HIV Boot Camp: Treatment Goals and Considerations
Editor's note: To date, our most reader requested topic has been HIV. We've written a guest post at MedEd101 to cover the most NAPLEX-worthy testing points. But we thought we'd dig in a little further here. Over the next few weeks, we're posting a series called HIV Boot Camp. We'll shore up your HIV fundamentals. Then we'll breakdown each drug class piece by piece to highlight what you need to know. For convenience, we'll link each part of the series here. Part I
Part II: Treatment Goals and Considerations
Alright. Last time we looked at the background and pathophysiology of HIV. We looked at a small glimpse of what a patient might experience in the early days of an HIV infection. As practitioners, we have to ask ourselves "Now what?" Is it time to just give the patient an Atripla and go on about our day?
First things first, we're gonna need to get some information. Some more intel. Some deets.
At a minimum, we need to check the baseline CD4 count, HIV viral load, a Basic Metabolic Profile (BMP), and a Complete Blood Count with differential (CBC w/ diff). However, while we're at it, we should also grab the viral genotype. And the patient's fasting lipid profile and liver panel. Finally, for an added bonus, we're going to throw in the HLA test too. There's a lot deeper we can dig as far as lab work goes. But this is a good "Start Here" list that will get you through most scenarios.
That's a lot of information. What do we need all of that for?
CD4 - Remember that CD4 is a receptor on the T-helper cells of your immune system. And that HIV specifically targets these CD4(+) T cells. So we measure and monitor CD4 counts for for a couple of reasons. For starters, some practitioners don't believe in starting Highly Active Antiretroviral Therapy (HAART) until the CD4 count drops below a certain number (this number is usually 500). There isn't a consensus on this though. Many other practitioners recommend in starting HAART as soon as possible. There's not necessarily a right or wrong answer here....
It's kind of like debating which way to load a toilet paper roll (but with slightly more at stake). You'll get strong proponents from each side. And each will have a list of reasons why they are right. But if you don't have small children/cats and you load toilet paper "bottom up," then you and I have nothing in common and could never develop any kind of meaningful relationship.
For what it's worth, some of the most recent guidelines recommend initiating HAART in every HIV patient....regardless of CD4 count. If you read that link, you'll see it's a pretty strong recommendation. So it's probably "more right" (much like loading the toilet paper "top down" is more right). Just be aware that you could see differing recommendations and practices.
Anyway, we also need a baseline CD4 count because certain drugs (I'm looking at you, nevirapine) cannot be initiated if the CD4 count is too high. We'll get more in why that is as we delve deeper into each drug class. Spoiler alert: For nevirapine, it's because of liver toxicity.
We'll also continue to monitor CD4 count throughout treatment as a way to determine the effectiveness of the regimen. In general, you're looking for an increase in CD4 count...or at least for it to hold steady. If you notice that the CD4 count is decreasing, it's time to re-evaluate the patient's therapy. Most likely you're either dealing with resistance from HIV or a lack of compliance from the patient.
Just for a quick review, HAART is basically considered synonymous with "HIV Treatment." It's the drugs that we give. HAART used to specifically mean 'triple therapy.' Prior to HAART, we treated HIV with zidovudine or another drug as monotherapy, so the name HAART carried some weight. But when we started moving to triple therapy as the standard of care, the name HAART became slightly less relevant. Either way, it's a term that is still used by basically everyone so now you're at least familiar with it.
HIV Viral Load - Next up, we need the viral load (ie. How many copies of HIV exist per ml of blood). Think of viral load as the opposite of CD4 count.
Low viral load = Good
High viral load = Bad
So we use viral load as another marker (along with CD4 counts) to measure how therapy is progressing. If the viral load is decreasing, and CD4 count is increasing....then our treatment is working.
If the viral load starts to rise (which will typically correlate with a decrease in CD4), however, then it's time to reassess therapy.
