CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

231 Evidence for More Major HIV-1M Lineages From the Early Stages of the HIV-1 Epidemic Marcel Tongo Passo 1 ;Wendy A. Burgers 2 ; Eitel Mpoudi-Ngole 3 ; Jeffrey Dorfman 1 ; Darren P. Martin 4 1 International Center for Genetic Engineering and Biotechnology, Cape Town, Cape Town, South Africa; 2 Division of Medical Virology, University of Cape Town, Cape Town, South Africa; 3 Institute of Medical Research and Study of Medicinal Plants (IMPM), Yaoundé, Cameroon, Yaounde, Cameroon; 4 Computational Biology Group, University of Cape Town, Cape Town, South Africa Background: One of the hallmarks of HIV-1 diversity is the occurrence of numerous mosaic circulating/unique recombinant forms (CRFs/URFs) which are not easily classifiable into any existing subtypes. There is, however, a lot of information stored within the genomes of these viruses which could be useful in efforts both to work out the early history of the HIV-1 pandemic, and to provide a better understanding on the origins and spread of different subtypes branching from near the roots of the HIV-1M phylogeny. Constantly improving phylogenetics-based analytical techniques and rapidly expanding HIV sequence datasets promise to yield important insights into how HIV first emerged. Methods: In an effort to study the phylodynamics of the HIV-1M epidemic, we analysed a set of 577 genomic sequences including all published lineages from the Congo basin region and a selection of HIV lineages from the rest of the world designed to represent the full diversity of each subtype. A fully exploratory screen for recombination using RDP4 was performed with recombinant viruses being decomposed into their constituent parts. All sequences, including those belonging to “pure subtypes” were tested for recombination. Maximum likelihood phylogenetic analyses were used to identify rare parental sequences branching from near the root of the HIV-1M tree. Results: Phylogenetic analyses of mostly recombination-free HIV-1M sequences indicated that many parental sequences of CRFs are not classifiable into the currently defined HIV-1M subtypes: Some of these parental lineages (including CRF02_AG, 04_cpx, 06_cpx and 11_cpx) contained more than 7000bp of unclassifiable sequence, suggesting that they are predominantly descended fromwhat were/are major previously unidentified HIV-1M lineages that were likely epidemiologically relevant during the early stages of the HIV-1M epidemic. In addition, the phylogenetic tree also indicated that predominant parental sequences of some CRFs such as CRF47_BF and 05_DF were/are respectively highly divergent subgroup of B and D viruses. Furthermore, numerous sequences from the Congo basin branch basal to each subtype cluster, a finding consistent with this region being the geographic origin of the global HIV epidemic. Conclusions: Our fully exploratory recombination screen suggests that many CRFs contain sequence fragments from previously unknown early diverging HIV-1 group M lineages. Such sequences could help tremendously with efforts to piece together the early evolutionary history of HIV-1M. 232 HIV-1/M+O Dual Infections and HIV-MO Recombinants in France From 2004 to 2014 Pierre Cappy 1 ; Fabienne De Oliveira 1 ;Veronique Lemee 1 ; Jean-Louis Gaillard 2 ; Laurence Bocquet 3 ; Jean-Dominique Poveda 4 ; Magali Bouvier 5 ; Anne Maillard 6 ; Thomas Mourez 1 ; Jean-Christophe Plantier 1 1 Rouen University Hospital, Rouen, France; 2 Ambroise Paré Hospital, Paris, France; 3 Lille University Hospital, Lille, France; 4 CERBA Laboratory, Saint-Ouen L’Aumone, France; 5 Henri Mondor Hospital, Créteil, France; 6 Pontchaillou Hospital, Rennes, France Background: Recombination is crucial for HIV evolution as pandemic HIV-M recombinants account for 20% of HIV-1 infections. HIV-M and -O co-circulation in Cameroon lead to dual infections and the subsequent generation of MO recombinants (MO). In France since 2004, one HIV-M/O superinfection, M+O dual infections and one MO have been described in patients linked to central Africa. In this study, we aimed to detect these forms in patients diagnosed in France with an HIV-O infection, and characterising the MO genomic patterns. Methods: 141 samples from HIV-O infected patients were gathered from 2004 to 2014 by the French HIV-O Surveillance Network. M+O dual reactivities were screened for by gp120/V3 serotyping. On