HIV-PrEP is currently being debated internationally and in Germany. Armin Schafberger, Medical & Health Policy Officer at Deutsche AIDS-Hilfe (DAH) and Holger Sweers, proofreader, author and editor at DAH, explain the basic facts for I KNOW WHAT I DO.
What actually is PrEP?
When HIV-negative people take HIV medication to protect themselves from becoming infected with HIV, this is known as "pre-exposure prophylaxis", or PrEP for short.
In the USA, the CDC recommended as early as 2011 that people with a persistently high risk of HIV, namely gay men and other men who have sex with men (MSM), take Truvada (a combination tablet of two HIV drugs) daily for months and years. The drug was approved for this purpose in the US in 2012. These initial CDC recommendations were clarified in May 2014. We are now talking about people with a "substantial" HIV risk. This includes HIV-negative partners of HIV-positive people (without further specification), MSM who have had anal intercourse without a condom and/or a sexually transmitted infection in the last six months, heterosexual women and men who do not always use condoms when having sex with partners with an increased HIV risk (injecting drug users/people with MSM as sex partners) and drug users who have shared injecting equipment with others in the last six months. As an option, PrEP should also be discussed with heterosexual HIV-serodifferent couples who wish to have children or who are pregnant.
In Europe, the approval of Truvada for long-term PrEP is apparently not currently pending; the manufacturer has not yet submitted a marketing authorisation application. In 2012, the European Medicines Agency (EMA) published a discussion paper with principles for a possible evaluation process of medicines for HIV PrEP and described PrEP as a "potentially valuable tool for an integrated approach to reducing individual HIV risk and combating the HIV epidemic". However, a critical assessment of the actual benefits can only be made when this instrument is used routinely under everyday conditions.
In addition to continuous oral PrEP, other forms of PrEP are currently being researched: creams containing medication for the vagina and rectum, dissolving "tampons" that release substances, vaginal rings, vaginal tablets, the three-month injection or taking tablets on demand could soon enhance prevention.
What are the side effects of Truvada and how much does PrEP cost?
Truvada is generally well tolerated. A rare but serious long-term side effect of the Truvada ingredient tenofivir is damage to the kidneys. For this reason, the kidney function of patients being treated with tenofovir must be checked regularly.
Another important point in the discussion about PrEP is funding. In the USA (and Canada), many insurance companies cover the costs, and there may be other programmes for those who are not insured. In Germany, on the other hand, PrEP with Truvada is not authorised. However, it can still be prescribed "off-label" on a private prescription, outside of its intended use. For their own legal protection, the doctor simply has to document more precisely than usual in the file why this step is indicated, as the manufacturing company is not liable for previously unknown side effects in the case of "off-label" use. The costs, which you then have to bear yourself (as is usually the case with contraceptive devices), are around 800 euros per month.
Who takes PrEP?
It is estimated that around 150 people in the USA took long-term HIV PrEP with Truvada in 2011, compared to 1,274 in 2012. 2,319 people outside of trials took PrEP between January 2012 and September 2013, 48 per cent of whom were women. In June 2014, the US health authority CDC estimated that 500,000 people in the USA were eligible for PrEP, but only 10,000 were taking it.
But PrEP is even more widespread: Many thousands of infants have been and continue to be protected from HIV infection. Babies who have to be breastfed (because there is no clean water for baby food) and whose mothers do not have access to complete antiretroviral therapy can be reliably (i.e. 98 to 99 per cent) protected from infection with PrEP with one or two drugs for six months or a year until they are weaned.
Two approaches: systemic or localised PrEP
Do the HIV drugs have to get into every cell of the body to protect against sexual HIV transmission (systemic PrEP)? Or can protection also be achieved by "saturating" only the mucous membrane that could come into contact with HIV (local PrEP)?
With systemic PrEP, the medication is administered to the entire body via tablets or an intramuscular injection. The advantage: the medication is everywhere and protects all mucous membranes. PrEP therefore offers protection during all sexual practices and even reduces the risk of infection through the shared use of syringes and needles during intravenous drug use. The disadvantage: you need more of the medication, PrEP is more expensive and has more side effects. Every systemic PrEP also includes a regular HIV test at least every three months, because anyone who becomes infected despite PrEP runs the risk of drug resistance - two drugs are usually not enough to keep HIV in check and suppress its spread completely.
Localised PrEP only works where it is supposed to: in the vagina or rectum. On the other hand, it is significantly cheaper and has fewer side effects, as only a very small proportion of the body's cells come into contact with the medication at all; they cannot be detected in the blood, or only in trace amounts.
Systemic PrEP
- Truvada permanent PEP
The daily intake of a Truvada tablet containing the substances tenofovir and emtricitabine, which are effective against HIV, provides fairly reliable protection against HIV infection. From the drug levels in the blood of the study participants, it is believed that four tablets per week are sufficient for protection that probably exceeds 901TP3. However, only some of the participants actually managed to take the tablets regularly. Data on "treatment adherence" under everyday conditions is not yet available.
- "Weekend" PEP
PrEP is more user-friendly when required. It could benefit those who only take a risk occasionally, for example at the weekend or only on holiday. In France, Canada and soon in some cities in Germany, gay men are therefore trialling the use of PrEP before a "planned risk". So far, it is not known how many days in advance you have to start taking Truvada in order to build up a protective drug level in the cells. The IPERGAY study is now investigating whether it is sufficient to take two tablets shortly (2 to 24 hours) before planned sex, followed by one tablet each on the first and second day after the risk contact. For sex at the weekend, you would then need a total of four to five tablets - depending on whether you have sex on one or two days. The costs and side effects would be reduced and you wouldn't have to take expensive prophylaxis if you didn't have sex or didn't have risky sex for a longer period. However, we will only know whether the intake regimen is not too complicated and whether the short "onset time" of the medication is sufficient once the study has been completed in 2016.
- Monthly or three-monthly injection
Two drugs are being trialled for use as monthly or three-monthly injections: rilpivirine, which has been approved for HIV therapy since 2011 under the trade name Edurant, and the HIV drug dolutegravir, which has been approved since 2014. Both substances are modified in such a way that they are effective for one or three months when injected into the muscle. The principle has worked well in monkeys. Clinical research is now beginning on humans: Will it be possible to build up a protective effect with just one substance? How high is the protective effect and how many months does it last? The monthly injection is a widely used contraceptive method, especially in some African countries, and acceptance could be high. Meaningful results on the extent of the protective effect are not expected before 2016.
Local PrEP
Is there a local PrEP for anal intercourse, i.e. rectal gels? The first attempts with a tenofovir gel failed. The gel contained too many soluble substances, so that water was sucked out of the delicate mucosal cells of the intestine and the intestine was severely damaged. Such a gel would even make HIV infection more likely. However, the gel is now well tolerated by the intestines. Now studies on many hundreds or thousands of people must show whether the use of the gel can prevent infections during anal intercourse. This research is now in the middle phase of clinical development.
The different facets of PrEP therapy are explained in the following blog posts. In the new magazine.hiv of Deutsche AIDS-Hilfe, readers are also cordially invited to take part in the debate. Further details at http://blog.aidshilfe.de/2014/09/08/hiv-prep-einladung-zur-diskussion/
