Making Sense of Side Effects
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Making Sense of Side Effects
Jennifer
Cocohoba, PharmD
The advent of potent com-
bination antiretroviral
therapy (ART) in the 1990s
allowed people with HIV to
live longer, healthier lives.
Current United States treat-
ment guidelines recommend
that all HIV positive people
start antiretroviral therapy
if their CD4 count (a key
marker of immune health)
drops below 350 cells/mm3,
and suggest those with a
CD4 count between 350
and 500 cells/mm3 consider
starting ART.
Despite the lifesaving benefits
of ART, many people still
struggle with the decision to
start taking antiretroviral
drugs. For some, the prospect
of committing to lifelong
Enis aut est prae quos drug therapy is daunting.
Others hesitate because medi-
dolorio cations remind them of their
rerumque in perio odiciis disease. For many, the biggest
factor in deciding whether
quam to start ART or change their
current regimen is the fear of
medication side effects.
FALL/WINTER 2011 BETA 19MAKING SENSE OF SIDE EFFECTS
Geri (who asked that her last Grade II, III, and IV side effects are experience side effects more fre-
name be withheld for privacy) is HIV considered moderate to severe. Timing, quently or more intensely than men
positive and currently on ART. “Think- when known, also helps to describe do on ART, which can lead to higher
ing about HIV medicine side effects side effects. Most antiretrovirals have rates of discontinuation in the clinical
is very scary,” she said in an inter- short-term side effects (such as nausea setting,” said Monica Gandhi of the
view. When Geri switched to a new and diarrhea) which typically occur University of California, San Francisco
antiretroviral regimen, she experi- soon after starting and subside within (UCSF), who conducts research in
enced nightmares—one of which was weeks to months, as well as long-term the national Women’s Interagency
particularly vivid: “It felt so real, and side effects which may develop more HIV Study. “One reason for this could
I just couldn’t wake up. I didn’t even slowly and persist for longer periods be that women have higher concen-
know it was a dream until I did wake (such as lipodystrophy, or body fat trations of antiretrovirals in their
up.” She also experienced pain and redistribution). bloodstream than men do with the
weakness in her legs after starting the Many factors contribute to the de- same dose of drug. Investigators are
new regimen. velopment of side effects. They can be still researching differences in drug
Side effects like these can oc- the result of a drug’s direct effect on exposure between men and women to
cur with any drug—even common the body, sometimes referred to as the determine whether this is the reason
medicines like aspirin—and the vast drug’s pharmacodynamic effect. Some why women may experience more
majority stop or reverse when people (but not all) are related to the dose of side effects on therapy.”
work with their doctors to manage the medication used. The way a per- A classic example of these sex
symptoms or change treatments. son’s body chemistry reacts with the differences is the occurrence of rash
Geri’s medical team was able to iden- medication (also known as the drug’s and liver toxicity with the antiretro-
tify her drug-related side effects and pharmacokinetics) can contribute to viral medication nevirapine (Vira-
stop the medications responsible for side effect development. For example, mune). Various studies have found
them. This article will discuss antiret- some people lack important enzymes that women may be anywhere from
roviral drug side effects, including risk that process certain medications, lead- 4 to 12 times more likely to develop
factors, preventive approaches, and ing to higher levels of the drug in the a nevirapine-related rash compared
steps to take when you are experienc- blood and possibly contributing to with men. Women are also 12 times
ing side effects yourself. the development of side effects. Other more likely to develop severe hepato-
people have enzymes that change toxicity, or liver inflammation, from
SIDE EFFECTS 101 the drug into an active metabolite using nevirapine.
The accepted definition of “side ef- (or byproduct) that in turn causes Other studies have found that
fect” is any effect of a medication that side effects. These differences in our women are at higher risk of experi-
is in addition to its intended effect, physiology explain why some patients encing diarrhea, fat accumulation,
especially an effect that is harmful experience certain side effects and changes in their blood lipids (fats
or unpleasant. Side effects can also others do not. in the bloodstream), and other side
be referred to as “adverse events” or effects from various antiretroviral
“adverse drug reactions.” Side effects WHO IS AT RISK FOR medications. Some of these may be
are categorized according to their fre- SIDE EFFECTS? manageable, but the heavy burden of
quency (how commonly they occur), Though many people tolerate antiret- side effects may drive women to stop
severity (how intensely they are expe- rovirals without significant problems, their regimen completely. For example,
rienced), and timing (when they occur everyone is at risk of experiencing a an Italian study with 826 participants
and how long they last). If a side effect medication side effect at least once in found that women were more likely
occurred in greater than 1 out of every their life. It is difficult for scientists than men to stop taking their antiretro-
10 persons in clinical trials (10%), it and clinicians to predict who might viral drugs due to side effects.
could be considered common. Very experience side effects while on ART. Gandhi encourages women to
rare side effects occur in less than 1 Factors such as sex, race or ethnic communicate with their health care
out of every 100 persons taking a drug background, age, and genetic makeup provider before deciding to stop fol-
(less than 1%). influence whether an individual will lowing their treatment regimen. “The
In clinical studies, the severity react poorly to a medication. best thing a woman on ART can do
of antiretroviral side effects reported A growing body of scientific is to stay in very close touch with
by trial participants is often classified research suggests that antiretroviral her treating clinician and pharma-
according to a grading system. Grade I side effects impact women more often cist about how she is feeling on her
side effects are considered mild, while or more severely. “Women seem to medications,” said Gandhi. “Right
20 BETA FALL/WINTER 2011MAKING SENSE OF SIDE EFFECTS
from the beginning, she should try to prone to. With these types of tests, men will be against their virus, and
get help with side effects. If they do HIV positive individuals will be able to potential side effects with their doctor
not get better with time, it is also very make better-informed choices regard- and pharmacist.
