(RITA!)HIV Treatment Alerts: Emergencies in HIV-infected people - July 2001
Edgardo Li-Espino, MD, Hilda Cuervo, & Roberto C. Arduino, MD
The University of Texas–Houston Medical School

Human immunodeficiency virus (HIV) is associated with several diseases that may be life threatening and need quick intervention by health care workers. These emergencies could be related to complications from the use of anti-HIV medication or to opportunistic infections that occur as the immune system gets weaker. This article summarizes some conditions that can be considered medical emergencies in HIV-infected individuals.

EMERGENCIES RELATED TO HIV THERAPY

Lactic Acidosis

The term "mitochondrial toxicity" describes a group of different clinical conditions that happen because of damage to parts of the cell called mitochondria. (The mitochondria are the energy factories inside cells.) One possible cause of damage to mitochondria may be anti-HIV drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). The most serious condition that can result from such damage is lactic acidosis (an increase of lactic acid in the blood). Lactic acidosis has been reported in patients receiving NRTI regimens including combinations of AZT (Retrovir) or d4T (Zerit) with ddI (Videx), ddC (Hivid), or 3TC (Epivir).

Lactic acidosis may or may not start suddenly. The initial symptoms may include nausea, vomiting, abdominal pain, weight loss, malaise, fatigue (feeling tired), shortness of breath, and occasionally fever. In addition, the patient may experience diarrhea, tachycardia (fast heart beat), and tachypnea (fast breathing). Laboratory tests usually show a high amount of lactic acid in blood, somewhat abnormal liver function tests, and moderate to severe acidosis. The management of lactic acidosis should include stopping anti-HIV drugs, and correction of these abnormalities. Patients may need to receive bicarbonate and glucose intravenously (into a vein). Treatment with riboflavin might help in some cases. As many as 60% of patients with lactic acidosis can die from it.

Abacavir hypersensitivity reaction

The use of the NRTI abacavir (Ziagen) can cause a serious hypersensitivity reaction in a small number of patients (about 3.6%). This drug is also found in a pill called "Trizivir," which combines abacavir with 3TC and AZT. The symptoms of abacavir hypersensitivity include fever, skin rash, nausea, vomiting, diarrhea, abdominal pain, malaise, and lethargy (sleepiness). Usually a hypersensitivity reaction will start within the first 6 weeks of taking abacavir. If a patient develops these symptoms, the abacavir should be stopped immediately. Whether hypersensitivity is suspected or confirmed, abacavir should never be restarted, as it may cause a more severe hypersensitivity reaction along with hypotension (low blood pressure), tachycardia (fast heart beat), and even death.

Indinavir-induced nephrolithiasis

Indinavir (Crixivan) tends to form crystals in the kidneys. These crystals can form kidney stones made up almost completely of this protease inhibitor. This can happen in 4% to 22% of patients treated with the standard dose of indinavir (800 mg three times a day). Patients with indinavir stones can feel like those with other kinds of kidney stones: pain on the sides, hematuria (blood in urine), nausea, and vomiting. The confirmation of kidney stones may be difficult because indinavir-containing stones are not visible using plain radiography or non-contrast CT scans. Most patients will respond to conservative treatment that includes intravenous fluids, pain control, monitoring kidney function, and discontinuation of indinavir. To prevent kidney stones caused by indinavir, patients should take more liquids—a minimum of 1.5 liters per day of non-caffeinated, non-alcoholic liquids.

Rash by non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Maculopapular rash. NNRTIs sometimes can cause a maculopapular rash (a rash made up of small, well-defined bumps on the skin). NNRTIs include delavirdine (Rescriptor), nevirapine (Viramune), and efavirenz (Sustiva). In clinical trials, 37% of patients treated with nevirapine and 27% of patients treated with efavirenz developed a rash. The rash can affect the trunk, face, arms, and legs. It usually appears within the first 4 to 6 weeks of taking the medication.

