The HIV pharmacist: helping patients pick and stick with lifesaving drugs
Wednesday, February 22, 2012
How do you convince patients who feel fine to take medicines that can have major side effects?
How can you help them stay on their lifesaving daily medications for years to come despite the obstacle course of everyday life?
How do you help patients and providers choose the best combination of three or more drugs from a selection of more than two dozen that work in multiple ways to fight a virus that can mutate to resist them?
Finding the right answers is the daily work of UCSF School of Pharmacy faculty member and clinical pharmacist Jennifer Cocohoba, PharmD, who specializes in antiretroviral drugs that fight HIV, the virus that—untreated—causes AIDS.
As part of the health care team at the Women’s HIV Program (WHP) at UCSF, Cocohoba’s job is on the front lines of a battle for both personal and public health; a job that demands the medication expertise of the clinical pharmacist, the acuity of a clinical scientist, and the people skills of a counselor and coach.
The drugs: antiretrovirals
Few medications better illustrate the promise and challenge of pharmacology than the ones used to treat HIV infection. Used in complementary combinations, antiretrovirals block the virus from destructively hijacking certain immune system cells—especially T-cells with CD4 surface proteins.
Most of the drugs work by inhibiting key viral enzymes—protease, integrase, and reverse transcriptase—that HIV uses in the process of making copies of itself. Unable to replicate, the virus, although not completely eliminated, can be reduced to such low levels that it is undetectable by current blood tests.
If treatment starts early enough and remains consistent, HIV’s damage to the immune system can be limited and will not result in AIDS.
But like many drugs, antiretrovirals can cause side effects ranging from mild to severe. These commonly include: nausea, vomiting, diarrhea, rashes, fatigue, sleep disturbance (e.g., vivid dreams), headaches, dizziness, pain/tingling/numbness in hands and feet, and more.
Since anti-HIV drugs are taken for many years, there can also be longer-term side effects, such as increased blood lipids (i.e., cholesterol), insulin resistance (increasing the risk of developing diabetes and heart disease),
liver and kidney toxicity, and even changes in overall appearance—with partial atrophy of the face and limbs but increased abdominal fat.
Nevertheless, patients’ close adherence to antiretroviral regimens is crucial because:
- Unsuppressed by medication, HIV replication is fast and sloppy, generating billions of copies a day, including genetic mutants resistant to existing drugs.
- Partial or inconsistent medication suppresses the typical viruses while drug-resistant mutant viruses increase in number until they become the dominant type.
- Patients will then have predominantly drug-resistant viruses, which they also might transmit to others.
The setting: women’s HIV clinic
Cocohoba, a faculty member in the Department of Clinical Pharmacy, UCSF School of Pharmacy, is part of a health care team including physicians, nurses, and social workers who provide primary care to about 200 HIV-positive female patients at the WHP clinic on UCSF’s Parnassus campus.
That team is tasked with monitoring and treating their patients’ HIV infections as well as side effects from their medications. Studies have found that many of the short- and long-term antiretroviral side effects are both more common and more severe in women.
WHP’s innovative one-stop clinic model also handles all other patient health needs—from flu shots and sprained ankles to psychotherapy and obstetrics.
Indeed, the clinic treats a patient group that would have been science fiction just a half-generation ago—HIV-positive women who are mostly middle-aged and living long, largely healthy lives.
The pharmacist: Jennifer Cocohoba, PharmD
At the clinic, Cocohoba applies her special expertise in antiretrovirals, but also answers questions about all patient medications, She routinely acts as both a community pharmacist, counseling patients one-on-one, and a health system pharmacist, helping to tailor antiretroviral regimens to maximize effectiveness while reducing drug interactions and side effects.
The first pharmacist from a Southern California family of Filipino nurses, Cocohoba was drawn to the challenge of “bugs and drugs” in which medication regimens must be regularly monitored and modified to combat evolving pathogens, such as bacteria and viruses.
“Infectious disease treatment is always cutting edge,” she says. “The HIV pipeline is a lot quicker than drugs for other diseases, and new guidelines can come out several times a year. So you really have to keep on your toes.”
