Resistance testing practices and prevalence of HIV drug resistance - - PowerPoint PPT Presentation

Daniel Schmidt, Christian Kollan, Barbara Bartmeyer

Robert Koch-Institute

• Dept. Infectious Disease Epidemiology

HIV/AIDS, STI unit

Resistance testing practices and prevalence of HIV drug resistance in the German ClinSurv resistance study

12.04.2013 Arevir Meeting 2013 1

HIV resistance surveillance - status quo in Germany

• Genotyping financed by statutory health insurances prior to first line

treatment and in case of treatment failure

• No resistance data through mandatory HIV reporting
• HIV drug resistance monitoring only in observational studies
• No information about prevalence of HIV resistance on population level
• No central repository for HIV sequence data exists
• storage of viral sequences in different labs
• At national level lack of knowledge:
• on data process algorithms in clinical settings
• frequency of resistance testing
• date of sampling vs. date of sequencing
• reasons for resistance testing of treatment experienced patients
• Pilot resistance study within the ClinSurv cohort to gain information about

HIV resistance in an unselected population

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The ClinSurv cohort

Cohort design/Treatment status

• Open, multi centre observational study cohort (since 1999)
• 15 study centres throughout Germany
• Only basic data recorded (VL, CD4, AIDS diagnoses, ART)

→ no written informed consent required

• Total study population (31.12.2011): 16,974 patients

(113,825 years of observation)

• 9,066 patients on ART per quarter of observation
• 172 patients ART initiation per quarter of observation
• Successful treatment: >80% of patients, without blips >90%

(VL <50 copies/ml, observation time >90 days of treatment)

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ClinSurv HIV Resistance study

ClinSurv HIV N=16,974

ClinSurv Resistance Study

N=9,528 (56% of ClinSurv patients) Pilot sites

Cologne Dusseldorf Hamburg Hannover Munich

Genotyped 34% (3,267/9,528) Sequences N=4,989 Treatment status of patients while genotyped: 47% therapy naive; 50% ART experienced

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Identification of ClinSurv patients with available sequences at local sites Replacement of local sample count numbers by pseudonymized identifiers Process through Stanford Interpretation algorithm; HIV db version 6.1.1F; 2012 Epidemiological analysis by using different lists of mutations (SDRM list 2009; IAS list 2011)

ClinSurv HIV Resistance study - Methods

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Patient characteristics

N=3,267

• Gender: 82% Men
• Transmission risk: 58% MSM, 14% Hetero, 12% HPC, 6% IDU
• Origin: 74% Germany, 12% Africa & Near East
• Subtype: 79% HIV-B, 10% HIV-A, 5% CRF, 3% HIV-C
• Transmission risk, origin, HIV subtype differed between men

and women

− Women: Origin: 40% Germany, 40% Africa, Near East Risk: 46% HPC, 34% Hetero, 11% IDU, Subtype: 38% HIV-B, 28% HIV-A, 14% CRF, 11% HIV-C

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Resistance testing practices

Testing frequencies

• 80% of resistance tests were performed after 2005
• Resistance testing frequency:

74% one single test, 16% two tests, 5% three tests

• Time between resistance tests decreased (median: 348 days)

Testing and treatment

• 8% of patients started treatment before 1996, 62% of patients

started treatment after 2004

• Treatment start in 48% within 4 weeks after first resistance test

(median 33days)

• 60% of patients were exposed to antiretroviral drugs

for more than 5 years, 25% for more than 10 years

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Prevalence of transmitted drug resistance TDR

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0,0% 2,0% 4,0% 6,0% 8,0% 10,0% 12,0% 14,0% 16,0% Total TDR NRTI resistance NNRTI resistance PI resistance

Prevalence of drug resistance in first Prot/RT sequences from treatment naive patients (n=1,950) by year according to

0% 5% 10% PI NNRTI NRTI

Overall prevalence

7% (95%CI 6-8; p=0.7) 3% (95%CI 2-4; p=0.6) 3% (95%CI 2-4; p=0.7)

Prevalence of TDR: 10.4% (95% CI 9.1-11.8) p for trend =0.6, 2001-2011

Prevalence of acquired drug resistance ADR

submitted for publication

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Prevalence of ADR in different drug classes

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submitted for publication

Single mutations

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submitted for publication

Treatment exposure with protease inhibitors among treated patients

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submitted for publication

Viral load in sequences from treated patients

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submitted for publication

• Prevalence of TDR stable over time (10%)
• Significant decline of ADR over time
• Broader resistance testing in the study population since

coverage of resistance testing by health insurances

• Treatment start in median within 4 weeks after first test
• No trend to test at low level viraemia in the study population
• High variety of PIs used for ART prescription
• Decline in ADR could be influenced by better treatment
• ptions, resistance test guided therapy and broader testing

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ClinSurv Resistance study - Conclusions

Participating sites

University of Düsseldorf PD Dr. Björn Ole Jensen University of Cologne

• Prof. Dr. Gerd Fätkenheuer, Eugen Schülter

University of Hannover

• Prof. Dr. Mathias Stoll

University of Munich

• Prof. Dr. Johannes Bogner, Prof. Dr. Eberle

ICH Study Centre Hamburg

• Prof. Dr. H.J. Stellbrink

Robert Koch-Institute

FG 18 Karolin Meixenberger, Claudia Kücherer FG34 Andrea Kühne, Bernd Reinhardt, Osamah Hamouda

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ClinSurv Resistance study