First year of #PrEP implementation in #France with daily or on-demand #tenofovir disoproxil fumarate/emtricitabine (J Antimicrob Chemother., abstract)

[Source: Journal of Antimicrobial Chemotherapy, full page: (LINK). Abstract, edited.]

First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine

M Siguier, R Mera, G Pialoux, M Ohayon, L Cotte, N Valin, J Ghosn, E Cua, C Pintado, J Chas, G Barriere, F Durand, J M Molina

Journal of Antimicrobial Chemotherapy, dkz220, https://doi.org/10.1093/jac/dkz220

Published: 20 June 2019

 

Abstract

Background

In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France.

Methods

Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients’ baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription.

Results

From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35–2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84–2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57–0.82 and 0.75, 95% CI 0.57–0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation.

Conclusions

In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

Issue Section: ORIGINAL RESEARCH

Keywords: HIV/AIDS; PrEP; Antivirals.

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#Risk of #HIV #transmission through condomless sex in serodifferent gay couples with the #HIV-positive partner taking suppressive #antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study

Prof Alison J Rodger, FRCP, Valentina Cambiano, PhD, Tina Bruun, RN, Prof Pietro Vernazza, MD, Simon Collins, Olaf Degen, MD, Giulio Maria Corbelli, BSc, Vicente Estrada, MD, Prof Anna Maria Geretti, FRCPath, Apostolos Beloukas, PhD, Dorthe Raben, PhD, Pep Coll, MD, Andrea Antinori, MD, Nneka Nwokolo, MBBS, Armin Rieger, MD, Prof Jan M Prins, PhD, Anders Blaxhult, MD, Prof Rainer Weber, MD, Arne Van Eeden, MD, Prof Norbert H Brockmeyer, MD, Amanda Clarke, MD, Jorge del Romero Guerrero, MD, Prof Francois Raffi, PhD, Prof Johannes R Bogner, MD, Gilles Wandeler, MD, Prof Jan Gerstoft, MD, Prof Felix Gutiérrez, PhD, Prof Kees Brinkman, PhD, Maria Kitchen, MD, Prof Lars Ostergaard, MedScD, Agathe Leon, PhD, Matti Ristola, PhD, Heiko Jessen, MD, Prof Hans-Jürgen Stellbrink, MedScD, Prof Andrew N Phillips, PhD, Prof Jens Lundgren, PhD, for thePARTNER Study Group †

Open Access / Published: May 02, 2019 / DOI: https://doi.org/10.1016/S0140-6736(19)30418-0

 

Summary

Background

The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships.

Methods

The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and envsequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods.

Findings

Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1–3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33–46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4–2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up).

Interpretation

Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV.

Funding

National Institute for Health Research.

Keywords: HIV/AIDS; Antivirals; STI.

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Standard dose #intradermal #influenza #vaccine elicits similar cellular immune responses when compared to intramuscular vaccine in #HIV-infected or uninfected men (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Standard dose intradermal influenza vaccine elicits similar cellular immune responses when compared to intramuscular vaccine in HIV-infected or uninfected men

Samuel Amoah, Margarita Mishina, Prabda Praphasiri, Weiping Cao, Jin Hyang Kim, Justine S Liepkalns, Zhu Guo, Paul J Carney, Jessie C Chang, Stefan Fernandez, Shikha Garg, Lauren Beacham, Timothy H Holtz, Marcel E Curlin, Fatimah Dawood, Sonja J Olsen, Shivaprakash Gangappa, James Stevens, Suryaprakash Sambhara

The Journal of Infectious Diseases, jiz205, https://doi.org/10.1093/infdis/jiz205

Published: 02 May 2019

 

Abstract

Background

HIV-infected persons are at a higher risk of severe influenza disease. Though we have shown that a standard dose intradermal (ID) versus a standard dose intramuscular (IM) influenza vaccine does not result in differences in hemagglutinin inhibition titers (HI) titers in this population, a comprehensive examination of cell-mediated immune responses remains lacking.

Methods

Serological, antigen-specific B cell and IL-2, IFN- and TNF-α secreting T cell responses were assessed in 79 HIV-infected and 79 HIV-uninfected men.

Results

The route of vaccination did not affect the IgA and IgG plasmablast or memory B cell response, though these were severely impaired in the CD4 <200 group. The frequencies of IgG memory B cells measured at D28 post-vaccination were highest in the HIV-uninfected group, followed by the CD4 ≥200 and CD4 <200 groups. The route of vaccination did not affect the CD4+ or CD8+ T cell responses measured at various times post-vaccination.

Conclusions

The route of vaccination had no effect on antibody responses, antibody avidity, T, or B cell responses in HIV-infected or HIV-uninfected subjects. With the serological and cellular immune responses to influenza vaccination in HIV-infected individuals with CD4 <200 being impaired, passive immunization strategies need exploring to protect this population.

