Virologie Université Paris 6 –A Derrache –Dr A Maiga –Dr G Carcelain –Dr AG Marcelin –Pr V Calvez Université Paris 7 –Dr D Descamps –Dr G Peytavin Université.

Présentation au sujet: "Virologie Université Paris 6 –A Derrache –Dr A Maiga –Dr G Carcelain –Dr AG Marcelin –Pr V Calvez Université Paris 7 –Dr D Descamps –Dr G Peytavin Université."— Transcription de la présentation:

1 Virologie Université Paris 6 –A Derrache –Dr A Maiga –Dr G Carcelain –Dr AG Marcelin –Pr V Calvez Université Paris 7 –Dr D Descamps –Dr G Peytavin Université Bordeaux 2 –Dr B Masquelier

2 Virologie Diagnostic –Tests sérologiques –Diagnostic chez l’enfant Suivi du traitement –Mesure de la charge virale (détection de la virémie résiduelle) Prise en charge de l’échec

3 Virologie Diagnostic –Tests sérologiques

4 Tests ELISA

5 Tests rapides

6 Tests salivaires

7 Problèmes ? Faux négatifs : exceptionnels Faux positifs : très rares

8 Virologie Diagnostic –Tests sérologiques –Diagnostic chez l’enfant

9 Avantages du papier buvard Étapes inutiles 4321 Possible

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11 Virologie Diagnostic –Tests sérologiques –Diagnostic chez l’enfant Suivi du traitement –Mesure de la charge virale (détection de la virémie résiduelle)

12 12 Échec à ABC+3TC+fosAPV/r chez un patient naïf (SOLO) Sax et al 1 000 000 100 000 10 000 1 000 100 10 080100120204060140160180 50 copies/ml 400 copies/ml 1 000 copies/ml Weeks on therapy Pro : M36I RT : None Pro : M36I, M46I, I50V RT : M184I Pro : M36I, M46I, I50V RT : M184V Pro : M36I, M46I, I50V RT : L74V, M184V * * Switch to 908/r bid Viral load (copies/ml)

13 Development of drug resistance in a sub-saharan cohort of HIV1-infected adult patients receiving fixed-dose combination of stavudine 30mg/lamivudine/nevirapine as standard first-line regimen OBJECTIVE: To characterize the resistance patterns at the time of failure after a first line regimen containing d4T+3TC+NVP as a fixed-dose combination in Mali. RESULTS: Out of the 109 patients included in the study, 83 (76%) had a VL < 200 copies/mL at a median time of 6.7 months after initiation. Among the 26 patients with detectable VL (median VL = 4150 copies/mL; range: 209 – 404000 copies/mL), viruses were not amplifiable in 4 cases. NumberVL (cp/mL)RT mutationsNVP (ng/mL) 07AP045810Y181C1802 17WA0414200M184V, V108I, V179I, Y181CNA 19WA043880M184V, V179I, Y181CNA 26HR0427400M184V, V106ANA 32HR04622M184V8862 35WA0439400M184V, V179I, Y181C7325 36WA041750M184V, K101E, G190A5321 42WA04404000M184V, Y181C4798 51AP0457800M184V, V179I, Y181CNA 53WA0411000M184V, K103N, G190A7722 63HR0467500M184V, K103N, G190A7463 Marcelin AG et al. Los Angeles CROI 2007 abs 662 AIDS 2007

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15 The intensity of virological monitoring is associated with resistance to first line HAART in HIV-1 infected adults receiving 1 st line therapy according to WHO guidelines: a systematic analysis of cohort and trial data Gupta RK, Hill A, Sawyer W, Cozzi-Lepri A, Phillips AN, von Wyl V, Yerly S, Gunthard HF, Gilks C, Pillay D

16 StudyTreatment Study Population TOTAL VF population (VL in copies/ml) Infrequent /no VLM Malawi cohort D4T or AZT /3TC/NVPProgrammatic COHORT398 Single VL >1000 DART NORA AZT/3TC/NVPOne arm of RCT300 Single VL>1000 Ugandan cohort d4T or AZT/3TC/NVPProgrammatic COHORT526 Single VL >400 Thai cohortd4T/3TC/NVPProgrammatic COHORT1700 Two VL>1000 Frequent VLM Cameroon study d4T/3TC/NVPOpen Label prospective60 Single VL>1000 UK CHICd4T or AZT/3TC/NNRTINational COHORT1352 Single VL>1000 Swiss cohortd4T or AZT/3TC/NNRTINational COHORT236 Single VL>1000

17 48 week GA resistance rates

18 48 week TOTAL resistance rates

19 Virologie Diagnostic –Tests sérologiques –Diagnostic chez l’enfant Suivi du traitement –Mesure de la charge virale (détection de la virémie résiduelle) Prise en charge de l’échec

20 Résistance acquise aux NRTIs d4T, AZT TAMs 3TC, FTC 184 ABC, ddI, TDF 65, 74

21 Résistance acquise aux IPs IDV, RTV, SQV, LPV (46, 54, 82, 84, 90) NVF (30, 90) TPV (36, 58, 69, 89) ATV (50) FosAPV, DRV (32, 47, 54, 50, 84)

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25 As previously describe, the predominant subtype circulating in Mali is CRF02_AG (A. Derache et al, Antivir Ther. 2007), and is in agreement with data from others coutries in West Africa. Recombinant CRF06_cpx proportion increase in 2006 and new complex recombinants appear, such as CRF09_cpx and CRF18_cpx. These results suggest an evolution in the dynamic of viral recombination in Mali.

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27 Prevalence of Resistance Mutations in Antiretroviral Naïve Chronically HIV-infected Patients in 2006/2007: a French Nationwide Study Diane Descamps, Brigitte Montes, Marie-Laure Chaix, Sophie Pakianather, Francis Barin, Georges Dos Santos, Anne Krivine, Constance Delaugerre, Jacques Izopet, Anne-Geneviève Marcelin, Anne Maillard, Laurence Morand-Joubert, Coralie Pallier, Jean-Christophe Plantier, Catherine Tamalet, Vincent Calvez, Bernard Masquelier, Françoise Brun-Vézinet 1, Dominique Costagliola on behalf the ANRS AC-11 Resistance Group.

28 Patients Characteristics D Descamps et al IHDRW 2008 Abs 140

29 ODYSSEE 2001 0DYSSEE 2006/2007 p value number of patients363466 PI0.84.70.001 IC 95%[0.3-1.7][1.9 - 11.3] NRTI3.45.80.101 IC 95%[2.1 - 5.4][2.9-11.1] NNRTI0.32.80.005 IC 95%[0.08-1.41][1.2-6.7] Mutations to at least 1 ARV (%)3.910.6< 0.001 IC 95%[2.6 - 6.0][6.7-16.3] D Descamps et al IHDRW 2008, Abs 140 virus with mutations, % [IC95] 1 class ARV3.3 [2.1-5.5]7.9 [5.3 -11.8] 2 classes ARV0.6 [0.2- 1.5]2.6 [0.6-9.6]0.001 3 classes ARV -0.1 [0.01-0.71] Weighted prevalence (% ) of virus with mutations to ARV classes