SIDA & VIH
Post Exposure Prophylaxis (PEP)and using treatment as prevention
What is Post Exposure Prophylaxis (PEP)?
Post Exposure Prophylaxis is antiretroviral drug treatment that is started immediately after someone is exposed to HIV. The aim is to allow a person’s immune system a chance to provide protection against the virus and to prevent HIV from becoming established in someone’s body. In order for Post Exposure Prophylaxis (PEP) to have a chance of working the medication needs to be taken as soon as possible, and definitely within 72 hours of exposure to HIV. Left any longer and it is thought that the effectiveness of the Post Exposure Prophylaxis treatment is severely diminished.
The antiretroviral drug stavudine, marketed as Zerit
Post Exposure Prophylaxis usually consists of a month long course of two or three different types of the antiretroviral drugs that are also prescribed as treatment for people with HIV. As with most antiretrovirals these can cause side effects such as diarrhoea, headaches, nausea/vomiting and fatigue. Some of these side effects can be quite severe and it is estimated that 1 in 5 people give up Post Exposure Prophylaxis treatment before completion. The most common drugs prescribed for Post Exposure Prophylaxis are zidovudine, lamivudine and nelfinavir.
Does Post Exposure Prophylaxis work?
Post Exposure Prophylaxis has been studied in animal and human trials. The evidence from each individual study is not enough to confirm whether Post Exposure Prophylaxis works or not. However, the cumulative evidence is enough to suggest that PEP might be effective in reducing the risk of HIV infection. This conclusion is widely recognised and as a result, a number of countries have produced guidelines suggesting the possible use of Post Exposure Prophylaxis in both occupational and non-occupational circumstances. They tend to suggest that, as it is not guaranteed to work, PEP should only be used as a very last resort.
Animal studies
Various animal studies have been carried out to test the effectiveness of Post Exposure Prophylaxis. Macaques, a type of old world monkey, tend to be used in animal HIV drug trials. As macaques cannot be infected with HIV, the drugs are tested against either HIV type-2, simian immunodeficiency virus (SIV) or a combination of HIV and SIV known as simian/human immunodeficiency virus (SHIV).
One monkey study investigated whether 16 pig-tailed macaques would be protected from infection when given the antiretroviral drug tenofovir after intravaginal exposure to HIV type 2.1 None of the 4 macaques that started the treatment 12 hours after exposure became infected. This was the case with the 4 macaques that received Post Exposure Prophylaxis 36 hours after exposure. In the 72-hour group, one of the macaques became infected after 16 weeks. The study concluded that early intervention with an antiretroviral form of Post Exposure Prophylaxis such as tenofovir might be successful in preventing infection after vaginal exposure.
The timing of administering PEP and the duration of the course of treatment has been a highly significant factor in all of the animal studies. HIV takes around 3 days to reach the lymph nodes (components of the immune system), and it takes a further 2 days to reach the blood cells. There is therefore a small temporary “window” during which the infection can be blocked. This can be seen in another study of tenofovir Post Exposure Prophylaxis tested on 24 macaques.2 The results showed that a 4-week regimen of tenofovir started within 24 hours of exposure completely protected the macaques from SIV. Starting the treatment between 48 and 72 hours of infection was largely ineffective. Treatment started within 24 hours of exposure but only administered for 3 days proved to be just as ineffective.
Human trials
A number of small-scale studies investigated the efficacy of Post Exposure Prophylaxis in humans by looking at occupational exposures to HIV. Health care workers tend to be at a slightly higher risk of being infected with HIV due to the nature of their work (although this risk is still very low). The most frequent exposures to HIV-infected blood in the occupational setting are caused by needle stick injuries or cuts with sharp objects. Zidovudine is the drug that is primarily prescribed after an occupational exposure to HIV and it is the only drug that has been tested in trials on health care workers. Nowadays most Post Exposure Prophylaxis starter packs contain a combination of zidovudine, lamivudine and nelfinavir, as it is generally thought that combination drug therapy is more effective than zidovudine alone.
