eMedicine Specialties > Neurology > Neurological Infections
HIV-1 Associated Myopathies
Updated: Feb 23, 2007
Introduction
Background
HIV-associated myopathies fall into several categories, including polymyositis and dermatomyositis, zidovudine (AZT) myopathy and rhabdomyolysis, nemaline (rod) myopathy, HIV wasting syndrome with type II muscle fiber atrophy, myopathy caused by local neoplasm, myopathy caused by local infection, myasthenic syndrome and chronic fatigue, and diffuse infiltrative lymphocytosis syndrome (DILS). HIV-wasting syndrome and opportunistic muscle infections are encountered in untreated patients, while treated patients may develop inflammatory myopathy related to immune restoration or drug-induced muscle involvement.
Pathophysiology
HIV induces muscle fibers to express major histocompatibility complex 1 (MHC-1) triggering cell-mediated muscle fiber injury. Particular types of myopathies reflect the clinical stage of the patient.
Possible disease mechanisms include the following:
- Polymyositis and dermatomyositis - Autoimmunity
- Drug effect - AZT and didanosine
- Secondary neoplasm - Lymphoma and Kaposi sarcoma
- Myasthenic syndrome and chronic fatigue - Autoimmune
- Rhabdomyolysis - Opportunistic infection, HIV, didanosine, lamivudine
- Secondary infection - Viruses (eg, cytomegalovirus [CMV]), parasites (eg, Toxoplasma gondii), fungi (eg, Cryptococcus neoformans, microsporidia), and bacteria (eg, Staphylococcus aureus, Mycobacterium avium-intracellulare, Escherichia coli)
- Malnutrition and vitamin deficiencies
- HIV muscle wasting syndrome - Elevated levels of 2 proinflammatory cytokines produced by macrophages and induced by HIV, cachectin, and tumor necrosis factor (may interfere with lipid metabolism in muscle)
- Diffuse infiltrative lymphocytosis syndrome - Persistent CD8 hyperlymphocytosis and multivisceral CD8 T-cell infiltration
Frequency
United States
According to some studies, up to 25% of AIDS patients suffer from a myopathic disease. In one study, mild inflammation, type II fiber atrophy, or evidence of denervation was detected in more than half of asymptomatic, untreated, HIV-seropositive patients without weakness. In another study, myalgias were present in 8% of patients treated with AZT. Other estimates of the frequency of AZT myopathy reach 17%.
Clinical
History
- Early HIV infection
- Nemaline rod myopathy - Slowly progressive weakness and wasting, negative family history, possibly autoimmune
- Immune-mediated polymyositis and dermatomyositis - Similar presentation as in non-HIV patients; usually generalized symptoms, occasionally focal ;polymyositis also possible as part of highly active antiretroviral therapy (HAART)–associated immune reconstitution syndrome
- Early or late HIV infection
- AZT myopathy - Fatigue, proximal muscle pain, and weakness, especially after a lifetime dose greater than 200 g
- Rhabdomyolysis - Same as in non-HIV population; caused by didanosine, other drugs, intercurrent illnesses (eg, CMV), or possibly HIV itself; at times associated with seroconversion
- Late HIV infection
- Myopathy caused by local infection - Focal or multifocal painful swollen muscles, fever
- Myopathy caused by local neoplasm - Painful swollen muscles, low-grade fever, HIV wasting syndrome (painless proximal weakness, fatigue)
Physical
- Polymyositis and dermatomyositis - Physical findings as in non-HIV patients
- Nemaline rod myopathy - Weakness and atrophy
- AZT myopathy - Proximal weakness and atrophy, myalgia, muscle tenderness
- Rhabdomyolysis - Same as in non-HIV population
- HIV wasting syndrome - Proximal weakness and atrophy in the setting of significant weight loss, diarrhea, and fever
- Myopathy caused by local neoplasm - Local or multifocal pain and swelling, fever
- Myopathy caused by local infection
