ExperimentalVirology

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

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.

C

B A

B

C

B,F

B,E

+++

A,D

C

B,C,B/C B

A/B

Figure 2

Global distribution of HIV-1 subtypes

Example: the origin of the HIV-1 epidemicamong IDUs in The Netherlands

First AIDS cases in The Netherlands:MSM – 1982IDUs – 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.

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.

The development of the HIV-1 epidemic in Eastern Europe / Central Asia:

a model of the global epidemic

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? 0

2000

4000

6000

8000

10000

12000

14000

16000

90 91 92 93 94 95 96 97

the UkraineRussiaBelarus

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

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:

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, Ukrainesubsequent 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:

Ukraine

Belarus

Russia

Moscow Perm

Tver

Rostov

Stavropol

Odessa

Nikolaev

Kaliningrad region, Russian Federation (enclave)

The onset and the initial developmentof the explosive HIV-1 epidemic in Eastern Europe

120 km(75 miles)

The extreme founder effect – the example of Svetlogorsk, Belarus:

single-source HIV-1 outbreak in >1,000 individuals

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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.

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

Currently

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

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.

Geographically-defined epidemiological networks and introduction of new viruses – Krasnoyarsk example

No risk group-associated clusters – geographical clusters.

Subtype B cluster.

1018

12 13

3

24 49

5

6566

7

2267

8

161

19

156

23

25

172

14

11

20

21

Other (homosexual, vertical)

Heterosexual

IDU

Transmission routes

Other (homosexual, vertical)

Heterosexual

IDU

Transmission routes

0

2

4

6

8

10

12

14

16

18

1 2 3 4 5 6 7 8 9 10 11 12

Krasnoyarsk

Borodino

Biysk

Uyar

Norilsk

Lesosibirsk

0

2

4

6

8

10

12

14

16

18

1 2 3 4 5 6 7 8 9 10 11 12

Divnogorsk

Partizanskoe

Kansk

Zheleznogorsk

Berezovka

Sosnovoborsk

Residence

0

2

4

6

8

10

12

14

16

18

1 2 3 4 5 6 7 8 9 10 11 12

Krasnoyarsk

Borodino

Biysk

Uyar

Norilsk

Lesosibirsk

0

2

4

6

8

10

12

14

16

18

1 2 3 4 5 6 7 8 9 10 11 12

Divnogorsk

Partizanskoe

Kansk

Zheleznogorsk

Berezovka

Sosnovoborsk

Residence

28

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4977

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63

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0.01Altayskiy kray

12

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Krasnoyarskiy kray

5

103 46

7

8

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1 Krasnoyarsk2 Berezovka3 Divnogorsk4 Zheleznogorsk5 Sosnovoborsk6 Borodino7 Kansk8 Lesosibirsk9 Partizanskoe10 Uyar11 Norilsk12 Biysk

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).

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%

IDUs (n=66)

A

B

A/B

other

heterosexual and perinatal (n=22+1)

A

B

A/B

other

homosexual (n=15)

A

B

A/B

other

unknown (n=4)

A

B

A/B

other

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

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.

Collaborators:

Vladimir Eremin Institute for Epidemiology and Microbiology,Elena Gasich Minsk, Belarus

Saulius Chaplinskas Lithuanian AIDS Centre, Vilnius, LithuaniaAlgirdas Griskevicius

Edward Karamov D.I. Ivanovsky Institute of Virology, Moscow, RussiaMarina BobkovaAlla Gilyazova

Olga Rumyantseva Krasnoyarsk Regional AIDS Center, Krasnoyarsk, Russia

Jaap Goudsmit Crucell B.V., Leiden, The Netherlands

Vladimir Loukachov Faculty of Natural Sciences, Mathematics, andInformatics, University of Amsterdam, Amsterdam, The Netherlands

Supported by the INTAS programme