Posts filed under ‘Profilaxis Pre-Exposición’

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

Influenza vaccination of pregnant women and protection of their infants.

N Engl J Med. 2014 Dec 11;371(24):2340.

Madhi SA, Nunes MC, Cutland CL.

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMc1412050

April 3, 2016 at 12:10 pm

Cellular immune correlates analysis of an HIV-1 preexposure prophylaxis trial.

Proc Natl Acad Sci U S A 2015 Jun 22;[e-pub].

Carlos del Rio, MD Reviewing Kuebler PJ et al.,

aDivision of Experimental Medicine, University of California, San Francisco, CA 94110;

bInstitute of Virology & Immunology, Gladstone Institutes, San Francisco, CA 94158;

cDivision of Clinical Immunology and Allergy, University of São Paulo, São Paulo, Brazil 01246;

dDepartment of Microbiology, Immunology and Tropical Medicine, George Washington University, Washington, DC 20037;

eDepartment of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158;

fDepartment of Medicine, University of California, San Francisco, CA 94143

HIV-1–specific T-cell responses in exposed seronegative subjects suggest that a viral breach of the exposure site is more common than current transmission rates would suggest and that host immunity can extinguish subsequent infection foci.

The Preexposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial provided an opportunity to rigorously investigate these responses in a case–control immunology study; 84 preinfection peripheral blood mononuclear cell samples from individuals enrolled in the iPrEx trial who later seroconverted were matched with 480 samples from enrolled subjects who remained seronegative from both the placebo and active treatment arms.

T-cell responses to HIV-1 Gag, Protease, Integrase, Reverse Transcriptase, Vif, and Nef antigens were quantified for all subjects in an IFN-γ enzyme-linked immunospot (ELISpot) assay. IFN-γ responses varied in magnitude and frequency across subjects. A positive response was more prevalent in those who remained persistently HIV-1–negative for Gag (P = 0.007), Integrase (P < 0.001), Vif (P < 0.001), and Nef (P < 0.001). When correlated with outcomes in the iPrEx trial, Vif- and Integrase-specific T-cell responses were associated with reduced HIV-1 infection risk [hazard ratio (HR) = 0.36, 95% confidence interval (95% CI) = 0.19–0.66 and HR = 0.52, 95% CI = 0.28–0.96, respectively].

Antigen-specific responses were independent of emtricitabine/tenofovir disoproxil fumarate use. IFN-γ secretion in the ELISpot was confirmed using multiparametric flow cytometry and largely attributed to effector memory CD4+ or CD8+ T cells.

Our results show that HIV-1–specific T-cell immunity can be detected in exposed but uninfected individuals and that these T-cell responses can differentiate individuals according to infection outcomes.

abstract

http://www.pnas.org/content/early/2015/06/17/1501443112

PDF

http://www.pnas.org/content/early/2015/06/17/1501443112.full.pdf

July 3, 2015 at 8:10 am

Editor’s Choice: Weighing the Risk of Drug Resistance With the Benefits of HIV Preexposure Prophylaxis

Journal of Infectious Diseases  April 15, 2015 211 (8) P.1202-1204

Robert M. Grant and Teri Liegler

The threat of drug resistance deserves careful attention from clinicians and public health officials advocating antiretroviral use as a way to control the human immunodeficiency virus (HIV) epidemic. Such antiretroviral use includes early treatment and preexposure prophylaxis (PrEP) and postexposure prophylaxis (PEP). Concerns about drug resistance were raised before rolling out widespread antiretroviral therapy in Africa, based on the assumption that adherence to therapy would be poor and drug resistance would become prevalent. Defying expectations, the benefits of antiretroviral therapy for improving health, averting death, and preventing transmission were subsequently proven to outweigh the risks of drug resistance, and adherence to therapy in African populations is often outstanding [1].

Fear of drug resistance is now raised as we consider rolling out PrEP. Daily oral PrEP using emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or TDF alone is safe and effective for preventing HIV acquisition [2–5] in sexually active adults. Adherence is essential for effectiveness [2, 6, 7]. Such regimens do not fully suppress systemic HIV infection, so starting PrEP in people already infected with HIV may lead to drug resistance [2–4]. Recommendations for PrEP emphasize the importance of HIV testing prior to starting or restarting PrEP.

