Trends in transmission of resistant HIV and HIV 1 subtypes Update - - PowerPoint PPT Presentation

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Trends in transmission of resistant HIV and HIV 1 subtypes Update - - PowerPoint PPT Presentation

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Trends in transmission of resistant HIV and HIV 1 subtypes Update German HIV 1 seroconverter study Kuecherer C, Meixenberger K, Scheufele R, Gunsenheimer- Bartmeyer B, Hamouda O in behalf of the seroconverter study group Kuecherer C

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SLIDE 1

Kuecherer C AREVIR Meeting

  • 5. Mai 2011, Köln

Trends in transmission

  • f resistant

HIV and HIV‐1 subtypes

Update German HIV‐1 seroconverter study

Kuecherer C, Meixenberger K, Scheufele R, Gunsenheimer- Bartmeyer B, Hamouda O in behalf of the seroconverter study group

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SLIDE 2

Transmission of resistant HIV

  • Resistant

HIV are transmitted

‐ Patients with treatment failure ‐ Onward transmission by patients in the viremic phase

  • Impact on treatment
  • ptions

and success

‐ Persistence

  • f resistance

mutations ‐ Minor resistant variants not detected by bulksequencing

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SLIDE 3

HIV‐1 seroconverter study

  • Prospective

longitudinal observational study since 1997

‐ Open cohort ‐ Patients with known infection date ‐ Date of seroconversion as best approximation to the infection date

  • Laboratory diagnostic

criteria

  • Documented

seroconversion last negative and confirmed first positive antibody test (< 3 years apart) ‐ "Acute seroconversion“ first reactive test, before seroconversion is completed

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SLIDE 4

AIMS

  • Monitoring the spread of resistant HIV and subtypes
  • Trend analyses
  • In vivo persistence of resistant HIV during drug‐naïve course
  • Impact on disease progression and treatment success
  • Identification of factors influencing progression of disease
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SLIDE 5

Study partners in Germany

68 centers

Sample transport within 24 h to the RKI

health services ‐ blue hospitals ‐ red medical practices ‐ green 2141 seroconverters enroled (end of 2010)

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SLIDE 6

Genotypic resistance testing

  • f HIV

1800 920

718 440 bp PI RTI INI EI FI

  • RT‐PCR ‐> population

sequences

  • Identification
  • f resistance

associated mutation

  • Surveillance

drug resistance mutation list for drug‐naive patients (PI, RTI (Bennett et al. 2009)

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SLIDE 7

Drug‐naive study population

characteristics Year of seroconversion 1996-2009 %

Patients drug-naïve at entry 1639 100 Age median (range) 33 14-76 Sex male 1553 94,6 female 84 5,4 unknown 2 0,1 Living in Berlin 946 59,0 Transmission route MSM. 1429 87,2 HET 137 8,4 HPL 13 0,8 IVD 21 1,3 Professional contacts 5 0,3 unknown 34 2,1 Genotyped* 1603 97,8

* 21 PCR neg

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SLIDE 8

Stable Transmissionrate

  • f resistant

HIV

no decrease 1996‐2009

10 20 30 40 50 60 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Year of seroconversion Resistant HIV (%)

15 27 29 31 33 60 71 155 192 227 206 195 196 166

Prevalence 12,2% 195/1603 [CI 95% 10,8 -13,7] pfor trend 0,374 N=1603

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SLIDE 9

Trends drug classes

NRTI decrease Pfor trend 0.04 NNRTI stable Pfor trend 0.39 PI stable Pfor trend 0.29 NRTI 6.2% NNRTI 2.4% PI 2.1% Prevalence TDR Dual- 1.5%

NRTI

2 4 6 8 10 12 14 16 18 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 2 1 2 2 2 3 2 4 2 5 2 6 2 7 2 8 2 9

Year of seroconversion Resistant HIV (%) NRTI NNRTI

2 4 6 8 10 12 14 16 18 1 2 3 4 5 6 7 8 9 1 1 1 1 2 1 3 1 4

Year of seroconversion Resistant HIV (%) NNRTI PI

2 4 6 8 10 12 14 16 18 1 2 3 4 5 6 7 8 9 1 1 1 1 2 1 3 1 4

Year of seroconversion Resistant HIV (%) PI

Multi- 0.3%

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SLIDE 10

TDR by single resistance mutations

0,5 1 1,5 2 2,5 3 3,5 4 4,5

prevalence (%)

1 NRTI > 1 NRTI 1 NNRTI > 1NNRTI 1 PI > 1PI 1 TAM > 1 TAM

NNRTI and PI resistance mainly caused by singletons

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SLIDE 11

Risk for TDR: subtype B

Subtype B strains 4,4 fold more likely to be resistant

191/1479 4/124

OR 4,41 p=0,00267

0,0 2,0 4,0 6,0 8,0 10,0 12,0 14,0 16,0 18,0 B non-B

Proportion TDR (%)

