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Experimental Virology

Experimental Virology. HIV in Eastern Europe / Central Asia Epidemiological, virological and sociological factors associated with the transition from a small-scale to a large-scale epidemic Vladimir V. Lukashov. Understanding the HIV-1 epidemic

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Experimental Virology

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  1. Experimental Virology HIV in Eastern Europe / Central Asia Epidemiological, virological and sociological factors associated with the transition from a small-scale to a large-scale epidemic Vladimir V. Lukashov

  2. Understanding the HIV-1 epidemic The HIV-1 pandemic is the sum of local epidemics, affecting various human populations – epidemiological networks, defined by behavioral (risk group), geographical, social factors, etc. Drug users in Italy – commercial sex workers and their clients in Botswana. To understand the epidemic and to develop effective prevention strategies – the epidemiological characteristics of those networks must be studied (their structure, stability, overlapping with other networks, etc.). Traditional tasks of epidemiology. Using molecular (sequence) data in epidemiological studies. Different epidemiological networks – different viruses. Virus genetic markers to trace virus migration.

  3. Global distribution of HIV-1 subtypes

  4. Example: the origin of the HIV-1 epidemic among IDUs in The Netherlands • First AIDS cases in The Netherlands: • MSM – 1982 • IDUs – 1985 •  the virus came to IDUs from MSM? • Experimental data–HIV-1 strains from IDUs in The Netherlands (and Northern Europe) are evolutionary related to virus strains from US IDUs. • epidemiological link of the epidemic among Dutch and US IDUs. 2009 data – the same separation between viruses from Dutch IDUs and MSM. So, two separate stable epidemiological networks.

  5. The global evolution of the AIDS epidemic: from a low-scale HIV-1 circulation to the pandemic The AIDS epidemic has been recognised in the early 1980s. Yet, HIV-1 is decades older: - HIV-1 M subtypes are originating from a single cross- species transmission (1930s); - 1959 HIV-1 strain from Zaire HIV-1 has been circulating in the human population for decades without being recognised. Epidemiological and virological issues associated with the transition of the epidemic from a small-scale to the large-scale.

  6. The development of the HIV-1 epidemic in Eastern Europe / Central Asia: a model of the global epidemic

  7. The HIV-1 epidemic in Eastern Europe – the three stages Statistics: - 1985-1995/1996 – no large-scale epidemic: +- 1,000 HIV-1 cases in total, among 250,000,000 population - 1995-1997 – the first large-scale HIV-1 outbreak: Southern Ukraine (Odessa and Nikolaev), Southern Russia, Belarus (Svetlogorsk) Belarus example: 1985-1996 – 113 HIV-1 cases in total; July 1996 – 60 new HIV-1 cases in Svetlogorsk, Gomel region; by November 1997 – 1,728 HIV-1 cases in Belarus - 1997-2009 – the rise of the epidemic: +-1,000,000 HIV-1 cases - currently – stabilization?

  8. The HIV-1 epidemic in Eastern Europe – • the three stages • Risk groups involved: • - 1985-1995/1996 – no large-scale epidemic: • +- 90% of infections – nosocomial and sexual transmissions • - 1995-1997 – the first large-scale HIV-1 outbreak: • >85% of infections are among IDUs • - 1997-2009 – the rise of the epidemic: • the proportion of individuals infected through heterosexual contacts has been growing, exceeding 50% among new cases

  9. The HIV-1 epidemic in Eastern Europe – the three stages Molecular epidemiology: - 1985-1995/1996 – no large-scale epidemic: high heterogeneity of circulating strains, mostly subtype G (nosocomial cases), C (heterosexual transmission), and B (MSM) - 1995-1997 – the first large-scale HIV-1 outbreak: - 1997-2009 – the rise of the epidemic:

  10. The HIV-1 epidemic in Eastern Europe – the three stages Molecular epidemiology: - 1987-1995/1996 – no large-scale epidemic: - 1995-1997 – the first large-scale HIV-1 outbreak: introduction of a subtype A virus into IDUs in Odessa and a subtype B virus – in Nikolaev, Ukraine subsequent dissemination of the IDU-A strain in Eastern Europe, its recombination with the IDU-B virus – IDU-A/B CRF03_AB (Kaliningrad, Russia) - 1997-2009 – the rise of the epidemic:

  11. Belarus Kaliningrad region, Russian Federation (enclave) Tver Ukraine Moscow Perm Odessa Russia Nikolaev Rostov Stavropol The onset and the initial development of the explosive HIV-1 epidemic in Eastern Europe 120 km (75 miles)

