Posts filed under ‘HIV/SIDA Controladores de elite’

GeSIDA/National AIDS Plan: Consensus document on antiretroviral therapy in adults infected by the human immunodeficiency virus (Updated January 2014).

Enferm Infecc Microbiol Clin. 2014 Aug-Sep;32(7):446.e1-42.

Article in Spanish

Panel de expertos de GeSIDA; Plan Nacional sobre el Sida.

Abstract

OBJECTIVE:

This consensus document is an update of combined antiretroviral therapy (cART) guidelines for HIV-1 infected adult patients.

METHODS:

To formulate these recommendations a panel composed of members of the Grupo de Estudio de Sida and the Plan Nacional sobre el Sida reviewed the efficacy and safety advances in clinical trials, cohort and pharmacokinetic studies published in medical journals (PubMed and Embase) or presented in medical scientific meetings. Recommendations strength and the evidence in which they are supported are based on modified criteria of the Infectious Diseases Society of America.

RESULTS:

In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation varies with the clinical circumstances: CDC stage B or C disease (A-I), asymptomatic patients (depending on the CD4+ T-lymphocyte count: <350cells/μL, A-I; 350-500 cells/μL, A-II, and >500 cells/μL, B-III), comorbid conditions (HIV nephropathy, chronic hepatitis caused by HBV or HCV, age >55years, high cardiovascular risk, neurocognitive disorders, and cancer, A-II), and prevention of transmission of HIV (mother-to-child or heterosexual, A-I; men who have sex with men, A-III). The objective of ART is to achieve an undetectable plasma viral load. Initial ART should always comprise a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors and a third drug from a different family (non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or integrase inhibitor). Some of the possible initial regimens have been considered alternatives. This update presents the causes and criteria for switching ART in patients with undetectable plasma viral load and in cases of virological failure where rescue ART should comprise 2 or 3 drugs that are fully active against the virus. An update is also provided for the specific criteria for ART in special situations (acute infection, HIV-2 infection, and pregnancy) and with comorbid conditions (tuberculosis or other opportunistic infections, kidney disease, liver disease, and cancer).

CONCLUSIONS:

These new guidelines updates previous recommendations related to cART (when to begin and what drugs should be used), how to monitor and what to do in case of viral failure or drug adverse reactions. cART specific criteria in comorbid patients and special situations are equally updated.

PDF

http://apps.elsevier.es/watermark/ctl_servlet?_f=10&pident_articulo=90340091&pident_usuario=0&pcontactid=&pident_revista=28&ty=107&accion=L&origen=zonadelectura&web=www.elsevier.es&lan=es&fichero=28v32n07a90340091pdf001.pdf

June 13, 2015 at 10:40 am

Infrequent Recovery of HIV from but Robust Exogenous Infection of Activated CD4+ T Cells in HIV Elite Controllers

Clin Infect Dis. July 15, 2010 V.51 N.2P.233-238

Julg1, F. Pereyra1, M. J. Buzón3, A. Piechocka-Trocha1,2, M. J. Clark1, B. M. Baker1, J. Lian1, T. Miura1,2,5, J. Martinez-Picado3,4, M. M. Addo1, and B. D. Walker1,2

1Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Boston, Massachusetts

2Howard Hughes Medical Institute, Chevy Chase, Maryland

3irsiCaixa Foundation, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

4Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain

5Institute of Medical Science, University of Tokyo, Tokyo, Japan

Reprints or correspondence: Dr Bruce D. Walker, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, 149 Thirteenth St, Charlestown, MA 02129 (bwalker@partners.org).

Abstract

Background

Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV-1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4+ T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication.

Methods

We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8+ T cell—depleted CD4+ T cells from HIV elite controllers (mean viral load, <50 copies/mL), viremic controllers (mean viral load, <2000 copies/mL), chronic progressors, and individuals receiving highly active antiretroviral therapy.

Results

Although we successfully detected autologous virus production in ex vivo activated CD4+ T cells from all chronic progressors and from most of the viremic controllers, we were able to measure robust autologous viral replication in only 2 of 14 elite controllers subjected to the same protocol. In vitro activated autologous CD4+ T cells from elite controllers, however, supported infection with both X4 and R5 tropic HIV strains at comparable levels to those in CD4+ T cells from HIV-uninfected subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contribute to difficulty in isolation of virus.

Conclusions

These data indicate that elite control is not due to inability of activated CD4+ T cells to support HIV infection, but the relative contributions of host and viral factors that account for maintenance of low-level infection remain to be determined.

PDF

http://cid.oxfordjournals.org/content/51/2/233.full.pdf+html

September 22, 2014 at 2:31 pm

How Do HIV Elite Controllers Do What They Do?

