Doctors: Side Effects of HIV Medicines Can Be Managed 

HIV drug side effects

Two patients have reportedly been cured of the HIV (human immunodeficiency virus) through bone marrow transplants intended to treat their cancer. A third was cured without the transplant. For most people, however, the disease still requires lifelong treatment, often with a combination of multiple drugs, which can lead to multiple HIV drug side effects.

The first drugs for HIV didn’t do much to prolong people’s lives, says Edwin Bosa-Osorio, MD, a family physician at Community Health of South Florida. Over time, though, researchers learned that the most effective approach to managing the disease was for patients to take an amalgam of medications. “We learned through time that the medicine cannot be just one pill or just one kind of medicine,” says Bosa-Osorio. “It has to be a combination in order to be sure that we can control this virus.”

Nowadays, you can take a single pill that combines two to three medicines that treat the virus in different ways. Taking more medications generally means more side effects, but Bosa-Osorio emphasizes that over the past decade scientists have developed combinations with fewer side effects. In January 2021, the FDA approved a monthly injection called Cabenuva. It is a combination of two HIV drugs: cabotegravir and rilpivirine.

“Side effects that are way, way better [less damaging] than they used to be,” he says.

 Still, some patients, like Masonia Traylor, a patient advocate, struggle with them. Over the past 10 years, Traylor has been prescribed several different drug regimens in hopes of finding a combination that controls her HIV symptoms without agonizing side effects like diarrhea, fatigue and weight gain. 

She’s not alone. There’s a movement to include more women in clinical trials, especially for HIV drugs. Historically, women have been underrepresented and that means doctors don’t always know how a medication is likely to affect them. 

“There is a concern that the doses are not designed for women, that we don’t know if women have different side effects ” says Monica Gandhi, MD, MPH, who works with HIV patients at the University of San Francisco General Hospital. Some of her patients adjusted their own doses, a dangerous practice that can lead to the virus developing resistance against the drugs.

 

Types of HIV Medicine and Their Side Effects

“Usually it’s within the first two weeks that they [patients] will get problems — either a headache or general ill feeling, sometimes muscle aches. And these are not very common,” says Bosa-Osorio. “It may be gastrointestinal side effects, abdominal discomfort, maybe diarrhea.”

Side effects you may experience early on with any HIV medication are diarrhea, fatigue, headache, upset stomach and liver problems. While you will recognize most side effects, liver damage usually doesn’t cause symptoms until it is severe. Because of that potential outcome, your doctor will need to regularly test your blood for signs of problems.

Gandhi says it’s important for her “to be really in touch and coach patients through” those initial stages of adjusting to a treatment.

Bosa-Osorio explains that researchers in the late 1990s found that the most effective treatments combined drugs from three different treatment classes. Each class consists of several drugs that use the same strategy to control the virus. In the late 2000s, scientists introduced a fourth class of drugs, called integrase inhibitors. The side effects of each drug class are broad, and can also be a result of pre existing conditions.

NUKES Nucleoside or Nucleotide Reverse Transcriptase Inhibitors (NRTIs, sometimes called “nukes”) 

When the virus enters your immune cells, it makes copies of its own DNA. This DNA tricks your cells into making more copies of the virus, which go on to infect more of your cells. NRTIs stop the virus from taking the first step of copying its DNA. 

The first treatment the physician prescribed Traylor was a combination of multiple NRTIs. She had been pregnant when she was diagnosed, so it wasn’t clear right away if her nausea and fatigue were due to pregnancy or the medication. After she gave birth, her symptoms continued, and she says, “I begged [the doctor] to take me off of it.”

Drugs in This Class:

  • Abacavir
  • Didanosine
  • Emtricitabine
  • Lamivudine
  • Stavudine
  • Tenofovir alafenamide (TAF)
  • Tenofovir disoproxil fumarate (TDF)
  • Zidovudine 

Side Effects Include:

  • Blood problems like anemia, which causes fatigue or decreases in white or red blood cells
  • Insomnia
  • Lactic acidosis, a dangerous buildup of lactic acid
  • Nerve problems
  • Thinning bones

What you can do:

A multivitamin with iron can reduce your risk of anemia, but other blood issues may require prescription medications. A variety of lifestyle changes and supplements, ranging from guided meditations to taking melatonin, may help you sleep

Another condition, lactic acidosis can be life-threatening. If you experience an upset stomach and vomiting, extreme exhaustion or unusual shortness of breath, see a doctor right away. 

Nerve problems can range from mild tingling in the hands and feet to severe pain. If the conditions are mild, try massages, soaking your feet in cool water, avoiding tight footwear and standing for long periods. Exercising and taking supplements like vitamin D and calcium can mitigate thinning bones.

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Like NRTIs, NNRTIs prevent the virus from copying its DNA, but they do so by blocking different proteins than NRTIs. Traylor tried a combination of two NNRTIs and one NRTI. She says she experienced diarrhea for the first time in her life, which was particularly debilitating because it made it difficult for her to travel to work. 

Drugs in This Class:

  • Delavirdine
  • Efavirenz
  • Etravirine
  • Nevirapine
  • Rilpivirine 

Side Effects Include:

  • Dry, itchy skin
  • Rash
  • Fever
  • Vomiting and abdominal pain

What you can do:

For dry, itchy skin without a rash, try moisturizer or a topical antihistamine cream. If you develop a rash, or symptoms like fever and vomiting, call your doctor right away. For diarrhea, try over-the-counter medications or ask your provider to prescribe additional drugs. If symptoms persist, you may need a different HIV medicine.

Protease Inhibitors (PIs):

Protease Inhibitors prevent the virus from breaking down into replicable proteins, another way to prevent it from infecting more cells.