important for a woman taking ART to ing which antiretrovirals they want The U.S. Department of Health
know that she does not need to live to take. Clinicians are already using and Human Services’ current anti-
with side effects that are too difficult pharmacogenomics for this purpose: A retroviral treatment guidelines list
for her.” Gandhi suggested explor- special blood test called the HLA-B5701 four “preferred” regimens—based on
ing other, less challenging treatment can help determine whether someone NNRTIs, PIs, and an integrase strand
options: “There are a number of HIV is hypersensitive (severely allergic) to transfer inhibitor (INSTI)—for people
medications now available, and she the nucleoside reverse transcriptase in- first starting antiretroviral therapy
may be able to try other regimens hibitor (NRTI) drug abacavir (Ziagen). (Table 1). Side effects for the ART
until she finds one that is tolerable for To understand side effects in spe- medications recommended for initial
her and that works well.” cific populations, better information therapy are discussed on page 22.
Race and ethnic background, must be gleaned from clinical trials
which are linked to a person’s genet- involving a broader, more representa- TENOFOVIR (VIREAD) PLUS
ics, may also play an important role in tive sample of participants. As Monica EMTRICITABINE (EMTRIVA)
the development of side effects. One Gandhi explained, “a number of drugs These two NRTIs (part of the combina-
example of this interplay is illustrated available on the market today—includ- tion pills Truvada, Atripla, and Com-
by the central nervous system side ing antiretrovirals—have been studied plera) are recommended for inclusion
effects associated with the non-nucle- in homogeneous populations, predomi- in every new antiretroviral regimen,
oside reverse transcriptase inhibitor nantly Caucasian men. Therefore, we unless there is a condition that prohib-
(NNRTI) efavirenz (Sustiva), a drug are unable to tell whether women or its their use.
contained in the widely used Atripla patients of other ethnic backgrounds Common side effects include
combination pill. will tolerate a drug’s side effects.” weakness or fatigue, headaches, diar-
People taking efavirenz may Gandhi stressed the importance of rhea, nausea, and gas. Other possible
experience grogginess, dizziness, and increasing gender balance and ethnic side effects include kidney injury, Fan-
“fuzzy thinking.” A study by the AIDS diversity among clinical trial partici- coni’s syndrome (in which the kidneys
Clinical Trials Group found that African pants: “The only way to know whether spill glucose, magnesium, and other
Americans experienced more of these a drug will work well in a specific essential electrolytes into the urine
side effects than other people and population (like women) is for those instead of reabsorbing them), osteope-
had higher levels of efavirenz in their people to be well represented in clinical nia and osteomalacia (decreased bone
blood. Other studies have reported studies. Because of this, it is extremely density and other bone abnormali-
similar findings. Researchers suggest important for all types of HIV positive ties), and darkening of the skin on the
that these higher levels and more com- persons to participate in clinical trials of palms and soles of the feet.
mon side effects may be due to differ- new ART drug formulations.” People with hepatitis B virus who
ences in the functioning of a metabolic start this medication are advised to
enzyme, CYP2B6 (cytochrome P450,
WHAT TO EXPECT talk with their health care provider
family 2B6), that helps rid the body of WHEN STARTING NEW before discontinuing it, as the liver
efavirenz through the urine. These en- ANTIRETROVIRAL DRUGS disease may flare up when tenofovir
zymes are genetically encoded: A spe- It is important to weigh many pieces is stopped. The treating clinician can
cific arrangement in the CYP2B6 gene of information when choosing an monitor the kidneys and liver through
is more common in African Americans antiretroviral regimen. HIV positive in- blood and urine tests and the bones
and Latinos and can cause CYP2B6 to dividuals should discuss convenience, through bone density tests before and
work more slowly or not at all. This in number of pills, how potent the regi- during treatment.
turn can lead to an excess build-up of
efavirenz in the blood and an increased
risk of side effects.
Table 1. Preferred Initial Antiretroviral Therapy Regimens
In the future, clinicians using the NNRTI-Based Regimen tenofovir + emtricitabine + efavirenz
science of pharmacogenomics (also PI-Based Regimens tenofovir + emtricitabine + atazanavir + ritonavir
known as personalized medicine) or
will be able to take a drop of blood, tenofovir + emtricitabine + darunavir + ritonavir
analyze a person’s genes, and figure
out which side effects their body is INSTI-Based Regimen tenofovir + emtricitabine + raltegravir
FALL/WINTER 2011 BETA 21MAKING SENSE OF SIDE EFFECTS
EFAVIRENZ (SUSTIVA) toxicity, decreased insulin sensitivity, Pneumocystis pneumonia, Mycobacte-
changes in body shape, and increased rium avium complex, and cytomega-
The NNRTI efavirenz is also part of bleeding in hemophiliacs. Individu- lovirus retinitis (a viral eye disease)—
the combination pill Atripla. Com- als and their physicians can monitor and ultimately to ensure a longer and
mon side effects seen with efavirenz drug-related changes in liver health, healthier life with HIV.
