Near Full-length Genomic Sequencing and Molecular Analysis of HIVInfected Individuals in a Network-based Intervention (TRIP) in Athens, Greece: Evidence that Transmissions Occur More Frequently from those with High HIV-RNA

Abstract

Background: TRIP (Transmission Reduction Intervention Project) was a network-based, contact tracing approach to locate and link to care, mostly people who inject drugs (PWID) with recent HIV infection. Objective: We investigated whether sequences from HIV-infected participants with high viral load cluster together more frequently than what is expected by chance. Methods: Paired end reads were generated for 104 samples using Illumina MiSeq next-generation se-quencing. Results: 63 sequences belonged to previously identified local transmission networks of PWID (LTNs) of an HIV outbreak in Athens, Greece. For two HIV-RNA cut-offs (105 and 106 IU/mL), HIV transmissions were more likely between PWID with similar levels of HIV-RNA (p<0.001). 10 of the 14 sequences (71.4%) from PWID with HIV-RNA >106 IU/mL were clustered in 5 pairs. For 4 of these clusters (80%), there was in each one of them at least one sequence from a recently HIV-infected PWID. Conclusion: We showed that transmissions are more likely among PWID with high viremia.

Phylodynamics Helps to Evaluate the Impact of an HIV Prevention Intervention

“…Absence of such an association in our analysis can be explained potentially by the low number of observed clusters. Clustering was associated with higher viral load in our sample (though this association lost significance after multiple test correction), which is similar to the findings from the TRIP intervention undertaken in Athens and can be interpreted as a marker of recent infection [24], but could also be explained by other factors (e.g., co-infections, late-stage HIV infection). Being in a phylogenetic cluster in our study was correlated with younger age, which might be a proxy for more recent transmission events; this is similar to the result of a previous report from Belgium [49], but unlike the results reported for some other European countries and Canada [50].…”

“…Thus, within the TRIP data, we differentiated between samples that (a) came from people screened for recent infection who were not recently infected, and thus were not invited to further participate in the network intervention component of TRIP (Non-participant TRIP samples, NPTS) and samples which (b) came from TRIP participants-either recently infected people or their 1st or 2nd degree network contacts (participant TRIP samples, PTS). Further details on the TRIP data collection and genetic sequencing procedures can be found in the original publications [13,24]. We obtained 197 sequences of the subtype A pol gene (84 newly generated) from patients of AIDS Centres (HIV treatment clinics) in Odessa (n = 105) and Kyiv (n = 84) collected in 2012-2019.…”

Exploring HIV-1 Transmission Dynamics by Combining Phylogenetic Analysis and Infection Timing

“…The goal of this initiative is to identify not yet diagnosed infections through partner tracing of the newly diagnosed individuals. The project has been successfully implemented in Ukraine, Greece, and the US [11,[48][49][50]. The combination of partner tracing initiatives with real-time phylogenetics and infection time analysis may increase the effectiveness of the approach because it will allow to focus on the most active transmission clusters.…”

A Nationwide Study about the Dispersal Patterns of the Predominant HIV-1 Subtypes A1 and B in Greece: Inference of the Molecular Transmission Clusters

“…Phylogenetic analyses of HIV-1 have several applications in public health, including investigation of transmission dynamics and dispersal and outbreak investigation [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Recently, the Centers for Disease Control and Prevention (CDC) has discussed the benefits of HIV cluster analysis for public health action [ 17 ].…”

“…Recently, the Centers for Disease Control and Prevention (CDC) has discussed the benefits of HIV cluster analysis for public health action [ 17 ]. Investigation on HIV molecular clusters can provide important data about the dispersal patterns of the epidemic, as well as the characteristics of people living with HIV (PLHIV) infected within clusters [ 4 , 5 , 6 , 7 , 8 , 9 , 11 , 12 , 13 , 14 , 15 , 16 , 18 ]. Moreover, by investigating the molecular clusters, we can identify those at higher risk for HIV infection (e.g., the social links of recently infected PLHIV through contact tracing programs) and intervene with targeted strategies to prevent HIV [ 17 ].…”