How to Manage the Most Common Side Effects of Your First HIV Antiretroviral Regimen

Tips From an Activist and a Physician

Table of Contents

Ben Young, M.D.




Starting on HIV medications can be a stressful period. While most medication regimens are easy to handle, side effects occur in many people -- and if you're not prepared to deal with them, they can undermine treatment success.

Side effects are most likely to occur during the first few weeks after you've started taking HIV medications. After that, they usually fade away. If side effects are severe or they cause significant persistent disruption to normal daily activities, be sure to talk to your health care provider; in these cases, additional treatments or a switch to a different medication can usually improve the situation.

However, in many cases, there are simple steps you and your doctor can take to manage side effects during your first few weeks on treatment. You don't always have to "just deal with it."

Here are a few of the most common side effects that the average HIV-positive person might experience while on their first treatment regimen, along with some tips on how to manage them.

Anxiety and Mood Changes


What to Know: Anxiety and other mood problems are an uncommon, but occasionally reported side effect of certain HIV medications, especially Sustiva (efavirenz, Stocrin), which is part of the combination pill Atripla (efavirenz/tenofovir/FTC). (More rarely, people have reported such problems on Ziagen [Abacavir], which is contained in the combo pills Epzicom [abacavir/3TC] and Trizivir [AZT/3TC/abacavir].)

In general, while there are some steps you can take to control anxiety-related side effects, it's important to figure out whether your mood problems are being caused by the meds themselves or by other issues going on your life.

Tips to Discuss With Your Health Care Provider:

  • Consider seeking out the help of a support group, case manager or treatment counselor to help you reduce feelings of depression or stress. This will also help you and your health care provider determine how much of the problem is being caused by the meds themselves and how much is due to other issues in your life.
  • Standard anti-anxiety medications (called "anxiolytics") may reduce feelings of anxiety; these include lorazepam and alprazolam. However, note that such medicines are potentially addictive, so they ideally should only be taken for a relatively short period of time. Many psychiatrists believe that antidepressants are a better choice for long-term use.
  • If the symptoms of anxiety you feel after starting HIV medications persists for several weeks and no other cause is identified (for example, underlying mood problems or depression), then you and your doctor should talk about the possibility of switching out the offending antiretroviral for another HIV medication.

Brain Matters: Strange Dreams; Trouble Sleeping or Concentrating

What to Know: These problems are all considered central nervous system (CNS) side effects. The most common culprit is Sustiva (efavirenz, Stocrin), which is part of the combination pill Atripla (efavirenz/tenofovir/FTC). Insomnia has also been reported among a few people who started Isentress (raltegravir).


The CNS side effects of Sustiva are usually worst after you take your first-ever dose and diminish rapidly thereafter. Many people have unusually vivid dreams and some degree of insomnia (trouble sleeping) for 10 to 15 days after they start taking Sustiva, but it's rare to see this continue more than more than six weeks after starting. So be patient if you can, and see if they subside on their own.

Keep in mind that, although HIV meds can cause sleep problems, many of these problems have other causes, including behavioral/lifestyle issues and psychological issues. Sorting out the true cause of problems like insomnia can help direct the best approach for dealing with the symptoms.

Tips to Try on Your Own:

  • The more food is in your stomach, the more Sustiva is absorbed into your bloodstream, which may increase the side effects. So make sure to take the medication on an empty stomach, especially when starting out.
  • If you take Sustiva or Atripla at night (most people do), be sure you don't have any critical events scheduled in the first few mornings after you start taking the drug.
  • Try to avoid drinking or eating anything with caffeine for several hours before bedtime.
  • Try to avoid nicotine for 4 hours before bedtime.
  • Do not exercise 2-4 hours before bedtime. Also avoid bright lights, watching a computer screen or television before bedtime.
  • Relax before bedtime by reading, indulging in a bath or drinking non-caffeinated herbal teas like chamomile.
  • If you are a light sleeper, take extra steps to ensure uninterrupted sleep, such as ear plugs or an eye mask.
  • There are several effective over-the-counter drugs available that can usually be used safely for the occasional bout of insomnia, such as Advil PM, Tylenol PM or diphenhydramine (the generic name for Benadryl, an antihistamine).