include skin rash, dizziness, grog- cholesterol, and blood sugar through
giness, vivid dreams or nightmares, regular blood tests. INSIDE THE BLACK BOX
liver inflammation, and increases in The U.S. Food and Drug Administra-
cholesterol. Pregnant women should DARUNAVIR (PREZISTA) BOOSTED tion (FDA) requires drug manufac-
avoid taking this medication during WITH RITONAVIR turers to highlight any very severe
their first trimester, as it has been Darunavir also belongs to the PI drug medication side effects in a special
linked to brain and spinal cord defects class. Common side effects from “black-box warning” in the product
in the developing fetus. darunavir use include skin rash, liver package insert. Boxed warnings are
In addition, a small minority of toxicity or liver inflammation, nausea, surrounded by a border or a box
people may experience severe depres- diarrhea, and headaches. The low (hence the name) to bring special at-
sion, angry outbursts, and disturb- dose of ritonavir used with darunavir tention to them.
ing or even suicidal thoughts while may cause stomach upset, nausea, As explained by Christine Cheng,
taking efavirenz. These psychiatric vomiting, diarrhea, taste distur- who studies black box warnings at
issues tend to emerge more frequently bances, and numbness and tingling the UCSF School of Pharmacy, “the
in people with pre-existing mental around the mouth. Other possible side purpose of a boxed warning is to alert
health problems. For this reason, it is effects include high cholesterol, body prescribers to a serious, potentially
especially important to discuss your shape changes, and increased bleeding life-threatening side effect that may be
current mental health state and any in hemophiliacs. Darunavir contains associated with use of a medication.”
past mental health issues with your a sulfonamide structure in its chemi- These warnings describe the serious
clinician before considering a regimen cal makeup, so some (though not all) side effect and outline ways to mini-
that includes efavirenz. people with a sulfa allergy may also be mize the risk. “For example, Accutane
allergic to darunavir. (isotretinoin) is an acne medication
ATAZANAVIR (REYATAZ) BOOSTED that has a boxed warning about the
WITH RITONAVIR (NORVIR) RALTEGRAVIR (ISENTRESS) potential for birth defects, and the
Atazanavir and ritonavir belong to the Raltegravir belongs to the integrase warning includes specific information
protease inhibitor class. Ritonavir is strand transfer inhibitor (or simply about a program that ensures that
a “pharmacoenhancer” or “booster” integrase inhibitor) class. HIV positive women who take the medication do
drug: Low doses of ritonavir are used individuals starting raltegravir may not become pregnant,” said Cheng.
to raise levels of atazanavir (and other experience headaches, stomach upset, Black-box warnings may be as-
PIs) in the blood. nausea, and diarrhea. Other possible signed to individual medications or
Common side effects experienced side effects include drug-induced to a whole drug class. For example, a
with atazanavir include hyperbilirubi- fevers, muscle pain and weakness, and black-box warning about lactic acido-
nemia (an increase in the body’s level rhabdomyolysis (breakdown of muscle sis (severe build-up of lactate, one’s of
of bilirubin, a byproduct of red blood fibers). Physicians can monitor muscle the body’s toxic waste products, in the
cells), jaundice (yellowing of the skin health via blood tests. blood) is placed in every NRTI’s prod-
and eyes due to increased levels of uct package insert. Black-box warn-
bilirubin in the blood), skin rash, and OTHER DRUGS ings associated with antiretrovirals are
liver inflammation. The jaundice and Table 2 lists side effects typically asso- listed in Table 2.
hyperbilirubinemia caused by atazana- ciated with currently available antiret- Should people avoid taking
vir may cause self-consciousness, but roviral drugs. While it is important for medications with black-box warn-
they are not dangerous and go away people with HIV to be aware of poten- ings? Not necessarily, according to
when the medication is discontinued. tial drug side effects, it is also essential Cheng. “Whether you should avoid
Ritonavir may cause stomach to remember all the benefits associated taking a drug due to a boxed warning
upset, nausea, vomiting, diarrhea, with treatment. The goal of antiretro- depends on...what the boxed warning
taste disturbances, and numbness and viral therapy is to build and maintain is, whether it is clinically applicable to
tingling around the mouth. Other pos- the immune system’s strength to avoid you, and whether an alternate therapy
sible side effects include increases in contracting debilitating or life-threat- is available. There are hundreds of
cholesterol, weakness, fainting, liver ening opportunistic infections such as medications with boxed warnings, and
22 BETA FALL/WINTER 2011MAKING SENSE OF SIDE EFFECTS
many people take them without serious used to prevent chemotherapy-in- diarrhea sufficiently, a treating clini-
side effects.” Cheng emphasized the duced nausea and vomiting. Ondanse- cian may consider prescribing medica-
importance of good patient-provider tron blocks the uptake of the chemi- tions such as diphenoxylate/atropine
communication about the potential for cal serotonin in both the brain and (Lomotil) or tincture of opium.
serious side effects from drugs with peripherally in the body, which helps Calcium supplements (200–500
black-box warnings: “As with any medi- to reduce nausea. Ondansetron is mg) have been shown to help control
cation, you and your clinician need to typically not covered by prescription loose stools, especially for those taking
discuss the risks and benefits.” drug insurance companies unless the the protease inhibitor nelfinavir. Main-
patient is undergoing treatment for taining a healthy amount of fiber in
DEALING WITH SIDE EFFECTS cancer, however, so it may be prefer- the diet by eating whole grains, apples,
Although the side effects that most able to start with prochlorperazine. and other fruits and vegetables can
people experience are not the seri- In addition to medications to help also help reduce diarrhea.
ous, potentially life-threatening ones control nausea and vomiting, there Lastly, drinking plenty of fluids
described in black-box warnings, they are several non-pharmacologic (non- and staying well hydrated is crucial, as
can still be challenging to handle. drug) ways to soothe a queasy stom- diarrhea can result in significant water
Common side effects such as nausea, ach—most of which involve changing loss to the body. Drinks to replace
diarrhea, rash, and fatigue can weaken eating habits. electrolytes (such as Gatorade) are not
your resolve to continue treatment. Consuming smaller meals more necessary but can be used.