- Local or multifocal pain and swelling, fever
- Sepsis, fluctuance, and destruction of involved muscles in late stages
- Myasthenic syndrome-myasthenia gravis - Reported occasionally; manifests as fluctuating weakness improving with immunosuppression
- Diffuse infiltrative lymphocytosis syndrome - Parotid gland enlargement, multiorgan infiltration, polyneuropathy, and polymyositis
Differential Diagnoses
Dermatomyositis/Polymyositis
Endocrine Myopathies
Focal Muscular Atrophies
Inclusion Body Myositis
Other Problems to Be Considered
Hereditary adult-onset myopathies
Viral myositis
Deep venous thrombosis
Rhabdomyolysis caused by severe illness
Non-Hodgkin lymphoma
Workup
Laboratory Studies
- Serum creatine kinase
- Polymyositis and dermatomyositis - Normal or high
- AZT myopathy and rhabdomyolysis - High
- HIV wasting syndrome - Normal
- Infectious or neoplastic focal myopathy - Normal or high
- Possible elevation of other muscle enzymes (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase)
- Electromyography and nerve conduction studies
- Myopathic (brief, low-amplitude, polyphasic) motor unit potentials, increased insertional activity and spontaneous activity
- Positive sharp waves
- Fibrillation potentials
- Often associated neuropathic features
- Blood cultures occasionally positive in pyomyositis
- Minor salivary gland biopsy and gallium Ga 67 scintigraphy - Major diagnostic help when DILS is suspected
Imaging Studies
- Radiologic studies (eg, CT, MRI with contrast,67 Ga scan, ultrasound) are helpful when pyomyositis is suggested.
- MRI may distinguish infectious and neoplastic myopathies.
- Infection - No changes in subcutaneous tissue
- Lymphoma and Kaposi sarcoma - Cutaneous and subcutaneous involvement
Procedures
- Muscle biopsy may be required to distinguish different etiologies and guide treatment.
- Needle aspiration may be diagnostic in pyomyositis.
Histologic Findings
Muscle biopsy permits histologic differentiation of various clinical phenotypes and identification of causative infectious agents by staining and culture. HIV rarely is identified by in situ hybridization or electron microscopy in infiltrating inflammatory cells and never in muscle fibers. Several types of pathology may coexist (eg, polymyositis, AZT myopathy).
- Polymyositis - Fiber necrosis, inflammatory infiltrates of CD8+ lymphocytes and macrophages
- AZT myopathy - Myopathic changes, dose-dependent numbers of ragged red fibers, cytochrome C oxidase-negative fibers, rods, lipid and glycogen accumulation, inflammatory infiltrates, paracrystalline mitochondrial inclusions, decreased numbers of mitochondria (reversible over several months, if AZT administration is stopped)
- Nemaline rod myopathy - Muscle fiber necrosis, variable inflammation, red-blue cytoplasmic structures in small type I fibers best observed in Gomori trichrome stain
- Neoplastic myopathy - Evidence of lymphoma or Kaposi sarcoma
- Infectious myopathy - Histologic evidence for the responsible organism, frank pus, or positive cultures; necrotic or degenerating fibers; inflammatory infiltrates
- Diffuse infiltrative lymphocytosis syndrome - Histological confirmation of CD8 T-cell infiltration; presence of thin intranuclear inclusion helps distinguish DILS-associated myositis from polymyositis
Treatment
Medical Care
- Polymyositis and dermatomyositis improve with steroids.
- In AZT myopathy, discontinue AZT or decrease dose and begin administration of an alternative drug. Muscle enzymes and strength return to normal 1-2 months after the drug is discontinued.
- Carnitine has been shown to prevent development of this condition and progression of AZT myopathy when already present.
- In didanosine-induced rhabdomyolysis, discontinue didanosine.
- Patients with nemaline myopathy have responded to steroid therapy.
