High effectiveness of efavirenz-based highly active antiretroviral therapy in HIV-1-infected patients with fewer than 100 CD4 cells/μl and opportunistic diseases: the EfaVIP Study (Efavirenz in Very Immunosuppressed Patients)

Arribas, José Ramón; Pulido, Federico; Jm, Miró; Ma, Costa; González, Juan; Rubio, Rafael; Jm, Peña; Torralba, Miguel; Loncá, Montserrat; Lorenzo, Alicia; A, del Palacio; Jj, Vázquez Rodríguez; Jm, Gatell

doi:10.1097/00002030-200207260-00014

Cited by 22 publications

(6 citation statements)

References 7 publications

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“…EFV was chosen for the present study based on its effectiveness to provide viral suppression when compared with nevirapine, with fewer severe adverse effects. [131415] The main objective of this study was to formulate albumin nanoparticles of Efavirenz with sustained release effect. The EFV incorporated nanoparticles are promising tools to improve the aqueous solubility of drugs, may minimize the side effects and also provide successful delivery/targeting of drugs to HIV infected immune cells.…”

Section: Introductionmentioning

confidence: 99%

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug-Efavirenz

Jenita

Chocalingam

Wilson

2014

Int J Pharma Investig

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Purpose of the study:The antiretroviral therapy (ART) has dramatically improved human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treatment, prevention and also has been found to increase the lifespan of HIV/AIDS patients by providing durable control of the HIV replication in patients. Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1. The purpose of this study is to formulate efavirenz-loaded bovine serum albumin nanoparticles to improve efavirenz delivery into various organs.Materials and Methods:Nanoparticles were prepared by desolvation technique and coated with polysorbate 80. Ethanol, glutaraldehyde, and mannitol were used as desolvating, cross linking agent, and cryoprotectant, respectively. Drug to polymer ratio was chosen at five levels from 1:2, 1:3, 1:4, 1:5, and 1:6 (by weight). The formulated nanoparticles were characterized for Fourier Transform Infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) studies, entrapment efficiency, particle size, surface charge, surface morphology, in vitro drug release, release kinetics, stability studies, and biodistribution studies.Results and Major Conclusion:The particle size of the prepared formulations was found below 250nm with narrow size distribution, spherical in shape and showed good entrapment efficiency (45.62-72.49%). The in vitro drug release indicated biphasic release and its data were fitted to release kinetics models and release pattern was Fickian diffusion controlled release profile. The prepared nanoparticles increased efavirenz delivery into various organs by several fold in comparison with the free drug.

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Section: Introductionmentioning

confidence: 99%

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug-Efavirenz

Jenita

Chocalingam

Wilson

2014

Int J Pharma Investig

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“…3). Consistent with the clinical potency of the NNRTI EFV (1,21,55), this drug demonstrated extraordinary potency (31). Interactions affecting absorption and metabolism alter drug concentrations in the blood and are compensated for clinically by adjustments in dosage so that optimal blood levels are achieved.…”

Section: Resultsmentioning

confidence: 61%

“…Using this assay, we compared the potencies of available antiretroviral drugs by examining the ratio of the C min and C max values to the IC 50 determined in this system. Our data highlight the extraordinary potency of the NNRTI EFV (1,21,55), which has a C min /IC 50 ratio of Ͼ1,000 in our system. In contrast, the commonly used NRTIs d4T and ddI are relatively inefficient at inhibiting viral replication in this system.…”

Section: Vol 78 2004 Assay For Hiv Replication Capacity and Drug Rementioning

confidence: 61%

Novel Single-Cell-Level Phenotypic Assay for Residual Drug Susceptibility and Reduced Replication Capacity of Drug-Resistant Human Immunodeficiency Virus Type 1

