Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “containment”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cloning and sequencing of a copper-containing, topa quinone-containing monoamine oxidase from human placenta.

A 4040-bp cDNA was cloned from a human placenta library by screening with a polymerase chain reaction-amplified fragment. The fragment was generated from the library using primers corresponding to conserved sequences encompassing the topa quinone (TPQ) cofactor sites of the copper-containing proteins, bovine serum amine oxidase (BSAO) and human kidney diamine oxidase (DAO). The cloned cDNA contains a coding sequence from positions 161 to 2449. Between bases 2901 and 2974, in a very long 1591-bp 3'-untranslated region, there is a G/A-rich region in the minus strand, which contains a (AGG)5 tandem repeat. The human placenta cDNA sequence and its translated amino acid sequence are 84% and 81% identical to the corresponding BSAO sequences, while the identities for the placenta sequences and those for human kidney DAO are 60% and 41%, respectively. The TPQ consensus nucleotide and protein sequences are identical for the placenta enzyme and BSAO, but the corresponding sequences for human kidney DAO are nonidentical. Three His residues that have been identified as Cu(II) ligands in other amine oxidases are conserved in the human placenta amine oxidase protein sequence. It was concluded that the placenta cDNA open-reading frame codes for a copper-containing, TPQ-containing monoamine oxidase. A putative 19-amino acid signal peptide was identified for human placenta amine oxidase. The resulting mature protein would be composed of 744 amino acids, and would have a Mr of 82,525. Comparison of the human placenta amine oxidase with DNA sequences found in GenBank suggests that the gene for this enzyme is located in the q21 region of human chromosome 17, near the BRCA1 gene.

Amine Oxidase (Copper-Containing)↗
PubMed2000

Effects of Src homology domain 2 (SH2)-containing inositol phosphatase (SHIP), SH2-containing phosphotyrosine phosphatase (SHP)-1, and SHP-2 SH2 decoy proteins on Fc gamma RIIB1-effector interactions and inhibitory functions.

Coaggregation of Fc gamma RIIB1 with B cell Ag receptors (BCR) leads to inhibition of BCR-mediated signaling via recruitment of Src homology domain 2 (SH2)-containing phosphatases. In vitro peptide binding experiments using phosphotyrosine-containing sequences derived from the immunoreceptor tyrosine-based inhibitory motif (ITIM) known to mediate Fc gamma RIIB1 effects suggest that the receptor uses SH2-containing inositol phosphatase (SHIP) and SH2-containing phosphotyrosine phosphatase (SHP)-1, as well as SHP-2 as effectors. In contrast, coimmunoprecipitation studies of receptor-effector associations suggest that the predominant Fc gamma RIIB1 effector protein is SHIP. However, biologically significant interactions may be lost in such studies if reactants' dissociation rates (Kd) are high. Thus, it is unclear to what extent these assays reflect the relative recruitment of SHIP, SHP-1, and SHP-2 to the receptor in vivo. As an alternative approach to this question, we have studied the effects of ectopically expressed SHIP, SHP-1, or SHP-2 SH2-containing decoy proteins on Fc gamma RIIB1 signaling. Results demonstrate the SHIP is the predominant intracellular ligand for the phosphorylated Fc gamma RIIB1 ITIM, although the SHP-2 decoy exhibits some ability to bind Fc gamma RIIB1 and block Fc receptor function. The SHIP SH2, while not affecting Fc gamma RIIB1 tyrosyl phosphorylation, blocks receptor-mediated recruitment of SHIP, SHIP phosphorylation, recruitment of p52 Shc, phosphatidylinositol 3,4,5-trisphosphate hydrolysis, inhibition of mitogen-activated protein kinase activation, and, albeit more modestly, Fc gamma RIIB1 inhibition of Ca2+ mobilization. Taken together, results implicate ITIM interactions with SHIP as a major mechanism of Fc gamma RIIB1-mediated inhibitory signaling.

Animals↗
PubMed2001

Ultrastructural features of the nitric oxide synthase-containing interneurons in the nucleus accumbens and their relationship with tyrosine hydroxylase-containing terminals.