- Myasthenic syndrome is treated similar to myasthenia gravis, with steroids, intravenous immunoglobulin G, pyridostigmine, and HAART.
- Corticosteroids are effective in treating life-threatening DILS manifestations, including rapidly progressive neuromuscular complications.
Medication
Treatment of HIV-associated myopathies critically depends on establishing a firm diagnosis. One patient may benefit from discontinuing AZT, another from steroid treatment for polymyositis, while yet another requires tuberculostatic therapy.
For HIV-associated polymyositis, pulsed IV methylprednisolone is preferable to long-term oral prednisone to minimize immunosuppression. (See Dermatomyositis/Polymyositis for further information.)
A 3-drug regimen combination (rifabutin, clarithromycin, ethambutol) is the treatment of choice for Mycobacterium avium-intracellulare myopathy. The treatment is suppressive and not curative and as a result, it must continue for life.
An alternate 4-drug regimen consists of rifampicin, clofazimine, ciprofloxacin, and ethambutol. In the situation of a relapse that is not caused by noncompliance or insufficient dosing, clarithromycin alone or combined with pyrimethamine, sulfadiazine, and minocycline may be used.
In treating CMV myopathy, either ganciclovir or foscarnet is recommended. Use a ganciclovir-foscarnet combination in cases of prior therapy. Prompt initiation is essential.
Use the combination of pyrimethamine/sulfadiazine to treat toxoplasma myopathy. To prevent bone marrow suppression, folinic acid is recommended. Treatment often continues for life.
Antibiotics for tuberculous myositis
Empiric antimicrobial therapy should cover all likely pathogens in the clinical setting. Antibiotic combinations are recommended to prevent the emergence of resistant strains and to provide an additive or synergistic effect.
Rifabutin (Mycobutin)
An ansamycin antibiotic that inhibits DNA-dependent RNA polymerase and thus transcription initiation in susceptible strains.
Dosing
Adult
300-600 mg PO qd
Alternate dose: 10-20 mg/kg/d, not to exceed 600 mg/d; to reduce adverse GI affects, dose bid and administer with food
Pediatric
Not established
Suggested dose: 5 mg/kg/d PO; to reduce GI adverse effects, dose bid and administer with food
Interactions
Steady-state plasma levels may decrease after repeated dosing; does not affect inhibition of HIV by zidovudine
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Periodically perform hematologic studies since rifabutin may be associated with neutropenia and thrombocytopenia
Clarithromycin (Biaxin)
Reversibly binds to the P site of the 50S ribosomal subunit of susceptible organisms; may inhibit RNA-dependent protein synthesis by stimulating the dissociation of peptidyl tRNA from ribosomes.
Dosing
Adult
2 g PO qd/bid
Pediatric
7.5 mg/kg PO bid
Interactions
Coadministration with fluconazole may increase clarithromycin levels significantly; coadministration with pimozide may result in toxic clarithromycin levels and possibly death; antimicrobial effects of clarithromycin may decrease when taken with rifabutin or rifampin, while frequency of GI adverse effects may increase; monitor anticoagulant function in patients receiving anticoagulants concurrently with any macrolide antibiotic
Cardiovascular adverse effects, including death, cardiac arrest, torsades de pointes, and other ventricular effects, may occur when astemizole and clarithromycin are taken concurrently; plasma levels of certain benzodiazepines may increase, prolonging CNS depressant effects; carbamazepine concentrations may increase when taken concurrently with clarithromycin
Serious cardiac arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsades de pointes, QT interval prolongation) may occur when cisapride is taken concomitantly with clarithromycin; in more than 10% of patients, serum digoxin concentrations may increase as a result of antibiotic's effects on gut flora that metabolize digoxin; disopyramide plasma levels may increase when taken concurrently with clarithromycin, causing arrhythmias and increasing QTc intervals; acute ergot toxicity (characterized by severe peripheral vasospasm and dysesthesia) may occur when taken concurrently with clarithromycin; monitor patients receiving ergot alkaloids and any macrolide antibiotic; risk of severe myopathy or rhabdomyolysis associated with HMG CoA inhibitors may increase when taken concurrently with clarithromycin
