CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Conclusion: Measuring HIV-1 diversity over multiple regions using PID can be a useful tool to identify recent infection from diagnostic samples. The sequences can be used for drug resistance and phylogenetics to track transmission networks offering additional tools to direct prevention. The high capacity of NGS makes this approach feasible on a large scale. 199 CHARACTERIZATION OF RECTAL TRANSMISSION BOTTLENECK USING SIV-MACAQUE MODEL Zhe Yuan 1 , Fangrui Ma 1 , Andrew J. Demers 1 , Dong Wang 2 , Jianqing Xu 3 , Mark G. Lewis 4 , Qingsheng Li 1 1 Univ of Nebraska–Lincoln, Lincoln, NE, USA, 2 Dow AgroScis, LLC, Indianapolis, IN, USA, 3 Fudan Univ, Shanghai, China, 4 BIOQUAL, Inc, Rockville, MD, USA Background: Anorectal intercourse is a common route of HIV-1 transmission and a better understanding of the transmission mechanisms is critical for developing HIV-1 preventative strategies. However, it is a big challenge in human studies to unambiguously define the composition of the HIV-1 population present on mucosal surfaces of the recipient, to sample and analyze founder viruses at or near the time of transmission, or to compare the founder viruses in different recipients who have been exposed to an identical virus population to determine if founder viruses in one individual also have an advantage in other individuals. To overcome above limitations and better understand the mechanisms of HIV-1 rectal transmission, we studied the very early virological events using SIV-rhesus macaque model. Methods: We analyzed 524 full-length env sequences from the inoculum, rectal mucosae, axillary lymph node tissues, and plasma of six rhesus macaques at 6 and 10 days post SIV rectal transmission using single genome amplification and Sanger’s sequencing. Results: We found founder virus sequences were primarily derived from rare variants in the inoculum. Despite exposure with identical viral inoculums, founder virus sequences from different animals are largely different, indicating founder viruses are animal-specific. We also identified the founder virus signature (FVS) that can distinguish dominant founder variants fromminor founder variants and untransmitted variants in the inoculum. Importantly, post-transmission defective variants were mainly resulted from frameshift mutations rather than APOBEC derived mutations. Conclusion: Founder viruses in rectal transmission are animal-specific and primarily deriving from low-abundant variants in the inoculum. Our data support a model of rectal transmission, after viruses gain entry through the anorectal mucosa, the host reduces viral diversity by converting some of the transmitted functional viruses into defective viruses mainly via frameshift mutation. Future study to elucidate the role of FVS and mechanism of frameshift mediated conversion of functional viruses into defective variants may gain new insight into the rectal transmission bottleneck, which may inform the design of new strategies to prevent HIV-1 transmission. 200 HIV-1 SUPERINFECTION AFTER RECENT INFECTION IS UNCOMMON IN SUB-SAHARAN AFRICA Gabriel A. Wagner 1 , Parris S. Jordan 1 , Sergei L. Kosakovsky Pond 2 , Matt A. Price 3 , Eric Hunter 4 , Susan Allen 4 , William Kilembe 5 , Douglas D. Richman 1 , Antoine Chaillon 1 , for the IAVI 1 Univ of California San Diego, La Jolla, CA, USA, 2 Temple Univ, Philadelphia, PA, USA, 3 Intl AIDS Vaccine Initiative, New York, NY, USA, 4 Emory Univ, Atlanta, GA, USA, 5 Zambia–Emory HIV Rsr Proj, Atlanta, GA, USA Background: Although recent studies have described the rate of HIV-1 superinfection among primary infection cohorts at high risk for HIV, the frequency of superinfection in heterogeneous-risk populations remains unknown. Our objective was to apply deep sequencing to longitudinally collected blood samples from recently infected individuals in sub-Saharan Africa to identify instances of superinfection and determine its rate in a mixed-risk population background. Methods: Participants were selected from the International AIDS Vaccine Initiative (IAVI) Protocol C, a large multi-site primary infection cohort in sub-Saharan Africa, who had longitudinal follow up greater than 12 months, and remained antiretroviral (ART) naive throughout follow up (N=45). Blood plasma samples were collected, RNA was extracted, and coding regions within HIV-1 env, gag, and pol were amplified using PCR. Amplified PCR products underwent deep sequencing (454, Roche). Bioinformatics and phylogenetic analyses were applied to interrogate for evidence of superinfection. Participants were categorized as superinfected when (i) phylogenetic reconstruction demonstrated divergent viral populations in a background of epidemiologically unlinked viral sequences, and (ii) divergent clustering was confirmed in a second plasma. Results: Forty-five participants were included from: Kigali, Rwanda (8), Masaka, Uganda (3), Kilifi, Kenya (11), Lusaka, Zambia (20), and Copperbelt, Zambia (3). A median of 3 study timepoints (IQR: 3 – 4 timepoints) were analyzed per participant, with a median follow up time of 18.4 months (IQR: 11.2 – 28.3 months) after primary infection. 