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.

——

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.

——

#PrEP for #MERS in #Healthcare workers (J Hosp Infect., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Hosp Infect. 2018 Sep 18. pii: S0195-6701(18)30484-5. doi: 10.1016/j.jhin.2018.09.005. [Epub ahead of print]

Post-exposure prophylaxis for Middle East respiratory syndrome in Healthcare workers.

Park SY1, Lee JS2, Son JS3, Ko JH4, Peck KR4, Jung Y5, Woo HJ6, Joo YS7, Eom JS1, Shi H1.

Author information: 1 Division of Infectious Diseases, Kangdong Sacred Heart Hospital, Hallym University School of Medicine, Seoul, South Korea. 2 Division of Infectious Diseases, Kangdong Sacred Heart Hospital, Hallym University School of Medicine, Seoul, South Korea. Electronic address: rem324@naver.com. 3 Division of Infectious Diseases, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, South Korea. 4 Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. 5 Division of Infectious Diseases, Hallym University Sacred Heart Hospital, Hallym University School of Medicine, Anyang, Gyeonggi, South Korea. 6 Division of Infectious Diseases, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Hwasung, Gyeonggi, South Korea. 7 Department of Occupational and Environmental Medicine, Hallym University Sacred Heart Hospital, Hallym University School of Medicine, Anyang, Gyeonggi, South Korea.

 

Abstract

An effective post-exposure prophylaxis (PEP) strategy may limit the spread of infection. However, there is no consensus regarding PEP for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. We assessed the efficacy of ribavirin and lopinavir/ritonavir as PEP for healthcare workers (HCWs) exposed to patients with severe MERS-CoV pre-isolation pneumonia. We assessed the safety of PEP regimen. We retrospectively enrolled HCWs with high-risk exposure to MERS-CoV pre-isolation pneumonia. HCWs who received PEP therapy were classified into the PEP group. PEP therapy was associated with a 40% decrease in the risk of infection. There were no severe adverse events during PEP therapy.

KEYWORDS: Middle East respiratory syndrome coronavirus; Post-exposure prophylaxis; healthcare worker; high-risk exposure; outbreak; pre-isolation pneumonia

PMID: 30240813 DOI: 10.1016/j.jhin.2018.09.005

Keywords: MERS-CoV; Antivirals; PrEP; Nosocomial Outbreaks; Ribavirin; Lopinavir; Ritonavir.

——

Cost-effectiveness of #PrEP for #HIV #prevention in #MSMs in the #UK: a modelling study and health economic evaluation (Lancet Infect Dis., abstract)

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

Cost-effectiveness of pre-exposure prophylaxis for HIV prevention in men who have sex with men in the UK: a modelling study and health economic evaluation

Dr Valentina Cambiano, Alec Miners, PhD, David Dunn, PhD, Sheena McCormack, FRCP, Koh Jun Ong, MSc, O Noel Gill, FFPH, Anthony Nardone, PhD, Monica Desai, MRCP, Nigel Field, PhD, Graham Hart, PhD, Valerie Delpech, PhD, Gus Cairns, MA, Alison Rodger, PhD, Andrew N Phillips, PhD

Published: 17 October 2017 / DOI: http://dx.doi.org/10.1016/S1473-3099(17)30540-6

© 2017 Elsevier Ltd. All rights reserved.

 

Summary

Background

In the UK, HIV incidence among men who have sex with men (MSM) has remained high for several years, despite widespread use of antiretroviral therapy and high rates of virological suppression. Pre-exposure prophylaxis (PrEP) has been shown to be highly effective in preventing further infections in MSM, but its cost-effectiveness is uncertain.

Methods

In this modelling study and economic evaluation, we calibrated a dynamic, individual-based stochastic model, the HIV Synthesis Model, to multiple data sources (surveillance data provided by Public Health England and data from a large, nationally representative survey, Natsal-3) on HIV among MSM in the UK. We did a probabilistic sensitivity analysis (sampling 22 key parameters) along with a range of univariate sensitivity analyses to evaluate the introduction of a PrEP programme with sexual event-based use of emtricitabine and tenofovir for MSM who had condomless anal sexual intercourse in the previous 3 months, a negative HIV test at baseline, and a negative HIV test in the preceding year. The main model outcomes were the number of HIV infections, quality-adjusted life-years (QALYs), and costs.