The ultrastructural features of neuronal nitric oxide synthase (NOS) -immunoreactive interneurons of rat nucleus accumbens shell and core were studied and compared. The NOS-containing subpopulation displayed characteristics similar to those previously described for nicotinamide adenine dinucleotide phosphate diaphorase-, neuropeptide Y, or somatostatin-containing striatal neurons, but also showed properties not previously associated with them, particularly the formation of both asymmetric and symmetric synaptic junctions. Inputs derived mainly from unlabeled terminals, but some contacts were made by NOS-immunolabeled terminals, by means of asymmetric synapses. Immunopositive endings that formed symmetric synapses were mainly onto dendritic shafts, whereas those that formed asymmetric synapses targeted spine heads. Morphometric analysis revealed that the core and shell NOS-stained neurons had subtly different innervation patterns and that immunostained terminals were significantly larger in the shell. A parallel investigation explored synaptic associations with dopaminergic innervation identified by labeling with an antibody against tyrosine hydroxylase (TH). In both shell and core, TH-positive boutons formed symmetric synapses onto NOS-containing dendrites, and in the core, TH- and NOS-immunolabeled terminals converged on both a single spiny dendrite and a spine. These results suggest that, in the rat nucleus accumbens, NOS-containing neurons may be further partitioned into subtypes, with differing connectivities in shell and core regions. These NOS-containing neurons may be influenced by a dopaminergic input. Recent studies suggest that nitric oxide potentiates dopamine release and the current study identifies the medium-sized, densely spiny neurons as a possible site of such an interaction.

Animals↗
PubMed2026

Distinct HLA Associations for Antibody Multireactivity With Citrulline-Containing Type II Collagen Epitopes Versus More Limited Antibody Reactivity With Citrulline-Containing IgG Epitopes in Rheumatoid Arthritis.

OBJECTIVE: Anticitrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA) can be promiscuous, with cross-reactive binding to many antigens containing short motifs, or private with little cross-reactivity. Also, ACPA reactivity patterns differ among patients with RA, including for motif-containing epitopes in important self-antigens like collagen and IgG (bound by RA-associated rheumatoid factors [RFs]), with limited understanding of the underlying mechanism. The objective of this study was to determine if HLA alleles associate with ACPA reactivity patterns. METHODS: For 100 ACPA+RF+ participants with RA, serum IgG binding was quantified by enzyme-linked immunosorbent assay to 10 citrulline-containing peptides derived from Type II collagen and IgG1 (nine with motifs), and HLA loci were genotyped. Also, antibody and serum multireactivity were evaluated. HLA alleles present differentially in RA participants with high versus low IgG binding to specific peptides, as well as with multireactivity versus limited reactivity were identified by Fisher's exact test. RESULTS: Serum IgG multireactivity for citrulline-glycine motif-containing collagen peptides was high, at least partially due to promiscuous antibodies. HLA-DQA1*01:02 was present in more participants with anticitrullinated collagen antibodies and multireactive sera. In contrast, serum multireactivity was low for IgG1-derived peptides due at least in part to more private antibodies. Shared epitope-containing HLA-DRB1*04:01 was present more frequently in participants with RA-associated RFs irrespective of the citrulline-serine motif and less frequently in participants with anticitrullinated collagen antibodies. Several HLA alleles associated with specific antibody reactivities. CONCLUSION: Different HLA alleles may contribute to the different reactivity patterns of promiscuous anticitrullinated collagen antibodies and more private RA-associated RFs.

Humans↗
PubMed1994

Interactions of cimetidine and ranitidine with aluminum-containing antacids and a clay-containing gastric-protective drug in an "artificial stomach-duodenum" model.