Below are some tips to combat these frequently (rather than eating two
common side effects and help you or three large meals per day), eating RASH
stick to your regimen. lukewarm meals instead of piping hot Several antiretrovirals can cause rash-
food, and avoiding fatty, fried, spicy, es. Medications in the NNRTI class
NAUSEA or dairy-containing foods may help of antiretrovirals have been found to
Many antiretrovirals can cause avoid or relieve nausea. Bland foods cause rashes in as many as one out of
nausea, especially during the first such as bread, rice, toast, bananas, every five persons taking them!
four weeks of treatment. Intractable and crackers can also help quell quea- Antiretroviral-related rashes typi-
nausea (severe nausea that continues siness, as may ginger (fresh or in the cally occur within the first two weeks
for long periods of time and does not form of capsules, sodas, or teas) or of therapy. A common drug-related
get better with supportive treatment) teas made from mint leaves. rash may look like tiny pimples spread
can occur and may require a switch over the arms, legs, and trunk. The
in therapy. However, for most people, DIARRHEA skin may be erythematous (red and
ART-associated nausea does get better As with nausea, diarrhea is usually irritated) and the rash may appear to
with time. a transient side effect that can occur be worse where the skin is exposed to
HIV positive persons taking with antiretrovirals, predominantly sunlight.
abacavir should pay special attention protease inhibitors. It tends to be Rashes in people on ART should
to nausea symptoms; nausea that is worst during the first few weeks of be reported to the treating clinician
persistent or worsens over time may treatment. immediately. Most drug-related rashes
be an indicator of abacavir hyper- If diarrhea occurs, non-antiret- are not dangerous and go away on
sensitivity and warrants a call to the roviral causes should be ruled out; their own over two to four weeks, but
treating clinician. lactose intolerance, unfamiliar foods, some can be dangerous. Watch for
Prescription medications are and food-borne illnesses can also severe peeling of the skin, rashes in
available to help reduce nausea. A cause diarrhea. Unusual symptoms unusual places (such as the mouth,
common medication prescribed for such as bloody or very foul-smelling nose, eyes, and genitals), painful
nausea is prochlorperazine (Com- stools should be reported to a clini- rash, fevers, or abdominal pain. These
pazine). Prochlorperazine works to cian so that other diarrhea causes can symptoms suggest that there may be
block certain neurotransmitters in be explored. a dangerous rash developing which
the brain; this slows the release of Various medications are available requires immediate medical attention.
brain hormones that trigger nausea to control diarrhea associated with If your rash is not threatening
and vomiting. For nausea that is not ART. Loperamide, available over the and your treating clinician recom-
controlled by prochlorperazine, some counter as Immodium AD, slows the mends you continue your treatment
clinicians may prescribe a stronger muscles of the intestines and allows regimen, you can take extra steps to
antinauseal medication such as on- more water to be absorbed from the pamper your skin. Take lukewarm (not
dansetron (Zofran), which is mostly stool. If loperamide does not control hot) showers and use mild, fragrance-
FALL/WINTER 2011 BETA 23MAKING SENSE OF SIDE EFFECTS
Table 2. Side Effects Commonly Associated with Antiretroviral Drugs
Drug Class Drug Name Side Effects Black Box Warnings
NRTI Abacavir Nausea, rash, drug hypersensitivity reaction Drug hypersensitivity
(Ziagen; in reaction or allergy (especially
Trizivir and during the first 8 weeks of
Epzicom) treatment), lactic acidosis, liver
enlargement with fatty liver
Didanosine Nausea, vomiting, pancreatitis, peripheral neuropathy, lactic Pancreatitis, lactic acidosis
(Videx) acidosis with fatty liver (especially in pregnant
women also using didanosine
and stavudine), and liver
enlargement with fatty liver
Emtricitabine Discoloration (spotting) of the palms and soles of feet, flare-up of Lactic acidosis, liver
(Emtriva; in hepatitis B disease when treatment is stopped enlargement with fatty liver,
Truvada, Atripla, and flare-up of hepatitis B
and Complera) disease when treatment is
stopped
Lamivudine Flare-up of hepatitis B disease when treatment is stopped Lactic acidosis, liver
(Epivir; in enlargement with fatty liver,
Combivir, Trizivir, flare-up of hepatitis B disease
and Epzicom) when treatment is stopped
Stavudine (Zerit) Nausea, pancreatitis, peripheral neuropathy, lipoatrophy (loss of fat Pancreatitis (especially when
in arms and legs, cheeks, and buttocks), lactic acidosis with fatty combined with didanosine),
liver, increased cholesterol, changes in the way the body handles lactic acidosis (especially in
sugars pregnant women using the
combination of didanosine
and stavudine), and liver
enlargement with fatty liver
Tenofovir Nausea, gas, diarrhea, kidney damage, Fanconi syndrome, changes Lactic acidosis, liver
(Viread; in in bone tissue and bone density, flare-up of hepatitis B disease enlargement with fatty liver,
Truvada, Atripla, when treatment is stopped and flare-up of hepatitis B