Findings

Introduction of such a PrEP programme, with around 4000 MSM initiated on PrEP by the end of the first year and almost 40 000 by the end of the 15th year, would result in a total cost saving (£1·0 billion discounted), avert 25% of HIV infections (42% of which would be directly because of PrEP), and lead to a gain of 40 000 discounted QALYs over an 80-year time horizon. This result was particularly sensitive to the time horizon chosen, the cost of antiretroviral drugs (for treatment and PrEP), and the underlying trend in condomless sex.

Interpretation

This analysis suggests that the introduction of a PrEP programme for MSM in the UK is cost-effective and possibly cost-saving in the long term. A reduction in the cost of antiretroviral drugs (including the drugs used for PrEP) would substantially shorten the time for cost savings to be realised.

Funding

National Institute for Health Research.

Keywords: UK; PrEP; STI; HIV; Antivirals.

——-

#Tenofovir disoproxil fumarate associated #Fanconi #syndrome in an #HIV uninfected man receiving HIV #PrEP (Open Forum Infect Dis., abstract)

[Source: Open Forum Infectious Diseases, full page: (LINK). Abstract, edited.]

Tenofovir disoproxil fumarate associated Fanconi syndrome in an HIV uninfected man receiving HIV pre-exposure prophylaxis

Short title: Fanconi syndrome during PrEP

Soheb KHAN1, Connie A. FUNK1, Katya CORADO2, Sheldon MORRIS3, Michael P. DUBE1

1 University of Southern California Keck School of Medicine, Los Angeles, CA; 2 Los Angeles; Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles CA; 3 University of California at San Diego School of Medicine, San Diego CA.

Corresponding author: Michael P. Dubé, MD, USC Keck School of Medicine, 1300 N. Mission Road, Room 349, Los Angeles CA 90033, Phone: (323) 343-8288, E-Mail: mdube@usc.edu

Accepted Manuscript / Word count: 819

Keywords: Tenofovir, PrEP, Fanconi, renal dysfunction

Support: California HIV Research Program

 

INTRODUCTION

Tenofovir disoproxil fumarate (TDF) has been used worldwide in antiretroviral regimens of HIV infected patients since being approved by the U.S. Food and Drug Administration in 2001. TDF can cause renal tubular dysfunction and reduced renal function [1]. In its fully developed form, TDF renal dysfunction is associated with hypophosphatemia, renal phosphate wasting and other features of Fanconi syndrome [1]. Cases of TDF-associated Fanconi syndrome have been reported predominantly among patients with HIV infection [1]. There has been no excess risk of renal tubular toxicity with TDF-emtricitabine (TDF-FTC) detected in large placebo controlled trials of HIV pre-exposure prophylaxis (PrEP) [2, 3]. One other well-documented likely Fanconi syndrome has been reported in an online supplement to the latter paper [3]. Herein, we report an additional case of this previously described phenomenon.

(…)

Keywords: HIV/AIDS; Antivirals; PrEP; Tenofovir; Fanconi Syndrome.

——

#PrEP in #Italy: The time may be ripe but who’s paying the bill? A nationwide survey on physicians’ attitudes towards using antiretrovirals to prevent HIV infection (PLoS One, abstract)

[Source: PLoS One, full page: (LINK). Abstract, edited.]

OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE

PrEP in Italy: The time may be ripe but who’s paying the bill? A nationwide survey on physicians’ attitudes towards using antiretrovirals to prevent HIV infection

Antonio Di Biagio, Niccolò Riccardi , Alessio Signori, Renato Maserati, Silvia Nozza, Andrea Gori, Stefano Bonora, Marco Borderi, Diego Ripamonti, Maria Cristina Rossi, Giancarlo Orofino, Tiziana Quirino, Giuseppe Nunnari, Benedetto Maurizio Celesia, Salvatore Martini, Caterina Sagnelli, Giovanni Mazzola, Pietro Colletti, Dario Bartolozzi, Teresa Bini, Nicoletta Ladisa, Filippo Castelnuovo, Annalisa Saracino, Sergio Lo Caputo

Published: July 20, 2017 / DOI: https://doi.org/10.1371/journal.pone.0181433

 

Abstract

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians’ knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP’s financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

_____

Citation: Di Biagio A, Riccardi N, Signori A, Maserati R, Nozza S, Gori A, et al. (2017) PrEP in Italy: The time may be ripe but who’s paying the bill? A nationwide survey on physicians’ attitudes towards using antiretrovirals to prevent HIV infection. PLoS ONE 12(7): e0181433. https://doi.org/10.1371/journal.pone.0181433

Editor: Garrett Prestage, University of New South Wales, AUSTRALIA

Received: November 22, 2016; Accepted: July 2, 2017; Published: July 20, 2017

Copyright: © 2017 Di Biagio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting Information files.