Stevens-Johnson syndrome. This is the most dramatic form of rash caused by NNRTIs. This severe and life-threatening rash can affect the skin but also mucosal surfaces (like inside the mouth or nose). It is sometimes known as toxic epidermal necrolysis. Up to 8% patients treated with nevirapine and less than 1% of patients treated with efavirenz may experience this type of rash. The symptoms are a diffuse rash with peeling of large areas of the skin, blistering inside of the mouth, conjunctivitis (swelling and reddening of the eyes), bronchitis, and general symptoms including fever, myalgia (muscular pain), arthralgia (joint pain), and malaise. This condition is an extreme emergency and most of the time patients are treated in burn units where close medical observation is necessary.

EMERGENCIES RELATED TO OPPORTUNISTIC INFECTIONS

Ocular (Eye) Emergencies

Cytomegalovirus (CMV). Retinitis caused by CMV is the most common vision-threatening condition in people with AIDS. When it starts, the T cell counts are typically below 50. About 50% to 75% of the patients complain of blind spots, visual field loss, flashing lights, floaters, or decreased or blurred vision. The goal of treatment of CMV retinitis is to slow down the progression of the disease, prevent further spread of the infection in the retina, and preserve visual function. Currently, 3 drugs have been approved for the treatment of this condition: ganciclovir, foscarnet, and cidofovir. All of them are given in 2 steps. Initially, a high dose of the anti-CMV medication is given to control the infection and afterwards a lower dose is given for maintenance to prevent another infection.

Varicella zoster virus (VZV). VZV infection is the second most common eye condition in HIV-infected people. The virus causes shingles around the eyes, which can affect 3% to 4% of patients with HIV infection. VZV may also affect the retina causing 2 different conditions. The first is acute retinal necrosis (a rapid deterioration of the retina) that can occur at any stage of HIV infection. Patients with this condition may have a history of cutaneous shingles occurring either before or at the same time as the retinitis. The treatment is acyclovir for 10 to 14 days followed by long-term suppression (usually with a lower dose to prevent the infection from coming back). The second syndrome occurs in patients with T cell counts typically less than 50 and is known as progressive outer retinal necrosis syndrome. Approximately two thirds of patients with this disease will develop it in both eyes. This disease is different from acute retinal necrosis syndrome. The treatment for this form of Varicella zoster retinitis is difficult and seems not to respond to intravenous acyclovir or other forms of treatment with one medication only. A majority of patients (70%) with this syndrome will develop retinal detachment resulting in poor vision.

Pulmonary (lung) emergencies

Pneumocystis carinii pneumonia (PCP). The pneumonia caused by the microorganism Pneumocystis carinii is the leading AIDS-defining condition in the United States, and perhaps one of the most common HIV-related emergencies. The most important risk factors for the development of this opportunistic infection are T cell counts less than 200 and a history of thrush. In the patient, PCP causes fevers, an increasing shortness of breath when an effort is made, and a dry cough. Extreme fatigue usually accompanies these symptoms. Rapidly changing fevers, chills, shaking, and purulent sputum are common in bacterial infections, but not in PCP. The chest x-ray is the most important test for the diagnosis of PCP. The examination of sputum is a simple, inexpensive, and effective means to confirm the diagnosis. If sputum is not diagnostic, special medical procedures like a bronchoscopy with bronchoalveolar lavage (BAL) may be performed. Trimethoprim-sulfamethoxazole (Bactrim) is the drug of choice for the treatment of PCP. It is given for 21 days followed by prophylactic therapy to prevent the high likelihood of PCP happening again. The drug is available as tablets, suspension, and intravenous solution. The most frequent side effects include rash, fever, and abnormal laboratory tests. If the patient has an allergy to sulfa drugs, alternative regimens include intravenous pentamidine, trimethoprim and dapsone, clindamycin and primaquine, or atovaquone and trimetrexate. In cases of severe PCP, the use of corticosteroids has clearly decreased clinical failures and lowered death rates.

