CROI 2018 Abstract eBook

Abstract eBook

Poster Abstracts

948 GREATER THAN RANDOM HLA-B HOMOGENEITY IN HIV-1 TRANSMISSION CHAINS Huyen Nguyen 1 , Christian Thorball 2 , Jacques Fellay 2 , Jürg Böni 3 , Sabine Yerly 4 , Matthieu Perreau 5 , Thomas Klimkait 6 , Huldrych F. Günthard 1 , Roger Kouyos 1 1 University Hospital Zurich, Zurich, Switzerland, 2 École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland, 3 University of Zurich, Zurich, Switzerland, 4 University Hospitals of Geneva, Geneva, Switzerland, 5 Lausanne University Hospital, Lausanne, Switzerland, 6 University of Basel, Basel, Switzerland Background: The capacity of HIV to escape immune recognition by Human Leukocyte Antigen (HLA) on cytotoxic T cells is one of the most important and complex components of HIV pathogenesis. Thus, insights into how the individual makeup of HLA class I in HIV-infected patients manifests within transmission chains could have implications for vaccine development. Methods: Approximately 300 transmission pairs and 400 clusters were identified among participants in the Swiss HIV Cohort Study (SHCS) using HIV pol sequences from the drug resistance database for the 11,000 SHCS patients with viral genome data, in addition to Los Alamos background sequences. HLA class I data, available for 5,000 participants, was compiled at three levels of specificity: four-digit and two-digit alleles, as well as HLA-B supertype. The analysis consisted of two ways to calculate allelic homogeneity. The first looked at the proportion of transmission pairs with at least a single matching HLA allele between the two individuals. The second method was to tabulate the average percentage of HLA allele matches within all clusters (e.g. across 4 individuals in a cluster, the proportion of the 6 possible comparisons between themwith a matching HLA allele). These values from the SHCS data were compared to the mean value across 1,000 or 10,000 randomizations (for clusters or pairs, respectively) where the individuals in the clusters or pairs were randomly assorted. The analysis was repeated for the different HLA classification levels and separately for HLA-A, -B, and -C. Results: In both the cluster and pair analyses, HLA-B showed significantly greater homogeneity, as demonstrated by HLA allelic matching within the clusters/pairs compared to random assortment, at the 2-digit- and supertype- level analyses (Table 1). The HLA-A analyses showed no significantly different results between the randomizations and the actual clusters/pairs. HLA-C was significant for pairs at a 4-digit-level analysis. Conclusion: HLA class I alleles of the HIV infected individuals in transmission clusters are not randomly distributed, but instead aggregate into significantly more homogenous clusters and pairs compared to random assortment. This indicates that HIV transmission or superinfection may preferentially occur among individuals with similar HLA class I alleles.

947 HIV-1 SUPERINFECTION IN THE SWISS HIV COHORT STUDY: A LARGE SCALE SCREEN Sandra E. Chaudron 1 , Karin Metzner 1 , Alex Marzel 1 , Jürg Böni 2 , Sabine Yerly 3 , Thomas Klimkait 4 , Matthieu Perreau 5 , Roger Kouyos 1 , Huldrych F. Günthard 1 1 University Hospital Zurich, Zurich, Switzerland, 2 University of Zurich, Zurich, Switzerland, 3 University Hospitals of Geneva, Geneva, Switzerland, 4 University of Basel, Basel, Switzerland, 5 University of Lausanne, Lausanne, Switzerland Background: HIV-1 superinfection (SI) is the infection of HIV-1 infected individuals by another viral strain. SI has been associated with disease progression, viral recombination and immune escape. Identifying SI remains challenging for various reasons: 1. SI strain may outcompete or be outcompeted by the first strain. 2. SI is difficult to discern from co-infection. 3. SI is difficult to prove within viral subtypes, especially if caused by viruses from similar transmission clusters. 4. Sampling frequencies are too low and systematic screens of large populations to date are missing due to lack of needed longitudinal samples in untreated patients. Here we benefit from historic samples of 2 well characterized longitudinal studies; the Zurich Primary HIV Infection Cohort Study (ZPHI, >360 patients with documented PHI) and the Swiss HIV Cohort Study (SHCS, >19,000 HIV infected individuals). Methods: Sequences of the HIV-1 pol gene from 11,738 patients in the SHCS drug resistance database were used for phylogenetic reconstruction. Then, patients with ≥2 longitudinal sequences were kept. From the distribution of our dataset; 2 criteria were used to select HIV-1 superinfected patients: 1. a phylogenetic cluster diversity of at least 20 patients for each individual patient’s cluster and 2. a genetic distance ≥5% between a patient’s sequences. Finally, to address potential samples mislabelling, patients were categorized on their number of longitudinal sequences and the spatial positioning of these sequences in the phylogeny. Category 1 patients have 2 sequences; categories 2 and 3 patients have >2 sequences and respectively 1 sequence or none spatially away from the others. Results: Of 4,558 HIV-infected individuals with ≥2 sequences, 330 candidates for HIV-1 superinfection (figure) including 7 enrolled in the ZPHI, were found. 111 patients are men having sex with men, 117 heterosexuals and 90 intravenous drug users. In addition, 123 patients show evidence of ≥ 2 viral subtypes. In category 3, mislabelling can be excluded due to patients’ sequences clustering pattern corresponding to 31 strong candidates for SI. Based on the 25 patients in category 3 and the 1,224 individuals with ≥ 4 longitudinal sequences, we estimated a minimum rate of SI in our cohorts of 2%. Conclusion: Our molecular epidemiology approach is the largest screen to identify HIV-1 superinfection using longitudinal samples so far. This work sets the basis to validate and characterize HIV-1 SI using next generation sequencing and our cohorts.

Poster Abstracts

CROI 2018 362