We report a case of HIV-1 superinfection (HSI) with a clade B, triple-class resistant virus in a patient successfully controlling viremia with continuous combination antiretroviral therapy started 8 years earlier during primary HIV infection. The course of HIV infection prior to HSI was monitored in both the source partner and recipient (8 and 11 years, respectively) and 4 years following HSI. This case report demonstrates re-infection with HIV-1 despite effective combination antiretroviral therapy

Castro, E.

Zhao, H.

Cavassini, M.

Mullins, J.I.

Pantaleo, G.

Bart, P.A.

Erika Castro

Hong Zhao

Matthias Cavassini

James I. Mullins

Giuseppe Pantaleo

Pierre-Alexandre Bart

MUCC (Crossref)

HIV-1 superinfection with a triple-class drug-resistant strain in a patient successfully controlled with antiretroviral treatment

Crossref

AIDS

Esta publicación compila los resúmenes expandidos de los trabajos científicos presentados en la XXVIII Reunión Científica de la Asociación Argentina de Geofísicos y Geodestas (AAGG 2017) y en el Tercer Simposio sobre Inversión y Procesamiento de Señales en Exploración Sísmica (IPSES'17) realizados en la ciudad de La Plata del 17 al 21 de abril de 2017. Ambos eventos fueron organizados por la Facultad de Ciencias Astronómicas y Geofísicas de la Universidad Nacional de La Plata. Los resúmenes expandidos fueron evaluados por el Comité Organizador Científico que estuvo integrado por los siguientes docentes – investigadores: Agosta Scarel, Eduardo (FCAG-UCA-CONICET); Badi, Gabriela (FCAG-UNLP); Dasso, Sergio (FCEN-IAFE); Del Cogliano, Daniel (FCAG-UNLP); Gende, Mauricio (FCAG-CONICET); Guarracino, Luis (FCAG-FCNyM-CONICET); Lenzano, María Gabriela (IANIGLA-CONICET); Meza, Amalia (FCAG-CONICET); Perdomo, Santiago (FCAG-CONICET); Rosa, María Laura (FCAG-UNLP); Sallago, Patricia (FCAG-UNLP); Velis, Danilo (FCAG-CONICET); Yuchechen, Adrian (UTN-CONICET); Zyserman, Fabio (FCAG-CONICET)
La compilación general fue realizada por las Geofísicas Yenni Roa y Micaela Maugeri y el diseño por la Srta. Natalia Torres.Facultad de Ciencias Astronómicas y Geofísica

Roa, Yenni

Maugeri, Micaela

Tocho, Claudia Noemí

SEDICI - Repositorio de la UNLP

Spanish

Libro de resúmenes expandidos de la XXVIII Reunión Científica de la Asociación Argentina de Geofísicos y Geodestas (AAGG 2017) y Tercer Simposio sobre Inversión y Procesamiento de Señales en Exploración Sísmica (IPSES'17)

El Servicio de Difusión de la Creación Intelectual

Esta publicación compila los resúmenes de los trabajos científicos presentados en la XXVIII Reunión Científica de la Asociación Argentina de Geofísicos y Geodestas (AAGG 2017) y en el Tercer Simposio sobre Inversión y Procesamiento de Señales en Exploración Sísmica (IPSES'17) realizados en la ciudad de La Plata del 17 al 21 de abril de 2017. Ambos eventos fueron organizados por la Facultad de Ciencias Astronómicas y Geofísicas de la Universidad Nacional de La Plata.
Los resúmenes fueron evaluados por el Comité Organizador Científico que estuvo integrado por los siguientes docentes-investigadores: Agosta Scarel, Eduardo (FCAG-UCA-CONICET); Badi, Gabriela (FCAG-UNLP); Dasso, Sergio (FCEN-IAFE); Del Cogliano, Daniel (FCAG-UNLP); Gende, Mauricio (FCAG-CONICET); Guarracino, Luis (FCAG-FCNyM-CONICET); Lenzano, María Gabriela (IANIGLA-CONICET); Meza, Amalia (FCAG-CONICET); Perdomo, Santiago (FCAG-CONICET); Rosa, María Laura (FCAG-UNLP); Sallago, Patricia (FCAG-UNLP); Velis, Danilo (FCAG-CONICET); Yuchechen, Adrian (UTN-CONICET); Zyserman, Fabio (FCAG-CONICET). La compilación general fue realizada por las Geofísicas Yenni Roa y Consuelo Sagarra y el diseño por la Srta. Natalia Torres.Facultad de Ciencias Astronómicas y Geofísica

