A Comparative Trial of Didanosine or Zalcitabine after Treatment with Zidovudine in Patients with Human Immunodeficiency Virus Infection

Abrams, Donald I.; Goldman, Anne; Launer, Cynthia A.; Korvick, Joyce A.; Neaton, James D.; Crane, Lawrence R.; Grodesky, Michael J.; Wakefield, Steven; Muth, K; Kornegay, Sandra; Cohn, David L.; Harris, Allen C.; Luskin-Hawk, Roberta; Markowitz, Norman; Sampson, James H.; Thompson, Melanie; Deyton, Lawrence

doi:10.1056/nejm199403103301001

Cited by 196 publications

(99 citation statements)

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“…Decreased distal superficial sensibility was the common sign occurring in 73.5% of the patients, one (3%) had only absent ankle jerks and 8 (23.5%) had sensibility and tendon reflexes altered.Two patients had only symptoms and two had sub-clinical peripheral neuropathy with neither symptoms nor signs -the peripheral neuropathy was diagnosed by the neurophysiologic study. Thirty two (94.1%) patients were taking drugs supposed to be neurotoxic (d4T,ddI, ddC, isoniazid) [22][23][24][25] .Thirty nine patients had electroneuromyography performed. Thirteen (33.3%) of those had features of peripheral neuropathy.…”

Section: Resultsmentioning

confidence: 99%

“…The types of peripheral neuropathy are shown in Table 2. Seventy five per- [22][23][24][25] . Laboratory analysis did not show any significant abnormalities (42 patients were tested), except in four who had VDRL positive.…”

Section: Resultsmentioning

confidence: 99%

“…It can be caused by the direct or indirect action of HIV and antibody production, or secondary to infections (CMV,MAC ), toxic effects of certain drugs (isoniazid, vincristine, d4T, ddi, ddC), or nutritional deficiencies (vitamin B12) 4,7,[22][23][24][25][26][34][35][36] . In our study, almost all the patients that had diagnosis of peripheral neuropathy were taking drugs probably neurotoxic (ddi, d4t,ddC isoniazid).…”

Section: Discussionmentioning

confidence: 99%

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The frequency of peripheral neuropathy in a group of HIV positive patients in Brazil

Zanetti

Manzano

Gabbai

2004

Arq. Neuro-Psiquiatr.

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-Peripheral neuropathy is a common neurological complication occurring in asymptomatic and symptomatic stages of HIV infection.The most common syndromes are distal symmetric polyneuropathy, inflammatory demielinating polyneuropathy, poliradiculopathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. Purpose: To evaluate the frequency of peripheral neuropathy in a group of HIV seropositive outpatients in São Paulo, Brazil. Method: Over a period of 17 months, 49 HIV+ patients where evaluated clinically. Laboratory analysis and electroneuromyography were requested to all patients. Results: Thirty four (69.4%) of the 49 patients had the diagnosis of peripheral neuropathy established on clinical grounds. The most common sign was impairment (97.1%) of sensibility. Thirteen (33.3%) of the 39 that were subjected to electroneuromyography had features of peripheral neuropathy, being a sensitive-motor axonal neuropathy the most common. No abnormalities were found in the laboratory analysis performed in 42 patients, except in four who had VDRL positive. Conclusion: A peripheral neuropathy was frequently found upon clinical examination in our group of HIV positive individuals.KEY WORDS: peripheral neuropathy, HIV, AIDS. Freqüência da neuropatia periférica no Brasil em um grupo de pacientes HIV positivoRESUMO -A neuropatia periférica é complicação neurológica comum, podendo ocorrer nas fases assintomáticas e sintomáticas da infecção pelo vírus da imunodeficiência humana (HIV). As síndromes mais comuns são a polineuropatia distal simétrica, polineuropatia desmielinizante inflamatória, polirradiculopatia, mononeuropatia, mononeuropatia múltipla e neuropatia autonômica.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The frequency of peripheral neuropathy in a group of HIV positive patients in Brazil

Zanetti

Manzano

Gabbai

2004

Arq. Neuro-Psiquiatr.

