HIV transmission chains exhibit greater HLA-B homogeneity than randomly expected.

Nguyen, Huyen; Thorball, Christian W; Fellay, Jacques; Böni, Jürg; Yerly, Sabine; Perreau, Matthieu; Klimkait, Thomas; Kusjeko, Katharina; Bachmann, Nadine; Chaudron, Sandra E; Paioni, Paolo; Thurnheer Zürcher, Maria Christine; Battegay, Manuel; Cavassini, Matthias; Vernazza, Pietro; Bernasconi, Enos; Günthard, Huldrych F; Kouyos, Roger (2019). HIV transmission chains exhibit greater HLA-B homogeneity than randomly expected. Journal of acquired immune deficiency syndromes JAIDS, 81(5), pp. 508-515. Lippincott Williams & Wilkins 10.1097/QAI.0000000000002077

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BACKGROUND

HIV's capacity to escape immune recognition by Human Leukocyte Antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA Class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to host HLA type, and could better improve therapeutic strategies against HIV.

MATERIALS AND METHODS

301-325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA Class I data was compiled at three specificity levels: four-digit, two-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as two measures: the proportion of transmission pairs which are HLA-concordant as well as the average percentage of allele matches within all clusters. These measures were compared to the mean value across randomizations with randomly assorted individuals.

RESULTS

We repeated the analysis for different HLA classification levels and separately for HLA-A, -B, and -C. Subanalyses by risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs.0.251, p-value=0.009; supertype clusters: 0.659 vs. 0.611, p-value=0.002; supertype pairs: 0.655 vs. 0.608, p-value=0.014). Risk group restriction caused the effect to disappear for men-who-have-sex-with-men (MSM) but not other risk groups. We also examined if protective HLA alleles B27 and B57 were under- or overrepresented in the transmission chains, though this yielded no significant pattern.

CONCLUSIONS

The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.

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