Coadministration of omeprazole and clarithromycin may increase plasma levels of both drugs; concurrent use of tacrolimus and clarithromycin may be associated with elevated serum tacrolimus levels, increasing risk of adverse effects such as nephrotoxicity
Contraindications
Documented hypersensitivity; in patients taking pimozide, astemizole (recalled from US market), cisapride, or terfenadine (recalled from US market)
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Not recommended in combination with ranitidine or bismuth citrate therapy with a creatinine clearance below 25 mL/min; no dose adjustment is necessary with hepatic impairment and normal renal function; regardless of hepatic impairment, halve the dose or double the dosing interval when creatinine clearance is below 30 mL/min; pseudomembranous colitis may occur (as with nearly all antibacterial agents); consider this when diarrhea occurs after treatment; prolonged or repeated use of antibiotics may result in bacterial or fungal overgrowth of nonsusceptible organisms and a secondary infection; take appropriate measures if this occurs
Ethambutol (Myambutol)
Diffuses into actively growing mycobacterium cells and inhibits synthesis of one or more metabolites, thus causing impairment of cell metabolism, arrest of multiplication, and cell death; no demonstrated cross-resistance with other agents; in patients who have received previous therapy, mycobacterial resistance to the initial drugs is frequent; can be useful when administered with at least one of the second-line drugs that were not previously used and with proven bacterial susceptibility to these agents.
Dosing
Adult
15-25 mg/kg PO qd
Pediatric
<13 years: Not recommended
>13 years: Administer as in adults
Interactions
Aluminum salts may delay and reduce absorption; delay administration by several hours
Contraindications
Documented hypersensitivity; in optic neuritis, unless benefit outweighs risk
Precautions
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Patients with decreased renal function require reduced dosage; may have adverse effects on vision, which generally are reversible after prompt discontinuation
Clofazimine (Lamprene)
Inhibits mycobacterial growth and binds preferentially to mycobacterial DNA but always should be used with other antibiotics.
Dosing
Adult
100 mg PO qd
Pediatric
Not established
Interactions
Some reports suggest that dapsone may inhibit anti-inflammatory activity
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Severe abdominal symptoms and signs may require exploratory laparotomies; caution in patients who have GI problems (eg, abdominal pain, diarrhea); skin discoloration may result in depression or even suicidal ideation; for skin dryness and ichthyosis, apply oil to the skin
Rifampin (Rifadin, Rimactane)
Inhibits DNA-dependent RNA polymerase activity in susceptible cells; specifically, interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme; cross-resistance has been demonstrated only with other rifamycins.
Dosing
Adult
550-600 mg PO/IV qd
Pediatric
10-20 mg/kg PO/IV qd, not to exceed 600 mg qd
Interactions
Induction of microsomal enzymes may decrease therapeutic effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, and digoxin; a significant increase in blood pressure is reported in patients on enalapril and rifampin; hepatotoxicity and hepatic encephalopathy can occur when rifampin and isoniazid are given after halothane anesthesia; isoniazid and rifampin coadministration may result in a higher rate of hepatotoxicity than with either agent alone; discontinue one or both agents if alterations in LFTs occur
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Obtain a CBC prior to and periodically throughout therapy; because of possible transient transaminase and bilirubin rise, obtain blood for baseline values before dosing; liver failure can lead to death in patients who receive rifampin with other hepatotoxic agents; since an increased risk may exist for individuals with liver disease, weigh benefits against risk of further liver damage; thrombocytopenia may occur, primarily with high-dose intermittent therapy, after resumption of interrupted treatment but is rare during well-supervised qd therapy; this is reversible if the drug is discontinued as soon as purpura occurs; cerebral hemorrhage and fatalities have occurred when rifampin is continued or resumed after appearance of purpura
Ciprofloxacin (Cipro)
Inhibits DNA-gyrase in susceptible organisms, inhibiting relaxation of supercoiled DNA and promoting breakage of dsDNA; useful against some mycobacterium strains in combination with rifampin.
