A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity

Grossman, Zehava; Avidor, Boaz; Mor, Zohar; Chowers, Michal; Levy, Itzchak; Shahar, Eduardo; Riesenberg, Klaris; Sthoeger, Zev; Maayan, Shlomo; Shao, Wei; Lorber, Margalit; Olstein-Pops, Karen; Elbirt, Daniel; Elinav, Hila; Asher, Ilan; Averbuch, Diana; Istomin, Valery; Gottesman, Bat Sheva; Kedem, Eynat; Girshengorn, Shirley; Kra-Oz, Zipi; Avni, Yonat Shemer; Sade, Sara Radian; Turner, Dan; Maldarelli, Frank

doi:10.1371/journal.pone.0135061

Cited by 13 publications

(12 citation statements)

References 34 publications

(44 reference statements)

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“…Our analysis showed that there were multiple introductions of subtype B into Bulgaria from at least 8 different countries, which then spread amongst Bulgarians, including within three large clusters with 14, 67, and 552 Bulgarian members. Interestingly, HIV-1 subtype B sequences from Israel from 2005-2013 were frequently associated with Bulgarian sequences in our study [39]. Most subtype B-infected participants in that study were Israeli-born (73%), reporting high MSM exposure (83%) and suggesting possible MSM interactions between Israel and Bulgaria.…”

Section: Discussionmentioning

confidence: 48%

Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria

Alexiev

Campbell

Knyazev

et al. 2020

Viruses

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HIV-1 subtype B is the predominant strain in Bulgaria, yet little is known about the molecular epidemiology of these infections, including its origin and transmissibility. We used a phylodynamics approach by combining and analyzing 663 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1988–2018 and associated epidemiologic data to better understand this sub-epidemic in Bulgaria. Using network analyses at a 1.5% genetic distance threshold (d) we found several large phylogenetic clusters composed mostly of men who have sex with men (MSM) and male heterosexuals (HET). However, at d = 0.5%, used to identify more recent transmission, the largest clusters dissociated to become smaller in size. The majority of female HET and persons with other transmission risks were singletons or pairs in the network. Phylogenetic analysis of the Bulgarian pol sequences with publicly available global sequences showed that subtype B was likely introduced into Bulgaria from multiple countries, including Israel and several European countries. Our findings indicate that subtype B was introduced into Bulgaria multiple times since 1988 and then infections rapidly spread among MSM and non-disclosed MSM. These high-risk behaviors continue to spread subtype B infection in Bulgaria as evidenced by the large clusters at d = 0.5%. Relatively low levels of antiretroviral drug resistance were observed in our study. Prevention strategies should continue to include increased testing and linkage to care and treatment, as well as expanded outreach to the MSM communities.

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Section: Discussionmentioning

confidence: 48%

Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria

Alexiev

Campbell

Knyazev

et al. 2020

Viruses

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“…Association between MSM transmission route and clustering within the subtype B infected cases has been previously reported in various cohorts [ 18 , 19 , 25 , 36 , 37 , 38 ]. Clinical characteristics of the clustered sequences followed the patterns observed in other studies including lack of prior antiretroviral treatment exposure, higher CD4 lymphocyte counts, earlier stage of HIV disease and more recent sampling [ 16 , 21 ].…”

Section: Discussionmentioning

confidence: 88%

“…This is consistent with the identification of large, interregional clusters in our analysis including the ones comprising of 13 and 20 sequences. These large clusters may reflect rapidly growing sub-epidemics [ 19 ] and have been found throughout subtype B infected populations worldwide [ 38 , 42 , 43 , 44 , 45 ], however the exact transmission pattern within the transmission clusters is difficult to analyze in the cohort of chronically infected individuals. As expansion of the clusters over time has been reported [ 19 , 46 ] this finding supports the need for early introduction of antiretroviral therapy in populations with frequent clustering aiming to break the transmission chains [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Expanding HIV-1 subtype B transmission networks among men who have sex with men in Poland