Bacterial pneumonia. Bacterial pneumonia is much more common in HIV-infected persons than in HIV-negative persons. Several studies show a direct relationship between bacterial pneumonia and the degree of immunosuppression estimated by T cell counts. Also, the possibility of getting bacterial pneumonia is increased among smokers and injection drug users. People with bacterial pneumonia usually have fever, chills, sputum production, shortness of breath, and an abnormal chest x-ray.

Central nervous system emergencies

Cerebral toxoplasmosis. Toxoplasma gondii, a parasite, is the most common cause of focal brain lesions in people with AIDS. The definitive host of this parasite is the cat, but the parasite spreads to humans when eggs are ingested in raw or undercooked meats, particularly lamb and pork. Almost all cases of cerebral toxoplasmosis in people with AIDS are the result of reactivation of an infection that may have occurred much earlier, but was kept under control by the healthy immune system. The risk of reactivation increases as the T cells decrease, with the highest risk in persons with T cell counts less than 50. Patients with cerebral toxoplasmosis complain of headache, confusion or altered mental status, and fever (in about half the cases). Up to 50% of patients with this infection may develop seizures as an initial sign of the disease, and even more will have a stroke. The diagnosis is based on the clinical findings, low T cell count, evidence of the infection in the blood (positive IgG antibodies against Toxoplasma), and CT scan or MRI of the head. Treatment for cerebral toxoplasmosis consists of a combination of pyrimethamine, sulfadiazine, and folinic acid. Alternative therapies for patients with allergies to sulfa drugs include pyrimethamine and folinic acid, in addition to one of the following: clindamycin, clarithromycin, dapsone, or azithromycin. Improvement is expected after 7 to 10 days of therapy. If no improvement is seen by then, a brain biopsy is recommended.

Cryptococcal meningitis. Cryptococcus neoformans is the most common fungus responsible for infections in patients with AIDS. The most severe type of cryptococcal infection is chronic meningitis. The symptoms may include headaches, fever, altered mental status, nausea, vomiting, or malaise. All these symptoms usually increase and decrease over the course of 2 or 3 weeks before the diagnosis is made. A serum cryptococcal antigen test may be used to screen HIV-infected patients with these nonspecific symptoms and low T cell counts. A spinal tap is the preferred diagnostic procedure. The level of cryptococcal antigen in cerebrospinal fluid (CSF) or a CSF fungal culture provides a definite diagnosis. Treatment of HIV-associated cryptococcal meningitis is with intravenous amphotericin B for 2 weeks with or without flucytosine, followed by oral fluconazole for 8 to 10 weeks. Once this therapy is finished, patients will have to stay on suppressive therapy with oral fluconazole. Increased intracranial pressure (pressure inside the head) may be frequent and could be a life-threatening complication of acute cryptococcal meningitis that may require a series of spinal taps or the placement of a special shunt to help relieve pressure.

EMERGENCIES RELATED TO IMMUNE RECONSTITUTION SYNDROMES

The arrival of highly active antiretroviral therapy (HAART) has made it possible to control HIV viral load, allowing at least a partial recovery of the immune system. This partial recovery is sometimes called "immune reconstitution." One benefit of this recovery is an increase in T cells, but this can lead to a strong immune response to opportunistic infections that were hidden. A number of conditions have been described, some of which may represent medical emergencies in HIV-infected persons.

Patients co-infected with HIV and Mycobacterium tuberculosis (turberculosis or TB) who are receiving HAART and drugs against tuberculosis may develop severe inflammatory reactions including fever, worsening of pulmonary conditions, shortness of breath, and enlargement of lymph nodes or cerebral masses (tuberculomas). Similar kinds of reactions have been described with CMV, Mycobacterium avium complex (MAC) infections, and hepatitis C infections. In certain circumstances, corticosteroids are recommended to treat the acute symptoms associated with restored immune function.