Tips to Discuss With Your Health Care Provider:

  • Certain Sustiva problems can be resolved by rescheduling the dose. If it's causing insomnia, talk to your doctor or nurse about taking it in the morning instead of at bedtime (although keep in mind that the drug's other mind-altering effects can make it difficult to function during the day). If daytime drowsiness is the problem, take it earlier in the evening.
  • If over-the-counter drugs don't help you, many healthcare providers may prescribe trazodone , zolpidem (Ambien), zalepion (Sonata) or eszopiclone (Lunesta).
  • Consider being checked for sleep apnea, a disorder in which a person briefly stops breathing or breathes shallowly many times during sleep and therefore does not get enough restful sleep. (Sleep apnea is not associated with HIV medications, but it can be an issue if poor sleep and daytime fatigue were also common before you started treatment.)
  • If you still have these side effects after three weeks, let your provider know so that he/she can recommend options. If after trying different options you have no relief, then it may be time to switch to another HIV medication.


What to Know: Many HIV medications can cause it, but protease inhibitors -- especially Norvir (ritonavir) -- are particularly associated with diarrhea.


Of course, like many of the side effects we discuss in this article, diarrhea can have multiple causes. These include infections, lactose intolerance, digestive issues (such as your body not absorbing fat properly, or "malabsorption"), diet issues (such as ingesting too much sugar or caffeine) and stress.

While some degree of softer stools might be an acceptable side effect, any drug-induced diarrhea that causes a significant impact in your daily activities (when/how you eat, work or play) should prompt a discussion with your health care provider.

Tips to Try on Your Own:

  • Over-the-counter drugs like Immodium, Kaopectate and Pepto-Bismol can work for diarrhea by slowing down the activity of your gut. However, if your diet or the way you schedule your meals is contributing to your diarrhea, it's best to address those problems rather than just treat the symptoms with more drugs.
  • Drink lots of good liquids (i.e., those that are not loaded with sweeteners or caffeine) and eat plenty of healthy food to replace what's lost through diarrhea. It's easy to forget just how many nutrients are passing through your body; diarrhea can make you more prone to problems like dehydration if you don't pay attention.
  • Avoid milk-based products (including whey protein supplements) if you suspect that you may have lactose intolerance.
  • Avoid spicy foods.
  • Glutamine supplements and probiotics can be helpful, especially when used in combination. Take 1 rounded tablespoon of glutamine 3 to 5 times per day (ideally in powdered form, which you can mix with water), for a total daily dose of 30 to 40 grams. Even after your diarrhea is eliminated, consider long-term use of at least 5 to 10 grams daily.
  • Fiber supplements, such as Citrucel or Benefiber, can help, but be careful not to take them around the same time as your medications, since soluble fiber can affect how HIV medications are absorbed into your bloodstream.
  • Metamucil wafers can help: Try taking two 3 oz. wafers before bedtime.
  • Taking pancreatic enzymes (taken in a formula that also contains lipase) with meals can greatly reduce drug-induced gas and bloating and will sometimes also help reduce diarrhea.
  • Calcium carbonate (TUMS): Try 500 to 1,000 mg of calcium carbonate in the middle of meals two to three times per day, but don't go over 2,500 mg total per day.

Tips to Discuss With Your Health Care Provider:

  • In cases of severe diarrhea, a complete medical evaluation is in order.
  • If your health care provider feels it will be helpful, a prescription anti-diarrheal medications such as Lomotil can help control the problem.
  • Diarrhea can sometimes be caused by invading microbes or illnesses. If your health care provider diagnoses you with such an illness, she or he might prescribe you a medication such as metronidazole or rifaximin to treat it.
  • Ultimately, if your diarrhea doesn't go away or is severely impacting the way you live your life, and if it looks like your HIV medications are the cause, you and your doctor should discuss switching to another drug or regimen.

