ART in patients w ith prim ary prim ary HI V HI V- - resistance - - PowerPoint PPT Presentation

SLIDE 1

ART in patients w ith ART in patients w ith prim ary prim ary HI V HI V-

• resistance

resistance The RESI NA study The RESI NA study

SLIDE 2

• Ongoing prospective study in Nordrhein-Westfalen
• Inclusion: Untreated HIV-infected subjects before HAART initiation
• Study period: 2001-2009, 1936 patients until 2008
• Aims of study:

– Epidemiology of primary resistance in chronically HIV-infected patients – Evaluation of efficacy of HAART guided by resistance testing – Bioinformatic analysis of resistance data

• Coordinating centers:

University of Cologne MPI in Saarbrücken University of Düsseldorf

The RESINA Study The RESINA Study

(Genotypic (Genotypic HIV HIV-

• Resistance

Resistance in Treatment in Treatment -

• Naives)

Naives)

SLIDE 3

• 1. Yerly et al. XV International Drug Resistance Workshop; June 13-17, 2006; Sitges, Spain. Abstract 105; 2. Eshleman et al. XV International Drug Resistance Workshop; June 13-17, 2006; Sitges,
• Spain. Abstract 109; 3. Truong et al.; XV International Drug Resistance Workshop; June 13-17, 2006; Sitges, Spain. Abstract 102; 4. Ross, et al. XV International Drug Resistance Workshop; June

13-17, 2006; Sitges, Spain. Abstract 107; 5. Little S, et al. XV International Drug Resistance Workshop; June 13-17, 2006; Sitges, Spain. Abstract 97; 6. Wensing et al. XV International Drug Resistance Workshop; June 13-17, 2006; Sitges, Spain. Abstract 98; 7. Bennett, et al. XV International Drug Resistance Workshop; June 13-17, 2006; Sitges, Spain. Abstract 103; 8. Garcia A, et al. HIV Med 2006;7:1; 9. Oette et al. HIV 8, Glasgow 2006, P236; 10. Tebit et al. J AIDS 2006:43:144;

Prevalence of drug resistance Prevalence of drug resistance in ART in ART-

• na

naï ïve persons ve persons

Switzerland1 1996–2005

8%

Switzerland1 1996–2005

8%

USA2 1999–2003

16%

USA2 1999–2003

16%

San Francisco3 2004 STD

9%

PHI

10%

San Francisco3 2004 STD

9%

PHI

10%

USA/Australia5 2000–6

13%

USA/Australia5 2000–6

13%

Europe6 2002–3

9-14%

Europe6 2002–3

9-14%

USA4 2000–4

10%

USA4 2000–4

10%

Chicago7 2003–5

25%

Chicago7 2003–5

25%

Los Angeles7 2003–5

20%

Los Angeles7 2003–5

20%

London8 2004–5

7%

London8 2004–5

7%

Germany9 2001–5

9%

Germany9 2001–5

9%

Burkina Faso10

4.8%

Burkina Faso10

4.8%

France 2006-7

10%

France 2006-7

10%

SLIDE 4

Altogether 9.5 % 10.6 % NRTI 6.4 % 5.8 % NNRTI 3.0 % 2.8 % PI 2.0 % 4.7 % Males vs. females p=0.04 NS Subtype B vs. others p=0.002 NS CD4 / VL NS NS Age NS NS transmission group NS NS Ethnicity NS NS disease stage NS NS

RESINA RESINA FRANCE FRANCE

Descamps-D CROI 2009

SLIDE 5

Prävalenz der HIV‐1 Primärresistenz 5 10 15 20 2001 2002 2003 2004 2005 2006 2007 2008

% übertragene Resistenz

Prävalenz

Prevalence Prevalence of

• f primary

primary resistance resistance

SLIDE 6

Prevalence Prevalence of

• f primary

primary resistance resistance England, England, Chilton Chilton et al. 2008 et al. 2008

SLIDE 7

• Prospective follow-up of first-line ART

– Wild type virus vs. resistant virus

• Association with treatment success:

– Homosexual transmission (76 vs. 67 %; p=0,01)

• No associaton with treatment success:

Age, gender, time since HIV-diagnosis, CD4-cell and viral load at baseline, ethnic origin, nationality, other transmission routes, resistance within substance groups NRTI, NNRTI, PI, and revertants, HIV subtype

• Similar results for OT- and ITT-analysis

(48 wks, vl < 50 c/mL)

Treatment Treatment cohort cohort (n= 677) (n= 677)

SLIDE 8

Screening Screening for for HBV HBV

Patients analysed for HBsAg, anti-HBs and antiHBc n=767 HBsAg n=32 (4,2%) anti-HBs n=214 (27,9%) anti-HBc n=331 (43,2%) HBV-DNA n=271 HBV-DNA pos. n=18 (6,6%) HBV-DNA, HBsAg+ n=7 HBV-DNA, HBsAg – n=11

SLIDE 9

54 untreated patients with 2 resistance analyses Changes Changes in in mutational mutational profile profile before before treatment treatment

n = 17 Resistance mutations n = 37 No resistance mutations n = 9 <180 days No alterations n = 8 >180 days 6 x increasing number of mutations 2 x decreasing number of mutations ⇒ superinfection ? ⇒ selection pressure ?

SLIDE 10

• Continued surveillance of resistance in NRW
• Subgroup analyses

(risk factors, treatment responses)

• Representative primary resistance data

for Germany by cooperative network

• Development of prediction tool for

treatment naive patients

• Clinical validation of newly developed

prediction tools

The Future The Future

SLIDE 11

PrEP Prä-Expositions-Prophylaxe

Thank Thank you you for for your your attention attention