Sagarra, Consuelo

Libro de resúmenes de la XXVIII Reunión Científica de la Asociación Argentina de Geofísicos y Geodestas (AAGG 2017) y Tercer Simposio sobre Inversión y Procesamiento de Señales en Exploración Sísmica (IPSES'17)

Serveur académique lausannois

       Serveur Acade´mique Lausannois SERVAL serval.unil.chAuthor ManuscriptFaculty of Biology and Medicine PublicationThis paper has been peer-reviewed but does not include the final publisherproof-corrections or journal pagination.Published in final edited form as:Title: HIV-1 superinfection with a triple-class drug-resistant strain in apatient successfully controlled with antiretroviral treatment.Authors: Castro E, Zhao H, Cavassini M, Mullins JI, Pantaleo G, Bart PAJournal: AIDS (London, England)Year: 2014 Jul 31Issue: 28Volume: 12Pages: 1840-4DOI: 10.1097/QAD.0000000000000342In the absence of a copyright statement, users should assume that standard copyright protection applies, unless the article containsan explicit statement to the contrary. In case of doubt, contact the journal publisher to verify the copyright status of an article.1 HIV-1 superinfection with a triple class drug resistant strain in a patient successfully controlled with antiretroviral treatment  Running head:   HIV-1 superinfection despite successful cART Erika CASTRO1,3, Hong ZHAO2, Matthias CAVASSINI1 , James I MULLINS2, Giuseppe PANTALEO3 and Pierre-Alexandre BART3,4.    1Service of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 2Departments of Microbiology, Medicine and Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America. 3Laboratory of AIDS Immunopathogenesis, Service of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. 4Service of Internal Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.   Corresponding author: Erika Castro Current mailing address: Centre Saint-Martin – Addiction Medicine – CHUV. Rue Saint-Martin 7. 1003 Lausanne, Switzerland. E-mail: erika.castro-bataenjer@chuv.ch Some of these data were presented as poster 480 at the 17th Conference on Retroviruses and Opportunistic Infections. San Francisco, USA, February 16 – 19, 2010.  Word count: 1153   2 Abstract We report a case of HIV-1 superinfection (HSI) with a clade B, triple class-resistant virus in a patient successfully controlling viremia with continuous cART started 8 years earlier during primary HIV infection. The course of HIV infection prior to HSI was monitored in both the source partner and recipient (8 and 11 years, respectively) and 4 years following HSI. This case report demonstrates re-infection with HIV-1 despite effective cART. Background HIV-1 superinfection (HSI), that is, infection with a second strain after the first has been established, has been reported since 2002 mainly involving HIV group M clades {1-6} and in a smaller proportion as inter-group recombinant forms {7-8}. Overall, HSI has been most often observed in untreated patients, during treatment interruption, and in seroconcordant couples with poor viral suppression {9}. Here we report the onset and 4 year follow-up of HSI with a triple class resistant clade B virus in a man on effective combined antiretroviral treatment (cART). HIV superinfection  Briefly, blood samples were obtained from 2 men (M1 and M2) chronically infected with HIV-1 and sexual partners since 2006. M2 was diagnosed with HIV infection in 1994 at stage A2 with full Western blot seroconversion, and developed triple class antiretroviral drug resistance as a consequence of weak adherence to ART, leading to virologic failure. M2 experienced uncontrolled viremia (range: 3 to 4 logs of viral RNA) until September 2008 when a salvage treatment regimen reduced his viral load to undetectable for the first time (Figure 1a).  M1 was diagnosed in 2000 with primary HIV infection, initiated cART in 2000, and remained on cART with undetectable viremia and no drug resistance mutations through the end of 2007 (Figure 1b).  