by Jordan Wilkerson
figures by Aparna Nathan

Every morning when I wake up, I take a swig of water and swallow a blue pill. I don’t have an illness that the drug is treating. In fact, I’m quite healthy. I take the pill to keep from getting ill. Referred to as PrEP, or Pre-Exposure Prophylaxis, the pill protects me from potential infection by the infamous virus HIV (Human Immunodeficiency Virus). The main reason I’m on it is because I’m a gay man. By far, the people most affected by HIV in the US have been, and still are, gay and bisexual men. Representing less than 5% of the US population, they accounted for 67% of the 40,000 new HIV diagnoses in 2016. Yet, the Center for Disease Control and Prevention (CDC) also reports that over 600,000 heterosexual Americans have “substantial risks” of contracting the virus and should consider taking PrEP. So what makes HIV dangerous enough to warrant preventative treatment?

Like all viruses, HIV’s goal is simple: replicate. But the difference is that HIV targets cells crucial to our immune system, creating a macabre irony. The immune system exists to thwart viral takeovers, but HIV uses it, instead, to fast-track its deadly spread through our bodies. Upon first making its way into the body, HIV kickstarts mass production of the viruses by attaching itself to an immune cell. The virus then injects two materials that create HIV DNA within the cell: a molecule that has instructions to build the DNA and an enzyme that builds DNA using those instructions (Figure 1). This newly generated viral DNA is then used to trick the cell into producing many more copies of the virus. The outpour of new viruses destroys the cell, and the fresh pack hunts for more immune cells to infect.

Figure 1: Schematic of HIV replication.

The immune system does put up a fight, though. Cells that are not yet infected will even commit suicide in a desperate attempt to stop the viral uprising. But HIV mutates quickly, resulting in many versions of the virus. As a result, the immune system simply can’t keep up with the motley crew of viral strains (this is also why HIV vaccines don’t exist). The battle continues until the cells composing our immune system are so depleted that we cross the threshold from HIV to AIDS (Acquired Immune Deficiency Syndrome). At this point, infections that a healthy immune system could easily quash start posing serious health risks. Without lifelong treatment to impede HIV’s insurgence, death can greet us in under a decade.

PrEP, a combination of the two drugs tenofovir disoproxil fumarate and emtricitabine, stops HIV before the infection can begin. Approved by the Food and Drug Administration (FDA) in July 2012, the treatment targets the DNA-building enzyme that HIV injects into the first cell, rendering it incapable of making DNA (see orange arrow in Figure 1). With sufficient levels of PrEP in the cells, the virus cannot replicate. Once someone already has HIV, however, PrEP is ineffective. But the treatment works quite well at preventing the virus from initially taking hold. PrEP reduces the risk of contracting HIV from sex by over 90%.

Despite this, there are way fewer people taking PrEP than people considered to be at high risk of getting HIV. In the US, just a little over 8% of people at high risk are on the treatment. For Latinos and African Americans, the percentage is even lower (Figure 2). Cost is one barrier. The only PrEP treatment on the market is Truvada, which is produced by Gilead Sciences. Truvada costs almost $2000 for a 30-day supply – kind of expensive. In fairness, Gilead does offer some assistance to help cover co-pays if you have commercial insurance. Another way to drive down cost is market competition. Generic versions sold overseas can be as cheap as $70 a year, and the FDA approved a generic version of the treatment last year for sale in the United States. When this version will actually be available to Americans, though, is uncertain, since Gilead still has patents that preclude competition. In the meantime, some people simply won’t be able to afford the treatment.

Figure 2: Numbers of high-risk individuals compared to those currently on PrEP. Despite more being at high risk, fewer African Americans are on PrEP than white Americans by a factor of 6.

Another barrier may be hesitation from doctors. While most primary care physicians say they’ve heard of PrEP, only about a third have prescribed (or even suggested) the treatment to a patient. One concern is that gay and bisexual men may use PrEP to justify more frequently engaging in risky sexual behavior. This type of concern has also been brought up in other situations, such as increasing access to birth control. The worries turned out to be unfounded for birth control, but PrEP may be another story. A comprehensive look at medical data has found that cases for chlamydia, gonorrhea, and syphilis appear to increase among PrEP users. Most studies also confirmed via questionnaires that PrEP users are having more condomless sex. While this is a problem to be addressed, it’s important to note that unlike HIV, all three of the aforementioned STIs can be treated with a short course of antibiotics.

The spread of other STIs is increasing in communities with widespread PrEP adoption, but what about HIV rates? Does increased PrEP adoption in the gay community simply get negated by more frequent risky sex? Apparently not. A team of scientists examined this question by looking at new HIV diagnoses in the Australian state of New South Wales, where thousands of high-risk men recently started taking PrEP. Published in The Lancet HIV this past November, the research team found a 25% decline in new HIV diagnoses among men who have sex with men just a year after the PrEP rollout, despite decreased condom use. A similar decline for high-risk men in the US was reported at the International AIDS conference last year. Though arguably unsurprising, these findings are a big deal. They demonstrate that government programs that provide free PrEP prescriptions, such as the ones in California and Florida, actually contribute to the larger effort to eradicate HIV entirely. The findings also push back on resisting PrEP adoption based on the behavioral change it may encourage.

PrEP-skeptical physicians have concerns other than just increased promiscuity, though. They’re also less likely to be confident in the drug’s safety. Scientists at the National Institutes of Health feel differently, however, citing no serious side effects of taking the medication. The following insight could explain the discrepancy: the doctors that are least likely to adopt PrEP also tend to have the lowest self-rated knowledge of how it works.

These skeptical providers garner little sympathy from the Human Rights Campaign (HRC), the largest LGBT rights group in the US. The group refers to these reservations about PrEP as “misconceptions” and even suggests ways to push back if your doctor won’t prescribe you the treatment. And HRC isn’t the only force pushing for more PrEP adoption; the CDC also takes issue with the fact that high-risk US populations are not getting enough access to the medication.

While several major US organizations strongly advocate for PrEP adoption in their country, the battle against HIV is far from just an American one. Many other countries are faring much worse. A fifth of people living in Swaziland, for example, have HIV. And as of 2017, 37 million people have the disease worldwide. PrEP could be crucial artillery in preventing further spread of HIV, both in the US and across the world.

But we shouldn’t confuse PrEP with a vaccine that could end the epidemic globally with one shot. High-risk populations around the world will have to take the treatment daily for it to work. Speaking of which, it’s a new day. I need to take another pill.


Jordan Wilkerson is a Ph.D. student in the Chemistry and Chemical Biology program at Harvard University.

Aparna Nathan is a second-year Ph.D. student in the Bioinformatics and Integrative Genomics Ph.D. program at Harvard University. You can find her on Twitter as @aparnanathan.

For more information:

  • Here are thorough overviews of HIV/AIDS (National Institutes of Health) and PrEP(Center for Disease Control and Prevention).
  • Learn about the treatment antiretroviral therapy (ART) for people who are already HIV-positive (World Health Organization).
  • Stay updated on how PrEP adoption is progressing around the world (PrEPwatch.org).
  • Learn how homophobia and discrimination contribute to the HIV epidemic among gay/bi men (American Psychological Association).

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