Interactions of cimetidine and ranitidine with aluminum-containing antacids and clay-containing gastric-protective drugs were analyzed in vitro by using an artificial stomach-duodenum model. The model reproduced near-physiologic conditions, taking into account gastric and duodenal flux variations and interactions between gastric mucosa and drugs added to the gastric content. Clay bound cimetidine in acid medium, but the drug was released when the pH increased, resulting in cimetidine amounts in the duodenal site close to those in controls. In contrast, clay bound ranitidine in acid medium and did not release it in the duodenal site. Aluminum-containing antacids did not significantly modify the amount of cimetidine or ranitidine available for absorption. Several factors play a role in the interactions of cimetidine and ranitidine with aluminum-containing antacids and clay-containing gastric-protective drugs: the structure of the antisecretory drugs, gastroduodenal pH, interactions of the antacid and clay with the gastric mucosa, and release of aluminum that could adsorb the drugs or prevent their adsorption by the mucosa. These phenomena are intricate and difficult to analyze without using a physicochemical approach.

Aluminum↗
PubMed1987

The distribution and origin of calcitonin gene-related peptide-containing nerve fibres in feline dental pulp. Relationship with substance P-containing nerve fibres.

The origin and distribution of calcitonin gene-related peptide (CGRP)-like immunoreactivity in feline dental pulp were studied using indirect immunofluorescence. Nerve fibres with varicosities exhibiting CGRP-like immunoreactivity were observed to enter the pulp with blood vessels. Many CGRP-containing nerve fibres were found to extend along blood vessels in the central pulp, and some of these fibres exhibited a network arrangement in the walls of dental pulp blood vessels. However, some of fibres were apparently not associated with blood vessels. Some thin, CGRP-containing nerve fibres formed a part of the nerve plexus in the subodontoblastic area and penetrated into the odontoblastic layer. In animals that had undergone transection of the inferior alveolar nerve, no CGRP-containing nerve fibres were observed. Application of a double-immunofluorescence staining technique also revealed that the distribution of CGRP-containing nerve fibres is very similar to that of substance P-containing nerve fibres.

Animals↗
PubMed1992

Isolation and characterization of radiation-reduced hybrids containing portions of the proximal long arm of the human X chromosome: identification of hybrids containing the Menkes' disease locus.

The proximal long arm of the human X chromosome (Xcen----Xq13) encompasses an estimated 23 megabases of DNA and contains numerous identified genetic loci. In order to generate a highly enriched source of DNA from this region, radiation-reduced human-hamster hybrids were constructed and screened to identify those that contained at least part of proximal Xq. Eight such hybrids were identified and characterized by Southern blot and fluorescence in situ hybridization analyses to determine more precisely the human DNA complement in each. One hybrid contains the entire proximal long arm and will be useful for mapping Xcen----Xq13 in its entirety and for localizing genes within this region. Another hybrid contains a smaller portion of the proximal long arm that includes the region reported to contain the gene for Menkes' disease.

Base Sequence↗
PubMed1980

Comparative study of the effect of oral contraceptives containing 50 microgram of estrogen and those containing 20 microgram of estrogen on adrenal cortical function.

Because the adrenal cortex is an endocrine gland essential to life, its function was studied in women who were taking an oral contraceptive that contained either 50 microgram or 20 microgram of estrogen. Of 32 healthy women studied, 18 used an oral contraoceptive that contained 50 microgram of estrogen, and 14 used an oral contraceptive that contained 20 microgram of estrogen. With 50 microgram of estrogen, the total plasma cortisol level rose significantly, the level of urinary cortisol excretion did not change significantly, and the levels of 17-ketosteroids and 17-ketogenic steroids were significantly reduced. With 20 microgram of estrogen, there were no significant changes in the levels of total plasma cortisol, urinary cortisol excretion, and the excretion of 17-ketosteroids and 17-ketogenic steroids. Thus, adrenal cortical function was altered in women who used an oral contraceptive that contained 50 microgram of estrogen, but there was no significant effect with the use of an oral contraoceptive that contained only 20 microgram of estrogen. Our findings confirm previous ones in regard to the effects of 50 microgram of estrogen on adrenal cortical function, although no studies had been carried out previously on the effects of 20 microgram of estrogen.

17-Ketosteroids↗
PubMed1990

The preparation of antibodies reactive against citrulline-containing charge isomers of myelin basic protein but not against the arginine-containing charge isomers.