24% of participants were men who have sex with men, and 76% reported heterosexual transmission as their main risk factor. Of 45 participants, 2 had confirmed superinfection, resulting in an overall proportion of 4.44% (95% CI: 1.23 – 14.83). Both cases were from Lusaka: one subtype C infected individual was superinfected with another subtype C virus between 0 and 9 months after primary infection; the other was initially infected with a unique recombinant form (URF) and became superinfected with a subtype C virus between 2 and 23 months after primary infection. Conclusion: Two cases of HIV superinfection were observed in this study cohort, giving an overall rate of less than 5%. One superinfection case was intrasubtype-C, and the other was intersubtype URF-C. The rate was lower than previous studies, which might be associated with the risk composition of the study cohort. 201 FREQUENT INTRASUBTYPE HIV DUAL INFECTION IN TREATED CHRONICALLY INFECTED INDIVIDUALS Gabriel A. Wagner 1 , Antoine Chaillon 1 , Gemma Caballero 2 , Donald Franklin 1 , Sergei L. Kosakovsky Pond 3 , Robert K. Heaton 1 , Douglas D. Richman 1 , Davey M. Smith 1 , for the CHARTER 1 Univ of California San Diego, La Jolla, CA, USA, 2 VA San Diego Hlthcare System, La Jolla, CA, USA, 3 Temple Univ, Philadelphia, PA, USA Background: HIV dual infection (DI) has been increasingly described among global primary infection cohorts, and it has been associated with increased viral loads, decreased CD4+ T-cell counts, and HIV-associated neurocognitive disorder (HAND). Investigations into DI have relied mostly on extraction of viral RNA from the blood plasma of infected individuals. However, in the era of antiretroviral therapy (ART) estimates of DI have not been assessed. We hypothesized that characterizing HIV DNA populations from peripheral blood mononuclear cells (PBMC) using deep sequencing would identify instances of DI and determine its rate among chronically infected individuals on ART. Methods: Participants of the CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort were selected who had > 4 years between follow-up visits and were receiving ART (N=47). Deep sequencing (454 FLX Titanium, Roche) was performed on PBMC-derived HIV DNA populations using four PCR-amplified coding regions (env C2-V3, gag p24, pol RT, and pol PR). Participants were categorized as DI when (i) phylogenetic reconstruction demonstrated divergent viral populations in a background of epidemiologically unlinked viral sequences, and (ii) divergent clustering persisted over time. Results: Deep sequencing generated 4.9 million viral sequences from 96 PBMC samples from 47 participants, with a median number of 8,121 sequences per coding region per sample (IQR: 4049 – 14,647 sequences). Twelve out of 47 individuals had phylogenetic evidence of intrasubtype B DI present at the first study visit confirmed across longitudinal timepoints, resulting in a total proportion of DI of 25.5% (95% CI: 15.3% – 39.5%). Despite ART, 15 participants had detectable plasma viral load >500 copies/mL or >2.70 log10 copies/mL. Viremia was not associated with DI (p = 0.73, Fisher’s exact). Conclusion: In a US cohort of chronically infected individuals receiving ART, one quarter had intrasubtype DI before the initiation of treatment. Detectable plasma viral load was not associated with DI. Although clinically inapparent, DI is likely to be present more frequently than previously estimated and, given its association with HAND, end-organ sequelae should be further investigated. 202 FEW ACUTE HIV-1 SYMPTOMS AND HIGH SET-POINT VIRAL LOAD IN SUBTYPE-C INFECTIONS Amin S. Hassan 1 , Jonathan Hare 2 , Matt A. Price 3 , Per Bjorkman 4 , Susan Allen 5 , Jill Gilmour 2 , Thumbi Ndung’u 6 , Sarah Rowland-Jones 7 , Eduard Sanders 8 , Joakim Esbjörnsson 7 1 KEMRI Wellcome Trust Rsr Prog, Kilifi, Kenya, 2 Intl AIDS Vaccine Initiative Human Immunol Lab, London, UK, 3 Intl AIDS Vaccine Initiative, New York, NY, USA, 4 Lund Univ, Lund, Sweden, 5 Emory Univ, Atlanta, GA, USA, 6 KwaZulu-Natal Rsr Inst for TB and HIV, Durban, South Africa, 7 Univ of Oxford, Oxford, UK, 8 Kenya Med Rsr Inst, Kilifi, Kenya Background: HIV-1 disease progression varies between individuals and is likely determined during acute HIV infection (AHI). Newly infected individuals mount an immune response against the infecting virus, resulting in acute retroviral syndromes (ARS) that may impact disease progression. HIV-1 subtype A has been associated with more

Poster and Themed Discussion Abstracts

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CROI 2017