PrEP Schooling

The science behind HIV prevention drugs

By James Birtley

Credit: Sylvain Bruni; source imagesby Joe Photo Studio and Dave Becker.

The HIV pandemic is still very much amongst us, and this sophisticated virus is not going away any time soon. The most recent figures from the Center for Disease Control and Prevention (CDC) estimate that there are currently 1.2 million Americans and 35 million people worldwide living with HIV/AIDS. In addition, there will be around 50,000 newly infected individuals this year in the US. These are sobering statistics but the more we understand this virus and maintain our awareness the greater our chances will be of defeating it.

In the 1980s, being HIV-positive was a death sentence. Although there is still no cure and no effective vaccine for HIV, science has given us all much to be grateful for. Fortunately, the continuing development of more sophisticated testing, new treatments, and technological advances have greatly mitigated this previously grim prognosis.

A new health innovation is underway and it could make a big difference to the lives of many: HIV Pre Exposure Prophylaxis, or PrEP for short, is a scheme designedto help prevent new HIV infections from occurring and it is endorsed by the World Health Organization (WHO) and the CDC. Many branches of medicine have been using prophylaxis to prevent diseases; being vaccinated against the flu or wearing sunscreen are two common examples. PrEP is a new way for people to arm themselves against HIV – but it is not for everyone.

There are currently around 30antiretroviral drugs approved in the United States for treating individuals who are HIV positive. These drugs target different stages of the HIV life cycle. PrEP uses two of these potent drugs, tenofovir and emtricitabine. Only those who are currently HIV negative and are deemed to be at substantial risk of an HIV infection are recommended to take a once-daily pill called Truvada (manufactured by Gilead Sciences), which contains both these antiretrovirals. Highrisk individuals include HIV negative individuals who have an HIV positive partner and people engaging in sexual practices that place them at higher risk for HIV exposure.

Some may argue that PrEP will encourage condomless sex and lead to an increase in other STDs, such as syphilis, gonorrhea, hepatitis, and herpes. This is certainly a valid concern. Even in the case of HIV prevention, PrEP is not 100 percent effective. Wearing a condom during sex is still advisable.

When someone following a PrEP regimen gets infected, these drugs can prevent the virus from establishing a permanent infection. An HIV infection begins with a virus particle hijacking a host immune system cell. It does this first by attaching itself to the cell and then releasing its viral contents into it. Next, several viral enzymes (that were packaged along with the viral genetic information, including the reverse transcriptase, protease and integrase) get to work, helping not only to multiply the HIV genetic material but ensuring that a copy of it is permanently inserted into the host’s DNA. This infected cell will go on to produce new virus particles and initiate further rounds of infection in other cells. As the HIV infection persists an individual’s immune system cells die and as a result render the host unable to fight infection.

Experts estimate that if PrEP were implemented globally, we could see a 20-25 percent reduction in HIV incidence amongst MSM, potentially amounting to one million people within a decade.

The biomechanics behind PrEP are simple: the two drugs in Truvada adhere strongly and specifically to the HIV reverse transcriptase and prevent it from functioning normally. This disruption is critical. As a result, the virus cannot initiate key stages of its life cycle. The odds of clearing the virus swing heavily in favor of the patient.

PrEP for HIV came about following the ground-breaking iPrEx study (Pre-exposure Prophylaxis Initiative) in which 2,499 HIV negative participants were enrolled at 11 test centers on four continents and six countries. Of these participants, 1,251 were randomly given Truvada and 1,248 a sugar-containing placebo. Follow-up over a two-year period determined that there were 36 new HIV infections among the participants who were offered Truvada and 64 among those given the placebo. This equates to 44 percent additional protection against HIV in the Truvada group. However, protection rose to 96 percent for those who managed to take Truvada four times per week and to 99 percent for those who observed the recommended daily schedule.

PrEP does come with drawbacks. A daily regime will cost in the region of $15,000 annually, though insurance plans typically cover the costs and Gilead offers assistance for the uninsured. There are also side effects such as upset stomach, headache, and nausea, but the reported severity has been mild.

According to a WHO report ( July 2014), men who have sex with men (MSM) are 19 times more likely to be infected with HIV than the general population. This fact and the results of the iPrEx study form the basis of the recommendation that MSM be targeted for HIV PrEP. Experts estimate that if PrEP were implemented globally, we could see a 20-25 percent reduction in HIV incidence amongst MSM, potentially amounting to one million people within a decade.

While PrEP may not be for everyone, it remains a powerful new weapon in the fight against this terrible virus.

James Birtley

James Birtley, PhD is a molecular biologist at the University of Massachusetts Medical School, Worcester. His special interests include the structural biology of viral protein interactions with the human immune system.