Human myelin basic protein (MBP) is composed of several charge isomers, the result of various post-translational modifications. One of the charge isomers C-8, has been shown in our laboratory to contain six citrullinyl residues which replace arginyl residues at selected sites in the MBP. In order to determine the disposition of the citrulline-containing charge isomers in the myelin stack, we prepared specific antisera against the citrullinyl group. Since 9-fluorenylmethoxycarbonyl (Fmoc)-citrulline, required for the preparation of the synthetic peptides to be used for antibody production, was not commercially available, synthesis of the Fmoc-citrulline was a necessary prerequisite. The synthesis and purification of the N-9-fluorenylmethyloxycarbonyl derivative of citrulline is described. It was characterized by thin layer chromatography, 1H and 13C NMR spectroscopy, fast-atom bombardment mass spectroscopy, and thermal analyses. It was used in the automated peptide synthesis of a peptide Ala-Cit-His-Gly-Phe-Leu-Pro-Cit-His-Arg corresponding to residues 24-33 and Gly-Cit-Asp-Ser-Arg-Ser-Gly-Ser-Pro-Met-Ala-Cit-Arg, corresponding to residues 158-170 of the C-8 sequence, a naturally occurring charge isomer of human myelin basic protein, and a tetracitrulline peptide, Cit-Cit-Cit-Cit-Gly. The tetracitrulline peptide was used for the production of an antibody shown to react only with synthetic peptides and proteins containing citrulline. This antibody was used to distinguish between a citrulline-containing protein, C-8, a naturally occurring charge isomer of MBP, and a non-citrulline-containing charge isomer of MBP, C-1.

Amino Acid Sequence↗
PubMed1986

A quantitative analysis of the interrelationships between subpopulations of rat sensory neurons containing arginine vasopressin or oxytocin and those containing substance P, fluoride-resistant acid phosphatase or neurofilament protein.

In rat L5 dorsal root ganglia 50% of neurons contained arginine vasopressin-like immunoreactivity and 38% oxytocin-like immunoreactivity, the oxytocin entirely coexisting with the arginine vasopressin. Staining of alternate mirror-image sections with RT97 (an antibody to neurofilament protein, and a marker for large light neurons) and with arginine vasopressin antiserum showed that the two were entirely complementary, thus establishing arginine vasopressin as a marker for all small dark neurons. Mirror-image staining also showed that neurons containing substance P-like immunoreactivity and those containing fluoride-resistant acid phosphatase activity were each contained within the arginine vasopressin-positive population. Arginine vasopressin-like immunoreactivity was axonally transported in the dorsal root and (in greater quantity) in sciatic nerve. Arginine vasopressin-like immunoreactivity was present also in laminae I and II of the dorsal horn of the spinal cord and this reactivity was absent in animals which had been treated neonatally with capsaicin, suggesting that it was contained in primary afferent terminals. These results are discussed in terms of their implications for the classification of primary afferent neurons and of a possible physiological role for arginine vasopressin in these neurons.

Acid Phosphatase↗
PubMed2004

Potential roles of flavin-containing monooxygenases in sulfoxidation reactions of l-methionine, N-acetyl-l-methionine and peptides containing l-methionine.

Flavin-containing monooxygenases (FMOs) are microsomal enzymes that catalyze the NADPH-dependent oxidation of a large number of sulfur-, selenium-, and nitrogen-containing compounds. Five active isoforms (FMO1-5) have been identified and shown to be differently expressed in various mammalian tissues. Previous work from this laboratory has shown l-methionine to be S-oxidized by rat, rabbit and human FMO1-4, with FMO3 exhibiting the highest stereoselectivity for the formation of the d-diastereomer of methionine sulfoxide. In this report, we describe new studies aimed at determining if N-acetyl-l-methionine and peptides containing l-methionine can be substrates for FMOs. Experiments were carried out using either rabbit liver microsomes or human cDNA-expressed FMOs. The results show that while N-acetyl-l-methionine and peptides with a modified methionine amino group may not function as substrates for FMOs, peptides containing a free N-terminal methionine may act as FMO substrates. With human cDNA-expressed FMO1, FMO3, and FMO5, both FMO1 and FMO3 exhibited activity with the active peptides whereas FMO5 was inactive. With FMO3, the activity measured with methionine was similar (1 mM) or higher (5 mM) than the activity measured with H-Met-Val-OH and H-Met-Phe-OH. With FMO1, H-Met-Phe-OH and methionine exhibited similar activities whereas activity with H-Met-Val-OH was much lower. Collectively, the results show that FMOs can oxidize peptides containing a free N-terminal methionine. Thus, the role of FMOs in the oxidation of methionine in larger peptides or proteins warrants further investigation.