and Complera) disease when treatment is
stopped
Zidovudine Nausea, vomiting, headaches, muscle aches, lipoatrophy, anemia Neutropenia, severe anemia,
(Retrovir; in (low red blood cell count), neutropenia (low white blood cell count), muscle inflammation, lactic
Combivir and lactic acidosis with fatty liver, increased cholesterol, changes in the acidosis, and liver enlargement
Trizivir) way the body handles sugars with fatty liver
NNRTI Delavirdine Nausea, headaches, rash, liver inflammation None
(Rescriptor)
Efavirenz Grogginess, dizziness, vivid dreams/nightmares, depression, rash, None
(Sustiva; in liver inflammation, increased cholesterol, birth defects if used
Atripla) during pregnancy
Etravirine Nausea, rash, drug hypersensitivity reaction, Stevens-Johnson None
(Intelence) syndrome (a life-threatening skin reaction)
Nevirapine Rash, liver toxicity, drug hypersensitivity reaction, Stevens-Johnson Severe liver toxicity and
(Viramune) syndrome rashes/skin reactions
(especially during the first 6
weeks of treatment)
Rilpivirine Headache, nausea, rash, liver inflammation, depressive disorders
(Edurant)
24 BETA FALL/WINTER 2011MAKING SENSE OF SIDE EFFECTS
Table 2, continued
Drug Class Drug Name Side Effects Black Box Warnings
PI Atazanavir Rash, diarrhea, nausea, increases in bilirubin in the blood, yellowing None
(Reyataz) of the skin and eyes, liver inflammation, abnormal electrical
patterns in the heart, changes in the way the body handles sugars,
increased cholesterol, changes in body fat distribution, kidney
stones, increased bleeding in hemophiliacs
Darunavir Rash, diarrhea, nausea, liver inflammation and liver toxicity, None
(Prezista) changes in the way the body handles sugars, increased
cholesterol, changes in body fat distribution, increased bleeding in
hemophiliacs
Fosamprenavir Rash, diarrhea, nausea, liver inflammation and liver toxicity, None
(Lexiva) changes in the way the body handles sugars, increased cholesterol,
changes in body fat distribution, kidney stones, increased bleeding
in hemophiliacs
Indinavir Rash, diarrhea, nausea, weakness, dizziness, hair loss, kidney None
(Crixivan) stones, increases in bilirubin in the blood, yellowing of the skin
and eyes, liver inflammation, changes in the way the body handles
sugars, increased cholesterol, changes in body fat distribution,
increased bleeding in hemophiliacs
Lopinavir/ Nausea, vomiting, diarrhea, weakness, changes in the way the None
ritonavir body handles sugars, increased cholesterol, liver inflammation,
(Kaletra) pancreatitis, changes in body fat distribution, abnormal electrical
patterns in the heart, increased bleeding in hemophiliacs
Nelfinavir Diarrhea, increased cholesterol, liver inflammation, pancreatitis, None
(Viracept) changes in body fat distribution, increased bleeding in
hemophiliacs
Ritonavir (Norvir; Nausea, vomiting, diarrhea, weakness, increased cholesterol, Do not combine with some
also in Kaletra) changes in the way the body handles sugars, liver toxicity, taste sedative hypnotics (e.g.,
disturbances, numbness and tingling around the mouth, changes midazolam), antiarrhythmic
in body fat distribution, abnormal electrical patterns in the heart, cardiac drugs, and ergot
increased bleeding in hemophiliacs alkaloids (often used for
migraines) due to dangerous
drug interactions
Saquinavir Nausea, headaches, diarrhea, liver inflammation, abnormal None
(Invirase) electrical patterns in the heart, changes in the way the body
handles sugars, increased cholesterol, changes in body fat
distribution, abnormal electrical patterns in the heart, increased
bleeding in hemophiliacs
Tipranavir Rash, liver toxicity, nausea, diarrhea, changes in the way the Severe liver toxicity and
(Aptivus) body handles sugars, increased cholesterol, changes in body intracranial bleeding
fat distribution, rare increased intracranial bleeding episodes,
increased bleeding in hemophiliacs
Fusion Enfuvirtide Pain, redness, bruising, bumps/nodules at the injection site, None
Inhibitor (Fuzeon) drug hypersensitivity reaction, increased episodes of bacterial
pneumonia
CCR5 Maraviroc Dizziness, abdominal pain, rash, fevers, liver toxicity, low blood None
Antagonist (Selzentry) pressure upon standing
Integrase Raltegravir Headache, nausea, diarrhea, muscle weakness, muscle breakdown, Severe liver toxicity and drug
Inhibitor (Isentress) fevers, rash hypersensitivity reaction
FALL/WINTER 2011 BETA 25MAKING SENSE OF SIDE EFFECTS
free soaps (such as glycerin soaps or ONLINE RESOURCES
brands like Dove or Cetaphil) that are
marketed for sensitive skin. Keep your
skin moisturized with a fragrance-
AIDSinfo, an informational resource offered by the Department of Health
free lotion (brands such as Keri and
and Human Services, includes a searchable database of HIV meds, with
Eucerin may be useful). Wear loose
comprehensive descriptions of side effects and potential risk factors for
clothing and avoid excessive sun
adverse events for each drug.
exposure on rashy areas. Monitor your
skin every day to ensure that the rash http://aidsinfo.nih.gov/DrugsNew/Default.aspx
is improving.
AIDSmeds.com provides a full-color chart of approved and experimental
FATIGUE antiretroviral drugs; click the drug name to see side effect details.