dually-reactive samples, group M and O specific PCRs were performed in pol , acc and env regions. Moreover, on HIV-O mono-reactive samples, M specific PCRs were also carried out when O amplification failed. Lastly, whole-genome sequencing was performed when possible, to characterise parental and recombinant strains. Results: The presence of HIV-M and -O genomes was detected in 7% of patients (10/141). Two M+O dual infections were detected in 2 patients in 2004 and 2009. Two MO+O dual infections were detected on samples from 2005 and 2006 in epidemiologically linked patients and 1 MO+M+O triple infection in 2013. Finally 6 MO circulating alone were detected: 3 MO fully sequenced in 2008, 2010 and 2013 and 3 MO partially sequenced in 2010 (2 MO in one patient) and 2013. All the MO genetic patterns were different with breakpoints in the acc region (6/8), in LTRs (2/8) and p17 GAG (1/8), RT (3/8), INT (2/8) and gp41 (1/8) genes. The 2 viruses found in the same patient exhibited multiple breakpoints in acc (2 and 5 respectively) . Conclusions: Though all described in Cameroonian native patients, we showed HIV-M+O dual infections and MO recombinants circulate in France. Moreover, the presence of MO recombinants circulating alone and in epidemiologically linked patients demonstrate they are fit enough to be transmitted and spread. Finally, as HIV-O have still an impact on diagnosis and virological monitoring and are naturally resistant to non-nucleoside RT inhibitors, the transmission of HIV-M+O dual infections or MO recombinant forms carrying HIV-O genomic fragments underline the importance of searching for these forms, evaluate their spread dynamics and follow the possible emergence of a CRF_MO. 233 Evidence of Intra-Familial Transmission of an HIV-1 M/O Intergroup Recombinant Virus Paul Alain T. Ngoupo 1 ; Serge Alain Sadeuh-Mba 1 ; Fabienne De Oliveira 2 ;Valérie Ngono 1 ; Laure Ngono 1 ; PatriceTchendjou 4 ;Véronique Penlap Mbeng 3 ; Richard Njouom 1 ; Anfumbom Kfutwah 1 ; Jean- Christophe Plantier 2 1 Centre Pasteur of Cameroon, Yaounde, Cameroon; 2 Virology, CHU Rouen, Rouen, France; 3 University of Yaounde I, Yaounde, Cameroon; 4 Epidemiology, Centre Pasteur of Cameroon, Yaounde, Cameroon Background: HIV-1 groups M and O co-circulate in Cameroon and dual infections as well as HIV-1 M/O intergroup recombinant viruses have been reported in some patients. Recent data has described infection with HIV-1 M/O intergroup recombinant virus in the absence of dual infections thereby suggesting a direct transmission of the recombinant virus. In this study, we described and characterized an HIV-1 M/O intergroup recombinant virus in the absence of dual infection in a couple living in Cameroon. Here we provide for the first time evidence of a direct transmission of an HIV-1 M/O intergroup recombinant virus from one person to another. Methods: Consecutive samples were obtained from a couple presenting for routine HIV viral load analysis. Prior to viral load analysis, each sample was subjected to HIV serotyping using envelope (V3 and gp41) peptides. These samples were subsequently screened for the presence of potential recombinant virus using specific PCRs targeting the Protease (PROT), Reverse transcriptase (RT), Integrase (INT) and envelope (gp41) genes of HIV-1 groups M and O. The previously reported recombination hotspot in the vpr gene was investigated using RT- nested PCRs. Near full length genome sequences of the viruses detected in both spouses were determined by amplification and sequencing of seven partially overlapping sub-genomic regions. Phylogenetic and similarity profile analyses were performed to investigate the genetic relatedness between viruses from both spouses. Results: HIV serotyping indicated that samples from both patients (husband and wife) were reactive only with HIV-1 group O peptides thereby suggesting an infection with HIV-1 group O virus in both spouses. Molecular tests identified HIV-1 group M in the polymerase (PROT, RT and INT) and HIV-1 group O in the envelope (gp41) regions respectively. These results were consistent with phylogenetic analyses of corresponding sub-genomic regions. Altogether, phylogenetic analysis and similarity profile of the near full length genome sequences showed that both spouses were infected with a unique recombinant virus (M/O) having its recombination breakpoint in the vpr gene.

Poster Abstracts

214

CROI 2015