Funding: No funding or sources of support were received during this study.

Competing interests: The authors have declared that no competing interests exist.

Keywords: HIV/AIDS; Italy; Antivirals; PrEp.

——-

#Uptake of #HIV #PrEP among commercially insured persons — #USA, 2010–2014 (Clin Infect Dis., abstract)

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

Uptake of HIV preexposure prophylaxis among commercially insured persons — United States, 2010–2014

Hsiu Wu1, Maria C. B. Mendoza1, Ya-lin A. Huang1, Tameka Hayes1,2, Dawn K. Smith1, and Karen W. Hoover1

Author Affiliations: 1. Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA; 2. ICF International, Atlanta, GA

CORRESPONDENCE: Ya-lin A. Huang, PhD, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE MS E45, Atlanta, GA 30329 (yhuang@cdc.gov).

 

Abstract

Background:

Daily, oral use of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) for preexposure prophylaxis (PrEP) is an effective strategy to prevent acquisition of HIV infection. It is important to monitor PrEP uptake at the national level to increase our understanding of trends in its utilization, but national HIV surveillance data do not include PrEP uptake. Our objective was to develop feasible methods to estimate PrEP uptake, and to estimate uptake each year among commercially insured persons during 2010-2014.

Methods:

We conducted a retrospective analysis of the 2010–2014 MarketScan database, a national sample of persons with commercial health insurance in the United States. We developed an algorithm to identify persons aged ≥16 years who were prescribed TDF-FTC for PrEP each year. We generated nationally representative estimates of prevalence of persons prescribed PrEP.

Results:

We found a significantly increasing trend in the proportion of persons prescribed TDF-FTC for PrEP over the study period, with 417 users in 2010 and 9,375 users in 2014 (P < 0.001). In 2014, among PrEP users 97% were male and 98% resided in metropolitan areas. Over the time period studied, the numbers of women prescribed PrEP were low.

Conclusions:

Our analytic methodology provides the only feasible means to monitor PrEP uptake in the United States. While a marked increasing trend in uptake was observed for males, the number of females who used PrEP remained very low during the study period. Interventions are needed to increase PrEP use by women at substantial risk of acquiring HIV infection.

Key words: HIV – Preexposure prophylaxis – PrEP – Tenofovir – TDF-FTC

Received July 5, 2016.

Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Keywords: HIV/AIDS; Antivirals; USA; PrEP.

——

#PrEP Use by Breastfeeding #HIV-Uninfected #Women: A Prospective Short-Term Study of #Antiretroviral Excretion in #Breast #Milk and #Infant Absorption (PLoS Med., abstract)

[Source: PLoS Medicine, full page: (LINK). Abstract, edited.]

OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE

Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption

Kenneth K. Mugwanya , Craig W. Hendrix, Nelly R. Mugo, Mark Marzinke, Elly T. Katabira, Kenneth Ngure, Nulu B. Semiyaga, Grace John-Stewart, Timothy R. Muwonge, Gabriel Muthuri, Andy Stergachis, Connie L. Celum, Jared M. Baeten

Published: September 27, 2016 / http://dx.doi.org/10.1371/journal.pmed.1002132

 

Abstract

Background

As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women.

Methods and Findings

We conducted a prospective short-term, open-label study of daily oral emtricitabine–tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother–infant pairs between 1–24 wk postpartum (ClinicalTrials.gov Identifier: NCT02776748). The primary goal was to quantify the steady-state concentrations of tenofovir and emtricitabine in infant plasma ingested via breastfeeding. PrEP was administered to women through daily directly observed therapy (DOT) for ten consecutive days and then discontinued thereafter. Non-fasting peak and trough samples of maternal plasma and breast milk were obtained at drug concentration steady states on days 7 and 10, and a single infant plasma sample was obtained on day 7. Peak blood and breast milk samples were obtained 1–2 h after the maternal DOT PrEP dose, while maternal trough samples were obtained at the end of the PrEP dosing interval (i.e., 23 to 24 h) after maternal DOT PrEP dose. Tenofovir and emtricitabine concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays.

