Archive for December 18, 2011

Transcriptional profiling of CD4 T cells identifies distinct subgroups of HIV-1 elite controllers.

J Virol. 2011 Mar;85(6):3015-9.

Vigneault F, Woods M, Buzon MJ, Li C, Pereyra F, Crosby SD, Rychert J, Church G, Martinez-Picado J, Rosenberg ES, Telenti A, Yu XG, Lichterfeld M.

Source

Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Human immunodeficiency virus type 1 (HIV-1) elite controllers maintain undetectable levels of viral replication in the absence of antiretroviral therapy (ART), but their underlying immunological and virological characteristics may vary. Here, we used a whole-genome transcriptional profiling approach to characterize gene expression signatures of CD4 T cells from an unselected cohort of elite controllers. The transcriptional profiles for the majority of elite controllers were similar to those of ART-treated patients but different from those of HIV-1-negative persons. Yet, a smaller proportion of elite controllers showed an alternative gene expression pattern that was indistinguishable from that of HIV-1-negative persons but different from that of highly active antiretroviral therapy (HAART)-treated individuals. Elite controllers with the latter gene expression signature had significantly higher CD4 T cell counts and lower levels of HIV-1-specific CD8(+) T cell responses but did not significantly differ from other elite controllers in terms of HLA class I alleles, HIV-1 viral loads determined by ultrasensitive single-copy PCR assays, or chemokine receptor polymorphisms. Thus, these data identify a specific subgroup of elite controllers whose immunological and gene expression characteristics approximate those of HIV-1-negative persons.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3067917/pdf/1846-10.pdf

December 18, 2011 at 7:45 pm Leave a comment

HIV-1 diversity after a class switch failure.

AIDS Res Hum Retroviruses. 2010 Nov;26(11):1175-80.

Kolber MA, Buendia P, Degruttola V, Moore RD.

Source

Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. mkolber@med.Miami.edu

Abstract

The purpose of this study is to evaluate whether the choice of a PI- or an efavirenz (EFV)-based HAART initial regimen impacts on the viral diversity after failure from a second, class-switch salvage regimen. Sequential HAART failures after a class switch were identified for which the genotypes showed evidence of signature mutations at each failure. Each second failure was required to be from a viral burden <400 RNA c/ml. Thirteen cases of sequential failure from an initial EFV-containing to a PI-containing regimen (EP), and 19 sequential failures from an initial PI-containing to an EFV-containing regimen (PE) were identified. The persistence of signature mutations from the first failure were evaluated at second failure and compared between the EP and PE groups. Phylogenetic trees were constructed for a subgroup of cases from existing genetic sequence information and branch length analysis was used to determine evidence of viral diversity between groups. For EP sequential therapy, 10 of 12 cases carried forward a key non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation in the second failure compared to 5 of 13 cases for PE sequential therapy (p = 0.041). Phylogenetic analysis demonstrated that there was more viral diversity in the PE group as compared to the EP group, consistent with the interpretation that mutations at the second failure added to an ancestral virus closer to baseline rather than to the dominant virus at first failure. The development of HIV viral diversity after multiple HAART failures is determined by the sequence in which the regimens are ordered.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000642/pdf/aid.2010.0069.pdf

December 18, 2011 at 7:43 pm Leave a comment

Severe Cytomegalovirus Infection in Immunocompetent Patients

Clin Infect Dis January 1997 V.24 N.1 P.52-56

M. Eddleston, S. Peacock, M. Juniper, and D. A. Warrell

Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom

Reprints or correspondence: Dr. D. A. Warrell, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Headington, OX3 9DU, United Kingdom.

Abstract

Severe cytomegalovirus (CMV) infection is rare in previously healthy immunocompetent individuals; to our knowledge, only thirty-four such cases have been reported in the worldwide literature. Multiorgan involvement was associated with a high mortality rate among these patients. Disease that clinically involves only the liver or lungs could be fatal; in contrast, none of the patients with isolated central nervous system infection died. Although few patients were treated with specific antiviral therapy, five of six patients with severe infection recovered after receiving therapy with ganciclovir or foscarnet. The rarity of severe CMV disease in immunocompetent patients probably precludes the performance of a clinical trial to evaluate the efficacy of specific antiviral therapy. However, the historically poor prognosis in the absence of such therapy suggests that rapid diagnosis of CMV disease and early instigation of specific treatment may be important.

PDF

http://cid.oxfordjournals.org/content/24/1/52.full.pdf+html

 

December 18, 2011 at 7:40 pm Leave a comment

Cytomegalovirus-associated acute gastric mucosal lesion in an immunocompetent host.

Intern Med. 2009;48(17):1521-4.

Himoto T, Goda F, Okuyama H, Kono T, Yamagami A, Inukai M, Masugata H, Kobayashi M, Inoue H, Kinekawa F, Masaki T, Haba R, Ohashi E, Mori T, Senda S.

Source

Department of Integrated Medicine, Kagawa University School of Medicine, Kagawa. thimoto@med.kagawa-u.ac.jp

Abstract

Involvement of the gastrointestinal tract in cytomegalovirus (CMV) infection is commonly observed in immunocompromised hosts. We encountered an immunocompetent patient with CMV associated-acute gastric mucosal lesion (AGML). The emergence of inclusion bodies characteristic of CMV infection in the specimens obtained from the patient’s gastric ulcers was helpful in identifying the cause of AGML. The patient recovered without the administration of antiviral drugs. This case illustrates that CMV infection can be one of the causative agents that trigger AGML even in immunocompetent hosts, and that gastric biopsies are extremely useful for ascertaining the etiology of AGML.

Comment in

Intern Med. 2010;49(12):1265-7; author reply 1269.

PDF

http://www.jstage.jst.go.jp/article/internalmedicine/48/17/1521/_pdf

 

 

December 18, 2011 at 7:37 pm Leave a comment


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