  12. The extreme founder effect – the example of Svetlogorsk, Belarus: single-source HIV-1 outbreak in >1,000 individuals env V3 cons‑SV VMIRSENITDNGKIIIVQLTEPVNITCIRPGNNTRTSIRIGPGQTFYATGDVIGDIRKAYCNVSRAAWNSTLQKISTQLRKYFNNKTIIF A974696 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974697 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974698 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974699 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974700 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974701 ‑‑‑‑‑‑‑‑‑N‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A904703 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974704 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974705 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974706 ‑‑‑‑‑K‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑G‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974707 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑H‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974708 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974709 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974710 ‑‑‑‑‑K‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974711 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974712 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974713 ‑‑‑‑‑K‑‑‑E‑‑‑‑‑‑‑‑‑N‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974714 I‑‑‑‑K‑‑‑‑‑‑‑T‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑A‑T‑‑‑‑‑‑H‑‑‑‑‑‑‑‑‑R‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974715 ‑‑‑‑‑K‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑A‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ A974724 ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ cons‑IDU-A ‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑‑ cons‑A IV‑‑‑‑‑‑‑N‑A‑T‑‑‑‑‑VK‑‑K‑N‑T‑‑N‑‑‑‑K‑VH‑‑‑‑‑A‑‑‑‑‑‑I‑‑‑‑‑Q‑H‑‑‑‑‑TE‑‑K‑‑‑QVAE‑‑‑‑‑‑‑‑‑‑‑‑‑ Sequences from 20 persons had just 18 nuc differences compared to the Svetlogorsk consensus, sequences from 12/20 persons were identical. Samples from 1996 – early 1997 were even more homogeneous, with only 3 nuc differences compared to the consensus and 8 sequences (80%) being identical.

  13. The HIV-1 epidemic in Eastern Europe – the three stages Molecular epidemiology: - 1985-1995/1996 – no large-scale epidemic: - 1995-1997 – the first large-scale HIV-1 outbreak: - 1997-2009 – the rise of the epidemic: samples from >3,000 infected individuals

  14. Currently

  15. No post-Soviet borders. Speaking epidemiologically – Soviet Union still exists.

  16. Epidemiologically significant HIV-1 variants Subtype A IDU-A, +-90% of all infections in Eastern Europe. Subtype B IDU-B, considered to be epidemiologically significant rather traditionally, no propagation in population, limited to Southern Ukraine. CRF03_AB, IDU-A/B, mainly limited to Kaliningrad region, Russia, yet – multiple cases outside the region. CRF06_spx, outbreak in Estonia. CRF02_AG, several countries.

  17. Geographically-defined epidemiological networks and introduction of new viruses – Krasnoyarsk example No risk group-associated clusters – geographical clusters. Subtype B cluster.

  18. Differences among countries- Baltic example Lithuania, Latvia, Estonia: all three countries are very similar to each other in terms of their population structures, economic development, living standards… (highest in the former Soviet Union).

  19. Differences among countries- Baltic example However: Large difference in the HIV-1 epidemic Lithuania – 1,300 cases 0.1% population (Alytus prison outbreak – 300 cases) Latvia – 7,600 0.6% Estonia – 7,800 1.1% Russia – 500,000 0.4%

  20. Epidemiological networks in Lithuania – risk-group-defined: different viruses in circulation

  21. Conclusions 1. The transition of the HIV-1 epidemic in Eastern Europe from a low-scale to the large-scale was associated with - a profound decrease of heterogeneity of circulating virus strains and - the spread of IDU-specific virus diversity patterns to non-IDU risk groups. 2. Subtype A IDU-A viruses are dominating in the HIV-1 epidemic in Eastern Europe, accounting for ±90% of +- 1,000,000 infections in the region. 3. Epidemiological networks (risk group and geographical) define the development of the epidemic. 4. Introductions and propagation of other HIV-1 strains do continue.

  22. Collaborators: Vladimir EreminInstitute for Epidemiology and Microbiology, Elena Gasich Minsk, Belarus Saulius Chaplinskas Lithuanian AIDS Centre, Vilnius, Lithuania Algirdas Griskevicius Edward Karamov D.I. Ivanovsky Institute of Virology, Moscow, Russia Marina Bobkova Alla Gilyazova Olga Rumyantseva Krasnoyarsk Regional AIDS Center, Krasnoyarsk, Russia Jaap Goudsmit Crucell B.V., Leiden, The Netherlands Vladimir Loukachov Faculty of Natural Sciences, Mathematics, and Informatics, University of Amsterdam, Amsterdam, The Netherlands Supported by the INTAS programme

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