Literature DB >> 18769360

Drug-susceptible HIV-1 infection despite intermittent fixed-dose combination tenofovir/emtricitabine as prophylaxis is associated with low-level viremia, delayed seroconversion, and an attenuated clinical course.

Nicole Prada1, Brandi Davis, Patrick Jean-Pierre, Matthew La Roche, Fuh-Mei Duh, Mary Carrington, Michael Poles, Saurabh Mehandru, Hiroshi Mohri, Martin Markowitz.   

Abstract

BACKGROUND: Continued high rates of HIV-1 transmission have fueled interest in the use of antiretrovirals to prevent infection. Attenuated infection with failure of tenofovir as prophylaxis has been reported in animal models. Here, we report a case of HIV-1 infection despite intermittent use of fixed-dose combination tenofovir and emtricitabine (FTC).
METHODS: The patient was treated with tenofovir DF/FTC for reported repeated high-risk sexual exposures. After seroconversion, he was subjected to routine laboratory testing, CCR5 and HLA genotyping, and biopsy of gastrointestinal (GI) tissue. Resistance testing was performed both as bulk sequencing of plasma and cloning and sequencing of virus derived from plasma, peripheral blood mononuclear cells, and GI tissue.
RESULTS: In this patient with no readily identifiable modifying host factors, acute HIV-1 infection with tenofovir DF/FTC-susceptible HIV-1 was associated with an attenuated clinical course, very low postseroconversion HIV-1 RNA levels, slow kinetics of seroconversion, and relative sparing of mucosal CD4+ T cells in the GI tract.
CONCLUSIONS: Despite the failure of tenofovir DF/FTC as prophylaxis, selection for drug-resistant transmission did not occur and the blunting of postinfection levels of viremia likely reduced the probability of subsequent forward transmissions during the acute phase. These results support continued investigations of the use of antiretrovirals as a means to reduce HIV-1 transmission.

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Year:  2008        PMID: 18769360      PMCID: PMC2689390          DOI: 10.1097/QAI.0b013e3181869a9b

Source DB:  PubMed          Journal:  J Acquir Immune Defic Syndr        ISSN: 1525-4135            Impact factor:   3.731


  27 in total

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2.  Phase i/ii trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in human immunodeficiency virus-infected adults.

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3.  Tenofovir DF in antiretroviral-experienced patients: results from a 48-week, randomized, double-blind study.

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Journal:  AIDS       Date:  2002-06-14       Impact factor: 4.177

4.  Characterization of human immunodeficiency viruses resistant to oxathiolane-cytosine nucleosides.

Authors:  R F Schinazi; R M Lloyd; M H Nguyen; D L Cannon; A McMillan; N Ilksoy; C K Chu; D C Liotta; H Z Bazmi; J W Mellors
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5.  Diminished replicative fitness of primary human immunodeficiency virus type 1 isolates harboring the K65R mutation.

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6.  Predicting the impact of a nonsterilizing vaccine against human immunodeficiency virus.

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7.  In vitro selection and characterization of HIV-1 with reduced susceptibility to PMPA.

Authors:  M A Wainberg; M D Miller; Y Quan; H Salomon; A S Mulato; P D Lamy; N A Margot; K E Anton; J M Cherrington
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8.  Lack of mucosal immune reconstitution during prolonged treatment of acute and early HIV-1 infection.

Authors:  Saurabh Mehandru; Michael A Poles; Klara Tenner-Racz; Patrick Jean-Pierre; Victoria Manuelli; Peter Lopez; Anita Shet; Andrea Low; Hiroshi Mohri; Daniel Boden; Paul Racz; Martin Markowitz
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9.  Prevention of rectal SHIV transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir.

Authors:  J Gerardo García-Lerma; Ron A Otten; Shoukat H Qari; Eddie Jackson; Mian-Er Cong; Silvina Masciotra; Wei Luo; Caryn Kim; Debra R Adams; Michael Monsour; Jonathan Lipscomb; Jeffrey A Johnson; David Delinsky; Raymond F Schinazi; Robert Janssen; Thomas M Folks; Walid Heneine
Journal:  PLoS Med       Date:  2008-02       Impact factor: 11.069

10.  Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract.

Authors:  Saurabh Mehandru; Michael A Poles; Klara Tenner-Racz; Amir Horowitz; Arlene Hurley; Christine Hogan; Daniel Boden; Paul Racz; Martin Markowitz
Journal:  J Exp Med       Date:  2004-09-13       Impact factor: 14.307

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2.  HIV, transmitted drug resistance, and the paradox of preexposure prophylaxis.

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Review 3.  Preexposure prophylaxis for HIV prevention.

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Journal:  Curr HIV/AIDS Rep       Date:  2011-06       Impact factor: 5.071

Review 4.  Pre-exposure prophylaxis and antiretroviral resistance: HIV prevention at a cost?

Authors:  Christopher B Hurt; Joseph J Eron; Myron S Cohen
Journal:  Clin Infect Dis       Date:  2011-10-05       Impact factor: 9.079

5.  Real-life evaluation of a human immunodeficiency virus screening algorithm using a single combined p24 antigen-antibody assay.

Authors:  A N Fanmi; C Ramière; J C Tardy; P André
Journal:  Eur J Clin Microbiol Infect Dis       Date:  2012-10-23       Impact factor: 3.267

6.  Newly Acquired Infection With Multidrug-Resistant HIV-1 in a Patient Adherent to Preexposure Prophylaxis.

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8.  Impact of Pill Sharing on Drug Resistance Due to a Wide-Scale Oral Prep Intervention in Generalized Epidemics.

Authors:  Dobromir Dimitrov; Marie-Claude Boily; Benoît R Mâsse; Elizabeth R Brown
Journal:  J AIDS Clin Res       Date:  2012-07-08

Review 9.  AIDS vaccines and preexposure prophylaxis: is synergy possible?

Authors:  Jean-Louis Excler; Wasima Rida; Frances Priddy; Jill Gilmour; Adrian B McDermott; Anatoli Kamali; Omu Anzala; Gaudensia Mutua; Eduard J Sanders; Wayne Koff; Seth Berkley; Patricia Fast
Journal:  AIDS Res Hum Retroviruses       Date:  2010-12-16       Impact factor: 2.205

Review 10.  Analytic review of modeling studies of ARV Based PrEP interventions reveals strong influence of drug-resistance assumptions on the population-level effectiveness.

Authors:  Dobromir Dimitrov; Marie-Claude Boily; Elizabeth R Brown; Timothy B Hallett
Journal:  PLoS One       Date:  2013-11-25       Impact factor: 3.240

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