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“…The antiretroviral agent 2Ј,3Ј-dideoxyinosine (didanosine or ddI) is used to treat persons infected with HIV (1,10). Approximately 50 to 70% of the absorbed dose of ddI appears in urine as various metabolites, although the full metabolic profile is unknown (3a, 11a, 14).…”

mentioning

confidence: 99%

Effect of fluconazole on pharmacokinetics of 2',3'-dideoxyinosine in persons seropositive for human immunodeficiency virus

Bruzzese

Gillum

Israel

et al. 1995

Antimicrob Agents Chemother

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Fluconazole inhibits cytochrome P-450-mediated enzymatic metabolism of several drugs. Since hepatic metabolism is partially responsible for 2 ,3 -dideoxyinosine (didanosine or ddI) elimination, fluconazole therapy may lead to increased ddI concentrations in serum and subsequent concentration-dependent adverse effects. The purpose of this study was to determine if ddI pharmacokinetics are influenced by a 7-day course of oral fluconazole. Twelve adults with human immunodeficiency virus (HIV) who had received a constant dosage of ddI for at least 2 weeks were investigated. On study day 1, multiple serum samples for determination of ddI concentrations were obtained over 12 h. Then subjects received a 7-day course of oral fluconazole (200 mg every 12 h for two doses and then 200 mg once daily for 6 days) while ddI therapy continued. Following the last dose of fluconazole, serum samples for determination of ddI concentrations were again obtained over 12 h. ddI concentrations in serum were analyzed by radioimmunoassay. In contrast to previously published data, there was marked between-subject variability in ddI areas under the concentration-time curve, even when the dose was normalized for weight. No significant differences were found between mean ddI areas under the concentration-time curve from 0 to 12 h on study day 1 (1,528 ؎ 902 ng ⅐ hr/ml) and following fluconazole treatment (1,486 ؎ 649 ng ⅐ hr/ml). There were no significant differences in other pharmacokinetic parameters, such as ddI peak concentrations in serum (971 ؎ 509 and 942 ؎ 442 ng/ml) or half-lives (80 ؎ 32 and 85 ؎ 21 min.) before and after fluconazole treatment, respectively. We conclude that a 7-day course of oral fluconazole does not significantly alter ddI pharmacokinetics in adults that are infected with human immunodeficiency virus.Patients infected with human immunodeficiency virus (HIV) are commonly treated with multiple medications concurrently. Fluconazole is well absorbed in the HIV population and is frequently prescribed for prophylaxis and treatment of fungal infections (6). However, fluconazole inhibits a number of hepatic P-450 enzymes that are responsible for the metabolism of many drugs, such as theophylline, phenytoin, cyclosporin, and rifabutin (9,16,21). In addition, fluconazole has recently been shown to decrease clearance of zidovudine (ZDV), a drug which is metabolized primarily by glucuronidation (19). The mechanism for this latter interaction is unknown, but it demonstrates that the full spectrum of metabolic enzymes which are inhibited by fluconazole remains unknown.The antiretroviral agent 2Ј,3Ј-dideoxyinosine (didanosine or ddI) is used to treat persons infected with HIV (1, 10). Approximately 50 to 70% of the absorbed dose of ddI appears in urine as various metabolites, although the full metabolic profile is unknown (3a, 11a, 14). Dose-related toxicities of ddI include peripheral neuropathy and pancreatitis (5,15,22). Since fluconazole and ddI are commonly coadministered, fluconazole has the potential to inhibit the metabo...

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“…dideoxyinosine (didanosine; ddI) or dideoxycytidine (zalcitabine; ddC). These two compounds appears equally efficacious in delaying disease progression and death [31]. An alternative strategy is the use of combination drug regimens [32].…”

Section: Combination Therapy and Zdvmentioning

confidence: 99%

Zidovudine therapy in HIV infection: which patients should be treated and when.

Barry

Back

Breckenridge

1995

Brit J Clinical Pharma

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A Comparative Trial of Didanosine or Zalcitabine after Treatment with Zidovudine in Patients with Human Immunodeficiency Virus Infection

Abstract: For patients with HIV infection who have not responded to treatment with zidovudine, zalcitabine is at least as efficacious as didanosine in delaying disease progression and death.

Cited by 196 publications

References 12 publications

The frequency of peripheral neuropathy in a group of HIV positive patients in Brazil

The frequency of peripheral neuropathy in a group of HIV positive patients in Brazil

Effect of fluconazole on pharmacokinetics of 2',3'-dideoxyinosine in persons seropositive for human immunodeficiency virus

Zidovudine therapy in HIV infection: which patients should be treated and when.

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