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HIV integrase is the enzyme responsible for transferring the DNA encoded by HIV to host chromosomes, a necessary step for the replication of retroviruses. Raltegravir (RAL) is the first integrase inhibitor approved for HIV treatment of patients infected by this virus. RAL has demonstrated a marked antiretroviral activity against HIV strains resistant to other antiretroviral drug families and high virological efficacy in patients pre-treated so as naïve to antiretroviral treatment. In addition, its safety profile is very favourable.
Unlike what happens with other antiretrovirals such as protease inhibitors, there is not a relationship between the virological response to antiretroviral treatment with RAL and the trough concentration of drug in plasma. Similarly, in vitro studies have shown that, after infection of cultured cells, the rate of viral replication measured by p24 antigen production was continuing inhibited even when RAL was washed from the culture medium from the 8 hours after infection, suggesting the possibility of a post-antibiotic effect of the drug. Either way, as in the case of transcriptase inhibitor nucleoside analogues, this lack of correlation between pharmacokinetics and pharmacodynamics of RAL may only be the result of intracellular accumulation of drug in blood lymphocytes peripheral, which in turn could be explained either by setting the RAL to the pre-integration complex or through the saturation of certain cellular transporters responsible for pumping the RAL from the inside out-cell (efflux transporters). Anyway, the result would be a greater RAL intracellular half-life than plasmatic, which would translate into a clinically persistent antiretroviral effect compared with its concentration in plasma.
Based on the above is possible to suggest that the average life of RAL was longer in the peripheral blood lymphocytes than in plasma, and that this intracellular increased half-life could explain the absence of relationship between trough RAL concentration and its virological efficacy, post-antibiotic effect of RAL found in some studies in vitro which, on the other hand, could be relevant to the possible once-daily administration of raltegravir.
Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Hospital Germans Trias i Pujol
Active, not recruiting
Germans Trias i Pujol Hospital
Published on BioPortfolio: 2014-08-27T03:18:40-0400
The purpose of this study is to measure concentrations of Raltegravir in cerebrospinal fluid. The hypotheses are: - Raltegravir concentrations in CSF will be measurable ...
The purpose of this study is to: - Provide raltegravir to subjects with HIV and an undetectable viral load who are experiencing injection site reactions (ISR) to Enfuvirtide, ...
The purpose of this trial is to determine the effect of raltegravir on pravastatin pharmacokinetics and vice versa by intrasubject comparison.
The purpose of this study is to test whether there is a drug interaction between raltegravir (a medicine used to treat the human immunodeficiency virus or HIV) and antacids.
The purpose of this study is to determine whether treatment with Raltegravir further decreases HIV viral replication in HAART-suppressed, HIV-infected patients, potentially improving immun...
Raltegravir 1200 mg once daily vs 400 mg twice daily, with emtricitabine and tenofovir disoproxil fumarate, for previously untreated HIV-1 infection: Week 96 results from ONCEMRK, a randomized, double-blind, non-inferiority trial.
Raltegravir 1200mg (2x600mg tablets) once daily (QD) demonstrated non-inferior efficacy and similar safety to raltegravir 400mg BID at Week 48 of the ONCEMRK trial. Here we report the Week 96 results ...
Similar long-term efficacy of dual therapy containing raltegravir and a boosted protease inhibitor versus standard triple therapies in pretreated HIV-1-infected patients in a retrospective, real-life cohort of 14 years.
Raltegravir is used in many antiretroviral combinations, but its use in treatment-experienced patients without knowledge of baseline resistance is discussed controversially as a number of comparative ...
Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (R...
Dolutegravir (DTG) is a next-generation HIV integrase inhibitor (INI) with an increased genetic barrier to resistance with respect to raltegravir (RAL) or elvitegravir (EVG). Few data are available on...
The recent approval of raltegravir granules for suspension in the newborn population offers a new option for the antiretroviral prophylaxis of newborns for the prevention of perinatal transmission. Ho...
A pyrrolidinone derivative and HIV INTEGRASE INHIBITOR that is used in combination with other ANTI-HIV AGENTS for the treatment of HIV INFECTION.
Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of TOGAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; BUNYAVIRIDAE INFECTIONS; PICORNAVIRIDAE INFECTIONS; PARAMYXOVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RETROVIRIDAE INFECTIONS; and ARENAVIRIDAE INFECTIONS.
Viral infections of the leptomeninges and subarachnoid space. TOGAVIRIDAE INFECTIONS; FLAVIVIRIDAE INFECTIONS; RUBELLA; BUNYAVIRIDAE INFECTIONS; ORBIVIRUS infections; PICORNAVIRIDAE INFECTIONS; ORTHOMYXOVIRIDAE INFECTIONS; RHABDOVIRIDAE INFECTIONS; ARENAVIRIDAE INFECTIONS; HERPESVIRIDAE INFECTIONS; ADENOVIRIDAE INFECTIONS; JC VIRUS infections; and RETROVIRIDAE INFECTIONS may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, PHOTOPHOBIA, and signs of meningeal irritation. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)
Infections with viruses of the family PARAMYXOVIRIDAE. This includes MORBILLIVIRUS INFECTIONS; RESPIROVIRUS INFECTIONS; PNEUMOVIRUS INFECTIONS; HENIPAVIRUS INFECTIONS; AVULAVIRUS INFECTIONS; and RUBULAVIRUS INFECTIONS.
Pathogenic infections of the brain, spinal cord, and meninges. DNA VIRUS INFECTIONS; RNA VIRUS INFECTIONS; BACTERIAL INFECTIONS; MYCOPLASMA INFECTIONS; SPIROCHAETALES INFECTIONS; fungal infections; PROTOZOAN INFECTIONS; HELMINTHIASIS; and PRION DISEASES may involve the central nervous system as a primary or secondary process.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...