#CRISPR-Edited #StemCells in a #Patient with #HIV and Acute Lymphocytic #Leukemia (N Engl J Med., abstract)

[Source: The New England Journal of Medicine, full page: (LINK). Summary, edited.]

CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia

Lei Xu, M.D., Ph.D., Jun Wang, M.D., Ph.D., Yulin Liu, B.S., Liangfu Xie, B.S., Bin Su, Ph.D., Danlei Mou, M.D., Ph.D., Longteng Wang, B.S., Tingting Liu, M.D., Xiaobao Wang, B.S., Bin Zhang, M.D., Ph.D., Long Zhao, Ph.D., Liangding Hu, M.D., et al.



The safety of CRISPR (clustered regularly interspaced short palindromic repeats)–based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing–related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.)


Supported by grants from the Beijing Municipal Science and Technology Commission (D171100000517004), the National Key Research and Development Program of China (2017YFA0103000), the Science and Technology Planning Project of Beijing City  (Z181100001818004), and the National 13th Five-Year Grand Program on Key Infectious Disease Control (2017ZX10202102-005-003 and 2017ZX10202101-004-001).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

Dr. L. Xu, Dr. J. Wang, Mr. Y. Liu, and Mr. L. Xie and Drs. H. Wu, H. Deng, and H. Chen contributed equally to this article.

This article was published on September 11, 2019, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank Zeyu Chen, Shicheng Sun, Chengyan Wang, Weifeng Lai, and Shunyi Liao for assistance with the experiment design and with revising an earlier version of the manuscript; Edouard Stanley and Tung-Tien Sun for assistance with revising an earlier version of the manuscript; Yang Gao, Yang Liu, Huangfan Xie, Hanwei Li, Jingyi Wei, Kailong Xia, Cui Zhang, Qiang Shi, Guoliang Hu, Xiaoyue Gao, and Xuanling Shi for technical assistance; and Jing Zhang, Min Jiang, Yongfeng Su, Na Liu, Xiao Lou, Yizhi Wang, Ying Sun, and Yafei Wang, of the 307 Hospital of the People’s Liberation Army, for contributions to the care of the patient.

Author Affiliations

From the Department of Hematopoietic Stem Cell Transplantation (L. Xu, J.W., T.L., B.Z., L.H., H.N., Y.Z., H.C.) and the Cell and Gene Therapy Center (B.Z., L.Z., L.H., H.C.), 307 Hospital of the People’s Liberation Army, the Fifth Medical Center of the People’s Liberation Army General Hospital, the Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, and the Ministry of Education (MOE) Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking–Tsinghua Center for Life Sciences (Y.L., L. Xie, X.W., J.X., H.D.), and the School of Life Sciences, Center for Statistical Science and Center for Bioinformatics (L.W., C.L.), Peking University, and the Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing Key Laboratory for HIV–AIDS Research (B.S., D.M., L.L., X.L., T.Z., H.W.), Beijing, and the Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou (K.D.) — all in China.
Address reprint requests to Dr. H. Deng at the Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking–Tsinghua Center for Life Sciences, Peking University, No. 5, Yiheyuan Rd., Beijing 100871, China, or at hongkui_deng@pku.edu.cn.

Hu Chen, M.D., Ph.D., is deceased.

Keywords: HIV/AIDS; Leukemia; Crispr.



Structural Basis for #Tetherin #Antagonism as a #Barrier to #Zoonotic #Lentiviral Transmission (Cell Host Microbe, abstract)

[Source: Cell, Host & Microbe, full page: (LINK). Abstract, edited.]

Structural Basis for Tetherin Antagonism as a Barrier to Zoonotic Lentiviral Transmission

Cosmo Z. Buffalo, Christina M. Stürzel, Elena Heusinger, Dorota Kmiec, Frank Kirchhoff, James H. Hurley, Xuefeng Ren

Published: August 22, 2019 / DOI: https://doi.org/10.1016/j.chom.2019.08.002



  • Cryo-EM structure of AP-2, simian tetherin, and SIVsmm Nef complex at a 3.8-Å resolution
  • Nef refolds the β2 subunit of AP-2 for binding of the simian tetherin DIWK sequence
  • Tetherin binding site is distinct from those of Nef substrates MHC class I, CD3, and CD4
  • Tetherin binding site on Nef overlaps with the site for SERINC5 binding



Tetherin is a host defense factor that physically prevents virion release from the plasma membrane. The Nef accessory protein of simian immunodeficiency virus (SIV) engages the clathrin adaptor AP-2 to downregulate tetherin via its DIWK motif. As human tetherin lacks DIWK, antagonism of tetherin by Nef is a barrier to simian-human transmission of non-human primate lentiviruses. To determine the molecular basis for tetherin counteraction, we reconstituted the AP-2 complex with a simian tetherin and SIV Nef and determined its structure by cryoelectron microscopy (cryo-EM). Nef refolds the first α-helix of the β2 subunit of AP-2 to a β hairpin, creating a binding site for the DIWK sequence. The tetherin binding site in Nef is distinct from those of most other Nef substrates, including MHC class I, CD3, and CD4 but overlaps with the site for the restriction factor SERINC5. This structure explains the dependence of SIVs on tetherin DIWK and consequent barrier to human transmission.

Keywords: HIV – SIV – clathrin – adaptor protein – host-factor restriction – trafficking – cryo-EM – tetherin – hydrogen-deuterium exchange

Keywords: Retrovirus; Lentivirus; HIV; Tetherin.


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




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.


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.


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.


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


Keywords: HIV/AIDS; PrEP; Antivirals.


#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




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.


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.


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).


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.


National Institute for Health Research.

Keywords: HIV/AIDS; Antivirals; STI.


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




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.


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.


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.


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.


#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




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


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.


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.


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.


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.




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


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.


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).


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.