Posts filed under ‘HIV/SIDA Prevencion’

HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study.

PLoS Med November 7, 2017 V.14 P.e1002417.

Henrich TJ et al.

Abstract

Background

It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART.

Methods and findings

Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection.

Conclusions

We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.

FULL TEXT

http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1002417

PDF

http://journals.plos.org/plosmedicine/article/file?id=10.1371/journal.pmed.1002417&type=printable

 

 

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November 21, 2017 at 7:27 am

2017-07 Guidelines for the managing advanced HIV disease and rapid initiation of antiretroviral therapy. WHO 56 pags

Overview

The objectives of these guidelines are to provide recommendations outlining a public health approach to managing people presenting with advanced HIV disease, and to provide guidance on the timing of initiation of antiretroviral therapy (ART) for all people living with HIV.

The first set of recommendations addresses the specific needs of people with advanced HIV disease and defines a package of interventions aimed at reducing HIV-associated morbidity and mortality. WHO recommends that a package of screening, prophylaxis, rapid ART initiation and intensified adherence interventions be offered to everyone living with HIV presenting with advanced disease. This is a strong recommendation that applies to all populations and age groups. The guidelines also include an algorithm to support decision making for providing care for people with advanced HIV disease.

The second set of recommendations defines how rapidly ART should be initiated within the context of the “treat all” policy, especially when coinfections are present. WHO strongly recommends that rapid ART initiation should be offered to people living with HIV following confirmed diagnosis and clinical assessment. Rapid initiation of ART is defined as within seven days of HIV diagnosis. WHO further strongly recommends ART initiation on the same day as HIV diagnosis based on the person’s willingness and readiness to start ART immediately, unless there are clinical reasons to delay treatment. Both of these recommendations apply to all populations and age groups. People with advanced HIV disease should be given priority for clinical assessment and treatment initiation.

PDF

http://apps.who.int/iris/bitstream/10665/255884/1/9789241550062-eng.pdf?ua=1

August 7, 2017 at 9:56 am

Correspondence: Multidrug-resistant HIV-1 infection despite preexposure prophylaxis.

N Engl J Med 2017 Feb 2; 376:501

Knox DC et al.

To the Editor:

Preexposure prophylaxis with emtricitabine (FTC)–tenofovir disoproxil fumarate (TDF) has been shown to be efficacious in preventing human immunodeficiency virus type 1 (HIV-1) infection in men who have sex with men and in whom adherence to treatment is high, as measured by levels of tenofovir diphosphate (TFV-DP) in dried blood spots.1 We describe a case of HIV-1 infection despite FTC-TDF–based preexposure prophylaxis.2

A 43-year-old man in Toronto who reported having sex with men began to receive oral daily FTC-TDF in April 2013 and had seven nonreactive fourth-generation HIV screening tests over the next 21 months. Pharmacy dispensation records provided support for his report of “perfect” adherence to preexposure prophylaxis over 24 months……

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMc1611639

March 14, 2017 at 7:35 am

Recommendations for Use of Meningococcal Conjugate Vaccines in HIV-Infected Persons – Advisory Committee on Immunization Practices, 2016.

MMWR Morb Mortal Wkly Rep. November 4, 2016 V.65 N.43 P.1189-1194.

MacNeil JR, Rubin LG, Patton M, Ortega-Sanchez IR, Martin SW.

Abstract

At its June 2016 meeting, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of meningococcal conjugate vaccine (serogroups A, C, W, and Y; including MenACWY-D [Menactra, Sanofi Pasteur] or MenACWY-CRM [Menveo, GlaxoSmithKline]) for persons aged ≥2 months with human immunodeficiency virus (HIV) infection.

ACIP has previously recommended routine vaccination of persons aged ≥2 months who have certain medical conditions that increase risk for meningococcal disease, including persons who have persistent (e.g., genetic) deficiencies in the complement pathway (e.g., C3, properdin, Factor D, Factor H, or C5-C9); persons receiving eculizumab (Soliris, Alexion Pharmaceuticals) for treatment of atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria (because the drug binds C5 and inhibits the terminal complement pathway); and persons with functional or anatomic asplenia (including persons with sickle cell disease). Routine vaccination with meningococcal conjugate vaccine is also recommended for all healthy adolescents in the United States.

This report summarizes the evidence considered by ACIP in recommending vaccination for HIV-infected persons, and provides recommendations and guidance for use of meningococcal conjugate vaccines (serogroups A, C, W, and Y) among HIV-infected persons aged ≥2 months; the majority of meningococcal disease among HIV-infected persons is caused by these four serogroups.

PDF

https://www.cdc.gov/mmwr/volumes/65/wr/pdfs/mm6543a3.pdf

December 13, 2016 at 7:31 am

2016 BHIVA GUIDELINES for the treatment of HIV-1-positive Adults with antiretroviral therapy

The British HIV Association

Writing Group

Laura Waters (Chair)

N Ahmed, B Angus, M Boffito, M Bower, D Churchill, D Dunn, S Edwards, C Emerson, S Fidler, †M Fisher, R Horne, S Khoo, C Leen, N Mackie, N Marshall, F Monteiro, M Nelson, C Orkin, A Palfreeman, S Pett, A Phillips, F Post, A Pozniak, I Reeves, C Sabin, R Trevelion, J Walsh, E Wilkins, I Williams, A Winston

†Professor Martin Fisher died in April 2015 – he made a significant contribution to these, many other guidelines and our speciality as a whole – he is greatly missed.