Many people feel tired when they start www.aidsmeds.com/list.shtml
new antiretroviral medications. While
some of this is normal—remember, TheBody.com offers the online “Resource Center on Keeping Up with Your HIV
not only is the body adapting to the Meds,” with videos, personal stories, and tips and tricks for adhering to your
treatment, it may also be trying to ART regimen despite side effects.
process dead HIV particles as the regi-
www.thebody.com/content/63615/keeping-up-with-your-hiv-meds-
men starts working—everyone should
home.html
pay attention to the severity of the
fatigue and monitor how long it seems
to be lasting.
Very severe fatigue—sometimes Clinicians can try to lower the regular exercise, a healthy diet, and
described as the “worst fatigue of risk of long-term side effects by quitting smoking.
your life”—may be a sign of a more considering a person’s current health Regular medical visits can help
serious side effect such as anemia status and family risk factors before track any side effect symptoms and
(loss of red blood cells) and is a selecting antiretroviral medications. provide opportunities for your clinician
hallmark of lactic acidosis from NRTI For example, “for patients with pre- to perform non-invasive bone scans
medications. Simple blood tests can existing conditions such as heart dis- and check laboratory values. “This
rule out these conditions. ease or diabetes, a discussion should can help you to be vigilant about the
Fatigue due to starting new ART be had about the risks and benefits of development of any long-term side
medications has no prescription or protease inhibitors,” said Machtinger. effects, and can help you treat them
over-the-counter remedy other than However, for people with few early,” said Machtinger.
rest and time. If you are starting new risk factors, or for those with lim-
medications, you might consider wait- ited antiretroviral choices, “knowing HEY, THAT’S NOT IN THE
ing until you have a few days off from exactly which regimen will avoid all PACKAGE INSERT!
work or school so you can rest and long-term complications is nearly It is unusual but still possible to have
have some extra time to deal with side impossible. Usually, the data are not a side effect that is not normally as-
effects. As the initial fatigue passes robust enough to significantly affect sociated with a particular regimen or
and the medications control viral our treatment decisions.” medication.
replication, many people feel they gain When side effects such as in- Maizie (who asked that her last
more energy than they had before they creased cholesterol, pre-diabetes or name be withheld for privacy) had
started ART. diabetes, and bone changes do occur, taken abacavir/lamivudine (Epzicom)
they are treated in the same way as as part of her antiretroviral regimen
AVOIDING LONG-TERM they would be in HIV negative per- many years ago. When she changed
SIDE EFFECTS sons: with medications and therapeu- doctors, she started a new regimen
Are there ways to lower your risk of tic lifestyle changes. In Machtinger’s that worked well for a while, until her
developing long-term side effects? view, “being HIV positive and taking kidneys began to show signs of impair-
“Preventing long-term side effects ART are two more excuses to seize ment. Her doctor recommended she
from HIV medicines is one of the most every opportunity to prevent long-term switch back to abacavir/lamivudine to
challenging aspects of treating HIV,” illnesses by staying on top of your lower the risk of further kidney injury.
according to Eddy Machtinger, director health care maintenance,” including Soon after she switched, Maizie began
of the UCSF Women’s HIV Program. minimizing cardiovascular risk with to have occasional palpitations (rapid,
26 BETA FALL/WINTER 2011MAKING SENSE OF SIDE EFFECTS
strong heartbeats). It was then that challenging adverse events—and fear planned for next Thursday, but you are
she remembered why she had stopped of the unknown may get in the way more likely to forget to take a medica-
taking abacavir years before: She had of starting or changing ART. Preparing tion that is giving you side effects.”
experienced heart palpitations the last yourself well to begin new antiretro- Because having side effects can
time she used the drug. virals (and face any side effects) will make it that much harder to adhere to
Maizie’s doctor searched the give you the best possible start. your regimen, he explained, it may be
product package insert and the avail- necessary to plan ahead about “ways
able medical literature and could BEFORE YOU START ART to remember [your medicines] that
find no mention of heart palpitations The following strategies can prepare take into account any personal barriers
occurring with abacavir use, but her you for any side effects you might you have to taking medication, and us-
unusual side effect was added to her experience after starting or changing ing adherence strategies that motivate
medical chart to help ensure Maizie treatment, and help you stick to your you to take your medication.”
would not use the drug again unless new or altered treatment regimen. Your adherence strategies may
absolutely necessary. Inform yourself—and your include following some of the tips
ART medications are studied in doctor. The descriptions of side outlined below. You might also think
large clinical trials, but there is still effects provided in this article can about your daily routines and consider
the potential for emergence of “new” help prepare you to talk frankly with where taking your medicines will fit.
or previously unknown side effects your clinician about what to expect For example, you probably rarely for-
during postmarketing studies. There is after starting antiretroviral therapy get to brush your teeth in the morning,
also the possibility, if only a small one, or switching regimens. You can also so you might plan to take your medi-
for someone to experience a unique find information about drug side ef- cines right before brushing your teeth.
individual reaction to a medication. fects—and how to keep them from Also think about what motivates
Anyone experiencing an unusual interfering with adherence to your you in other areas of your life. Do
symptom that may be related to their regimen—from reliable online sources you reward yourself after cleaning the
HIV treatment should inform the (see sidebar on page 26). kitchen or hitting the gym? Can you
treating clinician, who will consider As you educate yourself about promise yourself the same (healthy!)
factors such as whether the side effect potential side effects from your new rewards after a week of no missed or
has been reported in others, the tim- medicines, it may be helpful to jot late doses?
ing of the drug dose and the appear- down any questions you want to ask Finally, it may be helpful to
ance of the side effect, and whether your clinician and take them with you examine your mindset about taking
the side effect is dangerous or merely to your medical visit. Also, be sure to ART. The pills or injections may at first
bothersome. inform your clinician about any past seem like an unwelcome reminder of
If the side effect is not dangerous, or present medical issues of your own your virus, but those medicines also
the clinician may try “discontinu- or in your family; for example, current show that you are working to beat that
ing and rechallenging.” If the drug depression may mean that efavirenz virus and manage your own health.
