eMedicine Specialties > Neurology > Neurological Infections
HIV-1 Associated Myopathies: Treatment & Medication
Updated: Feb 23, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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.
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
Steady-state plasma levels may decrease after repeated dosing; does not affect inhibition of HIV by zidovudine
Documented hypersensitivity
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.
Adult
2 g PO qd/bid
Pediatric
7.5 mg/kg PO bid
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
Documented hypersensitivity; in patients taking pimozide, astemizole (recalled from US market), cisapride, or terfenadine (recalled from US market)
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.
Adult
15-25 mg/kg PO qd
Pediatric
<13 years: Not recommended
>13 years: Administer as in adults
Aluminum salts may delay and reduce absorption; delay administration by several hours
Documented hypersensitivity; in optic neuritis, unless benefit outweighs risk
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.
Adult
100 mg PO qd
Pediatric
Not established
Some reports suggest that dapsone may inhibit anti-inflammatory activity
Documented hypersensitivity
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.
Adult
550-600 mg PO/IV qd
Pediatric
10-20 mg/kg PO/IV qd, not to exceed 600 mg qd
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
Documented hypersensitivity
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.
Adult
750 mg PO bid
Pediatric
<18 years: Not established
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
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
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.
Adult
100 mg PO bid
Pediatric
<8 years: Not recommended
>8 years: 4 mg/kg PO initially, followed with 2 mg/kg q12h
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
Documented hypersensitivity, severe hepatic dysfunction
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.
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
Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium
Documented hypersensitivity; enteritis, hepatic impairment, ulcerative colitis, and antibiotic-associated colitis
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.
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
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
Documented hypersensitivity
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.
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
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
Documented hypersensitivity; in megaloblastic anemia resulting from a folate deficiency
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.
Adult
10 mg/d PO
Pediatric
Administer as in adults
None reported
Documented hypersensitivity
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.
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
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
Documented hypersensitivity
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.
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
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
Documented hypersensitivity
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
More on HIV-1 Associated Myopathies |
| Overview: HIV-1 Associated Myopathies |
| Differential Diagnoses & Workup: HIV-1 Associated Myopathies |
 Treatment & Medication: HIV-1 Associated Myopathies |
| Follow-up: HIV-1 Associated Myopathies |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
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