The results of one occupational exposure study showed that taking a course of zidovudine after exposure reduced the risk of HIV infection by approximately 81 percent.3 These results cannot be taken as absolute, especially when there have been at least 13 reported cases where PEP has failed in health care workers worldwide.4 For some of these cases there was no plausible explanation for why Post Exposure Prophylaxis might have failed and therefore PEP cannot be considered as 100 percent effective.
A generic version of zidovudine (AZT) combined with lamivudine (3TC)
One study enrolled 891 people who had requested Post Exposure Prophylaxis after possible non-occupational HIV exposure (e.g. sexual exposure or injecting drug use).5 The participants were all provided with a 28-day course of various combinations of zidovudine, lamivudine, stavudine and didanosine. 6 out of the 700 that returned for testing after 12 weeks were HIV positive. However all 6 had had possible HIV exposures up to 6 months before commencing PEP. Therefore it was very difficult to determine the exact moment of exposure and whether PEP had been successful or not. There is a distinct lack of definitive evidence to show that Post Exposure Prophylaxis can be effective in non-occupational settings. Studies have generally concluded that PEP ‘might’ reduce the risk of HIV infection, but none have been able to say that it is a definite preventative.
Other observational evidence has been gathered from studies of survivors of sexual assault. In a South African study of 480 rape survivors taking a 6-week course of zidovudine and lamivudine, only one woman became HIV positive.6 Another study looked at 2,000 non-occupational exposures to HIV from four countries (Australia, France, Switzerland, and the United States). Out of 350 people treated with Post Exposure Propylaxis who reported being exposed to HIV-infected sources, none became infected as a result of PEP failure.
Who can benefit from Post Expsoure Prophylaxis?
Since the beginning of the 1990s in most areas of North America and Europe, Post Exposure Prophylaxis has been available to health workers as an important aspect of safety in the workplace. In 2005, clinical guidelines from the United States Department of Health and Human Services were drafted to extend the recommendations on using PEP to non-occupational circumstances. Nowadays in several different countries anybody who believes they have been exposed to HIV is able to ask for PEP treatment at accident and emergency areas in hospital, through GUM or HIV clinics, and via some medical doctors experienced in treating HIV.
The question of who should receive PEP has proved to be quite controversial. Several cost-benefit analyses have revealed that providing PEP to all non-occupational exposures is not an economically efficient use of limited HIV treatment resources.7 PEP appears to be cost-effective only when the patient has engaged in unprotected receptive anal intercourse or when the patient knows the HIV status of the partner.
Some believe that the increasing availability of Post Exposure Prophylaxis will lead to behavioural changes. The theory is that if PEP is readily available people will be less likely to use condoms or will be less cautious, knowing that there is a potential back up.8
“Rape survivors are not receiving vital anti-HIV treatment due to ignorance and a lack of basic treatment procedure at government health facilities and justice departments.”
It has also been suggested that due to its availability, people may use PEP repeatedly. However, various studies have shown that increasing awareness and availability of PEP does not lead to increasing risky behaviour. There is also little evidence showing that people will frequently rely on PEP, probably due to the adverse side effects that the treatment can involve. In particular a study in the US showed that “people reduced their risk behaviour after using PEP, rather than increasing it”.9
Unfortunately there are still some places around the world where PEP is being denied to people who need it. For example research in South Africa revealed that many victims of rape were not receiving PEP treatment.
“Rape survivors are not receiving vital anti-HIV treatment due to ignorance and a lack of basic treatment procedure at government health facilities and justice departments” - (IRIN, 2007)10.
Some men and young boys in South Africa have also been denied the treatment due to homophobia and general ignorance regarding male-on-male rape.
What is PrEP (Pre Exposure Prophylaxis)?
PrEP refers to a form of treatment that can be taken before exposure to a disease in an attempt to prevent infection. In respect of HIV/AIDS, PrEP consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection. The antiretroviral drugs that are currently being tested for PrEP treatment are tenofovir and emtricitabine or tenofovir alone. Taken once a day, these drugs have limited side effects and slow development of associated drug resistance.11
Does PrEP work?