Dosing
Adult
750 mg PO bid
Pediatric
<18 years: Not established
Interactions
Antacids, iron, and zinc salts may interfere with GI absorption of fluoroquinolones, resulting in decreased serum levels; administer antacids 2-4 h before or after fluoroquinolone; cimetidine may interfere with elimination of fluoroquinolones; ciprofloxacin may reduce phenytoin levels; probenecid may reduce ciprofloxacin renal clearance by 50% and increase serum concentration by 50%; total body clearance of caffeine is reduced, possibly resulting in increased pharmacologic effects; may increase nephrotoxic effect of cyclosporine; monitor digoxin levels as they may increase; may increase effects of anticoagulants; monitor PT
Contraindications
Documented hypersensitivity; in patients with viral infections of the eye, fungal diseases of the ocular structure, or a current regimen of steroid combinations after uncomplicated removal of a corneal foreign body
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Prolonged or repeated antibiotic therapy may result in bacterial or fungal overgrowth of nonsusceptible organisms and secondary infection; periodic assessment of organ system functions (eg, renal, hepatic, hematopoietic) is advisable during prolonged therapy; caution in patients diagnosed with renal impairment; dose reduction may be necessary; closely monitor patients on intermittent therapy for compliance and caution against intentional or accidental interruption of therapy because of increased risk of serious adverse reactions
Minocycline (Dynacin, Minocin)
Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species.
Dosing
Adult
100 mg PO bid
Pediatric
<8 years: Not recommended
>8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h
Interactions
Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Contraindications
Documented hypersensitivity, severe hepatic dysfunction
Precautions
Pregnancy
D - Unsafe in pregnancy
Precautions
Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines; hepatitis or lupuslike syndromes may occur
Antibiotics for toxoplasma myositis
Proven effective against toxoplasma infections.
Clindamycin (Cleocin)
Inhibits bacterial peptide chain initiation by binding preferentially to the 50S ribosomal subunit; may be used in combination with pyrimethamine as an alternative to sulfonamides.
Dosing
Adult
1200-2400 mg/d IV/IM divided q6-8h
Pediatric
8-16 mg/kg/d IM/IV divided tid/qid; increase to 16-20 mg/kg/d divided tid/qid in severe infections
Interactions
Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium
Contraindications
Documented hypersensitivity; enteritis, hepatic impairment, ulcerative colitis, and antibiotic-associated colitis
Precautions
Pregnancy
D - Unsafe in pregnancy
Precautions
Dose adjustment may be necessary in patients with severe hepatic dysfunction; no adjustment is necessary in patients with renal insufficiency; associated with severe, possibly fatal colitis
Sulfadiazine (Microsulfon)
Interferes with microbial growth through a competitive antagonism of PABA.
Dosing
Adult
1-2 g PO qid
Pediatric
<2 months: 100 mg/kg/d PO divided q6h
>2 months: Loading dose of 75 mg/kg; maintenance dose of 120-150 mg/kg/d divided q4-6h
Interactions
Increases effect of oral anticoagulants and hypoglycemic agents; sulfadiazine effects are decreased when administered concurrently with PABA or PABA metabolites of drugs such as proparacaine, tetracaine, sunscreens, and procaine
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in patients with impaired renal or hepatic function or G-6-PD deficiency; adjust dose in patients diagnosed with renal insufficiency
Pyrimethamine (Daraprim)
Folic acid antagonist.