Clin Infect Dis. July 15, 2010 V.51 N.2P.239-241

Editorial Commentary

Michael Saag1 and Steven G. Deeks2

1University of Alabama at Birmingham, Birmingham, Alabama

2San Francisco General Hospital, University of California, San Francisco, California

Reprints or correspondence: Dr Michael Saag, Center for AIDS Research, University of Alabama at Birmingham, 845 19th St South, BBRB 256, Birmingham, AL 35294-2170 (msaag@uab.edu).

Soon after the initial discovery of human immunodeficiency virus (HIV) as the cause of AIDS, a small group of HIV-infected patients were identified who did not seem to progress immunologically toward AIDS.

These “long-term nonprogressors” were initially defined on the basis of their ability to maintain high CD4 cell counts over many years in the absence of antiretroviral therapy [1].

Over the past decade, many of the long-term nonprogressors exhibited slow progression to lower CD4 cell counts, a process that was predicted in part by their level of viremia.

This prompted further refinement of the “nonprogressor” phenotype into one that was based primarily on viral load, with most studies now focusing on those who have undetectable viremia using conventional assays (HIV RNA <50 copies/mL, “elite controllers”) and those who have low but detectable viremia (HIV RNA <2000 copies/mL, “viremic controllers”) [2, 3].

It is widely hoped that knowledge gained regarding the mechanism of virus control could informboth the vaccine and the HIV eradication efforts…

PDF

http://cid.oxfordjournals.org/content/51/2/239.full.pdf+html

September 22, 2014 at 2:30 pm

Elite control of HIV Infection: implications for vaccines and treatment.

Top HIV Med. 2007 Aug-Sep;15(4):134-6.

Walker BD.

Author information

Harvard Medical School, Boston, MA, USA.

Abstract

Spontaneous and sustained (“elite,” or aviremic) control of HIV infection (ie, maintaining HIV RNA to less than 50 copies/mL in the absence of therapy) appears to occur in approximately 1 in 300 HIV-infected persons, and represents a distinct phenotype among HIV-infected individuals.

Through a recently established international collaboration called the HIV Controller Consortium, over 300 elite controllers have been identified and blood samples collected.

These ongoing studies will not only examine the immune responses to HIV that elite controllers generate, but will also make use of a newly available approach to defining the genetic basis of disease.

Specifically, the consortium is attempting to determine the genetic basis underlying spontaneous control by performing whole genome analysis scans together with functional immunology studies in a large population of elite controllers.

The goal of these studies is to provide insights that will help define the crucial parameters present in persons who are able to control HIV infection, similar to the control most people have with Epstein-Barr virus and varicella, namely by holding the virus in check. These findings could assist in the development of vaccines and new therapies.

This article summarizes a presentation on spontaneous control of HIV infection and its implications for vaccine development made by Bruce D. Walker, MD, at an International AIDS Society-USA Continuing Medical Education course in New York in March 2007. The original presentation is available as a Webcast at http://www.iasusa.org.

PDF

http://www.iasusa.org/sites/default/files/tam/15-4-134.pdf

September 19, 2014 at 4:04 pm

Increased coronary atherosclerosis and immune activation in HIV-1 elite controllers.

AIDS. 2012 Nov 28;26(18):2409-12.

Pereyra F1, Lo J, Triant VA, Wei J, Buzon MJ, Fitch KV, Hwang J, Campbell JH, Burdo TH, Williams KC, Abbara S, Grinspoon SK.

Author information

1Program in Nutritional Metabolism, Department of Radiology, Massachusetts General Hospital, Boston, USA.

Abstract

HIV-1 elite controllers spontaneously maintain suppressed levels of viremia, but exhibit significant immune activation.

We investigated coronary atherosclerosis by coronary computed tomography angiography (CTA) in elite controllers, nonelite controller, chronically HIV-1 infected, antiretroviral therapy (ART)-treated patients with undetectable viral load (‘chronic HIV’), and HIV-negative controls.

Prevalence of atherosclerosis (78 vs. 42%, P < 0.05) and markers of immune activation were increased in elite controllers compared with HIV-negative controls. sCD163, a monocyte activation marker, was increased in elite controllers compared with chronic HIV-1 (P < 0.05) and compared with HIV-negative controls (P < 0.05).

These data suggest a significant degree of coronary atherosclerosis and monocyte activation among elite controllers.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660105/pdf/nihms-471827.pdf

September 19, 2014 at 4:02 pm

Slow progressor of human immunodeficiency virus: 20 years follow-up of a case from North India.

Indian J Med Microbiol. 2014 Jan-Mar;32(1):75-6.