Although PrEP has been tested in animal studies and human trials, is has not yet been proven to provide protection against HIV infection.12
Animal studies
The drug used in most of the animal studies is an antiretroviral known by the brand name, Truvada. This fixed-dose antiretroviral is a combination of tenofovir and emtricitabine. One study involved injecting 6 macaque monkeys with a course of PrEP both before and after infecting them with SHIV.13 The results showed that all of the monkeys were protected from infection. 20 of the 21 monkeys that did not receive PrEP became infected with SHIV.
The combination of tenofovir and emtricitabine has also been tested on humanised BLT (Bone Marrow Liver Thymic) mice. These mice have fully developed human immune systems and can produce the infection-fighting cells that in humans are specifically targeted by HIV. In the study the mice were vaginally infected with HIV. Some were then given antiretrovirals once a day for seven days and some were not given any antiretroviral treatment. Among the mice that did receive the antiretrovirals none became infected with HIV, while seven of the eight mice that didn’t receive the drug, became infected. The researchers concluded that PrEP could be a very effective method for preventing vaginal HIV-1 transmission.14
Human trials
Due to the positive results from animal studies, there has been an urgent call for more studies of PrEP in both animals and humans. As yet there is no conclusive evidence proving that tenofovir and emtricitabine can prevent humans from becoming infected with HIV. The following table summarises the ongoing and planned PrEP trials as of December 2008.
| Location | Population | Expected completion date |
|---|---|---|
| United States |
400 men who have sex with men | 2009 |
| Thailand | 2,400 injecting drug users | 2010 |
| Peru, Ecuador, US, Brazil, South Africa, Thailand | 3,000 men who have sex with men | 2010 |
| Botswana | 1,200 heterosexual men and women | 2011 |
| Southern Africa, sites to be determined | 4,200 sexually active women | 2012 |
| Kenya, Malawi, South Africa, Tanzania, additional sites to be determined |
3,900 high risk women | 2012 |
| Kenya, Uganda | 3,900 couples where one partner is HIV positive and the other is HIV negative | 2012 |
*Table information from www.prepwatch.org/trials.htm
With human trials of PrEP there are ethical issues both with using a placebo and withholding a potentially effective treatment. There are also difficulties with finding a large enough sample size to ensure that the results are significant.
The dramatic protest at the International AIDS Conference 2004, Bangkok, Thailand.
Research trials in Cambodia, Cameroon and Nigeria were cancelled due to ethical concerns. Most notably the study of 960 female commercial sex workers in Cambodia was cancelled after a highly publicised demonstration at the XV International AIDS Conference in Bangkok, Thailand.15 The main reasons for the protesting included concerns about the level of health care for the volunteers before and after the trial; the apparently low level of counselling the volunteers were receiving before their trial; and the possibility that the volunteers might not get treatment if they became infected with HIV during the study. Family Health International (FHI), who led the trials, reassured that the FHI protocols would provide antiretroviral therapy if anyone did become infected.
Similarly the study of 400 sexually active women in Cameroon was halted by Cameroon’s Minister of Public Health in 2005. FHI agreed to comply with the Ministry’s recommendations, stating that “the safety and welfare of study participants is FHI’s highest priority.16” They further declared, “FHI is committed to addressing all concerns identified in the Ministry’s careful review of the tenofovir study and has already made significant progress in doing so”.
Who would be likely to benefit from PrEP?
Different groups of people could potentially benefit from PrEP in the antiretroviral drug form. A review of PrEP published by the Center for HIV Identification, Prevention, and Treatment Services, explains that in California PrEP would benefit men who have sex with men (MSM), female partners of MSM and injection drug users and their partners.17
There have been claims that people are taking tenofovir before a high-risk night out.18 The U.S. Centers for Disease Control and Prevention recently carried out a survey at four gay-pride events and found out that 7 percent of the interview sample had tried taking tenofovir.19
There are cases of couples wishing to conceive a child where one partner is HIV positive and the other HIV negative. It has been thought that couples with different HIV status may be able to conceive without transmitting infection by using the antiretroviral drug form of PrEP. PrEP could be used as an alternative to sperm washing, a procedure currently being used in many parts of the developed world by HIV different couples. Sperm washing is costly and is believed to have a low conception rate, which is why PrEP could be a more effective option.20
It has been suggested the PrEP would be an effective way to “protect women (and men) who are victims of sexual violence or coercion, or who are afraid to insist that their partners use condoms”.21 Worldwide the most common form of HIV transmission is through unprotected vaginal sex with an infected partner. Therefore millions of people could conceivably benefit from taking a pill a day as a way of reducing their risk of contracting HIV.