Dosing
Adult
Day 1: 100 mg PO bid
Thereafter: 50-100 mg PO qd
Pediatric
Day 1: 0.5 mg/kg PO bid for 2-4 d
Thereafter: 0.25 mg/kg PO bid
Interactions
Concurrent use of antifolic acids (eg, methotrexate, pyrimethamine) may increase risk of bone marrow suppression; mild hepatotoxicity reported with concomitant use of lorazepam and pyrimethamine
Contraindications
Documented hypersensitivity; in megaloblastic anemia resulting from a folate deficiency
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
If folate deficiency develops, reduce dose or discontinue (depending on patient response); caution in patients with hepatic or renal impairment; may precipitate hemolytic anemia in patients with G-6-PD deficiency, generally in the presence of other stressful events
Folic acid derivative
Used to rescue cells from the deleterious effects of folate antagonists.
Leucovorin (Folinic acid, Wellcovorin)
A reduced form of folic acid that does not require a reduction reaction by an enzyme for activation; allows for purine and pyrimidine synthesis, which is needed for normal erythropoiesis.
Dosing
Adult
10 mg/d PO
Pediatric
Administer as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Do not administer into CSF
Antivirals for CMV myositis
Goal is to shorten the clinical course, to prevent complications and the development of latency and/or subsequent recurrence, and to decrease transmission and established latency.
Ganciclovir (Cytovene, Vitrasert)
A synthetic, acyclic, nucleoside analog of 2'-deoxyguanosine active against CMV; inhibits replication of herpes viruses both in vitro and in vivo; ganciclovir levels are up to 100 times higher in CMV-infected cells than in uninfected cells, possibly because of preferential phosphorylation of ganciclovir in infected cells.
Dosing
Adult
Initial dose: 5 mg/kg IV bid for 14 d, followed by 5 mg/kg IV qd for 5-7 d
Lifetime dose: 500 mg PO q4h or 1 g tid
Pediatric
<3 months: Not established
>3 months: Administer as in adults
Interactions
Concomitant administration with cytotoxic drugs (eg, dapsone, pentamidine, flucytosine, vincristine, vinblastine, Adriamycin, amphotericin B, trimethoprim/sulfamethoxazole, other nucleoside analogs) may have additive toxicity in the replication of rapidly dividing cells (eg, bone marrow, spermatogonia, germinal layers of skin and GI mucosa)
Consider concomitant use of these drugs only if benefits outweigh risks; may cause generalized seizures in patients receiving ganciclovir and imipenem-cilastatin concurrently; use only when potential benefits outweigh risks; serum creatinine may increase following concurrent use of ganciclovir and either cyclosporine or amphotericin B; in presence of probenecid, ganciclovir renal clearance is reduced
When didanosine is administered either 2 h prior to or simultaneously with ganciclovir, its bioavailability may increase; conversely, steady-state bioavailability of ganciclovir may decrease when didanosine is administered 2 h prior to ganciclovir administration (but not when drugs are administered simultaneously); bioavailability of ganciclovir may decrease in presence of zidovudine; conversely, bioavailability of zidovudine increases in presence of ganciclovir; since both drugs can cause granulocytopenia and anemia, combination therapy at full dosing may not be possible
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Possible granulocytopenia, anemia, and thrombocytopenia; since PO ganciclovir is associated with a higher rate of CMV retinitis progression (compared to IV formulation), use only when benefits outweigh risks; caution with renal-function impairment; half-life and serum concentrations may increase because of reduced renal clearance; dosages larger than 6 mg/kg IV have resulted in increased toxicity; more rapid infusions also may result in increased toxicity; initially, reconstituted IV solutions have a high pH of 11; phlebitis or pain may occur at IV infusion site, despite further dilution in IV fluids; accompany with good hydration, since normal clearance depends on adequate renal function; photosensitization (photoallergy or phototoxicity) may occur; caution patients against unprotected UV or sunlight exposure until tolerance develops
Foscarnet (Foscavir)
An organic analog of inorganic pyrophosphate that inhibits CMV replication; exerts antiviral activity by selective inhibition at the pyrophosphate-binding site on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases. Consider viral resistance in patients with poor clinical response or persistent viral excretion.