Introduction

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection on antiretroviral therapy (ART).

The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii) support of people living with HIV (PLWH) on treatment; (iii) management of individuals experiencing virological failure; and (iv) recommendations in specific populations where other factors need to be taken into consideration.

The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection, and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.

The 2016 interim update to the 2015 BHIVA antiretroviral guidelines has been published online to include tenofovir-alafenamide/emtricitabine as a preferred NRTI backbone for first-line therapy. Changes were based on new data and the consensus opinion of the writing committee. All changes to the guideline are highlighted and include updates to the chronic kidney disease and bone disease sections of special populations and some small changes to managing virological failure. The next formal update to the guidelines in anticipated in 2017.

PDF

http://www.bhiva.org/documents/Guidelines/Treatment/2016/treatment-guidelines-2016-interim-update.pdf

December 3, 2016 at 9:33 am

2015 UK National GUIDELINE for the Use of HIV PEP Following Sexual Exposure

The British HIV Association

Introduction

We present the updated British Association for Sexual Health and HIV (BASHH) guidelines which aim to provide evidence-based recommendations for the most appropriate use of HIV post-exposure prophylaxis following sexual exposure (PEPSE).

The aim of PEPSE is to prevent HIV transmission. Risk of transmission, timing of PEP, preferred regimen, drug-drug interactions, follow-up, risk reduction and special scenarios are discussed. Consideration is given to the role of PEPSE within the broader context of HIV prevention and sexual health.

The guideline is intended to be complementary to existing Department of Health and Expert Advisory Group on AIDS (EAGA) guidance on PEP (1).

It is aimed primarily at clinicians and policymakers in sexual health, sexual assault referral centres (SARCs), and primary and emergency care providers within the UK who should consider the development of appropriate local pathways.

It is likely that this guideline will also be used for information provision by voluntary sector agencies to provide information for individuals.

The recommendations are aimed primarily at individuals aged 16 or older and may not be appropriate for use in all situations, including occupational exposures.

Decisions to follow these recommendations must be based on the professional judgment of the clinician and consideration of individual patient circumstances and available resources.

PDF

https://www.bashh.org/documents/PEPSE%202015%20guideline%20final_NICE.pdf

December 3, 2016 at 9:31 am

2015 BHIVA GUIDELINES on the use of vaccines in HIV-positive Adults

Writing Group

Chair and Editor: Prof Anna Maria Geretti

Members (in alphabetic order):

Dr Gary Brook, Central Middlesex Hospital, London

Ms Claire Cameron, Public Health England, London

Dr David Chadwick, James Cook University Hospital, Middlesbrough

Prof Neil French, University of Liverpool

Prof Robert Heyderman, University College London

Dr Antonia Ho, University of Liverpool

Dr Michael Hunter, Belfast Health and Social Care Trust

Dr Shamez Ladhani, Public Health England, London

Dr Mark Lawton, Royal Liverpool University Hospital

Dr Eithne MacMahon, Guy’s & St Thomas’ NHS Foundation Trust & King’s College London, London

Dr John McSorley, Central Middlesex Hospital, London

Dr Anton Pozniak, Chelsea and Westminster Hospital, London

Dr Alison Rodger, University College London

Introduction

These guidelines provide updated, GRADE-based recommendations on the use of vaccines in HIV-positive adults. Several factors have made the updating of HIV-specific vaccination guidelines important: effective antiretroviral therapy (ART) has substantially modified the natural history of HIV infection, vaccination practices are evolving, and a large number of novel vaccines are becoming available in clinical care.

The update contains important new guidance regarding the use of new vaccines against human papillomavirus (HPV), shingles (herpes zoster) and pneumococcus. Further key updates are related to the use of hepatitis B, meningococcus and pertussis vaccines.

Compared with HIV-negative individuals, HIV-positive adults often have an increased risk of infection or experience more severe morbidity following exposure to vaccine-preventable diseases, and therefore a lower threshold for extending indications and offering vaccination may be appropriate relative to the general population.

Improved health and prognosis mean that HIV-positive adults are also increasingly likely to engage in travel or occupations that carry a risk of exposure to infectious agents, and these otherwise healthy individuals should not be denied protection or engagement with such activities if evidence indicates vaccination is safe and immunogenic.

Immune responses to vaccination are often sub-optimal in HIV-positive patients, and while these improve with ART, they often remain lower and decline more rapidly than in HIV-negative individuals.

However, many of these vaccines still afford protection and for some vaccines it is possible to improve immunogenicity by offering modified vaccine schedules, with higher or more frequent doses, without compromising safety.

Since their publication, these guidelines have been endorsed by the British Infection Association (BIA), European Clinical AIDS Society (EACS) and the Royal College of General Practitioners (RCGP).

PDF

http://www.bhiva.org/documents/Guidelines/Vaccination/2015-Vaccination-Guidelines.pdf

December 3, 2016 at 9:28 am

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