A phylogenetic approach combining HIV pol sequences with laboratory and clinical data was undertaken to explore HIV transmissions between men who have sex with men (MSM). Combining putative transmission events (reconstructed through phylogenetic analyses of pol sequences) with clinical (e.g. viral load) and diagnostic (e.g. recently-acquired infection) data can enhance understanding of HIV transmission more than can be gleaned from each individual source. The thesis: assessed the consistency of phylogenetic reconstructions of HIV transmission events; explored transmissions from recently HIV-infected MSM at diagnosis and critiqued such analyses; and ascertained which groups of diagnosed HIV-infected MSM are generating HIV transmissions. Sensitivity analyses demonstrated that phylogenetic reconstructions of transmission events were 80% consistent as sample sizes were varied. Previous phylogenetic reconstructions overestimated transmission from recently HIV-infected MSM through failing to recognize that this infection stage is transitory. Comparison of infection dates between recently HIV-infected MSM involved in transmission events revealed only half of the transmissions were generated during recent infection. Through allowing infection stage (and other markers of transmission risk) to reflect the course of HIV infection it was established that the recently HIV-infected have a transmission risk of 3.04 (compared to the chronically HIV-infected population). Transmission rates were elevated among the untreated population; 72% (28/39) were generated from treatment-naïve MSM and 23% (9/39) from MSM interrupting treatment. Overall, 69% (27/39) of transmissions occurred from MSM with CD4 counts >350 cells/mm3. BHIVA guidelines recommend treatment discussions start when patients‟ CD4 counts reach 200-350mm3. This work contributes to the debate on the public health benefit of treating all HIV-diagnosed individuals, regardless of clinical need. Behavioural interventions need to increase awareness of recent HIV infection, and the elevated transmission risk from untreated populations. Phylogenetics has enormous potential to contribute to public health, but remains in its infancy; methods need rigorous assessment and results require cautious interpretation.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:564889 |
| Date | January 2010 |
| Creators | Brown, A. E. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/19626/ |
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