After earning her PharmD from UCSF, Cocohoba did two years of hospital residency training, including one at UCSF San Francisco General Hospital where she specialized in HIV/AIDS care.
During the latter, she rotated through five HIV clinics in San Francisco, spent six weeks at an HIV specialty community pharmacy, attended monthly meetings of a state panel that discusses difficult HIV drug-resistance cases and spent time at the National HIV/AIDS Clinicians Consultation Center, which runs national phone hotlines providing free HIV expert consultations for medical providers and information to health care workers exposed to HIV on the job.
Treatment advocate: motivating patients to start treatment now
The latest guidelines in HIV treatment argue for early treatment with antiretrovirals, but this often collides with patient concerns about side effects.
After all, patients come to the WHP clinic after learning they are HIV-positive through blood or oral (i.e., mouth swab) tests but they may have T-cell counts still in the normal range (above 600 CD4 cells per microliter of blood), well above the level that clinically defines AIDS (200 per microliter).
At the same time, they may have heard rumors—often exaggerated—about the drugs’ side effects: They may fear that nausea and fatigue will linger endlessly. But these conditions tend to be most intense during the initial weeks on medications then subside for many patients. Conversely, they might think changes in body shape will occur overnight, when they actually take years and may be less likely to occur with more recent regimens.
“It’s a rare patient that comes in and says, ‘I’m ready to start. I know these are going to be excellent for me,’” says Cocohoba.
“You can easily drown in all the negatives around HIV and antiretrovirals,” she concedes. “It’s my job to be honest about what it’s like to be on HIV medicines but also to provide positive balance—to help patients understand the reasons why you would take these medicines.”
In her role as a treatment advocate and educator, she explains the major considerations in favor of starting treatment:
- Reducing collateral damage: Beyond decreasing immune function, research shows that HIV causes damage to the gut, heart, brain, and other organs from infection-related inflammation.
- Keeping a high CD4 count: Unchecked, infection typically leads to a loss of 50 to 100 CD4 cells per microliter of blood per year from a healthy range of 600 to 1500. “The earlier you start, the better you reconstitute your CD4 cells,” says Cocohoba.
- Handling side effects better: The newer antiretrovirals can be easier on the gut and are better tolerated than earlier drugs. In any case, “the longer you wait, as your immune system get weaker, it’s harder for your body to withstand side effects,” Cocohoba explains.
- Minimizing transmission risk: “If you take HIV medicines and your viral load is undetectable, your chance of passing it to your partner or your unborn baby is really low.”
Ultimately, “treatment advocacy is combining your knowledge of the HIV medicine regimen’s effectiveness and side effects with the human aspect of taking medications,” says Cocohoba. “What are people willing to put up with and do for their health?”
Paternalistic prescriptions are more likely to lead to poor adherence. Given the risk of drug-resistant viral mutations if patients do not adhere to their regimens—and the threat that poses both to their own health and to others if such viruses spread—Cocohoba will not force the issue.
Instead, in multiple sessions over several months, she listens to and addresses patients’ concerns until they are ready to commit. The goal is to help them discover powerful motivations for themselves.
For instance, some patients may want to have a child, and a regimen of antiretrovirals is required to reduce the risk of transmitting HIV during childbirth. Other HIV-positive mothers want to be around for their kids or to see a grandchild graduate high school.
“There are a lot of personal goals that are very individualized,” says Cocohoba. “My job is not to create those personal goals for people, but to help them realize what they are, to help them find a reason to want to stay healthy.”
Medication expert: matching drugs to patients
When a patient is ready to start her medications, Cocohoba works with the medical team to select a combination of at least three antiretrovirals to keep HIV from replicating. She also tries to minimize the number of pills patients take via combination tablets, which allow two or more drugs to be taken in one pill.
The decision is informed by:
- Individual genetics. For example, patients’ genes are checked for a potentially severe allergic reaction to the reverse transcriptase inhibitor abacavir (e.g., Ziagen). Likewise, a patient with a family history of high cholesterol might not be given the protease inhibitor ritonavir (i.e., Norvir), which is more likely to increase blood lipids.