Table 1. Emergencies in HIV-infected people Emergencies related to HIV-therapy Lactic acidosis Abacavir hypersensitivity reaction Indinavir-induced nephrolithiasis Rash by NNRTI Maculopapular rash Stevens-Johnson Syndrome Emergencies related to opportunistic infections Ocular emergencies Cytomegalovirus retinitis Varicella zoster Pulmonary emergencies Pneumocystis carinii pneumonia Bacterial pneumonia Central nervous system emergencies Cerebral toxoplasmosis Cryptococcal meningitis Emergencies related to immune reconstitution syndrome

 

Remember this!

Midazolam (Versed) is a drug commonly used for general anesthesia in outpatient surgery and other routine medical procedures where the patient must be "knocked out." If you are taking any of the following anti-HIV drugs, be sure to remind your doctor, nurse, etc. These drugs have interactions with midazolam that can put you into a coma! The reason this happens is competition between the anti-HIV drugs and midazolam, causing the midazolam to build up in the body. The result is like getting an overdose of midazolam. Although your health care provider should always check for drug interactions, it never hurts to remind him or her. Another anesthetic agent can be substituted for the midazolam.

• Amprenavir (Agenerase)
• Delavirdine (Rescriptor)
• Efavirenz (Sustiva)
• Indinavir (Crixivan)
• Lopinavir/ritonavir (Kaletra)
• Nelfinavir (Viracept)
• Ritonavir (Norvir)
• Saquinavir (Fortovase or Invirase)

 

Acidosis: excess production of acid in the body that usually produces symptoms of sweet breath, headache, nausea and vomiting, and vision problems.

Acute: beginning suddenly or severely (as in a disease); progressing rapidly.

Antigen: a substance that stimulates an immune response (usually a foreign substance related to a disease).

Biopsy: a sample of tissue or fluids from a living body.

Cerebral: relating to the brain.

Chronic: lasting over a long period of time.

Cutaneous: relating to the skin.

Floaters: debris (like a dead cell) in the liquid of the eye that may be seen as a spot in the visual field.

Fungus: a type of organism that includes molds and mushrooms and lives off of living or dead material.

Lactic acid: a substance in blood and muscle tissue produced by the body when it is processing sugar for energy (usually when exercising or in the absence of sufficient levels of oxygen).

Lesion: an abnormal change to an area of the body, usually a well-defined mark.

Liver function tests: blood tests that can measure levels of liver proteins in the blood and detect stress or disease of the liver.

Malaise: a feeling of weakness or sickness that usually accompanies disease.

Microorganism: an organism that can only be seen with a microscope, like bacteria.

Necrosis: the death of living tissue.

Opportunistic infection: a disease caused by an organism that is usually harmless, but becomes activated when a person's immune system is impaired or damaged.

Parasite: an organism living with, in, or on another living creature.

Prophylactic: preventing the spread or occurrence of disease.

Pulmonary: relating to the lungs.

Purulent: containing pus, such as that produced during an infection.

Retinitis: inflammation of the retina of the eye, which helps turn light into visual messages for the brain.

Shingles: reactivation of the virus that causes chicken pox, usually affecting nerves and causing radiating feelings of pain.

Sputum: saliva and discharge that can be coughed up, usually during an infection.

Stroke: a rupture or clot of a blood vessel in the brain that can cause a loss of sensation, movement, or consciousness.

Sulfa drugs: a type of bacteria-inhibiting drug.

Thrush: a disease caused by a fungus that usually causes white patches inside the mouth.

Toxicity: the quality of being poisonous or damaging.

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Copyright © 2001 - Research Initiative Treatment Action (RITA!). Reproduced with permission. RITA! is published by The Center for AIDS. Contact Thomas Gegeny, MS, ELS, Editor, RITA! for permission to reproduce RITA!. tom@centerforaids.org. http://www.centerforaids.org

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