CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

235 Clinical and Virological Characterization of CRF07_BC infection Szu-Wei Huang 1 ; Sheng-FanWang 1 ; Chih-Hao Lee 1 ;Wing-WaiWong 2 ; Hung-ChinTsai 3 ; Chia-JuiYang 4 ; Chin-TienWang 5 ; Jaang-JiunWang 6 ; Daniel Kuritzkes 7 ;Yi-Ming A. Chen 1 1 Kaohsiung Medical University, Kaohsiung City, Taiwan; 2 Taipei Veterans’ General Hospital, Taipei, Taiwan; 3 Kaohsiung Veterans’ General Hospital, Kaohsiung City, Taiwan; 4 Far Eastern Memorial Hospital, New Taipei City, Taiwan; 5 National Yang-Ming University, Taipei, Taiwan; 6 Children’s Healthcare of Atlanta and Emory University School of Medicine, Atlanta, GA, US; 7 Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, US Background: The circulating recombinant form (CRF) 07_BC is the most prevalent HIV-1 strain among injection drug users in Taiwan. It contains a 7 amino-acid deletion (7d) in its p6 gag . The objectives of this study were to conduct a cohort study to compare viral load and CD4 cell count changes between patients infected with subtype B and CRF07_BC and to elucidate its mechanism. Methods: Twenty-one patients infected with CRF07_BC and 59 patients with subtype B were selected from a cohort of 667 HIV-1/AIDS patients whom have been followed up for more than 3 years. Generalized estimated equation was used for statistical analysis. The replicative kinetics, tropism and cytopathic effects were determined. HIV-1 NL4-3 which containing a 7 amino-acid deletion in p6 gag (7d virus) was generated and its virological properties were compared with the wild-type. Results: Patients infected with CRF07_BC had significantly lower viral load than patients with subtype B. CRF07_BC isolates had lower replicative capacity than subtype B isolates although they were all CCR5 tropic. 7d virus had significantly lower gag processing efficiency and slower viral life cycle. Electronic microscopy showed 7d virus had poorer viral maturation processes: virions attached to the cell membrane were largely immature. The interaction between p6 gag and Alix protein was less efficient in cells infected with 7d virus. Conclusions: Patients infected with CRF07_BC had significantly lower viral loads than patients infected with subtype B. Such phenomenon may be due to the deletion of 7 amino acids which overlap with the Alex protein-binding domain of CRF07_BC virus. 236 Reconstructing the HIV-1 Epidemics in Burkina Faso Using Early Samples Gonzalo Yebra 1 ; Marcia L. Kalish 2 ; Andrew J. Leigh Brown 1 1 University of Edinburgh, Edinburgh, United Kingdom; 2 Vanderbilt University, Nashville, TN, US Background: Two HIV-1 recombinants dominate the epidemics in Burkina Faso: CRF06_cpx (first described in this country) and CRF02_AG. Here, we reconstruct the phylodynamics of both epidemics in Burkina Faso and Western Africa using for the first time early sequences from samples taken in 1986 and modern sequences from GenBank. Methods: The early sequences were 52 protease (PR) and 37 gp41 sequences for CRF06_cpx and 15 PR and 25 gp41 for CRF02_AG; to which we added GenBank sequences (1993-2013). For CRF06_cpx, we analysed all sequences (163 PR / 41 gp41). For CRF02_AG, we analysed Burkina Faso sequences (142 / 39) and, in a second analysis, sequences from Western Africa (380 / 170) and the closest sequences from Central Africa (311 / 128). Owing to the short length of the sequences available, we analysed sequence data for both genes jointly using the BEAST multilocus analysis to improve convergence and confidence intervals on the growth curves. We also conducted a phylogeographic analysis by using the discrete traits analysis implemented in BEAST to reconstruct the main migration routes between countries. Results: The most recent common ancestor (MRCA) of global CRF06_cpx was 1979 (1977-1980) for both PR and gp41, with respective evolutionary rates of 5.5 (4.8-6.3) × 10 -3 substitutions/site/year (s/s/y) and 6.1 (4.8-7.5) × 10 -3 s/s/y. The phylogeographic