Clinical trial registration: NCT01538940 https://clinicaltrials.gov/ct2/show/NCT01538940

Influenza, vaccination, HIV, cell-mediated, intradermal, intramuscular

Issue Section: Major Article

This content is only available as a PDF.

Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: HIV/AIDS; Seasonal Influenza; Vaccines.

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#HIV-1 #Phylodynamics to Detect and Characterize Active #Transmission #Clusters in North Carolina (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

HIV-1 Phylodynamics to Detect and Characterize Active Transmission Clusters in North Carolina

Ann M Dennis, MD, Stéphane Hué, PhD, Rachael Billock, MSPH, Sara Levintow, MSPH, Joseph Sebastian, PhD, William C Miller, MD, PhD, Joseph J Eron, MD

The Journal of Infectious Diseases, jiz176, https://doi.org/10.1093/infdis/jiz176

Published: 27 April 2019

 

Abstract

Background

HIV-1 phylodynamics can be used to monitor epidemic trends and help target prevention through identification and characterization of transmission clusters.

Methods

We analyzed HIV-1 pol sequences sampled in North Carolina from 1997-2014. Putative clusters were identified using maximum-likelihood trees and dated using Bayesian Markov Chain Monte Carlo inference. Active clusters were defined as clusters including internal nodes 2009-2014. Effective reproductive numbers (Re) were estimated using birth-death models for large clusters that expanded ≥2-fold from 2009-2014.

Results

Of 14,921 persons, 7,508 (50%) sequences were identified in 2,264 clusters. Only 288 (13%) clusters were active from 2009-2014; 37 were large (10-36 members). Compared to smaller clusters, large clusters were increasingly populated by men and younger persons; however, nearly 60% included ≥1 women. Clusters with ≥3 members demonstrated assortative mixing by gender, age, and sample region. Of 15 large clusters with ≥2-fold expansion, nearly all had Re ~1 by 2014.

Conclusions

Phylodynamics revealed transmission cluster expansion in this densely sampled region and allowed estimates of Re to monitor active clusters, showing the propensity for steady, onward propagation. Associations with clustering and cluster characteristics vary by cluster size. Harnessing sequence-derived epidemiologic parameters within routine surveillance could allow refined monitoring of local sub-epidemics.

HIV-1, Molecular Epidemiology, Transmission, Phylogeny,Southeastern United States

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: HIV; USA.

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Association of #HIV #PrEP With Incidence of #STIs Among Individuals at High Risk of HIV Infection (JAMA, abstract)

[Source: The Journal of the American Medical Association, full page: (LINK). Abstract, edited.]

Original Investigation / April 9, 2019

Association of HIV Preexposure Prophylaxis With Incidence of Sexually Transmitted Infections Among Individuals at High Risk of HIV Infection

Michael W. Traeger, MSc1; Vincent J. Cornelisse, MBBS, PhD2,3,4,5; Jason Asselin, BSc1; et al Brian Price, MBA2; Norman J. Roth, MBBS4; Jeff Willcox, MBBS6; Ban Kiem Tee, MBBS7; Christopher K. Fairley, MBBS, PhD3,5; Christina C. Chang, MBBS, PhD2,5; Jude Armishaw, BNurs2; Olga Vujovic, MBBS2; Matthew Penn, MBBS8; Pauline Cundill, BM8; George Forgan-Smith, MBBS9; John Gall, MBBS, PhD9; Claire Pickett, MBBS10; Luxi Lal, BPharm1,2; Anne Mak, BPharm2; Tim D. Spelman, MBBS, MSc1,11,12; Long Nguyen, MCom1; Dean A. Murphy, PhD13,14; Kathleen E. Ryan, PhD1,2; Carol El-Hayek, MEpi1; Michael West, BA15; Simon Ruth, MSSc16; Colin Batrouney, BA16; John T. Lockwood, BN2; Jennifer F. Hoy, MBBS2; Margaret E. Hellard, MBBS, PhD1,2,11; Mark A. Stoové, PhD1,11; Edwina J. Wright, MBBS, PhD1,2,12; for the PrEPX Study Team

Author Affiliations: 1 Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia; 2 Department of Infectious Diseases, Alfred Health and Monash University, Melbourne, Victoria, Australia; 3 Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia; 4 Prahran Market Clinic, Melbourne, Victoria, Australia; 5 Central Clinical School, Monash University, Melbourne, Victoria, Australia; 6 Northside Clinic, Melbourne, Victoria, Australia; 7 Centre Clinic, Thorne Harbour Health, Melbourne, Victoria, Australia; 8 PRONTO! Clinic, Thorne Harbour Health, Melbourne, Victoria, Australia; 9 ERA Health, Melbourne, Victoria, Australia; 10 Ballarat Community Health Centre, Ballarat, Victoria, Australia; 11 School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; 12 The Peter Doherty Institute of Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia; 13 Department of Gender and Cultural Studies, University of Sydney, Sydney, New South Wales, Australia; 14 The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia; 15 Sexual Health and Viral Hepatitis Service, Department of Health and Human Services, Government of Victoria, Melbourne, Victoria, Australia; 16 Thorne Harbour Health, Melbourne, Victoria, Australia