et al. 2017

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IntroductionReconstruction of HIV transmission links allows to trace the spread and dynamics of infection and guide epidemiological interventions. The aim of this study was to characterize transmission networks among subtype B infected patients from Poland.Material and methodsMaximum likelihood phylogenenetic trees were inferred from 966 HIV-1 subtype B protease/reverse transcriptase sequences from patients followed up in nine Polish HIV centers. Monophyletic clusters were identified using 3% within-cluster distance and 0.9 bootstrap values. Interregional links for the clusters were investigated and time from infection to onward transmission estimated using Bayesian dated MCMC phylogeny.ResultsThree hundred twenty one (33.2%) sequences formed 109 clusters, including ten clusters of ≥5 sequences (n = 81, 8.4%). Transmission networks were more common among MSM (234 sequences, 68.6%) compared to other infection routes (injection drug use: 28 (8.2%) and heterosexual transmissions: 59 (17.3%) cases, respectively [OR:3.5 (95%CI:2.6–4.6),p<0.001]. Frequency of clustering increased from 26.92% in 2009 to 50.6% in 2014 [OR:1.18 (95%CI:1.06–1.31),p = 0.0026; slope +2.8%/year] with median time to onward transmission within clusters of 1.38 (IQR:0.59–2.52) years. In multivariate models clustering was associated with both MSM transmission route [OR:2.24 (95%CI:1.38–3.65),p<0.001] and asymptomatic stage of HIV infection [OR:1.93 (95%CI:1.4–2.64),p<0.0001]. Additionally, interregional networks were linked to MSM transmissions [OR:4.7 (95%CI:2.55–8.96),p<0.001].ConclusionsReconstruction of the HIV-1 subtype B transmission patterns reveals increasing degree of clustering and existence of interregional networks among Polish MSM. Dated phylogeny confirms the association between onward transmission and recent infections. High transmission dynamics among Polish MSM emphasizes the necessity for active testing and early treatment in this group.

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“…Subtype C was predominant (89%) in people emigrating from Africa, considered as those originating from counties with generalized HIV epidemics (OGE). Subtype A was prevalent (71%) among HIV-1-infected persons coming from the former USSR [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Comparison between next‐generation and Sanger‐based sequencing for the detection of transmitted drug‐resistance mutations among recently infected HIV‐1 patients in Israel, 2000–2014

Moscona

Ram

Wax

et al. 2017

Journal of the International AIDS Society

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Introduction: Transmitted drug-resistance mutations (TDRM) may hamper successful anti-HIV-1 therapy and impact future control of the HIV-1 epidemic. Recently infected, therapy-naïve individuals are best suited for surveillance of such TDRM. In this study, TDRM, detected by next-generation sequencing (NGS) were compared to those identified by Sanger-based population sequencing (SBS) in recently infected HIV-1 patients.Methods: Historical samples from 80 recently infected HIV-1 patients, diagnosed between 2000 and 2014, were analysed by MiSeq (NGS) and ABI (SBS). DeepChek-HIV (ABL) was used for interpretation of the results.Results: Most patients were males (80%); Men who have sex with men (MSM) was the major transmission group (58.8%). Overall, TDRM were detected in 31.3% of patients by NGS and 8.8% by SBS, with SBS TDRM restricted to persons infected with subtype B. All SBS-detected TDRM were identified by NGS. The prevalence of TDRM impacting protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) was 11.3, 26.2 7.5%, respectively, in NGS analyses and 0, 3.8 and 5%, respectively, in SBS analyses. More patients with NGS and SBS TDRM were identified in 2008–2014 (37.2% or 13.9%, respectively) compared to 2000–2007 (24.3% or 2.7%, respectively), and a significantly greater number of these patients had multiple NGS TDRM. The most abundant, albeit, minor-frequency RT TDRM, were the K65R and D67N, while K103N, M184V and T215S were high-frequency mutations. Minor TDRM did not become a major variant in later samples and did not hinder successful treatment.Conclusions: NGS can replace SBS for mutation detection and allows for the detection of low-frequency TDRM not identified by SBS. Although rates of TDRM in Israel continued to increase from 2000 to 2014, minor TDRM did not become major species. The need for ongoing surveillance of low-frequency TDRM should be revisited in a larger study.

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A Population-Structured HIV Epidemic in Israel: Roles of Risk and Ethnicity

Cited by 13 publications

References 34 publications

Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria

Molecular Epidemiology of the HIV-1 Subtype B Sub-Epidemic in Bulgaria

Expanding HIV-1 subtype B transmission networks among men who have sex with men in Poland

Comparison between next‐generation and Sanger‐based sequencing for the detection of transmitted drug‐resistance mutations among recently infected HIV‐1 patients in Israel, 2000–2014

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