Elske Hoornenborg1, Maria Prins2, Roel C A Achterbergh3, Lycke R Woittiez2, Marion Cornelissen4, Suzanne Jurriaans5, Neeltje A Kootstra6, Peter L Anderson7, Peter Reiss8, Henry J C de Vries9, Jan M Prins2, Godelieve J de Bree10. 1. Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, Netherlands; Department of Infectious Diseases, Clinic for Sexually Transmitted Infections, Public Health Service of Amsterdam, Amsterdam, Netherlands. Electronic address: ehoornenborg@ggd.amsterdam.nl. 2. Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Academic Medical Center, University of Amsterdam, Netherlands. 3. Department of Infectious Diseases, Clinic for Sexually Transmitted Infections, Public Health Service of Amsterdam, Amsterdam, Netherlands. 4. Department of Medical Microbiology, Experimental Virology, Academic Medical Center, University of Amsterdam, Netherlands. 5. Department of Medical Microbiology, Clinical Virology, Academic Medical Center, University of Amsterdam, Netherlands. 6. Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Netherlands. 7. Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. 8. Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Academic Medical Center, University of Amsterdam, Netherlands; Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, University of Amsterdam, Netherlands; HIV Monitoring Foundation, Amsterdam, Netherlands. 9. Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Academic Medical Center, University of Amsterdam, Netherlands; Department of Dermatology, Academic Medical Center, University of Amsterdam, Netherlands; National Institute of Public Health and the Environment, Center for Infectious Disease Control, Bilthoven, Netherlands. 10. Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Academic Medical Center, University of Amsterdam, Netherlands; Department of Global Health and Amsterdam Institute for Global Health and Development, Academic Medical Center, University of Amsterdam, Netherlands.
Abstract
BACKGROUND: Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate. METHODS: The patient participated in the Amsterdam PrEP project, a demonstration project of daily and event-driven PrEP. We did extensive testing for HIV, including plasma HIV RNA and nested PCR on bulk peripheral blood mononuclear cells (PBMCs) and sigmoid biopsies after seroconversion. FINDINGS: A 50-year-old man who has sex with men and had been on daily emtricitabine and tenofovir disoproxil fumarate for 8 months presented with fever, urinary tract infection caused by Escherichia coli, anal lymphogranuloma venereum infection, and a positive fourth-generation HIV test. We found an atypical seroconversion pattern, with initially only gp160 antibodies detected in the western blot. HIV RNA could not be detected in plasma, and nested PCR for HIV RNA and DNA on bulk PBMCs and sigmoid biopsies were negative. PrEP was discontinued; 3 weeks later HIV RNA was detected in plasma. No drug-resistant mutations were detected. Tenofovir diphosphate concentrations in dried blood spots were stable and high. INTERPRETATION: To our knowledge, this is the first detailed case report suggesting wild-type HIV-1 infection despite good adherence, evidenced by repeatedly high concentrations of tenofovir diphosphate in dried blood spots. PrEP providers need to be aware that infection can occur despite good adherence. Regular HIV testing and awareness of atypical patterns of seroconversion is highly recommended. FUNDING: ZonMw, National Institute for Public Health and the Environment, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.
BACKGROUND: Pre-exposure prophylaxis (PrEP) with emtricitabine and tenofovir disoproxil fumarate is highly effective against acquisition of HIV infection, and only two cases of infection with a multidrug-resistant virus have been reported under adequate long-term adherence, as evidenced by tenofovir diphosphate concentrations in dried blood spots. We report a case of wild-type HIV-1 infection despite consistent use of emtricitabine and tenofovir disoproxil fumarate. METHODS: The patient participated in the Amsterdam PrEP project, a demonstration project of daily and event-driven PrEP. We did extensive testing for HIV, including plasma HIV RNA and nested PCR on bulk peripheral blood mononuclear cells (PBMCs) and sigmoid biopsies after seroconversion. FINDINGS: A 50-year-old man who has sex with men and had been on daily emtricitabine and tenofovir disoproxil fumarate for 8 months presented with fever, urinary tract infection caused by Escherichia coli, anal lymphogranuloma venereum infection, and a positive fourth-generation HIV test. We found an atypical seroconversion pattern, with initially only gp160 antibodies detected in the western blot. HIV RNA could not be detected in plasma, and nested PCR for HIV RNA and DNA on bulk PBMCs and sigmoid biopsies were negative. PrEP was discontinued; 3 weeks later HIV RNA was detected in plasma. No drug-resistant mutations were detected. Tenofovir diphosphate concentrations in dried blood spots were stable and high. INTERPRETATION: To our knowledge, this is the first detailed case report suggesting wild-type HIV-1 infection despite good adherence, evidenced by repeatedly high concentrations of tenofovir diphosphate in dried blood spots. PrEP providers need to be aware that infection can occur despite good adherence. Regular HIV testing and awareness of atypical patterns of seroconversion is highly recommended. FUNDING: ZonMw, National Institute for Public Health and the Environment, Internal GGD research funds, Aidsfonds, Stichting AmsterdamDiner Foundation, Gilead Sciences, Janssen Pharmaceutica, M A C AIDS Fund, and ViiV Healthcare.
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