cART first regimen consisted of ZDV+3TC+EFV. In 2001 EFV was replaced by LPV/r due to EFV neurologic intolerance. Therapy was simplified in 2002 3 with the association of ZDV/3TC/ABC (Trizivir). M1 was also a vaccine recipient in the therapeutic HIV vaccine trial TheraVac01 {10}. Briefly, the trial was an open-label one arm study that took place in Lausanne, Switzerland. All subjects (n=10) were immunized with NYVAC-B (Gag/Pol/Nef polygene of HIV IIIB, and Env clade B of HIV BX08) intramuscularly (10E7.4 CCID50/mL) at weeks W0 and W4. M1 was assigned the code TH#04 and was immunized on May 17 (W0) and on June 14 (W4) 2006, respectively. In February 2008, M1 presented with a plasma viral load of 280 copies/mL that increased over the following year. Genotypic analysis from 2008 onward revealed 25 new drug resistance mutations to NRTI (6), NNRTI (5) and PI (14). Of note, this resistance profile shared 22 of 23 mutations (96%) found contemporaneously in M2. The shared mutations included  NRTI resistance mutations 41L, 74I, 184V, 215Y, NNRTI mutations, 98G, 103N, 108I and PI mutations 10V, 13V, 20R, 32I, 33I, 46I, 47V, 50V, 71I, 77I. M1 also developed 75T (NRTI), 115/Y (NNRTI) and 82A (PI) polymorphisms. Molecular and Phylogenetic analyses  We obtained viral gene sequences from M1 from July 2000 (N=11 ~9kb near full-length genomes, NFLG), February 2008 (N=12 gag and env genes) and May of 2008 (N=14 gag and N=16 env genes), and from M2 in January (N=10 NFLG) and March of 2008 (N=7 NFLG). All 86 viral sequences were assigned to clade B. Additionally, all sequences from M1 obtained from 2008 clustered with M2 sequences from the same year and were phylogentically unrelated to M1 sequences from 2000 (data not shown). This indicated HSI of M1 with substantial or complete replacement with virus from M2. No recombination between the M1 and M2 strains was observed. Four years follow-up M1’s viral load increased from undetectable to >3 logs after HSI, decreasing progressively from 2009 to 2012 without cART modification. A continuous drop of CD4+ cells of at least 4 10% was observed from time of HSI detection in February 2008 (30.8%) through April 2011 (18%). However, in April 2012, M1’s CD4+ count recovered to 25.4% (757 cell/mm3) (Figure 1b). Patient M2’s follow-up was taken over by a general practitioner in 2009 after 3 consecutive undetectable viral loads following start of salvage antiretroviral treatment (Figure 1a).   Discussion and conclusions We detected superinfection and replacement by HIV-1 clade B triple class-resistant virus in a patient on long-term cART controlled infection, with the initial indicator of HSI being a detectable and increasing viral load.   Other resistance mutations not found in the superinfecting strain also emerged following HSI, though their origin is unclear. They could have been present as minority populations prior to superinfection or transmitted with the superinfecting strain but below the detection level of our assessment of M2’s quasispecies (no additional specimen was available for massively parallel sequencing). Despite HSI with a triple class resistant virus, M1’s antiretroviral treatment remained unchanged. During 4 years of additional follow-up, a continuous drop of viral load occurred, followed by CD4+ recovery in the last year (Figure 1b). The impact of HSI in CD4+ decline and disease progression following subtype B coinfection was initially suggested by Gottlieb and colleagues {11}. Evidence of CD4+ T-cell decline as the initial indicator of HSI was also reported in untreated patients during primary HIV infection as well as in untreated elite controllers {12-14}. In contrast to previous reports of superinfecton among long-term known seroconcordant couples undergoing ART {9}, this