Chromatography, High Pressure Liquid↗
PubMed2004

Association behavior of fluorine-containing and non-fluorine-containing methacrylate-based amphiphilic diblock copolymer in aqueous media.

Fluorine-containing amphiphilic block copolymers, poly(sodium methacrylate)-block-poly(nonafluorohexyl methacrylate) (NaMAm-b-NFHMAn) (m:n = 61:12, 72:33, 64:57), and the corresponding non-fluorine-containing amphiphilic block copolymer, poly(sodium methacrylate)-block-poly(hexyl methacrylate) (NaMAm-b-HMAn) (m:n = 64:10, 69:37, 67:50), were synthesized. Both polyNaMA-b-polyNFHMA and polyNaMA-b-polyHMA formed micelles above critical micelle concentrations, (cmc's), around 3 x 10(-5) to 1 x 10(-4) mol/L, while neither polymer decreased surface tension of aqueous solutions. The size and shape of the micelles were examined by dynamic light scattering, small-angle neutron scattering, and small-angle X-ray scattering. PolyNaMA-b-polyHMA appeared to form only spherical micelles, while polyNaMA-b-polyNFHMA with a long NFHMA segment formed both spherical and rodlike micelles. The micelles of fluorine-containing block copolymers were obviously larger than those of non-fluorine-containing block copolymers with the same chain length and the same hydrophilic/hydrophobic chain ratio. The fluorine-containing block copolymer selectively solubilized fluorinated dye into the water phase when a mixture of decafluorobiphenyl and 2,6-dimethylnaphthalene was added to the micelle solution.

Journal Article↗
PubMed1985

Specific transcription of preformed nucleoprotein complexes, containing the adenovirus major late promoter, with a chromatographic fraction containing RNA polymerase II.

Incubation in a HeLa whole-cell extract converted a plasmid DNA containing the adenovirus type 2 major late promoter into ordered nucleoprotein complexes similar to those described for simian virus DNA [Sinha, S. N., Hellwig, R. J., Allison, D. P. & Niyogi, S. K. (1982) Nucleic Acids Res. 10, 5533-5552]. Purified nucleoprotein complexes containing the plasmid DNA were able to serve as template for accurate transcription in vitro. Use of such nucleoprotein complexes eliminated the need for addition of nontemplate DNA (poly[d(I-C)]) to transcription reaction mixtures with template concentrations too low to yield a detectable specific-transcription signal from "naked" DNA. Of the four fractions resulting from phosphocellulose column chromatography of the whole cell extract, only the fraction that contained the RNA polymerase II activity was needed to accurately transcribe these nucleoprotein complexes in the presence of human placental ribonuclease inhibitor. In contrast, specific transcription of naked template DNA under these conditions required at least one additional fraction containing specificity factors. These results show that the nucleoprotein complexes contain factor(s) needed for specific initiation of transcription and that these complexes may be useful in the purification and analysis of these factors.

Adenoviruses, Human↗
PubMed1993

Relationships between the responses of triglyceride-rich lipoproteins in blood plasma containing apolipoproteins B-48 and B-100 to a fat-containing meal in normolipidemic humans.