Zhang¹,

Zhou²,

Alcock³

et al. 2004

J Virol

167

172

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Human immunodeficiency virus type 1 (HIV-1)-infected individuals who develop drug-resistant virus during antiretroviral therapy may derive benefit from continued treatment for two reasons. First, drug-resistant viruses can retain partial susceptibility to the drug combination. Second, therapy selects for drug-resistant viruses that may have reduced replication capacities relative to archived, drug-sensitive viruses. We developed a novel single-cell-level phenotypic assay that allows these two effects to be distinguished and compared quantitatively. Patient-derived gag-pol sequences were cloned into an HIV-1 reporter virus that expresses an endoplasmic reticulum-retained Env-green fluorescent protein fusion. Flow cytometric analysis of single-round infections allowed a quantitative analysis of viral replication over a 4-log dynamic range. The assay faithfully reproduced known in vivo drug interactions occurring at the level of target cells. Simultaneous analysis of single-round infections by wild-type and resistant viruses in the presence and absence of the relevant drug combination divided the benefit of continued nonsuppressive treatment into two additive components, residual virus susceptibility to the drug combination and selection for drug-resistant variants with diminished replication capacities. In some patients with drug resistance, the dominant circulating viruses retained significant susceptibility to the combination. However, in other cases, the dominant drug-resistant viruses showed no residual susceptibility to the combination but had a reduced replication capacity relative to the wild-type virus. In this case, simplification of the regimen might still allow adequate suppression of the wild-type virus. In a third pattern, the resistant viruses had no residual susceptibility to the relevant drug regimen but nevertheless had a replication capacity equivalent to that of wild-type virus. In such cases, there is no benefit to continued treatment. Thus, the ability to simultaneously analyze residual susceptibility and reduced replication capacity of drug-resistant viruses may provide a basis for rational therapeutic decisions in the setting of treatment failure.

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“…In conclusion, although EFV‐containing antiretroviral regimen has been shown to be effective even in advanced HIV‐1 disease, however it must be used with caution during the first trimester when the teratogenic side effect of EFV is high. The aetiology of cleft palate in these three HIV‐exposed newborns is uncertain because of multiple suspected factors, which they were exposed to in utero.…”

Section: Discussionmentioning

confidence: 96%

Cleft palate in HIV‐exposed newborns of mothers on highly active antiretroviral therapy

et al. 2014

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Aims Cleft lip/palate, though rare, is the commonest head and neck congenital malformation. Both genetic and environmental factors have been implicated in the aetiopathogenesis but the role of in-utero exposure to human immunodeficiency virus (HIV) and highly active antiretroviral therapy (HAART) is still being investigated. This short communication reports the occurrence of cleft palate in three newborns exposed in-utero to HIV and HAART. Material and methods This is a case series of HIV-exposed newborns observed to have cleft palate among a larger cohort of HIV-exposed and unexposed newborns in a study evaluating the effect of HIV infection and HAART on newborn hearing. The Risk Ratio (RR) was calculated to detect a potential association between in-utero exposure to Efavirenz containing ART and cleft palate. Results Three HIV-exposed newborns with cleft palate were identified during hearing screening performed on 126 HIV-exposed and 121 HIV unexposed newborns. Two had exposure to tenofovir+lamivudine+efavirenz (TDF+3TC+EFV) while the third had exposure to zidovudine+lamivudine+nevirapine (ZDV+3TC+NVP) during the first trimester. There was no statistically significant association between presence of cleft palate and exposure to an EFV containing HAART regimen (p=0.07, RR=10.95 [0.94-126.84]). Conclusions This communication highlights the possible aetiologic role of HAART in cleft palate, the need for further prospective follow-up studies and establishment of antiretroviral pregnancy, birth and neonatal registries.

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High effectiveness of efavirenz-based highly active antiretroviral therapy in HIV-1-infected patients with fewer than 100 CD4 cells/μl and opportunistic diseases: the EfaVIP Study (Efavirenz in Very Immunosuppressed Patients)

Cited by 22 publications

References 7 publications

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug-Efavirenz

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug-Efavirenz

Novel Single-Cell-Level Phenotypic Assay for Residual Drug Susceptibility and Reduced Replication Capacity of Drug-Resistant Human Immunodeficiency Virus Type 1

Cleft palate in HIV‐exposed newborns of mothers on highly active antiretroviral therapy

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