12,9 3,2

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SLIDE 12

92,3 2,2 1,7 1,4 1,2 0,7 0,3 0,2 7,7 B CRF02_AG C A1 CRF01_AE nicht klassifizierbar, rekombinant G andere (A2, D, F2, CRF12_BF)

Prevalence

  • f non‐B

subtypes

7,7 % non-B infections 124/1603 [CI 95% 6,3-9,1]

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SLIDE 13

Origin

  • f non‐B infections

Origin N 124 % Country

  • f risk

% Germany 81 65,3 74 59,7 EU 5 4,0 3 2,4 Northafrica 2 1,6 Subsaharan Afr. 26 21,0 22 17,7 Latinamerica 4 3,2 Russia 3 2,4 2 1,6 Thail/Vietn/Phil 2 1,6 11 8,9 unknown 1 0,8 12 9,7

  • 41 % 50/124 German, infected

in Germany ‐ 25 % 31/124 German, infected in another country

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SLIDE 14

10 20 30 40 50 60 70 MSM HET HPL IVD unkn

proportion of non-B (%)

Non‐B infections in all transmission groups

57% of the non-B infections in heterosexually acquired infections

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SLIDE 15

Transmission routes and subtypes

10 20 30 40 50 60 70 80 C R F 2 _ A G C A 1 C R F 1 _ A E u n k l a s s i f . R e k . G a n d e r e

Anteil pro Subtyp (%) MSM HET HPL IVD unbek

N=124

  • All non‐B

subypes identified also observed in MSM (G n=4)

  • No hint

to preferential transmission

  • f subtypes
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SLIDE 16

Increase

  • f non‐B infection

(1996‐2009)

Non-B Infektionen: 124/1603 7,7% [KI 95 6,3 -9,1] Pfor trend =0,0168

20 40 60 80 100 120 1 9 9 6 1 9 9 8 2 2 2 2 4 2 6 2 8

prevalence (%) B non-B

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SLIDE 17

Non‐B subtypes in different risk groups

  • ver

time

N=124 20 40 60 80 100 120 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009

proportion nonB (%) HET MSM HPL IVD unbek

  • Non‐B

subtypes since 1998 (pol) in study cohort

  • Highest

prevalences in HET during the epidemic

  • In MSM since

2001 ‐> trend

  • f increase?
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SLIDE 18

Increase

  • f non‐B infections in MSM

Pfor trend =0.0129

1 2 3 4 5 6 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 2 1 2 2 2 3 2 4 2 5 2 6 2 7 2 8 2 9

Proportion TDR (%)

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SLIDE 19

Prevalence

  • f non‐B

infections parallels heterosexual HIV transmissions

2 4 6 8 10 12 14 16 18 1 9 9 6 1 9 9 8 2 2 2 2 4 2 6 2 8 relative proportion (%) HET non-B HET_rep

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SLIDE 20

1 2 3 4 5 6 8 10 12 11 13 7 9

Non‐B Transmis‐ sion clusters HET MSM HET/ MSM IDU 13 7 4 1 1

Evidence

  • f transmission
  • f non‐B

strains among MSM and IDU

MSM cluster no. 2, 5, 6,10 IDU cluster no. 12 with 4 members same city and treating center pol-NJ Tree

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SLIDE 21

Conclusions (1)

  • Study

is representative for MSM in Germany

  • Stable

rate of transmission

  • f resistant

HIV

  • Transmitted

NRTI resistance declines ‐ improved regimens

  • NNRTI resistance: no clear

cut evidence

  • f increase
  • Persistance
  • f resistance

mutations (e.g. K103N and T215 revertants) in combination with

  • nward

transmission

  • f TDR is

likely to contribute to the stable transmission rate of TDR

  • TDR is

correlated with HIV subtype B infections (OR 4.4)

  • Continued

monitoring

  • f TDR needed
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SLIDE 22

Conclusions (2)

  • Low but

increasing rate of HIV‐1 subtype B infections

  • Parallels

heterosexually transmitted HIV infections

  • Transmission of non‐B
  • bserved

for all routes

  • f

infection, trend

  • f increase

in MSM

  • Evidence

from closely related transmissicon clusters

  • f Non‐B

infections in MSM and IDU: Non‐B strains are endemically established in Germany

  • German Data are

shared with European HIV collaborations SPREAD/EHR (in the past), CASCADE, CHAIN, EuroCoord

  • ngoing.
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SLIDE 23

Acknowledgement

  • All study doctors and their patients
  • National reference center
  • Former SPREAD laboratories
  • BMG and BMBF for funding
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SLIDE 24