- The genes of the virus. These are checked to see if they carry mutations that make a patient’s HIV resistant to specific drugs. In urban areas such as San Francisco, “one out of every 10 persons has a virus with some mutation to some drug,” says Cocohoba.
- Gender. Some drugs, such as the reverse transcriptase inhibitor nevirapine (i.e., Viramune), are up to a dozen times more likely to cause rash and liver inflammation in women.
- Interactions with other drugs. For example, the protease inhibitor darunavir (i.e., Prezista) may significantly reduce efficacy of the common antidepressant paroxetine (e.g., Paxil).
Typically there are several potential drug combinations that would be effective for an initial regimen. Cocohoba will convey the pros and cons—even showing patients the different pill sizes and quantities. She explains which drugs should work despite occasional missed doses but how others, like the integrase inhibitor raltegravir (i.e., Isentress), require nearly perfect adherence.
Ultimately, she boils down complex issues, such as probable side effects, so patients are not overwhelmed. For example, a regimen of reverse transcriptase inhibitors may initially yield fuzzy thinking and strange dreams, while one dominated by protease inhibitors may cause more gastrointestinal distress early on.
“It’s not really that straightforward,” she says, “but that’s the essence: ‘Your gut or your head?’”
As Cocohoba notes, “The art is putting together a combination that’s going to be synergistic, effective, and will harm your patient as little as possible, because there is no perfect combination.”
In fact, she may already be planning future medication options, in case a patient cannot adhere to her initial regimen: “If I use this three-drug combo now, what’s going to be viable for this patient in the future should they fail this one? It’s a chess game. A delicate chess game.”
Adherence counselor: keeping the virus submerged
Cocohoba uses an analogy to stress the importance of regimen adherence:
“I tell my patients, ‘Your body is like a swimming pool, and HIV is trying to learn how to swim in it. So if your pool is empty, no problem: Virus walks around on the bottom. If you pour the pool full of water—if you take all of your HIV medicines—your pool will be full. Virus doesn’t know how to swim. Guess what? It’s going to drown.
“The worst scenario is when you fill your pool half full. So if you only take part of your drugs, you’ve got shallow water. That is the perfect condition for the virus to learn how to swim. And what we don’t want is a virus that knows how to swim.”
But there are social and structural challenges to HIV medication adherence such as:
- Insurance: “You can’t take them if you can’t pay for them,” notes Cocohoba. “Do patients have the means to pay for the medicines? If they don’t, what programs can we enroll them in?” Even with coverage, prior authorizations and refill paperwork can put continuity at risk.
- Privacy: HIV infection retains a unique stigma, so many patients do not want to share their status. Cocohoba can arrange to have medicines delivered to the clinic and placed in unmarked bottles. Pill-holding key fobs help patients stick to their regimens discreetly.
- Mental health: “Many of our patients suffer from depression,” she says. “If they have substance abuse or mental health issues that need to be addressed, those can be a huge barrier to them staying on medicines.”
- Daily life: Whether patients are busy rounding up their kids at dinnertime or falling asleep exhausted, Cocohoba works with them—setting cell phone alarms if necessary—to overcome everyday pill-scheduling obstacles.
“Setting up the space to just ask, ‘How is this going for you?’ and adjust these seemingly tiny little problems helps set patients up for long-term success,” she says.
Drug sentry: monitoring efficacy and side effects
Adherence coaching may be intense for the first several months, after which many patients do fine on their own, coming to the clinic a few times a year for tests. These include measuring the amount of virus in their blood (i.e., viral load), their CD4 cell count, as well as kidney and liver function.
Since the latter organs play key roles in removing drugs from the body and can be affected by antiretrovirals and other medications, Cocohoba keeps a close eye on the test results.
She cites the case of a patient in her late 50s who also took medications for diabetes, which is a chronic disease that can reduce kidney function.
After a year, Cocohoba noticed a test result showing decreased kidney function. “My job is to say, ‘Is this due to a drug?’ Oftentimes the first thing the physician thinks is, ‘What disease process is this due to?’ So we’re complementary.”
In this case, the problem was resolved by taking the patient off the reverse transcriptase inhibitor tenofovir (i.e., Viread), which can affect the kidneys. Substituting another drug increased the number of pills the patient had to take but preserved renal function.
