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Transmission Networks of Resistant HIV-1 among Men Who Have Sex with Men: The Netherlands
Daniela Bezemer*1,2, A Van Sighem1,2, V Lukashov2, L Van Der Hoek2, S Jurriaans2, R Schuurman3, C Boucher4, E Claas5, R Coutinho6, F De Wolf1,2,7, and the ATHENA Observational Cohort
1HIV Monitoring Fndn, The Netherlands; 2Academic Med Ctr, Univ of Amsterdam, The Netherlands; 3Univ Med Ctr, Utrecht, The Netherlands; 4Erasmus Med Ctr, Rotterdam, The Netherlands; 5Leiden Univ Med Ctr, The Netherlands; 6Natl Inst for Publ Hlth and the Environment, Bilthoven, The Netherlands; and 7Imperial Coll London, UK
Background: We used HIV-1 reverse transcriptase (RT) and protease (PR) sequences to
monitor transmission of resistant HIV-1, and analyze transmission networks
among men having sex with men (MSM) in the Netherlands.
Methods: A phylogenetic
tree was made of RT and PR sequences of 2877 HIV-1 subtype B infected patients from
the ATHENA national observational cohort in the Netherlands. For a selection of MSM with a known date of HIV-1 infection and RT and PR sequenced
within 18 months, potential transmission pairs were selected when the most
similar sequence of a different patient in the selection clustered together with
bootstrap value ≥99. The average time between infection and onward
transmission was estimated as the average difference between the known dates of
infection of these pairs. The transmitting source of MSM with a known date of
infection with a resistant strain was traced in the clusters.
Results: Of 404
RT and PR sequences of MSM with a known date of infection, 175 (43%) were sequenced
within 18 months between 1987 and 2007, and were in 63 clusters. The median
pair-wise sequence difference of potential transmission pairs was 0.9% (IQR 0.4 to 1.5) and the median time difference between the corresponding
dates of infection was 1.4 years (0.6 to 2.7), indicating that 50% (median) of
onwards transmission took place within 17 months and 25% (first quartile) of
transmissions within 7 months after infection. Of 404 MSM with a known date of
infection with RT and PR sequenced within 18 months after infection 24 (6%) carried
a resistant virus, 13 were in 8 significant clusters together with sequences of
MSM with an unknown date of infection. There were 4 clusters enclosed in a total
of 25 MSM infected between 1990 and 2006. Per cluster, all strains contained the
same RT 215 revertant mutant, amino acid C, F, or S. Only 1 cluster included 2
sequences of the possible source patient in whom the initial resistant 215 Y RT
strain was shown to be selected during antiretroviral treatment, and a second
patient infected with the same mutant.
Conclusions: Our results indicate that a significant part of onward HIV
transmission from infected MSM takes place soon after infection. Spread of
resistant strains from the treated population does occur but appeared to be
limited. HIV-1 RT 215 revertant strains are still part of the undiagnosed infectious
pool.
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