Pre-exposure prophylaxis (PrEP) is the use of antiretroviral (ARV) drugs to reduce transmission of HIV in HIV negative people who are at substantial risk of HIV. A combination of emtricitabine and tenofovir disoproxil (FTC-TDF) has been shown to effectively reduce HIV infections in heterosexual men and women, men who have sex with men (MSM) and people who inject drugs (PWID)1,2,3,4,5. This is probably also the case for transgender people, but because they are underrepresented in clinical trials, even though they are a disproportionately impacted group, more research is needed6. FTC-TDF has been registered for PrEP since 2012 in the United Stated and 2016 in Europe. This post will focus on the eligibility, safety, efficacy and different regimens of PrEP.
FTC-TDF
Currently, in most regions FTC-TDF is the only drug registered to use as PrEP. It is also known as Truvada, its original brand name. FTC-TDF was invented as a drug to treat people living with HIV, in combination with other ARV drugs. FTC-TDF itself is insufficient to treat HIV/AIDS and doing so can even lead to drug resistance: this means that if someone living with HIV/AIDS takes too few ARV drugs (either not daily or not enough different ARV drugs), the HIV virus can mutate and become resistant against the drugs that are being used. Since FTC and TDF are widely used ARV drugs as part of combined antiretroviral therapy (cART) (i.e. the treatment of HIV/AIDS), it is important to prevent drug resistance from occuring.
For whom is PrEP?
As mentioned in the introduction, PrEP is for people at substantial risk of HIV infection. However, the indication varies from region to region (depending on the prevalence within the population) and individual variables such as sexual behaviour, medication use and medical history.
Is PrEP safe to use?
When considering using a prophylactic drug, it is important to ask yourself whether the pros outweigh the cons. In the case of PrEP possible cons could be: side effects (registered as adverse events in studies) such as nausea, stomach aches, diarrhoea, vivid dreams, decreased renal function and decreased bone density. Other cons include drug-resistance and risk compensation (e.g. decreased use of condoms or increased sexual partners and therefore higher incidence of bacterial STI's). Because of this, PrEP users should receive regular medical checks to discuss side effects and adherence as well as getting tests of kidney function and STI’s.
A large paper gathered results from many different PrEP studies7. In the studies, half of the people got PrEP and the other half got a placebo (fake pill resembling PrEP). The paper found that the people who got the real PrEP did not experience more serious adverse events than the placebo group. Also, there were few new cases of drug-resistant HIV within the PrEP groups and no evidence of behavioural risk compensation.
Is PrEP effective?
They say there are no certainties in life. This sadly also includes PrEP. There are only a handful of cases described in the world in which persons with documented adequate levels of PrEP in their blood (i.e. they took PrEP according to the prescription and the drug levels in their blood were high enough to theoretically be effective) got infected with HIV8.
When measuring a drug's effectiveness, it is not simply the number of successful cases divided by the total number of cases. Instead, a confidence interval is used to translate trial results to a number more representative of the truth. Therefore, even if 0 out of 100 people would get HIV in a trial, the statistical effectiveness will not be 100%. PrEP was found most effective in trials where the adherence to PrEP was higher than 70% (risk ratio = 0.30, 95% confidence interval: 0.21–0.45, P < 0.001), whereas low PrEP use did not show a significant positive effect compared to placebo9.
Regimens
PrEP can roughly be used in two interchangeable ways: daily or in the period around having sex (intermittent use). The daily regimen offers continuous protection and suits people with frequent possible exposure to HIV, unpredictable sex lives and people who benefit from routine. Intermittent use entails taking a double dose two to 24 hours before sex, and single doses 24 and 48 hours after the first dose. Intermittent use can be beneficial for people with a predictable sex life and lower frequency of possible exposure to HIV, who prefer not to take pills on a daily basis and are well enough organised to adhere to the regimen. One does not have to choose a regimen, but can switch depending on so-called seasonal risk.
Before starting PrEP it is important to make sure one is HIV negative. Furthermore tests should be performed to evaluate renal function (to exclude pre-existing conditions) and hepatitis status. TDF is also used to treat hepatitis B infections and therefore intermittent use is disadvised for people currently infected with hepatitis B.
Since several years PrEP is being enrolled in different countries around the globe. It has become available to an increasing number of people looking for extra protection against HIV. PrEP is proven to be safe and effective and an important element in the fight to end AIDS.
1 Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587-2599.
2 Thigpen MC, Kebaabetswe PM, Paxton LA, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med 2012;367:423-434.
3 Choopanya K, Martin M, Suntharasamai P, et al. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2013;381:2083-2090.
4 Baeten JM, Donnell D, Ndase P, et al. Antiretroviral prophylaxis for HIV prevention in heterosexual men and women. N Engl J Med 2012;367:399-410.
5 McCormack, Sheena, et al. "Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial." The Lancet 387.10013 (2016): 53-60.
6 Anderson, Peter L., Daniel Reirden, and Jose Castillo-Mancilla. "Pharmacologic considerations for preexposure prophylaxis in transgender women." Journal of acquired immune deficiency syndromes (1999) 72.Suppl 3 (2016): S230.
7 Fonner, Virginia A., et al. "Effectiveness and safety of oral HIV preexposure prophylaxis for all populations." AIDS (London, England) 30.12 (2016): 1973.
8 Hoornenborg, Elske, et al. "Acquisition of wild-type HIV-1 infection in a patient on pre-exposure prophylaxis with high intracellular concentrations of tenofovir diphosphate: a case report." The Lancet HIV 4.11 (2017): e522-e528.
9 Fonner, Virginia A., et al. "Effectiveness and safety of oral HIV preexposure prophylaxis for all populations." AIDS (London, England) 30.12 (2016): 1973.