells, which can destroy HIV and prevent HIV from multiplying. Once antibodies to HIV have been produced, HIV replication begins to slow down and the amount of virus in the body (also known as the viral load) gradually decreases. Unfortunately, antibodies cannot fully control HIV infection. Antibodies are not produced immediately after infection. The amount of time it takes for the body’s immune system to produce them varies from person to person. In most people, it is possible to detect HIV antibodies in their blood within approximately 34 days of infection, although this can take up to three months in some individuals.4 The presence of antibodies in the blood marks the end of the first stage of HIV infection—known as acute HIV infection —and the beginning of the next stage, chronic HIV infection . The amount of virus in the bodily fluids is highest during the acute HIV infection stage. After antibodies are produced, the viral load slowly decreases but does not stabilize at a lower level until up to six months after 5 6 7 8 9 10 infection. , , , , , Why do people with recent HIV infection account for a disproportionate number of transmissions? Higher infectiousness The elevated viral load of someone recently infected with HIV is the main biological reason that they are more likely to transmit HIV to others at this time. The higher the viral load, the greater the risk is of transmitting HIV to others through unprotected sex. Researchers estimate that the risk of transmitting HIV to another person from one act of unprotected sex is 26 times higher during the first three months after infection than during the months and years "10",11 that follow. More high-risk behaviour A high viral load alone is not enough to transmit HIV to another person; a recently infected individual also needs to be engaging in activities that can lead to the transmission of HIV, such as unprotected sex. Unfortunately, a person who has recently been infected with HIV is more likely to be engaging in high-risk behaviours than a person who has 12 13 14 15 been infected for a longer period of time. , , , There are two possible explanations for this. First, a recently infected individual is more likely to be engaging in high-risk behaviours because this is what led to their HIV infection. Second, many recently infected individuals are unaware of their HIV status and therefore may not realize the importance of having safer sex. Reducing the number of transmissions from recently infected individuals: Challenges and solutions Because recently infected individuals account for a large number of HIV transmissions, identifying these individuals and helping them reduce their risk of passing HIV to others is critical to HIV prevention. Research shows that when people become aware of their HIV infection and are provided with access to prevention and care services, most take measures to reduce their risk of transmitting HIV to others."12" There are two major challenges to identifying recently infected individuals: 1. the low levels of HIV testing in Canada; and 2. the limitations of certain HIV tests. As a consequence, many people who have recently become infected are unaware of their infection, as are their partners. Those who are recently infected may therefore continue to engage in high-risk behaviours until they are diagnosed with HIV. Your organization may be able to play a role in overcoming these challenges, identifying these individuals, and reducing their risk of transmitting HIV to others. Challenge: Low levels of HIV testing It is estimated that 26% of people who are HIV-positive in Canada do not know that they are infected 16 and many 17 18 do not learn of their HIV status until they have been infected for several years. , The low levels of HIV testing in Canada means that most recently infected people probably pass through the brief stage of HIV infection when their viral load is elevated without getting tested for HIV. People who have recently become infected may be unlikely to get tested for several reasons. Firstly, many may believe that they are not at risk for HIV infection despite participating in behaviours that put them at risk. Secondly, there are no definitive signs that someone has become infected with HIV. Only some people who have recently become infected will experience symptoms and those symptoms are not specific to HIV infection. Therefore, many people who experience symptoms may confuse them with those of another illness and not get tested. Furthermore, for people who do believe that they are at risk of infection, there are several barriers that may prevent them from getting an HIV test, including stigma and discrimination, fear of criminalization, and barriers to accessing testing and other health services. Solutions Outreach and educational campaigns are needed to improve people’s awareness of their risk of infection and of the symptoms associated with recent HIV infection. People need to be encouraged to get tested if they are engaging in behaviours that put them at risk for HIV infection or have developed symptoms (such as fever, fatigue, night sweats, headache, diarrhea, sore throat and/or a rash) after a high-risk exposure. Frontline service providers need to increase awareness of the need for, and benefits of, HIV testing among people who are at risk of infection. It is important that HIV-positive people learn about their HIV status as soon as possible after infection, regardless of whether or not their viral load is still high, so that they can access treatment and support services for people living with HIV and counselling on ways to prevent transmitting HIV. Access to HIV testing, particularly for marginalized populations who are at risk of HIV infection, needs