report underscores the fragile chemoprophylactic barrier exerted by ART despite excellent adherence. Apart from the complex resistance profile of the superinfecting strain present in patient M2, we cannot rule out the role of viral escape to 5 preexisting CTL or antibody responses in the establishment of the second infection, which involves the same clade and therefore, to some extent challenged similar immune signatures in the superinfected individual, as reported elsewhere {15-16}. Of interest, M1’s HIV-specific T-cell responses were enriched following NYVAC-B immunizations (weeks 0 and 4) and 21 months prior to superinfection {10}. Briefly, two novel Env/Pol vaccine-induced responses emerged at W2 and remained present throughout the study with a clear decline by W48 {10}, greater than 1 year prior to HSI. The protective role of these vaccine-induced responses to prevent a second infection with a resistant virus, as well as their longevity, remains unproven.  Haplotypes such as HLA-B3503 have been shown to be associated with HIV-1 superinfection susceptibility as a consequence of late or weak immune response priming {15}. In this regard, patient M1 carries HLA haplotype A*30/23, B*35/44, DRB1*14/04 (performed by PCR-SSO using LabType® kit on the Luminex System). He also had no CCR5-delta 32 mutations (in-house PCR modified from Wilkinson DA et al., 1998) {17}.  In summary, patient M1’s superinfection onset agrees with current knowledge on host factors and re-exposure to a resistant strain, and demonstrates the previously unexpected scenario of re-infection during well-established chronic infection, despite continuously suppressed viremia with cART started during primary HIV infection.  Acknowledgments The authors are grateful to patients M1 and M2 for their written consent to participating in this study. We also thank Brendan Larsen for submission of sequences to GenBank. This work was supported by NIH grants R37AI47734 and the Bioinformatics Core of the University of Washington Centers for AIDS Research (NIH P30AI27757).  Sequence Data Nucleotide sequences were deposited in GenBank and are available under Accession numbers KC797171 - KC797229. 6 Footnotes Author contributions: E.C, G.P, J.I.M, M.C and P.A.B designed research; E.C and H.Z performed research; E.C, H.Z, J.I.M, M.C and P.A.B analyzed data; and E.C, G.P, J.I.M, M.C and P.A.B wrote the paper.   References 1. Ramos A, Hu DJ, Nguyen L, Phan KO, Vanichseni S, Promadej N et al. Intersubtype human immunodeficiency virus type 1 superinfection following seroconversion to primary infection in two injection drug users. J Virol. 2002;76:7444-7452.  2. Jost S, Bernard MC, Kaiser L, Yerly S, Hirschel B, Samri A et al. A patient with HIV-1 superinfection. N Engl J Med. 2002. 347:731-736. 3. Yerly S, Jost S, Monnat M, Telenti A, Cavassini M, Chave JP et al. HIV-1 co/super-infection in intravenous drug users. AIDS. 2004;18:1413-1421. 4. Hu DJ, Subbarao S, Vanichseni S, Mock PA, Ramos A, Nguyen L et al. Frequency of HIV-1 dual subtype infections, including intersubtype superinfections, among injection drug users in Bangkok, Thailand. AIDS. 2005;19:303-308. 5. Chohan B, Lavreys L, Rainwater SM and Overbaugh J. Evidence for frequent infection with human immunodeficiency virus type 1 of a different subtype. J Virol. 2005;79:10701-10708. 6. Altfeld M, Allen TM, Yu XG, Johnston MN, Agrawal D, Korber BT et al. HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus. Nature. 2002;420:434-439. 7 7. Takehisa J, Zekeng L, Miura ,  Ido E, Yamashita M, Mboudjeka I et al. Triple HIV-1 infection with group O and Group M of different clades in a single Cameroonian AIDS patient. J Acquir Immune Defic Syndr Hum Retrovirol, 1997;14:81-82. 8. Takehisa J, Zekeng L, Ido E, Yamaguchi-Kabata Y, Mboudjeka I, Harada Y et al. Human immunodeficiency virus type 1 intergroup (M/O) recombination in cameroon. J Virol.  