Photo: NIAID @ Flickr

Drugs to PrEPare for HIV

AIDS is one of the worlds most feared diseases claiming many lives and being heavily stigmatised over the past few decades. It arises after an individual has had their immune system severely compromised by the virus HIV. Since first jumping the species barrier over 50 years ago, HIV has travelled to every corner of the earth and claimed over 35 million lives.

However, with infection rates falling the future is getting brighter by the minute. So, what can we thank for fending off this viral villain? One contributor is PrEP, a tablet defending individuals against HIV pathogens before an infection has occurred; like a biological booby trap ready to strike if the target arrives.

PrEP, or pre-exposure prophylaxis, is the name given to a method of treatment aiming to stop HIV from being transmitted to uninfected individuals. The main candidates of this preventative approach are people who are HIV-negative and considered at high risk of developing it. In its current form PrEP is a tablet taken once a day and is comprised of two separate drugs. But before the details of its pathogen busting properties can be discussed, a little bit about HIV itself must be understood.

HIV attacks CD4 T-cells which, as part of our immune system, reduces the body’s ability to fight off infection making individuals vulnerable to illnesses that would otherwise be benign. The way it does this is by entering the cell, unravelling and using the machinery it finds to produce many viral particles, which accumulate and then burst out to cause infection elsewhere.

This process not only increases the number of HIV particles but also kills the T-cells. Therefore, there are fewer cells available to prevent other infections. HIV is also a retrovirus, meaning that its genome is comprised of RNA rather than the DNA found in the human genome. Hence, it relies on enzymes to convert it into DNA so that it can be replicated with human cells.

One such enzyme is HIV reverse transcriptase. Ordinarily, when a person is infected with HIV, this enzyme happily converts the virus’ genome from RNA to a form that cellular machinery can process, DNA. However, PrEP ends this. PrEP, also known as Truvada, contains two drugs, tenofovir and emtricitabine. The drugs are analogues of RNA building blocks adenosine and cytidine. This property is utilised to target the enzyme and block it from converting the virus’s genome, thus making the cell inhospitable to HIV.

The principle is that, if taken regularly, PrEP enables individuals to accumulate a high level of antiretroviral drugs in their circulation so that, should they ever come into contact with HIV, the virus will not be able to establish itself.

Other drugs are also being tested for use as PrEP therapies. Most work with the same mechanism of blocking the enzyme’s function to prevent viral replication. The appeal of these candidates is that they possess different delivery methods to Truvada, which may be more desirable or successful than a daily tablet.

It must be stressed that PrEP is not a vaccine. Much like birth control pills, it only provides protection for as long as it is taken as prescribed. The protection it does give however is highly effective: in its current form, Truvada, 99% reduced HIV risk is given if pills are taken daily, and a 76% reduced risk if only taken twice a week. With a 51% decrease in AIDS-related mortalities since its distribution in 2004, it is hoped that PrEP is a stepping stone in the pathway to global AIDS eradication.

Tags: Aids, Biology, healthcare, HIV, medicine, prep, science

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