We also check the viral load because if it's too high then it excludes certain drugs from being used. Specifically, rilpivirine is prone to treatment failures if the viral load is > 100,000 when initiating.
BMP - Primarily, this is all about renal function. As you'll soon see, NRTIs form the backbone of most HAART regimens. And every NRTI (except abacavir) requires a renal adjustment. Well how are we going know what renal function is without a BMP? Yes we could do a 24 hour urine collection and get an even more accurate picture of CrCl...but who has the time? The BMP will also let you assess if electrolytes are out of whack and need correcting.
CBC w/ diff - You can get a pretty decent picture of what the immune system is doing by looking at a CBC w/ diff. It won't tell you anything specifically pertaining to HIV, but remember that HIV's calling card is making people sick with other infections. The CBC w/ diff helps to evaluate that by breaking down white blood cell (WBC) counts. It also gives a good baseline on where your patient stands in terms of anemia (via hemoglobin) and if they are a bleeding risk (via platelets).
Viral Genotype - Also known as the "resistance panel," you have to check this to see which HIV medications will be effective against the actual virus you're fighting. As we mentioned in Part I of this series, retroviruses mutate all the damn time. This leads to resistance to medications and treatment failures. Just like bacteria have genes that make them resistant to methicillin, there are genes on the HIV genome that cause resistance to the entire class of NNRTIs.
Checking the viral genotype will make sure we're selecting an appropriate combination of drugs.
Lipid Profile - We'll check this at baseline especially if the patient will be using protease inhibitors as part of their HAART regimen. Many of the protease inhibitors can do wacky things to your lipid panel, so we can use this as a way to monitor that. Please note that this test must be done in a fasted state. One of the most common causes for crazy numbers on a lipid profile test is the patient eating a Denny's Grand Slam before coming to their appointment.
That "fasted" bit has a habit of showing up on tests as well. I've seen more than one patient case study question that snuck in a patient eating before taking a lipid test.
Liver Panel - First of all, it is unfortunately very common for HIV patients to be co-infected with hepatitis. So we should really check out what's going on with the liver. But secondly, many of the potential HAART drugs a patient may take can cause liver problems. Getting a baseline LFT helps us monitor and prevent liver complications.
HLA Test - HLA stands for Human Leukocyte Antigen. It's a protein that's on the surface of your macrophages. As pharmacogenomics has become more of a thing, HLA tests have played an increasing role in drug therapy. There are thousands of known variations (polymorphisms) of HLA.
We've found that certain drugs do bad things to people if they have the "wrong" HLA type. Specifically in HIV, if your patient has the type HLA-B*5701, you cannot give them abacavir. This is kind of a big deal, as you'll see one of our preferred HAART regimens contains abacavir.
What happens if you give abacavir to a person with HLA-B*5701 on their macrophages? Basically their immune system goes apeshit. They have a pretty decent chance of developing a huge hypersensitivity reaction. They may go into shock and die. They may develop SJS or TEN. Either way, it's just something to avoid.
HLA-B*5701 is a very important HLA to remember. It is one of the few HLA tests that are required before treatment. This will show up on the NAPLEX and other tests. If your patient has not had an HLA test, they cannot receive abacavir. The HLA type doesn't change, so it's just nice to grab an HLA test in the very beginning when you're initially working up the patient. Then you'll know from the get go if abacavir is ever an option.
What is our end game here? What are we actually trying to accomplish with HAART therapy? Unfortunately, we cannot eradicate HIV at this time. Once contracted, you're pretty much a lifer.
That being said....properly managed, HIV is not the death sentence it once was. Patients can live normal lives for decades with the treatment advances that have been made. So what are our treatment goals?
To suppress the HIV viral load.
To preserve and restore immune function
To reduce morbidity and prolong survival
And to prevent the transmission of HIV
With regular monitoring and adherence to HAART, these goals can be met pretty much indefinitely.