FIN

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SLIDE 25

Proportion of study patients in comparison to registred newly diagnosed patients

(2000 ‐ 2009)

9

NRW Berlin Bayern Ba.-Wü. Hessen Hamburg Niedersachsen Rheinland-Pfalz Sachsen Schleswig-Holstein Sachsen-Anhalt Bremen Brandenburg Meck.-Vorpommern 1000 2000 3000 4000 5000 4 % 36 % 5 % 5 % 1 % 14 % 3 % 7 % 9 % 1 % 2 % 2 % 5 % 3 % Meldedaten 2000-2009 Serokonverter

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SLIDE 26

Number

  • f mutations

causing resistance

1996 ‐ 2009

  • 1 NRTI decreases (not TAMs)
  • > 1 NRTI stable
  • > 1 NNRTI since 2002
  • > 1PI decreases

2 4 6 8 10 12 14 1 9 9 6 1 9 9 7 1 9 9 8 1 9 9 9 2 2 1 2 2 2 3 2 4 2 5 2 6 2 7 2 8 2 9

prevalence (%)

1 NRTI > 1NRTI 1 NNRTI > 1 NRTI 1 PI >1 PI

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SLIDE 27

5 10 15 20 25 30 35 40 45 MSM HET HPL IVD unkn

  • thers

proportion TDR (%)

Transmission groups and prevalence

  • f TDR

MSM more frequently infected with resistant HIV than HET

P=0,015 OR 2,67 12,9 5,3 8,3 5,0 11,8

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SLIDE 28

TC Nr subtype pol seRisiko yearInfDat DurInf (w) sex zip PatEpiOrt Entrysite Nation risk country patient inf TDR 1 C Hetero 2005 6 m 426 Solingen Düsseldorf Großbritannien Deutschland 1 C Hetero 2006 1 m 861 Augsburg Augsburg Deutschland Deutschland 2 C MSM 2009 28 m 121 Berlin Berlin Deutschland Deutschland 2 C MSM 2009 54 m 130 Berlin Berlin Deutschland Deutschland 3 C Hetero 2004 28 w 126 Berlin Berlin Deutschland Deutschland 3 C Hetero 2006 16 w 445 rural Berlin Deutschland Deutschland 4 C Hetero 2001 4 w 125 Berlin Berlin Deutschland Deutschland yes, diff 4 C Hetero 2008 5 w 133 Berlin Berlin Kenia Unbekannt 5 A1 MSM 2001 21 m 49 rural Berlin Deutschland Deutschland 5 A1 MSM 2001 25 m 107 Berlin Berlin

  • ohne-

Deutschland 6 A1 MSM 2006 30 m 108 Berlin Berlin Bosnien-Herzegow. Deutschland 6 A1 MSM 2007 3 m 101 Berlin Berlin Italien Deutschland 6 A1 MSM 2009 6 m 101 Berlin Berlin Deutschland Deutschland 7 A1 Hetero 2005 55 w 109 Berlin Berlin Deutschland Deutschland PI 7 A1 Hetero 2007 19 m 109 Berlin Berlin Kamerun Kamerun 8 CRF01_AE Hetero 2006 3 m 157 rural Berlin Deutschland Thailand yes 8 CRF01_AE Hetero 2006 3 w 109 Berlin Berlin Kolumbien Deutschland yes 9 G HPL 2005 36 m 701 Stuttgart Stuttgart Sierra Leone Unbekannt yes 9 G Hetero 2005 14 w 716 rural Stuttgart Sierra Leone Deutschland yes 10 CRF02_AG MSM 2009 39 m 147 rural Berlin Deutschland Deutschland 10 CRF02_AG MSM 2009 11 m 108 Berlin Berlin Deutschland Deutschland NNRT 11 CRF02_AG Hetero 2004 22 w 121 Berlin Berlin Kamerun Unbekannt 11 CRF02_AG Hetero 2005 1 m 105 Berlin Berlin Deutschland Deutschland 12 CRF02_AG IVDA 2004 51 m 441 Dortmund Dortmund Deutschland Deutschland 12 CRF02_AG IVDA 2006 6 w 594 rural Dortmund Deutschland Deutschland 12 CRF02_AG IVDA 2006 30 m 441 Dortmund Dortmund Russland Deutschland 12 CRF02_AG IVDA 2005 28 m 441 Dortmund Dortmund Nordafrika/NahOst Deutschland 13 CRF02_AG MSM 2006 m Stuttgart Stuttgart Deutschland Deutschland 13 CRF02_AG Hetero 2008 m Hamburg Hamburg Deutschland Deutschland

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SLIDE 29

Occurence

  • f subtypes
  • ver

time

2 4 6 8 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 p revalen ce (% ) C A1 CRF01_AE CRF02_AG (1996-2009)