analysis of gp41 showed that CRF06_cpx (or at least its parental subtype G lineage) emerged in the Democratic Republic of Congo (DRC) but arrived soon after (1981) in Burkina Faso. Both PR and gp41 showed that this recombinant radiated to the rest of Western Africa only around 1990. The MRCA of CRF02_AG in Burkina Faso was 1979 (1977-81) for both PR and gp41 with rates of 2.3 (1.8-2.9) × 10 -3 s/s/y and 5.7 (4.1-7.4) × 10 -3 s/s/y. In West Africa, the phylogenetic trees showed CRF02_AG sequences interspersed regardless of their sampling country, and the phylogeographic analysis showed much interconnection between countries with 3 main transmission hubs in Cameroon, Burkina Faso and Senegal. Conclusions: Burkina Faso presents a relatively young HIV epidemic, with the two main variants originating around 1980. CRF06_cpx might have emerged in DRC but radiated throughout Western Africa from Burkina Faso. However, CRF02_AG entered Burkina Faso though multiple introductions. Indeed, the CRF02_AG epidemic showed much interchange between Western African countries but also connections with Central Africa, which suggests a great mobility in the region. Background: Simian foamy viruses (SFVs) are efficiently transmitted from non-human primates to humans, establishing persistent infection in the new host. Neither pathogenic effects nor human-to-human transmission have been reported, suggesting that immune control of this retrovirus is efficient. Here, we aimed at studying the humoral response. We used viral strains isolated from animals and infected humans to study the neutralizing antibodies present in the plasma of SFV-infected people living in rural areas of South Cameroon. Methods: Serial dilutions of plasma samples from 46 SFV-infected individuals and seven uninfected subjects were incubated with SFV. Residual viral infectivity was quantified with an indicator cell line expressing the beta-galactosidase gene under the control of the LTR from the prototypic strain, SFVcpzPFV. Four strains from the chimpanzee clade were used: the SFVcpzPFV and SFVcpzSFV7 strains, from serogroups 6 and 7, respectively, and the SFVcpzBAD327 and SFVcpzAG15 strains, isolated from individuals from our study population. Results: Plasma samples from the six people infected with SFV from the chimpanzee clade neutralized either SFVcpzPFV or SFVcpzSFV7. Plasma samples from the seven uninfected individuals and the five individuals infected with SFV from small monkeys did not neutralize any SFVcpz strain. In total, 35 people were infected with SFV from the gorilla clade: 21 of these plasma samples neutralized the SFVcpzPFV strain, eight neutralized the SFVcpzSFV7 strain and one neutralized both strains. Neutralizing titers ranged from 1/30 to 1/2060. Five plasma samples did not neutralize any of the strains tested. The titers of neutralizing antibodies against the zoonotic SFVcpzBAD327 and SFVcpzAG15 strains were strongly correlated with the titers of neutralizing antibodies against the SFVcpzSFV7 strain (Spearman’s rho=0.998, P <0.0001 and rho=0.957 P <0.0001, respectively). Conclusions: SFVs from the chimpanzee and gorilla clades transmitted to humans had similar antigenic properties and belonged to at least two serogroups described in non- human primates. The conservation of the neutralizing epitopes may account for the efficient immune control of these retroviruses. No SFV RNA was detected in the peripheral blood and saliva of these individuals, but the relatively high titers of neutralizing antibodies in some of them suggest that active SFV replication may occur in humans with persistent zoonotic SFV infections. 237 Neutralizing Antibodies in Humans InfectedWith Zoonotic Simian Foamy Viruses Caroline Lambert 1 ; Julie Gouzil 2 ; Réjane Rua 1 ; Edouard Betsem 3 ; Antoine Gessain 1 ; Florence Buseyne 1 1 Institut Pasteur, Paris, France; 2 Ecole Vétérinaire, Maison-Alfort, France; 3 University of Yaounde, Yaounde, Cameroon

Poster Abstracts

216

CROI 2015