Fatigue (Feeling Tired, Even When You're Not Sleepy)


What to Know: Fatigue can be caused by many factors, including HIV medications. It's not too uncommon to have fatigue in the initial days of treatment, but mild to moderate symptoms often improve over time.

  • The tricky thing about fatigue is that it can have so many different possible causes. Some of them are tied to HIV medication side effects or other medications you're taking, while others may be related to physical or emotional problems you're going through.

Tips to Try on Your Own:

  • We mentioned earlier that Sustiva (which is found in Atripla) can cause sleep disturbances. Those problems can lead to daytime fatigue and lack of mental focus. If this is the case for you, try to follow the recommendations we provided previously to address sleep problems.

Tips to Discuss With Your Health Care Provider:

  • Over-the-counter supplements: Many supplements are billed as energy boosters, but not all can follow through on their promises, so approach them with caution. Among the authors of this article, Nelson is a fan of SAMe (SAM-e, S-adenosyl-methionine, or S-adenosyl-L-methionine), a naturally occurring compound that is found in every cell in the body and may offset some of the fatigue you feel, although it hasn't been tested in large clinical trials. Also talk to your doctor before taking it, since there is a risk for drug-drug interactions, including interactions with many standard antidepressants.
  • Prescription stimulants: Some physicians may prescribe drugs like armodafinil (Nuvigil), methylphenidate (Ritalin, Ritalin SR, Methylin, Methylin ER) or Adderall when other steps fail. However, there is some concerning data on the use of stimulants and increased cardiovascular risks, so it is important to talk to your doctor about this. If you and your doctor decide that stimulants are a reasonable option, you will need to review the many potential drug interactions, physical health and mental health complications that can occur.
  • If your fatigue is severe (meaning it's having a major impact on your daily life) or doesn't go away a few weeks after you've started treatment, it's important for you and your doctor to make sure that you've ruled out other possible medical causes. There are many causes (each of which has its own potential treatments), including:
    • adrenal gland problems
    • anemia
    • depression
    • heart disease
    • kidney disease
    • liver disease
    • low testosterone levels
    • poor nutrition
    • sleep disorders (including sleep apnea and restless leg syndrome)
    • thyroid disease
  • If after a careful evaluation, the only apparent cause or persistent fatigue is HIV medications, then you and your doctor can consider a switch to an alternative regimen.



What to Know: There are multiple causes of headaches that may or may not be related to HIV meds. It's important to distinguish between medication side effects and other causes. While most headaches are harmless in and of themselves (though painful), there are serious (but rare) problems that can have headaches as symptoms. To provide just a few examples, these non-medication-related causes of headache include:

  • High blood pressure
  • Magnesium deficiency (rare in general, but possible more common among HIVers)
  • Migraine or cluster headaches
  • Rarely, disorders of the brain or neck (infections, tumors, stroke, aneurysm)
  • Sleep disorders
  • Stress
  • Vision problems

Tips to Try on Your Own:

  • The most common way people treat mild headaches is with an over-the-counter medication, particularly aspirin, acetaminophen (Tylenol), ibuprofen (Advil, Motrin) or naproxen (Aleve). However, although you can do this on your own, be careful about it, and speak with your doctor if you have any concerns:
    • Be sure to stay within the recommended doses to avoid drug toxicity. Also be aware thateven over-the-counter pain relievers have their own potential risks, many of which can be in people with HIV:
    • People with active liver disease (including people with chronic hepatitis infection) should avoid the use of acetaminophen. People with low glutathione levels (common in people with HIV) should also taken acetaminophen with caution.
    • People with kidney problems, ulcers, low platelets and low serum albumin levels (common in those with wasting) should use caution when taking acetaminophen, aspirin and ibuprofen.

Tips to Discuss With Your Health Care Provider:

  • Persistent or severe headaches should be brought to the attention of your health care provider. If antiretroviral medications are the culprit and the headaches are making you miserable or having a big impact on your life, switching HIV medications will usually improve the situation if one of your current drugs is causing it.