Of the 50 mother–infant pairs enrolled, 48% were ≤12 wk and 52% were 13–24 wk postpartum, and median maternal age was 25 y (interquartile range [IQR] 22–28). During study follow-up, the median (IQR) daily reported frequency of infant breastfeeding was 15 times (12 to 18) overall, 16 (14 to 19) for the ≤12 weeks, and 14 (12 to 17) for the 13–24 wk infant age groups. Overall, median (IQR) time-averaged peak concentrations in breast milk were 3.2 ng/mL (2.3 to 4.7) for tenofovir and 212.5 ng/mL (140.0 to 405.0) for emtricitabine. Similarly, median (IQR) time-averaged trough concentrations in breast milk were 3.3 ng/mL (2.3 to 4.4) for tenofovir and 183.0 ng/mL (113.0 to 250.0) for emtricitabine, reflecting trough-to-peak breast milk concentration ratios of 1.0 for tenofovir and 0.8 for emtricitabine, respectively. In infant plasma, tenofovir was unquantifiable in 46/49 samples (94%), but emtricitabine was detectable in 47/49 (96%) (median [IQR] concentration: 13.2 ng/mL [9.3 to 16.7]). The estimated equivalent doses an infant would ingest daily from breastfeeding were 0.47 μg/kg (IQR 0.35 to 0.71) for tenofovir and 31.9 μg/kg (IQR 21.0 to 60.8) for emtricitabine, translating into a <0.01% and 0.5% relative dose when compared to the 6 mg/kg dose that is proposed for therapeutic treatment of infant HIV infection and for prevention of infant postnatal HIV infection; a dose that has not shown safety concerns. No serious adverse effects were recorded during study follow-up.

The key study limitation was that only a single infant sample was collected to minimize venipunctures for the children. However, maternal daily DOT and specimen collection at drug concentration steady state provided an adequate approach to address the key research question. Importantly, there was minimal variation in breast milk concentrations of tenofovir and emtricitabine (respective median trough-to-peak concentration ratio ~1), demonstrating that infants were exposed to consistent drug dosing via breast milk.

Conclusion

In this short-term study of daily directly observed oral PrEP in HIV-uninfected breastfeeding women, the estimated infant doses from breast milk and resultant infant plasma concentrations for tenofovir and emtricitabine were 12,500 and >200-fold lower than the respective proposed infant therapeutic doses, and tenofovir was not detected in 94% of infant plasma samples. These data suggest that PrEP can be safely used during breastfeeding with minimal infant drug exposure.

Trial Registration ClinicalTrials.gov, Identifier: NCT02776748

 

Author Summary

Why Was This Study Done?

Pregnancy and breastfeeding represent a period of heightened HIV risk for women and for their infant if acute HIV infection occurs. Preventing HIV acquisition in women is a priority.

Daily oral PrEP is a potent prevention option to reduce the risk of sexual HIV acquisition for women who are pregnant or breastfeeding, with the advantage relative to other prevention methods that it can be used discreetly and independent of sexual partners.

As HIV PrEP becomes more common worldwide, large numbers of women of child-bearing age will be using these medications during pregnancy and breastfeeding.

In order to appropriately evaluate the risk–benefit ratio of administering medications to breastfeeding women, evidence regarding infant drug exposure through breast milk is critical and very often completely lacking.

 

What Did the Researchers Do and Find?

We conducted an open-label, short-term, pharmacokinetic study among 50 HIV-uninfected breastfeeding women and infants.

Women were administered directly observed PrEP, and blood and breast milk were collected to measure the concentrations of PrEP medications (i.e., tenofovir and emtricitabine); no drug was administered directly to infants.

A single blood sample was obtained from the infant to determine the extent to which infants breastfed by women using PrEP absorb these medications via breast milk.

We found that the concentrations of PrEP medications in infant blood were very low, and tenofovir was undetectable in 94% of the infant samples.

The estimated doses of tenofovir and emtricitabine a breastfeeding infant would ingest each day were <0.01% and 0.5%, respectively, compared to the proposed pediatric doses for treatment of infant HIV infection and for prevention of infant postnatal HIV infection. No significant safety concerns were noted in mothers or infants.

 

What Do These Findings Mean?

The findings of this study provide important empirical evidence to anticipate safety for the breastfeeding infant after administering PrEP to breastfeeding HIV-uninfected women.

These findings suggest that PrEP can be safely used during breastfeeding with minimal infant exposure and will guide practice and policy decision-making for PrEP implementation programs in heterosexual populations.