The concentration of triglyceride-rich lipoproteins containing apolipoprotein (apo) B-48 (chylomicrons) and apo B-100 (very low density lipoproteins) was measured in blood plasma of healthy young men after an ordinary meal containing one-third of daily energy and fat. Plasma obtained in the postabsorptive state and at intervals up to 12 hr after the meal was subjected to immunoaffinity chromatography against a monoclonal antibody to apo B-100 that does not bind apo B-48 and a minor fraction of apo B-100 rich in apo E. Measurements of the concentrations of components of the total and unbound triglyceride-rich lipoproteins separated from plasma by ultracentrifugation showed that about 80% of the increase in lipoprotein particle number was in very low density lipoproteins containing apo B-100 and only 20% was in chylomicrons containing apo B-48 that carry dietary fat from the intestine. The maximal increments and the average concentrations of apo B-48 and B-100 during the 12 hr were highly correlated (r2 = 0.80), suggesting that preferential clearance of chylomicron triglycerides by lipoprotein lipase leads to accumulation of hepatogenous very low density lipoproteins during the alimentary period. The composition of the bulk of very low density lipoproteins that were bound to the monoclonal antibody changed little and these particles contained about 90% of the cholesterol and most of the apo E that accumulated in triglyceride-rich lipoproteins. The predominant accumulation of very low density lipoprotein rather than chylomicron particles after ingestion of ordinary meals is relevant to the potential atherogenicity of postprandial lipoproteins.

Adult↗
PubMed1995

Rat kidney papilla contains abundant synaptobrevin protein that participates in the fusion of antidiuretic hormone-regulated water channel-containing endosomes in vitro.

Antidiuretic hormone (ADH) regulates renal water excretion by altering the permeability of the collecting duct to water. ADH-responsive epithelial cells are the major cell type lining kidney tubules in the inner medulla and papilla. ADH modulates apical membrane water permeability by the insertion and removal of vesicles containing aquaporin collecting duct water channel protein (now termed AQP-2). To identify and characterize proteins responsible for trafficking of AQP-2-containing vesicles, we utilized antibody and cDNA probes to synaptobrevin b (also termed VAMP-2, for vesicle-associated membrane protein 2), a protein that mediates synaptic vesicle exocytosis in the brain and whose structural homologs are now considered to be components of a complex responsible for intracellular vesicle fusion in all cells. We now report that rat kidney inner medulla and papilla contain abundant synaptobrevin protein. Only light endosomes, one of two types of purified papillary AQP-2-containing endosomes, possess synaptobrevin. Light endosomes fuse in vitro by means of an ATP-dependent process that is significantly inhibited when endosomes are preincubated with either anti-synaptobrevin antibody or tetanus toxin. These data define a functional role for a synaptobrevin protein in the fusion of endosomes in vitro. The presence of abundant synaptobrevin proteins in endosomes containing AQP-2 water channels, as well as insulin-sensitive glucose transporters [Cain, C. C., Trimble, W. S. & Lienhard, G. E. (1992) J. Biol. Chem. 267, 11681-11684], and in cells of Malpighian tubules responsible for urine formation in insects [Chin, A. S., Burgess, R. W., Wong, B. R., Schwartz, T. L. & Scheller, R. H. (1993) Gene 131, 175-181] suggests a specialized role for synaptobrevin in vesicle-mediated membrane transport modulated by peptide hormones.

Animals↗
PubMed1999

A significant part of native gamma-aminobutyric AcidA receptors containing alpha4 subunits do not contain gamma or delta subunits.

Using a novel antibody directed against the alpha4 subunit of gamma-aminobutyric acidA (GABAA) receptors, 5% of all [3H]muscimol but only about 2% of all [3H]Ro15-4513 binding sites present in brain membrane extracts could be precipitated. This indicated that part of the alpha4 receptors containing [3H]muscimol binding sites did not contain [3H]Ro15-4513 binding sites. Immunoaffinity purification and Western blot analysis of alpha4 receptors demonstrated that not only alpha1, alpha2, alpha3, beta1, beta2, and beta3 subunits but also gamma1, gamma2, gamma3, and delta subunits can be colocalized with alpha4 subunits in native GABAA receptors. Quantification experiments, however, indicated that only 7, 33, 4, or 7% of all alpha4 receptors contained gamma1, gamma2, gamma3, or delta subunits, respectively. These data not only explain the low percentage of [3H]Ro15-4513 binding sites precipitated by the anti-alpha4 antibody but also indicate that approximately 50% of the alpha4 receptors did not contain gamma1, gamma2, gamma3, or delta subunits. These receptors, thus, either are composed of alpha4 and beta1-3 subunits only, or additionally contain epsilon, pi, or so far unidentified GABAA receptor subunits.

