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.

摘要

AIM:udThis work identifies recent HIV infection (RHI) in men who have sex withudmen (MSM) and the specific phylogenetically-linked transmission eventsudduring which they were infected. The overall aim is to identify the clinicaludcharacteristics of each infection source individual and evaluate theirudproportional contribution to transmission.udOBJECTIVES:ud1. Construct a dataset to capture cohort characteristics;ud2. Identify RHI in subtype B infection using the Serological TestingudAlgorithm for Recent HIV Seroconversion (STARHS);ud3. Identify the most-likely infection source individual for each RHI byudphylogenetic analysis;ud4. Observe the clinical characteristics of each infection sourceudindividual at the time of infection and estimate the proportionaludcontribution to transmission of unknown infection, disease stage andudHAART statusudMETHODOLOGY:udThe study population was a cohort of mainly MSM attending the single HIVudclinic in Brighton, UK. The study involved phylogenetic analysis of HIVudgenotypic sequences obtained for routine clinical care. Clinical data wereudalso collected. Written, informed consent was obtained and every studyuddescribed in this thesis had formal ethical approval.udRESULTS:ud1. STARHS confirmed RHI in 71/74 (96%) individuals identified as RHIudby conventional methods;ud2. Pol sequence data were obtained for 859/1144 (75%), of whomud159/859 (19%) were RHI at diagnosis;ud3. For only 41/159 (26%) RHI could an infection source individual beudidentified;ud4. RHI contributed 3% of follow-up time but 41/59 (27%)udtransmissions (RR 4.44, 95% CI 2.11-9.33, p=0.0001);ud5. 39/41 (95%) transmissions were from untreated individuals orudthose interrupting antiretroviral treatment (ART).udCONCLUSIONS:udThree-quarters of infections came from undiagnosed infections or fromudoutside Brighton. Of those from diagnosed infections, transmission wasudsignificantly associated with RHI, STI and viral load, and reduced byudeffectively-taken ART. These results demonstrate that effective behaviouraludinterventions to increase HIV testing and improve ART uptake andudadherence will reduce onward transmission.