September 28, 2012
Are the potential concerns large enough that there should be some kind of threshold where a clinician says, "This person's BMD is a little bit too low; I shouldn't even be prescribing Truvada or tenofovir/FTC for PrEP"?
With the bone mineral density loss, I think that's going to be a call by the provider. If the risk of that person acquiring HIV is greater than your concerns about any further bone mineral density loss -- there are also drugs that persons can take to reverse this loss -- then I think that would still be an appropriate patient for PrEP.
For the kidney function test, that's again why it's important to monitor baseline kidney function and to have the patient come in frequently to check the kidney function to make sure that there are not any increases or worsening of kidney function.
PrEP really hasn't been looked at closely in the real world. We don't know about the patients that are, let's say, abusing methamphetamine, and going on these binges, and getting severely dehydrated, and not drinking [water]. What does that mean with someone who is also taking a PrEP medication? Is that going to increase their risk for something bad happening to their kidneys? I don't think that we know that yet.
How about comorbid conditions? Are there any particular conditions that, if a person has it, they should either delay PrEP until that condition has been managed, or avoid PrEP entirely?
I don't think we have that data quite just yet. We know that we use these medications in patients that already have established HIV infection and we know that we can give them at the same time, and that as long as patients are monitored that they do OK.
But there is the potential that PrEP medications can interact with other disease states. For example, someone with hepatitis C is more at risk for liver toxicity. Someone who has diabetes or elevated blood pressure: They're more at risk for kidney toxicity. So when you're combining patients with these comorbid conditions and an antiretroviral medication, there is the potential.
That's the kind of data that we need now, when PrEP starts to get rolled out: this real world, community-level data about real people coming in who are not just young, healthy adults -- but elderly patients, patients with a lot of comorbid conditions, substance-using patients, etc.
I think that all of those have the potential to interact with each other. But I don't think that any of those is ultimately a reason for not prescribing PrEP.
How about pregnant or nursing women?
Right now, the guidance is that you really should screen women for PrEP, not just to make sure that they're not already HIV infected, but that they're not pregnant.
It isn't to say that you cannot prescribe PrEP for a pregnant woman, especially if you feel that she's at high-risk for HIV acquisition. But we don't really have good data in HIV-negative women about the effects of these medications on the fetus.
Also, it isn't just women who are pregnant, but also women who are breastfeeding. Because we know that these drugs do cross into the breast milk, and then the baby can be exposed to the PrEP medications.
Now, with that said, currently HIV-positive women who are pregnant are prescribed these same types of medications. There's this antiretroviral pregnancy registry that collects all data from HIV-positive women that have been exposed to these antiretroviral medications. And to date there really hasn't been a big signal for severe birth defects, with the exception of very specific antiretroviral agents [other than Truvada]. The data in HIV-positive pregnant women support that these drugs can be used safely.
But again, you really would want to identify women who are pregnant to let them know what the data is in HIV-positive women who have been exposed to these medications -- that there isn't that same type of data in women that are HIV negative and that there are potentially unknown risks, but that there has been extensive data [in pregnant women with HIV].
So, an HIV-negative woman who is pregnant but, let's say, at super-high risk for HIV acquisition: That's a decision that can be made between her and her provider about whether or not to start PrEP.
You referred previously to the importance of discussing adherence. We just walked through a few of the issues related to what needs to be discussed and considered with different populations. Let's take a step back and look broadly at: What is the informal checklist that health care providers should be going through in their heads when they are first broaching the subject of PrEP with a patient?
The CDC [U.S. Centers for Disease Control and Prevention] has issued guidances. Last January, they issued them for PrEP for MSM [men who have sex with men], and then just this summer they issued guidance for heterosexuals, serodiscordant couples.
You definitely want to determine eligibility. The first and most important thing is to document that the patient is HIV negative. This is really, really key -- I'll try to walk you through this: HIV tests can only pick up infection that's at least about a month old. These HIV tests, even the rapid test, those are what are called antibody tests. They take about a month [from the moment a person is infected with HIV] to come out positive.