JAMA. 2019;321(14):1380-1390. doi:10.1001/jama.2019.2947

 

Key Points

  • Question  – Is the use of HIV preexposure prophylaxis (PrEP) associated with increased risk of sexually transmitted infections (STIs) among individuals at high risk of HIV infection?
  • Findings  – In this longitudinal study of 2981 mostly gay and bisexual men who received daily HIV preexposure prophylaxis, STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 1378 participants with preenrollment STI testing data available, receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment (adjusted incidence rate ratio, 1.12).
  • Meaning  – Findings suggest the importance of frequent testing for STIs among gay and bisexual men using PrEP.

 

Abstract

Importance  

Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP).

Objective  

To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement.

Design, Setting, and Participants  

The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016–April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018.

Exposures  

Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring.

Main Outcomes and Measures  

The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378).

Results  

Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33]).

Conclusions and Relevance  

Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Keywords: HIV/AIDS; Antivirals; PrEP; STIs; Australia.

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#Opioids and #Infectious Diseases: A Converging #PublicHealth #Crisis  (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Opioids and Infectious Diseases: A Converging Public Health Crisis

Tara A Schwetz, Thomas Calder, Elana Rosenthal, Sarah Kattakuzhy, Anthony S Fauci

The Journal of Infectious Diseases, jiz133, https://doi.org/10.1093/infdis/jiz133

Published: 03 April 2019

 

Abstract

A converging public health crisis is emerging as the opioid epidemic is fueling a surge in infectious diseases, such as HIV/AIDS, the viral hepatitides, infective endocarditis, and skin and soft tissue infections (SSTIs). An integrated strategy is needed to tailor preventive and therapeutic approaches towards infectious diseases in people who misuse and/or are addicted to opioids and to concurrently address the underlying pre-disposing factor for the infections – opioid use disorder. This commentary highlights the unique and complimentary roles that the infectious diseases and substance use disorder communities can play in addressing this dual public health crisis.

infectious diseases, opioids, opioid use disorder, substance use disorder

Issue Section: Perspective

This content is only available as a PDF.

Published by Oxford University Press for the Infectious Diseases Society of America 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.

This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: Public Health; USA; Opioids; HIV/AIDS; Hepatitis C; Infectious Diseases.

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#Ibalizumab: A novel #monoclonal #antibody for the #management of #MDR #HIV-1 #infection (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Ibalizumab: A novel monoclonal antibody for the management of multidrug resistant HIV-1 infection

Mario V. Beccari [PharmD, BCPS, AAHIVP], Bryan T. Mogle [PharmD, BCPS, AAHIVP], Eric F. Sidman [PharmD, BCPS, AAHIVP], Keri A. Mastro [BA], Elizabeth Asiago-Reddy [MD, MS],Wesley D. Kufel [PharmD, BCIDP, BCPS, AAHIVP]

DOI: 10.1128/AAC.00110-19

 

ABSTRACT

Limited antiretrovirals are currently available for the management of multidrug resistant (MDR) HIV-1 infection. Ibalizumab, a recombinant humanized monoclonal antibody, represents the first novel agent for HIV-1 management in over a decade, and is the first monoclonal antibody for the treatment of MDR HIV-1 infection in combination with other ART in heavily treatment-experienced adults who are failing their current antiretroviral regimen. Ibalizumab demonstrates a novel mechanism of action as a CD4-directed post-attachment inhibitor, and has a favorable pharmacokinetic profile that allows for a dosing interval of every 14 days after an initial loading dose. Clinical studies have demonstrated reasonably substantial antiretroviral activity with ibalizumab among a complex patient population with advanced HIV-1 infection who are receiving an optimized background regimen, where limited therapeutic options exist. Ibalizumab was well-tolerated in clinical trials, and the most common adverse effects included diarrhea, nausea, dizziness, fatigue, pyrexia, and rash. Resistance to ibalizumab has also been observed via reduced expression or loss of the potential N-linked glycosylation sites in the V5 loop of the envelope glycoprotein 120. The mechanism of action, pharmacokinetic parameters, efficacy, and safety of ibalizumab present an advance in the management of MDR HIV-1 infection. Future studies and post-marketing experience will further determine longer-term clinical efficacy, safety, and resistance data for ibalizumab.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Antivirals; Drugs Resistance; HIV; Monoclonal antibodies; Ibalizumab.

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