Truvada: Early HIV Prevention, or Gateway to Resistance?

Some hail it as the beginning of the end of HIV, while others call it the beginning of the end of effective HIV medications. A Food and Drug Administration panel's recent recommendation that Gilead Science's Truvada be used by those at higher risk of contracting HIV has produced a lot of excitement on both sides of the argument, with issues of prevention coming up against those of high cost and potential side effects.

"I don't understand why someone would take a $40 pill and deal with the stress and side effects every single day when you could just put a condom on before you have sex," says Ted Canterbury, a San Diego social worker who has been working in the HIV community for more than 15 years. "It just doesn't make sense to me."

For those in favor of Truvada's use as a Pre-Exposure Prophylaxis (PrEP), any risk is outweighed by the number of new infections it can prevent. For those opposed, the risks involve an increase in new infections and rise to the real possibility that a more virulent strain of HIV can emerge, one that is resistant to current treatments. This, argue some medical professionals, can lead to the ineffectiveness of most, if not all, HIV medications.

Truvada has been on the market as an approved treatment for HIV since 2004. It is a combination of Gilead's Viread (tenofovir) and Emtriva (emtricitabine) and is used to help keep the HIV virus itself from replicating inside the body. If the virus cannot replicate, it cannot survive.

Studies have shown that Truvada could be a potential weapon in fighting new HIV infections. In fact, among those who strictly adhered to their dosing schedule, the drug was more than 90 percent effective in preventing HIV transmission. But one major study showed that only 10 percent of study participants took the medication as prescribed. In those with intermittent use, the drug was effective in reducing new infections by 44 percent.

Some estimate that the approval of Truvada as a preventative medicine could stop at least 40,000 new infections from occurring and some estimate the reduction could be in the hundreds of thousands. At an estimated cost of $618,000 for treatment over the lifetime of someone living with HIV, the financial savings would be in the tens of billions of dollars, all the while helping to stop the spread of this terrible pandemic.

But the risks of taking a medication while one is not technically sick can be great. First is the astronomical cost of the medication: roughly $1,200 per month.

The cost doesn't add up for some sero-discordant couples as well. Kevin (who for anonymity withholds his last name) is an HIV-positive man whose partner is negative. "Insurance would not cover the absolutely astronomical costs if my husband wanted to take Truvada," said Kevin. "Maybe it will work out well for some wealthy people, but I don't think the cost is reasonable for routine prophylaxis."

There is the idea that condom use will decrease as the belief increases that Truvada eliminates any real risk to HIV infection. There are also the side effects of the medication itself, which include nausea, vomiting, diarrhea, dizziness, loss of appetite, severe kidney and liver problems and loss of bone density. While these symptoms sound formidable (but pale in comparison to the effects HIV can have on the body), some studies have shown that roughly two-thirds of those questioned attribute their lack of adherence to these side effects.

Why is drug adherence so critical? First is the overall effectiveness of the drug. Remember that Truvada was effective in reducing new HIV infections by over 90 percent when taken regularly, compared to 44 percent who took it irregularly. Second is the danger that intermittent use can produce a drug-resistant virus.

HIV is a virus that has a short life expectancy, usually between 1.5-3 days, and can only survive by quickly reproducing itself. It is also a disease that, unfortunately, lacks the ability to double-check its own work. This means that, as the virus reproduces its DNA and RNA, it can make mistakes and never know it. This causes the HIV to mutate rapidly.

Currently, the most effective treatment is to stop the virus from reproducing in the first place. This is done with three general classes of HIV medication, each one affecting a different stage in cell reproduction.

Think of these medications as the safety net under a tightrope walker. If he falls, there is one net to catch him. If he falls through that net, there is a second and, should he be incredibly unlucky, a third. If the virus finds a way around one of the medications, there are two other nets there to catch it.

Acting in concert, all three of these drugs can prevent the virus from being able to attach itself and infect healthy cells. If one of these drugs is missing, the virus could replicate, thus creating a new set of DNA that makes it unaffected by the medications.

If the medicine is only taken periodically, that leaves large gaps in the safety net and if infection occurs, when the regimen is started up again the virus has a good chance of finding a way around it. It's like locking all the doors but leaving a window open.

More disturbingly, if this virus and its new DNA are transmitted to another individual, all of the secret codes and keys go along with it, making the individual with this new strain resistant to medications as well, and so on, and so on.

Not only does this new virus have the potential to infect those without HIV, it has the ability to infect those with HIV as well. While treatment may respond to the original infection, the new infection can progress unchecked, putting those with an already compromised immune system at even greater risk.

This is the main fear in Truvada's detractors: creating a new strain of HIV that renders current medications useless. But there are plenty of professionals on the other side of the aisle who are ready, and have been waiting, to add another tool to their efforts to stop new HIV infections and would welcome FDA approval within the next couple of weeks.

As with any policy decision, there are some unintended consequences as well. Kevin believes one of these will be the guilt some couples feel if one partner accidentally becomes infected.

"The awful part is that from now on, every accidental transmission between sero-discordant partners will bring a whole new level of grief... that there was something else they could have done, but didn't. Even if they couldn't have reasonably afforded it anyway," he said.

We are indeed on the cusp of a wonderful breakthrough in the fight against new HIV infections, one that shows tremendous promise and has some of the most creative minds in the medical field finding new ways to continue the fight against HIV. As for the newest medication about to be approved for HIV prevention, there are two words that hold the key to all of our hopes: doctor's orders.