So, if somebody was in very early infection and they went to get an HIV antibody test, or a rapid test, even though they were infected that test would read negative, because the HIV was still in that window period.
Typically, people with very early infection -- it's called acute or primary HIV infection -- have signs and symptoms. They're sick. They have fever, body aches, headache. Sometimes they'll have a rash, sore throat.
It's very similar to flu symptoms, right?
Very, very similar to flu symptoms. If someone comes in and you feel that they're eligible for PrEP, and their HIV antibody test is negative, yet they have these signs and symptoms, you need to defer starting PrEP until you can definitively say that this is not early HIV infection before you start. Because, again, what we talked about before: If you start someone on these medications [when they're already HIV positive], because it's not an optimal HIV regimen, then you will potentially cause them to select for resistance. And not only will they acquire HIV, but potentially a strain of HIV where they're actually resistant to the medication. So that's one thing that you definitely want to screen before starting a patient.
Before we move on from that, for those people, would the recommendation be, "Come back in a month; we'll do another rapid test, or maybe an ELISA"? Or would you recommend that they get, let's say, a PCR test to see whether they have an HIV viral load?
The guidance says you can do either one: You can either defer and test them in a month, once they're beyond that window; or you can do a test like a viral load test that can actually detect the presence of the virus. Either one.
I would probably want to do the viral load test, or a test that would specifically be able to detect virus. But the big issue here is that you pause and wait to either repeat the antibody test or to do another diagnostic test that will actually detect the virus.
Other things that you would want to screen for are just to make sure that their kidney function is normal. Also, importantly, the current medications for PrEP also have activity against hepatitis B, which could be a good thing, especially if a person has active hepatitis B. But if a person does have active hepatitis B, and you start them on this medication that will have activity against it, if all of a sudden you should interrupt or stop the Truvada, the patient is at risk for having a flare of their hepatitis B. Because once you take away the medication that's suppressing the hepatitis B virus, it can come back, and their liver enzymes can go up. They may become jaundiced, meaning a yellowing of the skin or under the eyes.
This is also a great opportunity, in terms of primary prevention, to actually immunize them or vaccinate them against hepatitis B, if they don't show any evidence of being infected.
Those are some of the things that you would want to do before initiating PrEP. Then, when you begin PrEP, you really want to have the patient understand that the medication has to be taken daily. Generally, you do not want to prescribe more than a 90-day, or three-month, supply. That's to ensure that they come back in for repeat HIV testing, but also so that you can monitor their adherence to the medications, and also monitor their labs. All of those are very important right at the start.
Then you basically would want to follow patients every two to three months, have them come in.
It's also recommended that you screen patients for any sexually transmitted infections. The reason for that is we know that if a patient acquires a sexually transmitted infection (STD) -- let's say, syphilis, gonorrhea or chlamydia -- that increases their chances of acquiring HIV. If a patient has an STD that enhances the efficiency of HIV gaining access into the body and causing infections, we know that we would want to treat those patients for their sexually transmitted infection.
Again, I think it's just a great opportunity to engage patients. In the iPrEx study, at baseline, 60% of the participants reported unprotected receptive anal intercourse. So that's already a pretty high rate.
iPrEx was a study specifically involving MSM, right?
Correct: MSM and transgendered women. What they found throughout the study was that those rates [of unprotected, receptive, anal intercourse] were nearly halved: By the end of the study, it was more like 30% of patients. So they were actually able to get more patients to use condoms consistently.
And that's an important message for PrEP, as well: PrEP has only been studied as part of a comprehensive prevention package, and that's how it was shown to be effective. It's about combining consistent condom use, lowering your number of sexual partners, treating any sexually transmitted infections and knowing your partner's status. All of these things really have to come together in order for PrEP to be most effective. It's not just giving somebody a medication and saying, "See you later." Because we know PrEP is not 100% effective. We know that there were [viral] breakthroughs even in patients that were on PrEP. And we know that certain behaviors can enhance the efficiency of HIV being acquired.
So, really, PrEP should not be used in isolation, but with a combination of all these other prevention practices and messaging.