Exploring Evolutionary and Transmission Dynamics of HIV Epidemic in Serbia: Bridging Socio-Demographic With Phylogenetic Approach

Abstract

Previous molecular studies of Serbian HIV epidemic identified the dominance of subtype B and presence of clusters related HIV-1 transmission, in particular among men who have sex with men (MSM). In order to get a deeper understanding of the complexities of HIV sub-epidemics in Serbia, epidemic trends, temporal origin and phylodynamic characteristics in general population and subpopulations were analyzed by means of mathematical modeling, phylogenetic analysis and latent class analysis (LCA). Fitting of the logistic curve of trends for a cumulative annual number of new HIV cases in 1984–2016, in general population and MSM transmission group, was performed. Both datasets fitted the logistic growth model, showing the early exponential phase of the growth curve. According to the suggested model, in the year 2030, the number of newly diagnosed HIV cases in Serbia will continue to grow, in particular in the MSM transmission group. Further, a detailed phylogenetic analysis was performed on 385 sequences from the period 1997–2015. Identification of transmission clusters, estimation of population growth (Ne), of the effective reproductive number (Re) and time of the most recent common ancestor (tMRCA) were estimated employing Bayesian and maximum likelihood methods. A substantial proportion of 53% of subtype B sequences was found within transmission clusters/network. Phylodynamic analysis revealed Re over one during the whole period investigated, with the steepest slopes and a recent tMRCA for MSM transmission group subtype B clades, in line with a growing trend in the number of transmissions in years approaching the end of the study period. Contrary, heterosexual clades in both studied subtypes – B and C – showed modest growth and stagnation. LCA analysis identified five latent classes, with transmission clusters dominantly present in 2/5 classes, linked to MSM transmission living in the capital city and with the high prevalence of co-infection with HBV and/or other STIs.Presented findings imply that HIV epidemic in Serbia is still in the exponential growth phase, in particular, related to the MSM transmission, with estimated steep growth curve until 2030. The obtained results imply that an average new HIV patient in Serbia is a young man with concomitant sexually transmitted infection.

Dynamics of HIV-1 Molecular Networks Reveal Effective Control of Large Transmission Clusters in an Area Affected by an Epidemic of Multiple HIV Subtypes

“…For example, in our study a large number of new cases were referred from other surveillance sites to the study center for treatment since 2014; therefore, a peak was observed in the cluster growth predictor curve of many clusters in 2014 (orange lines in Figure 4), whereas no corresponding change was observed in the PDR curves (blue lines in Figure 4). R e , the third phylodynamic parameter that is based on sequence diversity, reflects the efficiency with which an infectious agent is transmitted and is frequently used to model infection dynamics (Novitsky et al, 2015;Ragonnet-Cronin et al, 2018;Jovanovic et al, 2019;Lorenzin et al, 2019;Vasylyeva et al, 2019;Vinken et al, 2019;Zai et al, 2020). We found that R e was accurate and reliable.…”

“…R e of each large cluster (≥ 10 cases) was estimated with the birth-death skyline serial model in BEAST v2.4.2 (Jovanovic et al, 2019;Vasylyeva et al, 2019;Vinken et al, 2019;Dennis et al, 2020). R e represents the average number of secondary infections caused by a typical infected individual when only part of the population is susceptible.…”

“…HIV molecular networks can be used not only to guide targeted intervention in key subpopulations (Aldous et al, 2012;Lubelchek et al, 2015;Castley et al, 2017;Chaillon et al, 2017;Zhang et al, 2017;Stecher et al, 2018;Volz et al, 2018;Ragonnet-Cronin et al, 2019;Board et al, 2020), but also to reconstruct the history of HIV spread between populations (Kouyos et al, 2010;Brenner et al, 2017;Pineda-Pena et al, 2018;Delgado et al, 2019;Fabeni et al, 2019). Several local and national studies conducted in recent years have monitored the dynamics of HIV molecular clusters and evaluated their expansion speed (Chan et al, 2015;Mehta et al, 2018;Ragonnet-Cronin et al, 2018;Wertheim et al, 2018;Jovanovic et al, 2019;Dennis et al, 2020). However, most of these studies focused on areas with only subtype B or C HIV-1 epidemics, and few local studies have reconstructed HIV transmission history in an area with multiple HIV subtypes, which may be more complicated because of the variable transmission dynamics and evolution rates of different HIV-1 strains in the population.…”

Molecular network-based intervention brings us closer to ending the HIV pandemic

“…Therefore, molecular investigation of HIV-1 transmission is widely used to infer HIV transmission among populations [5,32], such as in a Dutch criminal case [3] and presumed transmission pairs in a heterosexual cohort of Attached to the study [28] Cluster discordant couples in Zambia [5]. Phylogenetic analysis has also been used to infer HIV transmissions in countries with large datasets [33][34][35][36]. With the combination of demographic, sociological, and epidemiological information, phylogenetic analysis can also help to characterize the source population of HIV infection.…”

“…They used effective reproductive number (Re) to monitor active clusters, which demonstrated the propensity of steady onward propagations [21]. Another phylodynamic analysis study in Serbia revealed that the Re remained over one during the complete period of the investigation; an MSM transmission group of subtype B was determined to have a recent tMRCA and steep growth curve until 2030, whereas heterosexuals with both subtypes B and C displayed minor growth and stagnation [34]. Valverde et al's study, which focused on HIV transmission dynamics among US immigrants who were disproportionately affected by HIV, revealed that the majority of new HIV infections appeared subsequent to the immigration of related individuals to the USA.…”