Drugs in This Class:

  • Atazanavir
  • Darunavir
  • Fosamprenavir
  • Indinavir
  • Lopinavir/ritonavir
  • Nelfinavir
  • Saquinavir
  • Tipranavir

Side Effects Include:

  • Increases or decreases in metabolism and fat storage
  • Added risk of heart attacks, heart disease or stroke
  • Extra risk of diabetes

What you can do:

Your doctor will need to test your blood regularly for signs of elevated sugar or cholesterol. To reduce your risk of cardiovascular or metabolic issues, try upping your exercise activity and maintaining a low-fat diet. Your provider can also prescribe medications to help reduce your cholesterol or control diabetes. If the effects are dramatic, your doctor may change your medications.

Integrase Inhibitors:

A newer kind of drug is the integrase inhibitor. Integrase breaks the strands of your DNA, so the virus can insert its own genetic material and begin to replicate it. Integrase inhibitors prevent this step. Integrase inhibitors are thought to have fewer side effects than other HIV drugs because they work on the virus rather than our own cells. Patients do sometimes experience the side effects common to all HIV drugs, like diarrhea and fatigue.

Traylor now uses a combination that includes an integrase inhibitor. Overall, she’s experienced fewer side effects than before, but says she’s gained about 40 pounds and wonders if it’s because of the medication. Gandhi says it’s likely. “There are lots of reports of integrase inhibitors leading to weight gain, especially in combination,” she says. “The biggest fears that we have with this are that it’s not just cosmetic, but can lead to metabolic side effects,” like heart disease and diabetes. This is an example, she explains, of why it’s so important to conduct clinical trials in women; the weight gain seems to be more pronounced in women than in men. 

Drugs in This Class:

  • Bictegravir
  • Cabotegravir
  • Dolutegravir
  • Elvitegravir
  • Raltegravir

What You Can Do:

Your doctor will start by recommending diet and exercise, but if the weight gain is substantial enough to put you at risk for heart disease or diabetes, your physician may prescribe an alternative drug.

Combinations 

More recently, researchers have developed drugs that combine two to three HIV drugs in one pill in fixed dosages. They’re listed below, based on the classes of drugs included in the combination.

Drugs that only include NRTIs:

  • Trizivir: abacavir, lamivudine and zidovudine
  • Epzicom: abacavir and lamivudine
  • Descovy: emtricitabine and tenofovir alafenamide fumarate
  • Truvada: emtricitabine and tenofovir disoproxil fumarate
  • Cimduo: lamivudine and tenofovir disoproxil fumarate
  • Combivir: lamivudine and zidovudine

 Drugs that include both NRTIs and NNRTIs:

  • Delstrigo: doravirine, lamivudine and tenofovir disoproxil fumarate
  • Symfi and Symfi Lo: efavirenz, lamivudine and tenofovir disoproxil fumarate
  • Atripla: efavirenz, emtricitabine and tenofovir disoproxil fumarate
  • Odefsey: emtricitabine, rilpivirine and tenofovir alafenamide fumarate
  • Complera: emtricitabine, rilpivirine and tenofovir disoproxil fumarate

Drugs that only include a PI and a CYPA3A inhibitor (this works to increase the effect of the PI):

  • Evotaz: atazanavir and cobicistat
  • Prezcobix: darunavir and cobicistat
  • Kaletra: lopinavir and ritonavir

Drugs that include NRTIs, an integrase inhibitor, and the CYP3A inhibitor:

  • Stribild: elvitegravir, cobicistat, emtricitabine and tenofovir disoproxil fumarate
  • Genvoya: elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide fumarate

Drugs that include one or more NRTIs and an integrase inhibitor:

  • Triumeq: abacavir, dolutegravir and lamivudine
  • Biktarvy: bictegravir, emtricitabine and tenofovir alafenamide fumarate
  • Dovato: dolutegravir and lamivudine

This drug includes an NNRTI and an integrase inhibitor:

  • Juluca: dolutegravir and rilpivirine
  • Cabenuva: cabotegravir and rilpivirine

This drug includes NRTIs, a PI, and the CYP3A inhibitor:

  • Symtuza: darunavir, cobicistat, emtricitabine and tenofovir alafenamide fumarate

 

What the Future Holds  

Traylor emphasizes that it’s important that women — especially those who are pregnant and women of color — be included in clinical trials for HIV medications. In 2019, The New York Times reported on the disparity of women in HIV trials, which limits our knowledge both of how well the drugs work for women and of how differently side effects may impact women and men. The NIH started a study to compare various HIV drugs in pregnant women in 2018. Researchers recently completed the trial, but not all results have been published. 

Gandhi emphasized that many HIV specialists are at the forefront of a movement to increase the numbers of both women and pregnant women in clinical trials. “This is an infection that tends to affect women of reproductive age, because the risk factors for pregnancy are the same risk factors for HIV: sexual activity,” she says. “It has struck many of us treating HIV in women how few of the medications have been adequately studied in pregnancy.”

It’s crucial to continue taking your HIV medication even if you experience side effects, unless your healthcare provider tells you to stop. One of the reasons HIV can be so difficult to treat is that the virus mutates inside your body and can develop resistance to certain medications. Over time, if your disease worsens, you may need to change medications. However, if you skip doses, the virus may mutate faster than it normally would. It can become resistant not only to the medication you are taking, but potentially to similar drugs within that treatment class. Foregoing doses can severely limit your options. 

Bosa-Osorio acknowledges the temptation to skip doses, especially at the start of treatment, He says, “If they [patients] push through and give it enough time, almost all HIV patients wind up finding that they tolerate the medicine well without any issues.” 

Gandhi adds, “We are so lucky to have a lot of options for treatment. If they [patients] can’t tolerate their first regimen, we can adjust the medications if needed.”

 


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