Antibodies, Monoclonal↗
PubMed2006

Comparative biological and clinical outcomes after a switch from a virologically unsuccessful first protease inhibitor-containing antiretroviral combination to a 3-drug regimen containing efavirenz, nevirapine, or abacavir.

BACKGROUND: Incomplete adherence is the main cause of antiretroviral therapy failure during initial combination antiretroviral therapy (cART). A switch to a protease inhibitor-sparing cART may be useful when a patient does not tolerate a first protease inhibitor-containing cART regimen. METHODS: To compare the biological and clinical outcomes of patients in whom a first protease inhibitor-containing cART regimen failed to control viral replication and whose treatment was switched to cART containing efavirenz, nevirapine, or abacavir, we studied 1440 patients from the French Hospital Database on HIV whose treatment was changed from a first protease inhibitor-containing cART to a 3-drug regimen with either efavirenz, nevirapine, or abacavir while their plasma viral load was detectable. RESULTS: Kaplan-Meier 12-month probabilities of virological suppression were 73.6%, 53.9%, and 66.1% among patients whose treatment was switched to efavirenz-cART, nevirapine-cART, and abacavir-cART, respectively. Factors associated with a lower likelihood of virological suppression were antiretroviral exposure before the first cART, higher plasma viral load values at the treatment switch, a stavudine-lamivudine backbone after the switch (instead of a zidovudine-lamivudine backbone), and a switch to nevirapine (adjusted hazard ratio, 0.63 [95% CI, 0.54-0.74], compared with efavirenz) or abacavir (adjusted hazard ratio, 0.84 [95% CI, 0.68-1.04] compared with efavirenz). There was no difference among the 3 groups with regard to immunological gain (>50 CD4+ T cells/mm3) or clinical outcome. CONCLUSION: When virological rebound occurs from receipt of protease inhibitor-containing cART, virological suppression can be obtained after a switch to a protease inhibitor-free cART--efavirenz-cART yielding the highest rate of virological suppression.

Adult↗
PubMed2006

Switch from a first virologically effective protease inhibitor-containing regimen to a regimen containing efavirenz, nevirapine or abacavir.

BACKGROUND: Treatment simplification in antiretroviral-experienced patients receiving protease inhibitor (PI)-containing antiretroviral regimens seems safe, but randomized trials have limited power to detect differences in virological rebound (VR) between different switch strategies. METHODS: From the French Hospital Database on HIV, we selected 2462 patients with undetectable viral load (VL) who switched from a first PI-containing antiretroviral combination (cART) to a combination containing efavirenz (EFV), nevirapine (NVP) or abacavir (ABC). Factors associated with VR and with immunological efficacy (gain of > or = 50 CD4(+) cells/microl) were identified by using Cox models. RESULTS: The 12-month Kaplan-Meier probabilities of VR were 6.8, 13.7 and 12.3% in patients switching to EFV-cART, NVP-cART and ABC-cART, respectively. Factors associated with VR were female sex, younger age, antiretroviral exposure before the first cART, time on first cART, higher VL at first cART initiation, a stavudine/didanosine backbone (rather than zidovudine/lamivudine) after the switch, and a switch to NVP or ABC [respective adjusted hazard ratio versus EFV: 1.53; 95% confidence interval (CI), 1.21-1.94; and 1.53; 95% CI, 1.12-2.08]. When the analyses were restricted to patients who were antiretroviral-naive before their first cART, NVP (but not ABC) was associated with VR. Immunological outcomes did not differ among the three switch regimens. CONCLUSION: When VL is undetectable on a first PI-cART regimen, switching to an EFV-containing regimen is more likely to avoid VR than switching to an ABC or NVP-containing regimen. ABC may be an alternative to EFV for patients who were not exposed to antiretroviral before their first cART regimen, after checking for ABC resistance mutations.

Adult↗