After the pharmacokinetic demonstration of minimal drug exposure in infants breastfed by women using PrEP, the next incremental step is to explore in implementation science studies the acceptability, adherence, and infant safety in women who choose to continue PrEP throughout their pregnancy or breastfeeding and investigate long-term effects of this low-concentration exposure.

_____

Citation: Mugwanya KK, Hendrix CW, Mugo NR, Marzinke M, Katabira ET, Ngure K, et al. (2016) Pre-exposure Prophylaxis Use by Breastfeeding HIV-Uninfected Women: A Prospective Short-Term Study of Antiretroviral Excretion in Breast Milk and Infant Absorption. PLoS Med 13(9): e1002132. doi:10.1371/journal.pmed.1002132

Academic Editor: Lynne Meryl Mofenson, Elizabeth Glaser Pediatric AIDS Foundation, UNITED STATES

Received: March 6, 2016; Accepted: August 19, 2016; Published: September 27, 2016

Copyright: © 2016 Mugwanya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: Data from the PrEP in Breastfeeding Study are available by contacting the International Clinical Research Center at the University of Washington (icrc@uw.edu).

Funding: This work was supported by the Bill and Melinda Gates Foundation (OPP47674). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Competing interests: I have read the journal’s policy, and the authors of this manuscript have the following competing interests: FTC-TDF was donated by Gilead Sciences. CWH reports a prior contract from Gilead Sciences outside the submitted work and a patent pending, both managed by Johns Hopkins. MM has grant funding via the NIH. GJS has research grants from NIH (unrelated), CDC (unrelated), Thrasher Foundation (unrelated), Bill and Melinda Gates Foundation (sponsor), royalties from UpToDate (unrelated), and salary support from the University of Washington. All authors declare no other conflicts of interest.

Abbreviations: BLQ, below limit of quantification; DOT, directly observed therapy; FTC, emtricitabine; IQR, interquartile range; LC-MS/MS, liquid chromatography-tandem mass spectrometry; M/P, maternal plasma concentration ratio; PrEP, pre-exposure prophylaxis; TDF, tenofovir disoproxil fumarate

Keywords: Research; Abstracts; HIV; Antivirals; Breast Milk.

——

#Cost-effectiveness #analysis of #PrEP for #HIV-1 #prevention in the #Netherlands: a mathematical modelling study (Lancet Infect Dis., abstract)

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

Cost-effectiveness analysis of pre-exposure prophylaxis for HIV-1 prevention in the Netherlands: a mathematical modelling study

Dr Brooke E Nichols, PhD, Prof Charles A B Boucher, PhD, Marc van der Valk, PhD, Bart J A Rijnders, PhD, David A M C van de Vijver, PhD

Article has an altmetric score of 1 / DOI: http://dx.doi.org/10.1016/S1473-3099(16)30311-5

© 2016 Elsevier Ltd. All rights reserved.

 

Summary

Background

Pre-exposure prophylaxis (PrEP) with tenofovir and emtricitabine prevents HIV infections among men who have sex with men (MSM). PrEP can be given on a daily or intermittent basis. Unfortunately, PrEP is not reimbursed in most European countries. Cost-effectiveness analyses of PrEP among MSM in Europe are absent but are key for decision makers to decide upon PrEP implementation.

Methods

We developed a deterministic mathematical model, calibrated to the well defined Dutch HIV epidemic among MSM, to predict the effect and cost-effectiveness of PrEP. PrEP was targeted to 10% of highly sexually active Dutch MSM over the coming 40 years. Cost-effectiveness ratios were calculated to predict the cost-effectiveness of daily and on-demand PrEP. Cost-effectiveness ratios below €20 000 were considered to be cost-effective in this analysis.

Findings

Within the context of a stable HIV epidemic, at 80% effectiveness and current PrEP pricing, PrEP can cost as much as €11 000 (IQR 9400–14 100) per quality-adjusted life-year (QALY) gained when used daily, or as little as €2000 (IQR 1300–3000) per QALY gained when used on demand. At 80% effectiveness, daily PrEP can be considered cost-saving if the price of PrEP is reduced by 70%, and on-demand PrEP can be considered cost-saving if the price is reduced by 30–40%.

Interpretation

PrEP for HIV prevention among MSM in the Netherlands is cost-effective. The use of PrEP is most cost-effective when the price of PrEP is reduced through on-demand use or through availability of generic PrEP, and can quickly be considered cost-saving.

Funding

None.

Keywords: Research; Abstracts; HIV; Pre Exposure Prophylaxis.

——-