1999;73:6810-6820. 9. Campbell MS, Gottlieb GS, Hawes SE, Nickle DC, Wong KG, Deng W. HIV-1 superinfection in the antiretroviral therapy era: are seroconcordant sexual partners at risk? PLoS One. 2009;4:e5690. 10. Harari A, Rozot V, Cavassini M, Enders FB, Vigano S, Tapia G et al. NYVAC immunization induces polyfunctional HIV-specific T-cell responses in chronically-infected, ART-treated HIV patients. Eur J Immunol. 2012;42:3038-48. 11. Gottlieb GS, Nickle DC, Jensen MA, Wong KG, Grobler J, Li F et al. Dual HIV-1 infection associated with rapid disease progression. Lancet 2004;363:619-622. 12. Cornelissen M, Pasternak AO, Grijsen ML, Zorgdrager F, Bakker M, Blom P et al. HIV-1 dual infection is associated with faster CD4+ T-cell decline in a cohort of men with primary HIV infection. Clin Infect Dis. 2012;54:539-547.  13. Clerc O, Colombo S, Yerly S, Telenti A, Cavassini M. HIV-1 elite controllers: beware of super-infections. J Clin Virol.  2010;47:376-378. 14. Rachinger A, Navis M, van Assen S, Groeneveld PH, Schuitemaker H. Recovery of viremic control after super-infection with pathogenic HIV type 1 in a long-term elite controller of HIV type 1 infection. Clin Infect Dis. 2008;47: e86–89 15. Pacold ME, Pond SL, Wagner GA, Delport W, Bourque DL, Richman DD et al. Clinical, virologic, and immunologic correlates of HIV-1 intraclade B dual infection among men who have sex with men. AIDS. 2012;26:157-65. 8 16. Mayr LM, Powell RL, Ngai JN, Takang WA, Nádas A, Nyambi PN. Superinfection by Discordant Subtypes of HIV-1 Does Not Enhance the Neutralizing Antibody Response against Autologous Virus. PLoS One 2012;7:e38989.  17. Wilkinson DA, Operskalski EA, Busch MP, Mosley JW, Koup RA. A 32-bp deletion within the CCR5 locus protects against transmission of parenterally acquired human immunodeficiency virus but does not affect progression to AIDS-defining illness. J Infect Dis. 1998; 178:1163-6.  1a. Patient M2: Source of superinfection 3.7 4.3 4.6 4 1.7 3.4 4.4 4.1 4.2 1.5 1.5 34.8 37.4 36.3 38 38 34.4 29.1 20.1 27 24.3 27.9 0 5 10 15 20 25 30 35 40 0 1 2 3 4 5 01.05.1996 01.05.1998 01.05.2000 01.05.2002 01.05.2004 01.05.2006 01.05.2008     CD4+ (%)     CD4+      Viral load (log copies/mL) Course of HIV infection (years) AZT+SAQ Set-point    1998    2000    2004    2006    2008 Lower limit of quantification AZT+3TC+IDV d4T+3TC+IDV ABC+EFV+LPV/r ABC+3TC+LPV/r RAL + MVC +  ETV + DV /r    2002 1996  Start of cART Time-points used for nucleotide sequencing   Set-point 6.6 3.9 1.5 1.5 1.5 1.5 2.4 2.7 3.4 2.9 2.6 2.4 2.3 23.7 30.5 28.7 32.2 33.5 29.9 30.8 29.5 27.2 25.3 23.2 18 25.4 0 5 10 15 20 25 30 35 40 0 1 2 3 4 5 6 7 01.07.2000 01.07.2002 01.07.2004 01.07.2006 01.07.2008 01.07.2010 CD4+ (%) Viral load (log copies/mL) Course of HIV infection (years)      2004   2006   2008  2010 ABC+3TC+AZT 1b. Patient M1: Recipient of superinfection 2000 Primary HIV  infection Lower limit of quantification 2002 2008 Documented superinfection 2006-2007 Theravac-01 study subject Time-points used for nucleotide sequencing   

HIV-1 superinfection with a triple-class drug-resistant strain in a patient successfully controlled with antiretroviral treatment.

Servicio de Difusión de la Creación Intelectual

http://sedici.unlp.edu.ar/bitstream/handle/10915/60718/Documento_completo.pdf?sequence=3

HIV-1 superinfection with a triple-class drug-resistant strain in a patient successfully controlled with antiretroviral treatment.

Abstract

Similar works

Full text

Available Versions

MUCC (Crossref)

Crossref

SEDICI - Repositorio de la UNLP

El Servicio de Difusión de la Creación Intelectual

El Servicio de Difusión de la Creación Intelectual

Serveur académique lausannois

MUCC (Crossref)

Servicio de Difusión de la Creación Intelectual

Servicio de Difusión de la Creación Intelectual