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Assessing HIV Transmission Networks in a Thai Cohort With Acute HIV Infection
Eugène Kroon1; Mark de Souza1; Frits van Griensven2; Donn Colby1; Peter P. Pham3; Sunee Sirivichayakul4; Nelson L. Michael5; Nittaya Phanuphak1; Jintanat Ananworanich6;Sodsai P. Tovanabutra7; for the RV254/SEARCH010 Study Team and MHRP Viral Sequencing Core.
1SEARCH, Bangkok, Thailand;2Thai Red Cross AIDS Rsr Cntr, Bangkok, Thailand;3Military HIV Rsr Prog, Silver Spring, MD, USA;4Chulalongkorn Univ, Bangkok, Thailand;5US Military HIV Rsr Prog, Bethesda, MD, USA;6Military HIV Rsr Prog, Bethesda, MD, USA;7US Military HIV Rsr Prog, Silver Spring, MD, USA
Bangkok has an ongoing HIV epidemic in MSM but phylogenetic support as to whether this occurs within networks or at random is lacking. Studies from other metropolitan areas suggest local transmission among networks of MSM with certain characteristics, which might allow for targeted interventions. The RV254 study enrolls subjects in the earliest stages of HIV infection. Baseline drug resistance genotyping allows for inventory of subtypes and clustering in this cohort.
Real-time screening of 141,233 samples, using nucleic acid testing and sequential EIA, identified 330 acute HIV-1 infections, of whom 93% were MSM. Demographic and risk-factor data were collected at baseline by interview and questionnaire. Date of infection was estimated from self-reported sexual exposure. Protease and reverse transcriptase gene sequences from 273 (268 Thai) subjects were retrieved from plasma. Maximum likelihood trees and pairwise genetic distances were generated. A distance of ≤ 1.5% and visual inspections of signature nucleotides were used to identify linked transmission clusters.
CRF01_AE was predominant at 86% (234) (N), followed by 8% (21) subtype B and 6% (15) CRF01/B. A West African CRF02_AG, a South African C and a B/C strain were also identified. 13/21 B strains clustered with Thai B’. The 5 non-Thai participants had 3 CRF01_AE, 1 subtype B and 1 CRF01/B. Thirty-three subjects (31 CRF01_AE and 2 B) formed 14 clusters: 11 of 2 , 2 of 3, and 1 of 5 individuals. All clusters represent only Thai MSM and CRF01_AE, but for one cluster of 2 B. Only 2 clusters of 2 are known to be linked. 30/33 clustering subjects live in the Bangkok area. Subjects who clustered were not significantly different from non-clustering participants in terms of age, Fiebig stage, plasma HIV-RNA level, days since exposure, reported drug use at exposure, and number of sexual partners preceding enrolment. Median (range) time between infections was 590 (0-1211) days for the clusters of 2, 158 (84-277) days for the clusters of 3, and 144 (43-194) for the cluster of 5 subjects.
The predominance of CRF01_AE sequence clusters suggests local MSM transmission networks. The majority of Bangkok MSM with acute HIV infection in our cohort do not cluster, suggesting that numerous sexual transmission networks contribute to the ongoing epidemic of HIV among MSM in the city. The presence of HIV-1 strains from other regions indicates global transmission networks.