Therapy adjustor: caring for patients as real life happens
Sometimes tests reveal an increase in viral load, typically when patients are unable to adhere to their drug regimens.
“Real life happens,” Cocohoba explains. “Someone could be on a regimen for five years, lose their insurance, and stop taking their drugs—or take half their drugs.
“As our patients cycle in and out of depression or substance abuse, life issues get in the way where people are not perfect for the rest of their lives, and that oftentimes can cost them their regimen.”
When patients’ viral loads rise to detectable levels, it may mean they now harbor drug-resistant mutant forms. So the next test ordered is usually for viral resistance, analyzing the genetic make-up of the predominant virus in the patient’s blood.
“You’re looking at the genome to find changes in the various important HIV enzymes that we’re trying to target with drug,” Cocohoba explains.
Once again, Cocohoba will be in a “chess match” with the virus, but now some of her pieces will have been taken off the board completely or will not work as well.
“Basically, you’ve got mutations which dictate which drugs will be weaker, which helps eliminate certain drugs,” she says. “You’ve also got to have contraindicated combinations in your head, ‘Oh, can’t put those together.’”
“You can construct the most beautiful regimen, and it might have 20 pills a day. So there’s a practicality aspect as well.”
“I’ll take my three best regimens, compare their efficacy, toxicity, drug interactions, and practicality. And often I’ll present those, usually to the physician first, we’ll talk about it and then together we’ll talk about it with the patient.”
A new regimen with different drugs and their side effects calls for a fresh round of adherence counseling that must also address old problems.
“Putting patients on a new regimen fixes the drug efficacy problem,” says Cocohoba, “but it may not fix some of the adherence issues that were present prior to the breakthrough of mutant virus. You want to make sure they’re successful on their second regimen, or third, or fourth.”
Cocohoba says most women in the WHP clinic are still on their first or second regimens, but she has worked with patients there and at other clinics whose poor adherence yielded HIV with drug resistance across virtually all classes of drugs.
At that point, providers must employ salvage therapy: “There are no really good choices left. There are no fully active drugs,” she says. “We’ll cobble together something for the patient. And hopefully, that tides them over until the next drug is developed.”
The research: learning how to improve adherence
From her years of direct experience with patients’ struggles, Cocohoba has become just as fascinated by the ways in which pharmacists and other providers can motivate and encourage adherence, as she is with the cutting-edge science of “bugs versus drugs.”
After all, HIV infection is not the only treatable but currently incurable condition requiring lifelong adherence to medications with side effects. Treatments for diabetes, mental illness, and high blood pressure require similar pharmacological fidelity. And the failure of patients to complete full courses of antibiotics has led to resistant strains of tuberculosis, staph, and other dangerous bacteria.
“Think about how many pharmacists there are,” says Cocohoba. “If each one had the ability to increase adherence to whatever chronic disease medication by just five percent, how much could that impact hospitalizations and the dire consequences of not being on medicines? My sense is the effect could be enormous.”
After additional training in motivational interviewing, Cocohoba earned her master’s degree in clinical research from UCSF in 2008.
Recently, she garnered funding from the National Institutes of Health (NIH) to focus on how pharmacists and other providers can best gain consistent adherence for anti-HIV drug regimens.
“There are so many subtle challenges and nuances to encouraging people to take their medicines,” says Cocohoba. “What are the most effective interventions?”
Adherence counseling from a pharmacist is crucial because existing medicines “aren’t comfortable all the time. They cause side effects. They’re hard to take. They’re not perfect.”
Nonetheless, there is reason for hope. In the last few years, new chess pieces have been added—including reverse transcriptase inhibitors that work on previously resistant mutants. There is also a new class of drug called entry inhibitors, such as maraviroc (e.g., Selzentry), which binds to receptors on the surface of CD4 cells and blocks HIV from gaining access.
As Cocohoba notes, “We have women in our clinic that are in their late 70s, and some have been infected for 20 years plus. Who would’ve thought, back in the day, that people with HIV were going to live ‘til they were 70 or 80 years old? So we know the drugs work.”
Making Sense of Side Effects - Cocohoba's cover story in BETA Fall/Winter 2011
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