is stopped and symptoms resolve or is not the right drug for you, and a These approaches can help keep you
improve, evidence is in favor of a family history of diabetes may warrant motivated and on track with your regi-
drug-related effect. (If the side effect close monitoring for metabolic side men even if side effects emerge.
continues despite the medication effects after starting ART. Ready your adherence devices.
being stopped, the symptom is likely Create an adherence plan. Adher- Part of your adherence plan may
due to other causes.) After stopping ing to a treatment regimen may not be include using medication reminder
the medication, the clinician may as straightforward as it seems. “The devices such as cell phone alarms or
suggest trying the drug again. If the underlying causes of missing your ART daily text messages. Personalizing the
symptom reappears after restarting medication are so much more complex alarm or text with a small motivating
the drug, as in Maizie’s case, there than ‘just forgetting,’” said Mallory message may help. ART medication
is even stronger evidence that it is Johnson of the UCSF Center for AIDS packaging can also make a difference;
related to the medication. Prevention Studies, who conducts re- some people prefer to keep their med-
search on ways to improve ART adher- icines in pillboxes marked with the
STARTING OFF RIGHT ence. “The things we forget the most days of the week so they can easily
Side effects can be unpredictable— tend to be things that are negative to see if they’ve already taken that day’s
some people experience only mild nui- us or things that feel unpleasant. For doses. Some HIV-specialized pharma-
sances from new antiretroviral drugs, example, you’re probably not going to cies can package ART in pillboxes or
whereas others struggle with more forget that you have a trip to Hawaii in special daily “bubble” packaging.
FALL/WINTER 2011 BETA 27MAKING SENSE OF SIDE EFFECTS
If getting to the pharmacy to pick plain foods from the grocery store hours the nausea seemed to last. If
up your medications is problematic, (such as bread, bananas, rice, toast, you’re having diarrhea, you may want
you may want to talk to the pharma- soups, mint tea, and ginger or ginger to tally how many times you had to
cist about getting medications deliv- ale) so you already have these on rush to the bathroom. If you’re hav-
ered or mail-ordered. You may also hand if you do experience nausea or ing a rash, you may want to describe
wish to set up automatic refills and diarrhea. what it looks like and where it is.
reminder calls when your prescrip- Other things you may want to You might also describe the sever-
tions are ready. have handy are “distractors”—things ity of your side effect using a 1 to 10
Assemble your support team. that can help keep your mind off of numerical scale: “1” would describe
Your adherence plan can also in- side effects. Books, DVDs, and other a very minimal, non-bothersome side
clude sharing your situation with hobbies can help take your mind off effect; “5” would describe a moder-
other people. For example, you might your symptoms. ately bothersome side effect; and “10”
assemble a team of “medication Finally, extra time to rest is not would describe a very bothersome
cheerleaders.” These can be friends, always easy to obtain but can be ex- side effect.
family members, or other people tremely helpful. Try to plan ahead for Talk to your medical team. De-
living with HIV—anyone who might some time off work or school. scriptions in a side effect diary can
provide support as you start on your help you take the most important
new medications. IF YOU HAVE SIDE EFFECTS step: talking to your clinician and
You might ask this team to check The “Dealing with Side Effects” sec- pharmacist about your side effects.
in on you via in-person visits, phone tion on page 23 has a wealth of tips on This is especially important if you’re
calls, texts, or online. If you are tak- relieving side effect symptoms. In addi- unsure whether the side effect you
ing a drug that may cause depression tion, keeping track of your symptoms are experiencing is normal or un-
or other psychiatric side effects, you and talking about them with your usual, mild or serious. If it is not
may want to ask your support team to medical team are crucial to managing dangerous, your medical team might
watch out for these symptoms and be side effects and getting the most from encourage you to treat the side effect
prepared to help you seek assistance. your ART. symptoms with supportive therapies
Sometimes just knowing that people Keep track of your symptoms. and “wait it out.” Many common
are watching out for you and are If you are experiencing a side effect ART side effects appear quickly after
available to talk to if you’re feeling which seems pretty common (nau- starting (within days), are at their
bad (or good) can be comforting and sea, diarrhea, or fatigue) and is not worst over the first two weeks of
motivating. very severe, the supportive therapies therapy, and get better over the next
You can also ask for extra sup- mentioned above may help. It may few weeks.
port from your medical provider when also be useful to keep a “side effect di- However, an honest conversa-
starting or switching ART regimens. ary.” This can be as simple as a piece tion with your health-care providers
For example, if you get care at a busy of paper on which you write down the is extremely important. If your side
clinic or are not always able to get ap- date, note what time you took your effects feel unbearable or are keeping
pointments on short notice, you might medicines, and describe your side you from working or taking care of
arrange follow-up appointments in effect symptoms (and when you first yourself, staying with the regimen for
advance, in case you need to discuss noticed them). a month or two may not be the right
any side effects with your clinician. This type of diary can help you choice for you.