Nausea, Upset Stomach, Vomiting


What to Know: Any HIV medication can potentially cause nausea and other related problems (called "gastrointestinal" problems).

Nausea and vomiting can be serious side effects. There are many different strategies for dealing with nausea. If you have serious nausea, especially when it's accompanied by abdominal pain, you should contact your health care provider right away. At its worst, nausea and vomiting can prevent you from digesting your meds properly, which can make your treatment less likely to succeed.

Tips to Try on Your Own:

  • Pay close attention to the dosing instructions on your HIV meds: Some meds need to be taken with a meal in order to avoid nausea, while for others an empty stomach helps.
  • Ginger. It's available in many forums, including a syrup that can be put in a beverage you can sip throughout the day; supplements (two 500-mg capsules, 2 or 3 times daily with meals); and ginger ale (brands that contain a potent blast of ginger, usually available in health food stores, work better than standard varieties). Chopped ginger root can be added to many dishes where it will add its spicy flavor along with its ability to counter nausea.
  • Eat small, frequent meals instead of two or three large ones (a full stomach makes nausea worse).
  • Munch on snacks every three hours; don't let your stomach get too empty or your blood sugar too low.
  • Crunch down on dry, salty crackers or pretzels prior to eating and taking meds. (Bonus: Salty foods are usually better to snack on than sweets.)
  • Sniff grated lemon peel or drink water with lemon in it just before eating.
  • Supplements containing "good bacteria," such as acidophilus and bifidus, can improve digestion and reduce gas.
  • Chew slowly and eat in a calm, relaxed environment.
  • Since maintaining your food and fluid intake is crucial for health, if your nausea waxes and wanes, try to be aware of the times you're feeling better. Use these times to drink lots of fluids and take in lots of protein and calories, in order to make up for the times when you don't feel as good.

Tips to Discuss With Your Health Care Provider:

  • Consult your doctor or pharmacist to determine whether it might help to take the offending HIV medication at a different time of day.
  • Anti-nausea (anti-emetic) drugs can often reduce or eliminate the problem. Ask your pharmacist to check for drug interactions before trying medications such as dronabinol, ondansetron, prochlorperazine, promethazine, trimethobenzamide , or medical marijuana (where it's legal).


What to Know: Skin rashes can occur as a side effect of many HIV medications, more commonly among people taking non-nukes (including Sustiva, which is part of Atripla; Viramune [nevirapine]; and Intelence [etravirine]) and some protease inhibitors.

skin rash

Rash is also one of the symptoms people experience if they have a hypersensitivity reaction to Ziagen (abacavir), one of the drugs in Epziom (abacavir/3TC) and Trizivir. However, this reaction is very rarely seen in people who have had a routine genetic screening test for it (called HLA B*5701) and know whether they need to avoid the drug.

Besides HIV medications, some non-antiretrovirals that are commonly taken by people with HIV (for example, Bactrim and Septra, which treat pneumonia) can make your skin sensitive to the sun and make it easier to get sunburned.

Rashes can either be localized (occurring on one specific part of your body) or generalized (occurring everywhere). Keep in mind that if your rash is localized, it's probably not a medication causing the problem -- it probably means that part of your body has come into contact with something that's irritating it.

Most rashes that develop after starting a new medication are caused by an allergic reaction to the medication, and they'll worsen with each dose that you take. If this happens to you, it should prompt a call to your health care provider.

Tips to Discuss With Your Health Care Provider:

  • If your rash is mild, it may not require you to stop or switch your HIV medications. If you tell your provider quickly, she or he can usually help prevent them from getting serious (and can hasten their improvement, too).
  • Signs of a serious drug allergy usually include more than just a rash: There can be fever, shortness of breath, oral sores, nausea and vomiting -- though not necessarily all of these symptoms have to happen in order for you to be having a severe allergic reaction. If you feel any of these symptoms during the first few days after you begin treatment, you should contact your healthcare provider immediately.