Sehgal S1, Minz RW, Saikia B, Pasricha N.

Author information

1Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Abstract

A case of human immunodeficiency virus (HIV) infection from North India is described with a 20-year follow-up.

Patient first reported in 1993 when he was detected HIV positive, remained healthy without treatment, married in 1999 and did not transmit the disease to his children or his wife and was lost to follow-up. He was thought to be an elite controller.

After 15 years of the initial visit, his CD4 cells, however, were found to be low, with a viral load of 10,000/copies/ml. He was negative for human leukocyte antigen B57 and B27 alleles with a normal expression of CCR5 and CXCR4 on CD4 cells. Lymphocytes showed a significant production of tumour necrosis factor alpha and interferon γ, but not of interleukin (IL)-2, IL4 or IL10.

It is possible that gut infection, common in India, could have triggered T cell activation in the ensuing years, resulting in activation of HIV.

The case illustrates the significance of long-term follow-up of these patients for timely institution of anti-retroviral therapy.

FULL TEXT

http://www.ijmm.org/article.asp?issn=0255-0857;year=2014;volume=32;issue=1;spage=75;epage=76;aulast=Sehgal

September 14, 2014 at 6:00 pm

Blunted response to combination antiretroviral therapy in HIV elite controllers: an international HIV controller collaboration.

PLoS One. 2014 Jan 17;9(1):e85516.

Boufassa F1, Lechenadec J2, Meyer L3, Costagliola D4, Hunt PW5, Pereyra F6, Deeks S5, Pancino G7, Taulera O8, Lichterfeld M9, Delobel P10, Saez-Cirion A7, Lambotte O11; ANRS CO18 HIV Controllers Cohort; Cascade Collaboration in Eurocoord; SCOPE Cohort; International HIV Controllers Study.

Author information

1Inserm, CESP Centre for research in Epidemiology and Population Health, Epidemiology of HIV and STI Team, le Kremlin-Bicêtre, France ; Univ Paris-Sud, Le Kremlin Bicêtre, France.

2Univ Paris-Sud, Le Kremlin Bicêtre, France.

3Inserm, CESP Centre for research in Epidemiology and Population Health, Epidemiology of HIV and STI Team, le Kremlin-Bicêtre, France ; Univ Paris-Sud, Le Kremlin Bicêtre, France ; AP-HP, Service de Santé Publique, Hôpital de Bicêtre, le Kremlin Bicêtre, France.

4UPMC Univ Paris 06, Paris, France ; INSERM, Paris, France.

5Laboratory Medicine, Departments of Medicine, Epidemiology, and Biostatistics, University of California San Francisco, San Francisco, California, United States of America.

6The Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, Massachusetts, United States of America.

7Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.

8Hôpital Saint-Louis, Paris, France.

9Infectious Disease Division, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

10Service des Maladies Infectieuses et Tropicales, Hôpital Purpan, Toulouse, France ; INSERM, Toulouse, France.

11AP-HP, Service de Médecine Interne, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.

Abstract

OBJECTIVE:

HIV “elite controllers” (ECs) spontaneously control viral load, but some eventually require combination antiretroviral treatment (cART), due to a loss of viral control or a decline in CD4 T-cell counts. Here we studied the CD4 T-cell count dynamics after cART initiation among 34 ECs followed in U.S. and European cohorts, by comparison with chronically viremic patients (VIRs).

METHODS:

ECs were defined as patients with at least ≥5 viral load (VL) measurements below 400 copies/mL during at least a 5-year period despite never receiving ART and were selected from the French ANRS CO18 cohort, the U.S. SCOPE cohort, the International HIV Controllers study and the European CASCADE collaboration. VIRs were selected from the ANRS COPANA cohort of recently-diagnosed (<1 year) ART-naïve HIV-1-infected adults. CD4 T-cell count dynamics after cART initiation in both groups were modelled with piecewise mixed linear models.

RESULTS:

After cART initiation, CD4 T-cell counts showed a biphasic rise in VIRs with: an initial rapid increase during the first 3 months (+0.63√CD4/month), followed by +0.19√CD4/month. This first rapid phase was not observed in ECs, in whom the CD4Tc count increased steadily, at a rate similar to that of the second phase observed in VIRs. After cART initiation at a CD4 T-cell count of 300/mm(3), the estimated mean CD4 T-cell gain during the first 12 months was 139/mm(3) in VIRs and 80/mm(3) in ECs (p = 0.048).

CONCLUSIONS:

cART increases CD4 T-cell counts in elite controllers, albeit less markedly than in other patients.

PDF

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894966/pdf/pone.0085516.pdf

September 12, 2014 at 8:43 am

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