Antiretroviral drugs causing

Neuropathy in human immunodeficiency virus infection has many causes. Multiple mechanisms cause neuropathy in patients with HIV. An immune-mediated, Guillain-Barre-like syndrome (see below) may occur at the time of HIV seroconversion. Later in the course of infection, patients may present with mononeuropathy multiplex, sometimes as a consequence of vasculitis associated with coinfection with hepatitis C. Distal sensory-autonomic axonal polyneuropathy may develop in patients with more advanced HIV, either as a consequence of high titers of HIV itself or of the neurotoxicity of antiretroviral drugs [18,19],... 

In several studies on the antiviral effects of NO on HIV-1 infection, the proviral or antiviral effects of NO seem to be strictly related to the active production of NO during HIV-1 infection. The universal speculative interpretation of the dichotomous effect of NO is that overproduction of this substance, especially in the primary infection and in late stages of the disease, leads to active viral replication with consequent harmful effects on the course of the disease. Conversely, low production of NO may cause a reduction in or inhibition of HIV-1 replication, especially during the symptomless stage of the disease, or during treatment with highly active combined antiretroviral drugs. 

Zidovudine is an antiretroviral drug that is clinically active against HIV-1 and is intended to treat HIV-infected patients. Zidovudine is an analog of thymidine that inhibits replication of the AIDS virus. It also turned into mono-, di-, and triphosphates by the same cellular enzymes that catalyze phosphorylation of thymidine and thymidine nucleosides. Zidovudine-triphosphate is then included in the terminal fragment of the growing chain of viral DNA by viral reverse transcriptase, thus causing the viral DNA chain to break apart in cells infected with the virus. 

The first approval of a therapeutic use for recombinant EPO was in 1989 for the treatment of anemia related to chronic renal failure. The treatment with EPO stimulates production of erythrocytes and improves the patient s quality of life, as well as reducing or eliminating the need for blood transfusion. There are other non-renal applications, such as the minimization of blood transfusion after surgery, the prevention of anemia after bone marrow transplantation, and the treatment of anemia caused by the use of antiretroviral drugs, by chemotherapy, and by prematurity. 

While no conclusive evidence was given for a causative role of either antiretroviral drug, the authors concluded that children taking antiretroviral therapy need to be monitored for possible ototoxicity. 

In a 39-year-old man efavirenz caused a confluent maculopapular rash, and pulmonary interstitial infiltrates without lymphadenopathy (21). The symptoms resolved when efavirenz was withdrawn while other antiretroviral drugs were continued. The patient was rechallenged, and the rash and fever reappeared however, recurrence of the pulmonary infiltrates was not addressed. 

The results of a questionnaire survey of 878 people with HIV infection treated with antiretroviral drugs confirmed the risk of arthralgias in patients taking indinavir. The authors suggested that crystal deposition in joints, analogous to the crystalluria with nephrolithiasis that indinavir and other protease inhibitors can cause, might be responsible. 

Metry DW, Lahart CJ, Farmer KL, Hebert AA. Stevens-Johnson syndrome caused by the antiretroviral drug nevirapine. J Am Acad Dermatol 2001 44(Suppl 2) 354-7. 

Lamivudine inhibits the intracellular phosphorylation of zalcitabine and antagonizes zalcitabine s antiretroviral activity in vitro, although the clinical significance of this interaction is unknown. Probenecid increases the zalcitabine AUC by about 50%, probably through inhibition of tubular secretion cimetidine increases the AUC by 36% via an unknown mechanism. Zalcitabine should be avoided in patients with a history of pancreatitis or neuropathy because the risk and severity of both complications increase. Coadministration of other drugs that cause pancreatitis or neuropathy also will increase the risk and severity of these symptoms. Ethambutol, isoniazid, vincristine, cisplatin, and pentamidine, as well as the antiretroviral drugs didanosine and stavudine, therefore, should be avoided. 

Items 1-3 A hospitalized AIDS patient is receiving antiretroviral drugs but no antimicrobial prophylaxis. He develops sepsis with fever, suspected to be caused by a gram-negative bacillus. Treatment will include antibiotics, and the drugs under consideration include aminoglycosides, cephalosporins, fluoroquinolones, and imipenem. 

Herb-drug interactions Echinacea purpurea In 15 HIV-infected patients who took antiretroviral drug therapy including darunavir-I-ritonavir for at least 4 weeks. Echinacea purpurea root extract capsules caused no changes in plasma concentrations of darunavir [120. ... 

Lipodystrophy is a feature of treatment with antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors. It has been attributed to inhibition of mitochondrial DNA polymerase y [53 ]. It is associated with other metabolic alterations, such as lactic acidosis, dyslipide-mia, and insulin resistance, and may in turn be associated with an increase in the longterm risk of cardiovascular diseases [54, 55 ]. It causes loss of fat from the face and limbs and can be accompanied by accumulation of fat in the trunk and the back of the neck. It affects up to 50% of the patients taking highly active antiretroviral drug treatment (HAART). 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

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