In this issue of The Journal of Infectious Diseases, Lehman et al report new information about the risk of antiretroviral resistance from the Partners PrEP Study of men and women in Africa who are partnered with a person living with HIV [8]. (The usual term, “discordant couple,” obscures their commitment, courage, and cooperation.) The Partners PrEP Study is exceptional among randomized trials in that the levels of adherence were very high, with 71% of people randomly assigned to the …

PDF

http://jid.oxfordjournals.org/content/211/8/1202.full.pdf+html

June 15, 2015 at 8:31 pm

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

Update on Recommendations for Use of Herpes Zoster Vaccine

MMWR AUG. 22, 2014 V.63 N.33 P.729-31

 

Craig M. Hales, MD1, Rafael Harpaz, MD1, Ismael Ortega-Sanchez, PhD1, Stephanie R. Bialek, MD1

1Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, CDC. (Corresponding author: Craig M. Hales, chales@cdc.gov, 404-639-6217)

Herpes zoster vaccine (Zostavax [Merck & Co., Inc.]) was licensed in 2006 and recommended by the Advisory Committee on Immunization Practices (ACIP) in 2008 for prevention of herpes zoster (shingles) and its complications among adults aged ≥60 years (1).

The Food and Drug Administration (FDA) approved the use of Zostavax in 2011 for adults aged 50 through 59 years based on a large study of safety and efficacy in this age group (2).

ACIP initially considered the use of herpes zoster vaccine among adults aged 50 through 59 years in June 2011, but declined to recommend the vaccine in this age group, citing shortages of Zostavax and limited data on long-term protection afforded by herpes zoster vaccine (2).

In October 2013, ACIP reviewed the epidemiology of herpes zoster and its complications, herpes zoster vaccine supply, short-term vaccine efficacy in adults aged 50 through 59 years, short- and long- term vaccine efficacy and effectiveness in adults aged ≥60 years, an updated cost-effectiveness analysis, and deliberations of the ACIP herpes zoster work group, all of which are summarized in this report.

No vote was taken, and ACIP maintained its current recommendation that herpes zoster vaccine be routinely recommended for adults aged ≥60 years. Meeting minutes are available at http://www.cdc.gov/vaccines/acip/meetings/meetings-info.html ….

FULL TEXT

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6333a3.htm?s_cid=mm6333a3_e

 

PDF (see P.729)

http://www.cdc.gov/mmwr/pdf/wk/mm6333.pdf

 

August 21, 2014 at 3:09 pm

Evaluation of oseltamivir prophylaxis regimens for reducing influenza virus infection, transmission and disease severity in a ferret model of household contact

Journal of Antimicrobial Chemotherapy SEPT 2014 V.69 N.9 P.2458-2469

 

Ding Yuan Oh1, Sue Lowther2, James M. McCaw3,4, Sheena G. Sullivan1, Sook-Kwan Leang1, Jessica Haining2, Rachel Arkinstall2, Anne Kelso1, Jodie Mcvernon3,4, Ian G. Barr1,5, Deborah Middleton2 and Aeron C. Hurt1,5,*

1WHO Collaborating Centre for Reference and Research on Influenza, North Melbourne, Victoria, Australia

2Australian Animal Health Laboratory, Geelong, Victoria, Australia

3Vaccine and Immunisation Research Group, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, Victoria, Australia

4Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia

5School of Applied Sciences and Engineering, Monash University, Churchill, Victoria, Australia

*Corresponding author. Tel: +61-3-93423914; Fax: +61-3-93423939; E-mail: aeron.hurt@influenzacentre.org

Objectives

The emergence of the pandemic influenza A(H1N1)pdm09 virus in 2009 saw a significant increase in the therapeutic and prophylactic use of neuraminidase inhibitors (NAIs) to mitigate the impact of this highly transmissible virus. Prior to the pandemic, many countries stockpiled NAIs and developed pandemic plans for the use of antiviral drugs, based on either treatment of high-risk individuals and/or prophylaxis of contacts. However, to date there has been a lack of in vivo models to test the efficacy of treatment or prophylaxis with NAIs, for influenza-infected individuals or exposed contacts, in a household setting.

Methods

A ferret model of household contact was developed to study the efficacy of different prophylaxis regimens in preventing infection in contact ferrets exposed to influenza A(H1N1)pdm09-infected index ferrets.

Results

Among the different prophylactic regimens, contact ferrets receiving oseltamivir prophylaxis twice daily showed better outcomes than those receiving oseltamivir once daily. Benefits included a significant delay in the time to secondary infection, lower weight loss and higher activity levels. The treatment of index ferrets at 36 h post-infection did not influence either secondary infection rates or clinical symptoms in exposed contact ferrets. Neither prophylaxis nor treatment prevented infection or reduced the duration of viral shedding, although clinical symptoms did improve in infected animals receiving prophylaxis.

Conclusions

Different oseltamivir prophylaxis regimens did not prevent infections, but consistently resulted in a reduction in symptoms in infected ferrets. However, oseltamivir prophylaxis failed to reduce viral titres, which warrants further investigation in humans.

PDF

http://jac.oxfordjournals.org/content/69/9/2458.full.pdf+html

August 20, 2014 at 1:53 pm

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