What is treatment as prevention?
There are three main types of treatment as prevention:
- To provide antiretroviral drugs (ARVs) to those who have been exposed to the virus, in order to prevent them from becoming infected (in the case of Post Exposure Prophylaxis (PEP)).
- To provide antiretroviral drugs to people who may in the future be exposed to the virus, in order to prevent them from becoming infected (in the case of Pre Exposure Prophylaxis (PreP)).
- To provide antiretroviral drugs to everyone who is infected with HIV, regardless of whether the immune system is damaged, in order to reduce the incidence of onward HIV transmission.
Of these three, Post Exposure Prophylaxis is the only one currently in use.
Providing all HIV positive people with ARVs
In recent years, there has been increasing support in some circles to use antiretroviral drugs to reduce and possibly eliminate, the risk of HIV transmission. The idea was prompted by a statement released by the Swiss Federal Commission for HIV/AIDS. Based on findings from a number of studies the report stated that an HIV positive person who is taking effective antiretroviral therapy, has an undetectable viral load and is free from STDs, has a negligible risk of infecting others.22 (For more information on this issue read AVERT's HIV transmission and antiretroviral therapy briefing sheet).
Advocates argue that the most effective way to reduce the global AIDS epidemic would be to test everyone in areas of generalised epidemics, and then immediately treat all of those diagnosed positive, regardless of whether their immune system is damaged.23 Supporters of the idea argue that although in the short term this would be very costly, in the long run it would be cheaper than current strategies.
However, a number of problems have been identified concerning the policy. If people were taking antiretroviral treatment for a potentially long period of time, there could be issues regarding drug resistance and other adverse effects from the medication. The policy also does not take into account those who have become infected with HIV recently and test negative because they are in their undetectable stage. It is at this point when they are most infectious.
Other doubts raised are whether it would be possible to achieve the desired high HIV detection levels even in well-resourced countries, especially when stigma, criminalization and human rights abuses act as strong deterrents to accessing such services. Also some countries are still struggling to provide treatment for those whose immune systems are already compromised and it is unlikely they would have the resources to treat those whose HIV has not yet done any damage. Furthermore, would people begin HIV treatment solely on public health grounds if it was not immediately beneficial for themselves, and how would those who refused treatment by viewed by society, and even the law?
Is there a future for Post Exposure Prophylaxis (PEP), PrEP and treatment as prevention?
Post Exposure Prophylaxis is not going to be enough to significantly reduce the worldwide spread of HIV. It is a short-term preventative measure that is used as an ‘emergency’ precaution. Post Exposure Prophylaxis is considered as the very last resort in HIV prevention and should only be used when all other methods of HIV prevention have failed. However, with increasing widespread availability and further awareness, PEP can offer more people control over their own health.
On the other hand, it has been argued that theoretically PrEP could have an enormous impact on the worldwide HIV-1 epidemic. Mathematical models estimate that if tenofovir PrEP was used by 90 percent of high-risk people and was effective 90 percent of the time, potentially the spread of HIV infection could be reduced by more than 80 percent in a few years.24 For sub-Saharan Africa, it is estimated that approximately 2.7 million to 3.2 million new HIV-1 infections could be prevented over the next ten years by using PrEP and preventing high-risk behaviours among the most sexually active population groups.25
Despite these estimates, it is highly unlikely that everybody who could benefit from PrEP would receive the antiretroviral drugs. Most of the countries that are facing the full impact of the HIV/AIDS epidemic do not have the infrastructure or economic resources to implement such a strategy. It is also important to avoid becoming too over-optimistic about PrEP, as there is still no evidence from the human trials to show that it is safe and that it actually works.
The concept of treating everyone with antiretroviral drugs once they test positive is still only an idea, and the benefits and drawbacks are currently being debated.