Ready your anti-side effect keep track of side effects and whether Keeping an open dialogue about
arsenal. Prior to starting or changing they are improving, getting worse, side effects is key to maintaining a
ART, gather any supportive therapies or staying the same. For example, if trusting partnership with your medi-
you might want to use. For example, you’re monitoring nausea, you may cal team so you can make the best de-
if you are worried about having nau- want to write down how many times cisions about your treatment strategy
sea, you might ask your doctor about you vomited that day, or how many and your health.
anti-nausea medications. (Make sure
you pick up any anti-nausea medi-
cines before you start your new regi- For more strategies for communicating with your clinician and getting the
men; if you do end up having nausea, best possible treatment wherever you access care, see “Making the Most of
the last thing you will want to do is
Your Medical Visits” in the Winter/Spring 2009 issue of BETA.
go back to the pharmacy!) You might
also want to stock up on soothing or
28 BETA FALL/WINTER 2011MAKING SENSE OF SIDE EFFECTS
CONCLUSION Jennifer Cocohoba, PharmD, is an as- Mallal, S. and others. HLA-B*5701 screening for hyper-
sensitivity to abacavir. New England Journal of Medicine
sociate clinical professor in the School of 358(6):568–79. February 7, 2008.
According to Geri, fear of side effects Pharmacy at the University of California,
shouldn’t stop anyone from taking HIV Mazhude, C. and others. Female sex but not ethnicity is a
San Francisco (UCSF). Since 2004, she has strong predictor of non-nucleoside reverse transcriptase
medicines. “I would tell people living worked as the clinical pharmacist for the inhibitor-induced rash. AIDS 16(11):1566–68. July 26,
with HIV to talk to other people living UCSF Women’s HIV Program, where she 2002.
with HIV,” she said. “You can ask them provides adherence support and medication Palella, F. Jr. and others. Declining morbidity and mortality
if they are on medications and ask information to patients and providers. among patients with advanced human immunodefi-
about their side effects. If you can’t ciency virus infection. New England Journal of Medicine
338(13):853–60. March 26, 1998.
ask an HIV positive person, ask an HIV Selected Sources
social worker if it would be OK to ask Palella, F. Jr. and others. Survival benefit of initiat-
Antinori, A. and others. Female sex and the use of
ing antiretroviral therapy in HIV-infected persons in
questions about the medicines. Most of anti-allergic agents increase the risk of developing
different CD4+ cell strata. Annals of Internal Medicine
the time people are going to say ‘yes’ cutaneous rash associated with nevirapine therapy. AIDS
138(8):620–26. April 15, 2003.
because they are willing to help.” 15(12):1579–81. August 17, 2001.
Panel on Antiretroviral Guidelines for Adults and Adoles-
Although medication side effects Bersoff-Matcha, S. and others. Sex differences in nevi-
cents. Guidelines for the Use of Antiretroviral Agents in
can be distressing or downright scary, rapine rash. Clinical Infectious Dieases 32(1):124–29.
HIV-1-Infected Adults and Adolescents. Department of
January 2001.
those associated with today’s more Health and Human Services. October 14, 2011. Available
d’Arminio Monforte, A. and others. Insights into the rea- at http://www.aidsinfo.nih.gov/ContentFiles/Adultand
tolerable antiretrovirals are mostly
sons for discontinuation of the first highly active antiretro- AdolescentGL.pdf. Accessed October 17, 2011.
mild, manageable, and transient—and viral therapy (HAART) regimen in a cohort of antiretroviral
Walensky, R. and others. The survival benefits of AIDS
are far outweighed by the longer-term naive patients. I.CO.N.A. Study Group. Italian Cohort
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Diseases 194(1):11–19. July 1, 2006.
March 31, 2000.
frightening experiences with side ef-
Wyen, C. and others. Cytochrome P450 2B6 (CYP2B6)
fects, Geri still manages to take her Haas, D. and others. Pharmacogenetics of efavirenz
and constitutive androstane receptor (CAR) polymor-
and central nervous system side effects: An Adult AIDS
medications every day. “That’s the phisms are associated with early discontinuation of
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thing about taking the HIV medicines,” efavirenz-containing regimens. Journal of Antimicrobial
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Kitahata, M. and others. Effect of early versus deferred
side effects, they are helping me live antiretroviral therapy for HIV on survival. New England
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HIV Testing and
HIV Health Resources
Knowing your HIV status is the first step toward staying healthy GMHC Helpline
with HIV or remaining negative. As a BETA reader, chances are you www.gmhc.org
already know your HIV status—but do your friends and family mem- 1-800-AIDS-NYC (1-800-243-7692)
bers know theirs? Not everyone knows they may be at risk for HIV, Hours: Tuesday, 2 pm to 5 pm ET; Wednesday, 10 am to 2 pm ET;
or where and how to get tested and what to do if they test positive. Friday, 2 pm to 5 pm ET
Please take advantage of these resources to help keep yourself and Project Inform HIV Health InfoLine
those you care about safe and healthy. 1-800-822-7422
Hours: Monday through Friday, 10 am to 4 pm PT
The following hotlines offer information and anonymous counseling
about HIV testing, prevention, transmission, and health.
The National Prevention Information Network, part of the U.S.
National AIDS Hotline Centers for Disease Control and Prevention (CDC), can help you or
1-800-CDC-INFO (1-800-232-4636) someone close to you find an HIV testing site, and can help answer
1-888-232-6348 (TTY) questions about HIV testing and HIV prevention.
Hours: 24 hours a day, 7 days a week
CDC National Prevention Information Network
California HIV/AIDS Hotline www.hivtest.org/contact
www.aidshotline.org 1-800-458-5231 (U.S.)
1-800-367-AIDS (Toll-free within California) 1-404-679-3860 (International)
Hours: Monday through Friday, 9 am to 4 pm PT Hours: Monday through Friday, 9 am to 6 pm ET
FALL/WINTER 2011 BETA 29You can also read
