Prospective Study of New-Onset Seizures in Patients With Human Immunodeficiency Virus Infection

Pascual-Sedano, Berta; Iranzo, Alejandro; Martí‐Fàbregas, Joan; Domingo, Peré; Escartín, Antonio; Fuster, Montserrat; Barrio, J. Lino; Sambeat, María A.

doi:10.1001/archneur.56.5.609

Cited by 60 publications

(94 citation statements)

References 26 publications

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“…NOS in this study accounted for 2% of neurological manifestations. In clade B regions 3% of HIV patients in a prospective study and between 11% and 17% in retrospective studies were found to have suffered a newonset seizure at some time during their illness [20]. We previously described our experience with NOS in HIV and noted that in 75% of such patients the cause for the NOS was either meningitis or a SOL.…”

Section: Discussionmentioning

confidence: 99%

The frequency and profile of neurology in black South African HIV infected (clade C) patients — A hospital-based prospective audit

Modi

Hari

Modi

et al. 2007

Journal of the Neurological Sciences

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Section: Discussionmentioning

confidence: 99%

The frequency and profile of neurology in black South African HIV infected (clade C) patients — A hospital-based prospective audit

Modi

Hari

Modi

et al. 2007

Journal of the Neurological Sciences

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“…The development of neurological symptoms in HIV-infected patients is not uncommon and is related either primarily to HIV infection or secondarily to opportunistic infections (19). Since the frequency of new-onset seizures in HIV infection has been estimated to be 3% (22), there is a medical need to use anticonvulsants in the management of these patients. Similar to efavirenz, carbamazepine exhibits an autoinduction property and increases the metabolism of concomitantly administered drugs.…”

mentioning

confidence: 99%

Model-Based Approach To Characterize Efavirenz Autoinduction and Concurrent Enzyme Induction with Carbamazepine

Zhu

Kaul

Nandy

et al. 2009

Antimicrob Agents Chemother

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Characterization of the time course and magnitude of enzyme induction due to multiple inducers is important for interpretation of clinical data from drug-drug interaction studies. A population interaction model was developed to quantify efavirenz autoinduction and further induction with concurrent carbamazepine coadministration. Efavirenz concentration data in the absence and presence of carbamazepine following singleand multiple-dose oral administrations in healthy subjects were used for model development. The proposed model was able to describe the time-dependent efavirenz autoinduction and the further induction with carbamazepine when the agents were combined. The estimated population averages of efavirenz oral clearance were 5.5, 9.4, 14.4, and 16.7 liters/h on days 1, 14, and 35 and at steady state for the interaction, respectively, for efavirenz monotherapy for 2 weeks followed by the coadministration of carbamazepine for 3 weeks. The estimated times to 50% of the steady state for efavirenz autoinduction and for the induction resulting from the concurrent administration of efavirenz and carbamazepine were similar (around 10 to 12 days). With this model-based analysis, efavirenz exposures can be projected prior to and at the steady state of induction, allowing a better understanding of the time course and magnitude of enzyme induction.Drug-drug interaction studies are an important aspect of clinical pharmacology research and can be a critical step to optimize the use of selected medicines. In the treatment of human immunodeficiency virus (HIV) infection and HIV complications, polypharmacy is compulsory, and this necessitates the conduct of numerous interaction studies (3). Interpretation of results from interaction studies may be challenging when multiple enzyme inducers or inhibitors are involved while study duration is restricted. In some cases, it may be difficult to know when steady state is achieved or only a "pseudo"-steady state may be achievable during a controlled study period.Enzyme induction has important clinical implications when enhanced drug metabolism results in lower drug concentrations, which leads to a suboptimal efficacious response or, even worse, the development of drug resistance. Enzyme induction can be due to (i) a drug affecting its own metabolism (autoinduction), (ii) comedication(s) with induction capability, or (iii) both, such as the concomitant use of efavirenz and carbamazepine.Efavirenz is a potent nonnucleoside reverse transcriptase inhibitor approved for the treatment of HIV-1 infection in combination with other antiretroviral agents (efavirenz [Sustiva] package insert for capsules and tablets; Bristol-Myers Squibb Co., Princeton, NJ) (1). It is metabolized mainly by cytochrome P450 2B6 (CYP2B6) and possibly CYP3A4 or other CYP isoforms to a less extent (efavirenz package insert for capsules and tablets; Bristol-Myers Squibb Co.) (1, 29). Thus, drugs that induce CYP2B6/3A4 (e.g., rifampin, carbamazepine, and phenobarbital) may increase the clearance of efavirenz, resulting...

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“…Three other subjects presented with seizure disorder but did not have confirmatory radiological investigations done as they died soon after presentation. Seizures have been reported in 3-17% of AIDS-sick patients and the usual causes are drug toxicity and intracranial lesions (Wong, Suite & Labar, 1990;Pascual-Sedano, Iranzo, Marti-Fabregas, Domingo, Escartin, Fuster, Barrio & Sambeat, 1999). Most patients with brain mass lesions present with generalised seizures.…”

Section: Discussionmentioning

confidence: 99%

“…Most patients with brain mass lesions present with generalised seizures. When partial seizures are present, they usually indicate an intracranial pathology, usually in the form of cerebral toxoplasmosis, cerebral lymphoma, cryptococcal meningitis and cerebral infarction (Wong et al, 1990;Pascual-Sedano et al, 1999). Direct HIV infection is also a cause of seizures without any brain lesion (Wong et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Neurological manifestations of HIV infection in Nigerians

Imam¹

2007

African Journal of AIDS Research

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Nervous system complications commonly accompany HIV infection and are associated with significant morbidity and mortality. HIV incidence has been progressively increasing in Nigeria, yet the neurological manifestations of the disease have not been systematically studied in Nigerians. This study aimed to describe the nature and frequency of neurological manifestations associated with HIV infection in a sample of 202 Nigerians. This was a prospective study of patients with documented HIV infection who attended a referral centre clinic in Abuja in 2003. A personal history, general and neurological examinations, and other relevant medical investigations were carried out for all subjects. A mini mental-state exam was carried out with those willing to cooperate. In all, 89 patients (44%) were diagnosed with at least one neurological disorder. Herpes zoster and cognitive impairment were the most frequent, each present in 12.3% of the study group. Peripheral neuropathy and facial palsy were also present, in 10.4% and 3.9% of subjects, respectively. Brain mass lesions, seizure disorder, cryptococcal meningitis, cord compression syndrome, and trigeminal neuralgia were also documented. There was no significant difference demographically between subjects with or without neurological impairment. Future studies in this area should utilise nerve conduction studies and more detailed testing of cognitive function to further characterise the neurological manifestations of HIV infection.

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Prospective Study of New-Onset Seizures in Patients With Human Immunodeficiency Virus Infection

Abstract: New-onset seizures are infrequent in patients with HIV. In most cases a definite or probable cause is identified, which is usually related to toxic and/or metabolic factors. Most seizures are generalized, and partial seizures suggest a focal cerebral lesion.

Cited by 60 publications

References 26 publications

The frequency and profile of neurology in black South African HIV infected (clade C) patients — A hospital-based prospective audit

The frequency and profile of neurology in black South African HIV infected (clade C) patients — A hospital-based prospective audit

Model-Based Approach To Characterize Efavirenz Autoinduction and Concurrent Enzyme Induction with Carbamazepine

Neurological manifestations of HIV infection in Nigerians

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