Pao, DS-P; (2012) The proportional contribution of disease stage and antiretroviral treatment to HIV transmission in men who have sex with men: an epidemiological phylogenetic approach incorporating the enhanced identification of recent infection. Doctoral thesis , UCL (University College London).

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Abstract

AIM: This work identifies recent HIV infection (RHI) in men who have sex with men (MSM) and the specific phylogenetically-linked transmission events during which they were infected. The overall aim is to identify the clinical characteristics of each infection source individual and evaluate their proportional contribution to transmission. OBJECTIVES: 1. Construct a dataset to capture cohort characteristics; 2. Identify RHI in subtype B infection using the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS); 3. Identify the most-likely infection source individual for each RHI by phylogenetic analysis; 4. Observe the clinical characteristics of each infection source individual at the time of infection and estimate the proportional contribution to transmission of unknown infection, disease stage and HAART status METHODOLOGY: The study population was a cohort of mainly MSM attending the single HIV clinic in Brighton, UK. The study involved phylogenetic analysis of HIV genotypic sequences obtained for routine clinical care. Clinical data were also collected. Written, informed consent was obtained and every study described in this thesis had formal ethical approval. RESULTS: 1. STARHS confirmed RHI in 71/74 (96%) individuals identified as RHI by conventional methods; 2. Pol sequence data were obtained for 859/1144 (75%), of whom 159/859 (19%) were RHI at diagnosis; 3. For only 41/159 (26%) RHI could an infection source individual be identified; 4. RHI contributed 3% of follow-up time but 41/59 (27%) transmissions (RR 4.44, 95% CI 2.11-9.33, p=0.0001); 5. 39/41 (95%) transmissions were from untreated individuals or those interrupting antiretroviral treatment (ART). CONCLUSIONS: Three-quarters of infections came from undiagnosed infections or from outside Brighton. Of those from diagnosed infections, transmission was significantly associated with RHI, STI and viral load, and reduced by effectively-taken ART. These results demonstrate that effective behavioural interventions to increase HIV testing and improve ART uptake and adherence will reduce onward transmission.

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