Dosing
Adult
Induction: 60 mg/kg/dose IV q8h or 100 mg/kg IV q12h for 14-21 d
Lifetime dose: 90-120 mg/kg IV qd as single infusion
Pediatric
<12 years: Not established
>12 years: Administer as in adults
Interactions
Because of its propensity for renal impairment, avoid use in combination with potentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) unless benefits outweigh risks; concomitant use with IV pentamidine may cause hypocalcemia
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Renal function usually declines; determine creatinine clearance at baseline and periodically thereafter to ensure correct dosing; discontinue if clearance drops below 0.4 mL/min/kg; hydration may reduce risk of nephrotoxicity; because of ability to chelate divalent metal ions and alter serum electrolytes, closely monitor patients for such changes; quickly assess mild or severe symptoms (perioral numbness, paresthesias, seizures) of electrolyte abnormalities; only administer into veins with adequate blood flow to permit rapid dilution and distribution and to avoid local irritation; because of a high incidence of granulocytopenia (17%) and anemia (33%), regularly monitor CBCs; do not administer by rapid or bolus IV injection; toxicity may increase as a result of excessive plasma levels
Follow-up
Further Outpatient Care
- Coordinate care with the primary care physician and an infectious disease specialist.
Prognosis
- Prognosis depends on the general condition of the patient and on the stage of HIV infection. Early diagnosis and treatment is important.
- Improvement of AZT myopathy begins several months after dose reduction or discontinuation but may be incomplete.
Miscellaneous
Medicolegal Pitfalls
- Failure to promptly make diagnosis and provide treatment can lead to death.
References
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Behbahani R, Moshfeghi M, Baxter JD. Therapeutic approaches for AIDS-related toxoplasmosis. Ann Pharmacother. Jul-Aug 1995;29(7-8):760-8. [Medline].
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Gendelman HE, Lipton SA, Epstein L. The Neurology of AIDS. New York: Chapman & Hall;1998.
Johnson RW, Williams FM, Kazi S, et al. Human immunodeficiency virus-associated polymyositis: a longitudinal study of outcome. Arthritis Rheum. Apr 15 2003;49(2):172-8. [Medline].
Klepser ME, Klepser TB. Drug treatment of HIV-related opportunistic infections. Drugs. Jan 1997;53(1):40-73. [Medline].
Moyle G. Clinical manifestations and management of antiretroviral nucleoside analog-related mitochondrial toxicity. Clin Ther. Aug 2000;22(8):911-36; discussion 898. [Medline].
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Whitley RJ, Jacobson MA, Friedberg DN. Guidelines for the treatment of cytomegalovirus diseases in patients with AIDS in the era of potent antiretroviral therapy: recommendations of an international panel. International AIDS Society-USA. Arch Intern Med. May 11 1998;158(9):957-69. [Medline].
Keywords
acquired immunodeficiency syndrome, AIDS, polymyositis, dermatomyositis, zidovudine myopathy, AZT myopathy, rhabdomyolysis, nemaline rod myopathy, HIV wasting syndrome with type II muscle fiber atrophy, local neoplasm, local infection, myasthenic syndrome and chronic fatigue, diffuse infiltrative lymphocytosis syndrome, DILS
Contributor Information and Disclosures
Author
Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine
Niranjan N Singh, MD, DNB is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.
Coauthor(s)
Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.
Medical Editor
William J Nowack, MD, Associate Professor, Department of Neurology, Epilepsy Center, University of Kansas Medical Center
William J Nowack, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Electroencephalographic Association, American Medical Informatics Association, and Biomedical Engineering Society
Disclosure: Nothing to disclose.
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Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
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Managing Editor
Neil A Busis, MD, Chief, Division of Neurology, Department of Medicine, University of Pittsburgh Medical Center - Shadyside, Clinical Associate Professor, Department of Neurology, University of Pittsburgh School of Medicine
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.
CME Editor
Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.
Chief Editor
Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
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