to be improved. Frontline organizations may be able to play a role advocating for improved access. Challenge: Limitations of HIV tests The limitations of tests used to detect HIV infection is another major barrier to identifying recently infected individuals. Several types of HIV tests are available but for each type of test there is a brief period of time after infection during which they are unable to detect infection in a person who is HIV-positive. The time period from when a person becomes infected with HIV to when an HIV test can detect their infection, is known as the “window period.” During the “window period,” an HIV test may find a recently infected person to be HIV-negative. The length of the “window period” is different for each type of test and varies from person to person.19 The HIV tests most commonly used in Canada look for antibodies to HIV in the blood. These tests cannot detect HIV infection in someone who has acute HIV infection because the body has not yet produced antibodies. The “window period” for antibody tests varies because some people produce antibodies faster than others. For most people (up to 95%), the window period of the antibody test is approximately one month, but for some individuals it may be as long as three months. This means that for people at high risk of HIV, testing can be done as early as one month after exposure using standard antibody assays and rapid point-of-care tests. People who test positive will know for certain they are HIVpositive. Of those who test negative, 95% are indeed negative. Up to 5% of people who test negative at one month could later test positive at three months. It is important to ensure that people who test negative at one month are advised to return for repeat testing once the three-month window period is over. Other HIV tests have been developed, which detect the virus itself—such as the HIV RNA or the p24 antigen tests. These have shorter window periods (from seven to 14 days) than antibody tests and so can potentially detect HIV infection during the acute phase.20 Unfortunately, access to these new testing technologies varies across Canada. Another limitation of HIV tests is the time it takes for many of them to produce results. Most HIV tests do not produce results immediately and require people to wait one to two weeks before getting the results. During this time, people may continue to engage in high-risk behaviours and some people may never return to get their test results. Tests known as rapid or point-of-care (POC) tests can provide results on the same day that a test is performed. Most rapid/POC tests can provide results within minutes. This ensures that a person receives their results. Rapid tests that detect antibodies are available in some parts of Canada but rapid tests that can detect HIV RNA or the p24 antigen do not yet exist. Solutions Frontline service organizations need to increase people’s awareness of the different “window periods” for each type of HIV test, and emphasize that a negative result does not necessarily mean that a person is HIV-negative. Messaging should emphasize that a person who has recently tested HIV-negative may be in the “window period” and may be highly infectious. Knowledge of the “window period” and the increased risk of transmission during this time is particularly important for people who base their decisions of whether or not to have unprotected sex on knowledge of their HIV status or their partner’s. People who test HIV-negative within the “window period” should be encouraged to refrain from high-risk behaviours and return for another HIV test at an appropriate time. A second test is important to rule out the “window period” as the reason for the test being negative. In Canada, we encourage people who test HIVnegative on an antibody test to test again at the end of the three-month “window period,” or sooner if appropriate. Organizations should learn if, and where, rapid antibody testing or RNA/p24 testing is available in their area. A person who is suspected of being in the acute stage of HIV infection (for example, if they have recently had a high-risk exposure or they have experienced flu-like symptoms after the exposure) should be referred to a site where RNA or p24 testing is available. Service providers may need to advocate for improved access to rapid antibody testing and RNA/p24 tests in their area. Conclusion The goal of HIV prevention is to reduce the number of HIV infections in the communities we serve. A large number of HIV transmissions in your communities may be occurring from recently infected individuals, and therefore represent an important priority for HIV prevention efforts. 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Late presentation for human immunodeficiency virus care in the United States and Canada. Clinical Infectious Diseases . 2010 Jun 1;50(11):1512-20. 18. Plitt SS, Mihalicz D, Singh AE et al. Time to testing and accessing care among a population of newly diagnosed patients with HIV with a high proportion of Canadian Aboriginals, 1998-2003. AIDS Patient Care and STDs . 2009 Feb;23(2):93-9. 19. Cohen MS, Gay CL, Busch MP, Hecht FM. The detection of acute HIV infection. Journal of Infectious Diseases . 2010 Oct 15;202 Suppl 2:S270-7. 20. Pilcher C, Christopoulos K, Golden M. Public health rationale for rapid nucleic acid or p24 antigen tests for HIV. Journal of Infectious Diseases . 2010 April 15;201 Suppl 1:S7-15. 1. About the author(s) James Wilton is the Project Coordinator of the Biomedical Science of HIV Prevention Project at CATIE. James has an undergraduate degree in Microbiology and Immunology from the University of British Columbia. 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