Side Effects

• Lactic acidosis
• Hepatotoxicity
• Lipodystrophy
• Dyslipidemia
• Hematologic Complications
• Hyperglycemia
• Osteopenia and Osteoporosis
• Rheumatic and Hypersensitivity Reactions
• Toxic neuropathy
• Dermatologic events

Many antiretroviral drugs have been "fast tracked" out of a compassionate concern for the suffering public. Fast tracking limits the amount of study that can be done. Special populations such as women, pregnant women, elderly, children and people with co-morbidities have not been fully studied.

Further complicating the subject of antirertoviral therapy side effects is the fact that current treatment guidelines support combining ARTs to increase efficacy and limit the viral resistance. To date the safety of combining many antiretroviral drugs has not been thoroughly studied.

Caregivers need to assimilate safety data as it becomes available. We must remain vigilant for side effects both expected and unexpected. Contributing to the accumulation of drug safety data for antiretrovirals is possible through a number of Therapeutic Drug Monitoring Registries:

• Multi-Sponsor Registry to Detect Any Major Teratogenic Effect Involving Any of the Registry Drugs When Administered to Pregnant Women.
• HIV Drug Resistance Database - Stanford University

Instant Feedback:
The most serious side effects of antiretroviral drugs are described in "black box" warnings.

All NRTIs are associated with lactic acidosis, hepatomegaly with stetosis and lipodystrophy. Lactic acidosis is a condition which causes damage to organs such as the liver and pancreas due to accumulation of excess lactic acid in blood and body tissues. Lactic acidosis results from the toxic effect of NRTIs on mitochondria. Damaged mitochondria become unable to metabolize lactic acid.

While lactic acidosis can be fatal if not treated, the initial symptoms of lactic acidosis can be quite mild. The most common symptoms of lactic acidosis include: fatigue, nausea, vomiting, abdominal pain and bloating, weight loss, increased heart rate, and shortness of breath. Muscle weakness or numbness in the feet or hands may also occur. Nausea and fatigue, that don’t resolve, are important signs of potential lactic acidosis. Because lactic acidosis can result in death, patients must be familiar with symptoms and bring them to their caregiver's attention ASAP.

N/V/D/HA Nausea/vomiting/diarrhea/headache

Side effects associated with protease inhibitors (PIs):

Protease Inhibitors are an important part of the HAART protocols. Current ART guidlines discourage the use of PIs as a monotherapy. Therefore, the severity of PI side effects will vary depending upon the combined drug regimen. The most common side effects attributed to protease inhibitors are: nausea, diarrhea, and other gastrointestinal problems, lipodystrophy, hepatotoxicity, hyperglycemia, hyperlidemia, coagulopathy.

Because protease inhibitors also affect an enzyme system in the liver that metabolizes drugs, they produce a number of other side effects when they interact with other medications. PIs may also elevate triglyceride levels and alter glucose metabolism.

The alterations in glucose metabolism may progress to Type 2 diabetes. PI induced hyperglycemia can exacerbate gestational diabetes.

Side effects associated with nonnucleoside reverse transcriptase inhibitors (NNRTIs):

This group of medications are relatively well tolerated. Skin rash is a major side effect of all drugs in this group. /p>

NNRTI	Side Effects
Efavirenz	Common - dizziness, altered dreams, sleeplessness, trouble concentrating, rash Rare - hepatotoxicity, congenital defects.
Nevirapine	Common - hepatotoxicity, rash Rare - severe to fatal hepatotoxicity, Stevens-Johnson syndrome or toxic epidermal necrolysis , peripheral neuropathy, women are at higher risk for adverse effects
Delavirdine	Common - moderate rash, fever, myalgia, arthralgia Rare - toxic epidermal necrolysis, hepatotoxicity

Side effects associated with fusion inhibitors:

Enfuvirtide (Fuzeon) is used in combination with other medication. It has not been studied in pregnant women.

Side effects associated with entry inhibitors:

Reference

Common and/or Severe Adverse Effects Associated with Antiretroviral Therapy. NIH. (n.d.). https://clinicalinfo.hiv.gov/en/table/table-17-common-andor-severe-adverse-effects-associated-antiretroviral-therapy.