You are in: eMedicine Specialties > Neurology > Neurological Infections HIV-1 Associated MyopathiesArticle Last Updated: Feb 23, 2007AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Niranjan N Singh, MD, DNB, Fellow in Neurophysiology, Department of Neurology, St Louis University School of Medicine Niranjan N Singh is a member of the following medical societies: American Academy of Neurology 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 Editors: William J Nowack, MD, Associate Professor, Department of Neurology, Epilepsy Center, University of Kansas Medical Center; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; 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; 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; Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants Author and Editor Disclosure Synonyms and related 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 INTRODUCTIONSection 2 of 10
  BackgroundHIV-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. PathophysiologyHIV 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:
FrequencyUnited StatesAccording 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%. CLINICALSection 3 of 10
History
Physical
DIFFERENTIALSSection 4 of 10
Dermatomyositis/Polymyositis Endocrine Myopathies Focal Muscular Atrophies Inclusion Body Myositis
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| Drug Name | Rifabutin (Mycobutin) |
|---|---|
| Description | An ansamycin antibiotic that inhibits DNA-dependent RNA polymerase and thus transcription initiation in susceptible strains. |
| Adult Dose | 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 Dose | Not established Suggested dose: 5 mg/kg/d PO; to reduce GI adverse effects, dose bid and administer with food |
| Contraindications | Documented hypersensitivity |
| Interactions | Steady-state plasma levels may decrease after repeated dosing; does not affect inhibition of HIV by zidovudine |
| 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 |
| Drug Name | Clarithromycin (Biaxin) |
|---|---|
| Description | 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. |
| Adult Dose | 2 g PO qd/bid |
| Pediatric Dose | 7.5 mg/kg PO bid |
| Contraindications | Documented hypersensitivity; in patients taking pimozide, astemizole (recalled from US market), cisapride, or terfenadine (recalled from US market) |
| 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 |
| 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 |
| Drug Name | Ethambutol (Myambutol) |
|---|---|
| Description | 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. |
| Adult Dose | 15-25 mg/kg PO qd |
| Pediatric Dose | <13 years: Not recommended >13 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; in optic neuritis, unless benefit outweighs risk |
| Interactions | Aluminum salts may delay and reduce absorption; delay administration by several hours |
| 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 |
| Drug Name | Clofazimine (Lamprene) |
|---|---|
| Description | Inhibits mycobacterial growth and binds preferentially to mycobacterial DNA but always should be used with other antibiotics. |
| Adult Dose | 100 mg PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | Some reports suggest that dapsone may inhibit anti-inflammatory activity |
| 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 |
| Drug Name | Rifampin (Rifadin, Rimactane) |
|---|---|
| Description | 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. |
| Adult Dose | 550-600 mg PO/IV qd |
| Pediatric Dose | 10-20 mg/kg PO/IV qd, not to exceed 600 mg qd |
| Contraindications | Documented hypersensitivity |
| 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 |
| 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 |
| Drug Name | Ciprofloxacin (Cipro) |
|---|---|
| Description | 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. |
| Adult Dose | 750 mg PO bid |
| Pediatric Dose | <18 years: Not established |
| 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 |
| 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 |
| 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 |
| Drug Name | Minocycline (Dynacin, Minocin) |
|---|---|
| Description | Treats infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma species. |
| Adult Dose | 100 mg PO bid |
| Pediatric Dose | <8 years: Not recommended >8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h |
| Contraindications | Documented hypersensitivity, severe hepatic dysfunction |
| 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 |
| 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 |
Proven effective against toxoplasma infections.
| Drug Name | Clindamycin (Cleocin) |
|---|---|
| Description | 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. |
| Adult Dose | 1200-2400 mg/d IV/IM divided q6-8h |
| Pediatric Dose | 8-16 mg/kg/d IM/IV divided tid/qid; increase to 16-20 mg/kg/d divided tid/qid in severe infections |
| Contraindications | Documented hypersensitivity; enteritis, hepatic impairment, ulcerative colitis, and antibiotic-associated colitis |
| Interactions | Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium |
| 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 |
| Drug Name | Sulfadiazine (Microsulfon) |
|---|---|
| Description | Interferes with microbial growth through a competitive antagonism of PABA. |
| Adult Dose | 1-2 g PO qid |
| Pediatric Dose | <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 |
| Contraindications | Documented hypersensitivity |
| 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 |
| 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 |
| Drug Name | Pyrimethamine (Daraprim) |
|---|---|
| Description | Folic acid antagonist. |
| Adult Dose | Day 1: 100 mg PO bid Thereafter: 50-100 mg PO qd |
| Pediatric Dose | Day 1: 0.5 mg/kg PO bid for 2-4 d Thereafter: 0.25 mg/kg PO bid |
| Contraindications | Documented hypersensitivity; in megaloblastic anemia resulting from a folate deficiency |
| 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 |
| 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 |
Used to rescue cells from the deleterious effects of folate antagonists.
| Drug Name | Leucovorin (Folinic acid, Wellcovorin) |
|---|---|
| Description | 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. |
| Adult Dose | 10 mg/d PO |
| Pediatric Dose | Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Do not administer into CSF |
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.
| Drug Name | Ganciclovir (Cytovene, Vitrasert) |
|---|---|
| Description | 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. |
| Adult Dose | 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 Dose | <3 months: Not established >3 months: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| 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 |
| 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 |
| Drug Name | Foscarnet (Foscavir) |
|---|---|
| Description | 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. |
| Adult Dose | 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 Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| 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 |
| 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 |
HIV-1 Associated Myopathies excerpt
Article Last Updated: Feb 23, 2007