In the interest of time and space, what follows is far from an exhaustive list. There are phenomenal resources here and here if you really want some handy info. What follows is more of a tl;dr summary. These are the biggest points you need to orient yourself with HAART therapy. And again, we'll be drilling down into a lot more drug-specific information when we go through each of the respective drug classes.
1. Never use monotherapy
Back in the day, one drug may have been enough. Zidovudine monotherapy was pretty much our treatment strategy for much of the '80s (AZT Break). But much like the NBA, you generally need a big 3 to succeed now (Lebron/Wade/Bosh, any three Spurs, Green/Curry/Thompson, Kobe's left hand/Kobe's right hand/Fisher...you get the idea). So the standard of care is triple therapy. There are always exceptions, of course. But start by assuming that everyone gets triple therapy.
What makes up that triple therapy? The "backbone" of any HAART regimen is two NRTIs + "something else." That something else is usually an integrase inhibitor, a protease inhibitor, or an NNRTI.
Lucky for us (and patients), there are plenty of single tablet regimens out there to make things easy. Atripla, Complera, Stribild, Triumeq, Genvoya, Odefsey. There's a growing list of options to choose from. These all contain an NRTI backbone and the "something else" in a convenient once daily tablet.
2. Preferred regimens
There are several HAART regimens that are considered "preferred." They're preferred because they have a solid efficacy and safety profile. They work, and they are tolerated with minimal side effects.
Assuming your patient doesn't have resistance to one of the components (which we check through the viral genotype), or some other baseline lab abnormality, you'd start them with one of the following regimens. The brand name has been included if the regimen exists as a single-tablet combination pill.
dolutegravir + abacavir + lamivudine [Triumeq]
dolutegravir + emtricitabine + tenofovir
elvitegravir/c + emtricitabine + tenofovir [Stribild]
elvitegravir/c + emtricitabine + tenofovir alafenamide [Genvoya]
raltegravir + emtricitabine + tenofovir
darunavir + emtricitabine + tenofovir
These are the preferred regimens. You'll notice that all of them contain an integrase inhibitor, except darunavir (a protease inhibitor). You'll also see that the preferred list does not include an NNRTI. You'll find these under "alternative" regimens. They're still good choices. In fact, NNRTIs combinations like Atripla and Complera were the preferred regimens just a few years ago. But the new integrase inhibitors (and their wonderful tolerability) have moved them to the forefront.
You may also be confused by tenofovir alafenamide. You can read more about this new formulation of tenofovir on our post here.
3. Opportunistic Infection Prophylaxis
Remember from Part I, that we discovered HIV from otherwise healthy males becoming infected with a rare pneumonia. Opportunistic infections are things that don't normally cause disease in healthy patients. But when you lack a functioning immune system (ala HIV, leukemia, etc) then they can start showing up.
With HIV specifically, we've been able to correlate when these infections start causing problems to a CD4 count. There are 3 main bugs to worry about here. Pneumocystis jirovecii pneumonia (PCP), Toxoplasma gondii encephalitis, and Mycobacterium avium complex (MAC). What you need to memorize are the CD4 counts where you'd need to begin prophylaxis. And the drugs we actually use for prophylaxis.
For PCP, we begin prophylaxis when the CD4 count dips below 200. For toxo, the count is 100. And for MAC, the CD4 count is 50. Conveniently, sulfamethoxazole-trimethoprim (SMZ/TMP) covers both PCP and toxoplasma. So when you start a patient on PCP prophylaxis, you're also covering toxo. MAC is covered with either azithromycin (preferred) or clarithromycin. To summarize:
CD4 < 200 = PCP (SMZ/TMP)
CD4 < 100 = Toxo (also SMZ/TMP)
CD4 < 50 = MAC (azithromycin or clarithromycin)
That's all for now. In Part III, we start breaking down each drug class. We'll start with NRTIs, as they make up the backbone of most regimens. Stay tuned!
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