A Short-Term Assessment of Nascent HIV-1 Transmission Clusters Among Newly Diagnosed Individuals Using Envelope Sequence-Based Phylogenetic Analyses

AIDS Res Hum Retroviruses. 2019 Oct;35(10):906-919. doi: 10.1089/AID.2019.0142. Epub 2019 Sep 10.

Abstract

The identification of transmission clusters (TCs) of HIV-1 using phylogenetic analyses can provide insights into viral transmission network and help improve prevention strategies. We compared the use of partial HIV-1 envelope fragment of 1,070 bp with its loop 3 (108 bp) to determine its utility in inferring HIV-1 transmission clustering. Serum samples of recently (n = 106) and chronically (n = 156) HIV-1-infected patients with status confirmed were sequenced. HIV-1 envelope nucleotide-based phylogenetic analyses were used to infer HIV-1 TCs. Those were constructed using ClusterPickerGUI_1.2.3 considering a pairwise genetic distance of ≤10% threshold. Logistic regression analyses were used to examine the relationship between the demographic factors that were likely associated with HIV-1 clustering. Ninety-eight distinct consensus envelope sequences were subjected to phylogenetic analyses. Using a partial envelope fragment sequence, 42 sequences were grouped into 15 distinct small TCs while the V3 loop reproduces 10 clusters. The agreement between the partial envelope and the V3 loop fragments was significantly moderate with a Cohen's kappa (κ) coefficient of 0.59, p < .00001. The mean age (<38.8 years) and HIV-1 B subtype are two factors identified that were significantly associated with HIV-1 transmission clustering in the cohort, odds ratio (OR) = 0.25, 95% confidence interval (CI, 0.04-0.66), p = .002 and OR: 0.17, 95% CI (0.10-0.61), p = .011, respectively. The present study confirms that a partial fragment of the HIV-1 envelope sequence is a better predictor of transmission clustering. However, the loop 3 segment may be useful in screening purposes and may be more amenable to integration in surveillance programs.

Keywords: HIV-1 transmission networks; clusters; envelope gene sequences; pairwise genetic distance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Chronic Disease
  • Cluster Analysis*
  • Consensus Sequence
  • Female
  • Genes, env*
  • Genetic Variation
  • HIV Core Protein p24 / blood
  • HIV Envelope Protein gp120 / genetics
  • HIV Infections / epidemiology
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / classification*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / genetics
  • Phylogeny*
  • Population Surveillance
  • Predictive Value of Tests
  • Quebec / epidemiology
  • Risk Factors
  • Sensitivity and Specificity
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Young Adult

Substances

  • HIV Core Protein p24
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments