High viral load in patients failing first line ART is associated with multidrug resistance in resource limited countries.

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1 High viral load in patients failing first line ART is associated with multidrug resistance in resource limited countries. Avelin Aghokeng 1,2, Emilande Guichet 1,2, Laetitia Serrano 1, Guillaumme Bado 3, Coumba Toure Kane 4, Adrien Sawadogo 4, Cheick Tidiane Ndour 5, Sinata Koulla-Shiro 6, Sabrina Eymard-Duvernay 1, Eric Delaporte 1, Laura Ciaffi 1, Martine Peeters 1 and the 2LADY-study group. 1. UMI233-TransVIHMI, IRD and University of Montpellier, France, 2. IMPM/CREMER, Yaoundé, Cameroun, 3. Hopital de jour de Bobo-Dioulasso, Bobo- Dioulasso, Burkina Faso, 4. Laboratoire de Virologie CHU A Le Dantec, Dakar, Sénégal, 5. UCAD, Dakar, Sénégal, 6. Université Yaoundé 1, Yaoundé, Cameroun

2 ART in resource limited countries number of people receiving ART has tripled over the last five years. About 60% on ART in Africa (WHO 2010 guidelines) Public health approach Standardized first line drug regimens CD4 counts and VL recommended Limited access to viral load monitoring no timely diagnoses of treatment failure < 5% of patients in RLS are on second line

3 Objective describe drug resistance mutations in patients eligible for a second line treatment 2LADY-ANRS12269/EDCTP trial conducted in Africa: Burkina-Faso, Cameroun and Sénégal Evaluation of 3 second line ART regimens during 48 weeks ( ): FTC + TDF + LPV/r (2013 WHO guidelines) ABC + DDI + LPV/r FTC + TDF + DRV/r

4 Patients and methods Cross-sectionnal Viral load for patients on first line ART> 6 months (3TC+AZT/d4T+EFV/NVP) January 2010 september 2012 VL > 1000 copies/ml Adherence intervention during 1 month VL > 1000 copies/ml Switch to second line ART Retrospective genotypic drug resistance testing (ANRS v algoritm)

5 Patients included Cross-sectional consecutive VL screening : 584 patients with VL >1000 adherence intervention: 454 (77%) eligible for inclusion 451 patients included Cameroun n=302 Burkina-Faso n= 90 Sénégal n= 59 First line drugs taken at failure: 3TC (100%) AZT (85%), d4t (15%) EFV (29%), NVP (71%)

6 Patient characteristics with VF on first line ART Age, median (IQR) 38 (32-46) Women, n (%) 324 (72%) Duration first ART months, median (IQR) 49 (33-69) CD4, median (IQR) 183 (87-290) VL log10, median (IQR) 4,5 (4,0-5,1) VL > 4 log10 copies/ml 340 (76%) Asymptomatic at switch, n (%) 411 (91%)

7 HIV drug resistance in patients with VF on first line ART 446/451 (98.9%) samples amplified drug resistance mutations: 440/446 (98.7%) Burkina Faso 85/87 (97.7%) Senegal 56/57 (98.2%) Cameroon 299/302 (99.0%) 2 consecutive VL > 1000 copies/ml + Adherence intervention Good strategy to identify patients with treatment failure

8 HIV drug resistance in patients with VF on first line ART

9 HIV drug resistance in patients with VF on first line ART Number (%) of patients with drug resistance to the different drugs of first line ART Country n 0 drug 1 drug 2 drugs 3 drugs Burkina-Faso 87 2 (2.3%) 4 (4.6%) 39 (44.8%) 42 (48.3%) Cameroon (1.0%) 2 (0.7%) 124 (41.0%) 173 (57.3%) Senegal 57 1 (1.8%) 4 (7.0%) 22 (38.6%) 30 (52.6%) Total (1.3%) 10 (2.2%) 185 (41.5%) 245 (54.9%) > 40 % mono therapy (AZT or D4T) > 50 % NO therapy

10 Accumulation of mutations and cross-resistance At least 3 NRTI mutations(+m184) 80/191 (42%) «3 NNRTI mutations 218/191 (50%)

11 HIV drug resistance and viral load Higher VL in multiresistant strains resistant to 1 or 2 drugs (n=191) 4.2 log10 (IQR: ) resistant to all drugs (n=244) 4.8 log10 (IQR: ) (p<0.001) Proportion of multi-resistant strains increases with VL n=122 n=218 n=106

12 Conclusion Two consecutive VL test with adherence intervention efficient to detect treatment failure (99% drug resistance) > 50% no active drugs 90% of patients with VF and drug resistance were asymptomatic High viral load does not always correspond to non-adherence Increasing probability of transmission of these strains. accumulation of HIVDR may compromise second-line regimens Lower respons to second line regimens

13 Conclusion importance of early detection of treatment failure and biological monitoring Recommend more robust first-line regimens? need continuous surveillance of HIV drug resistance in resource limited countries.

14 Acknowledgements: 2-LADY study group Investigateurs Coordinateurs: KOULLA SHIRO Sinata (Sud) DELAPORTE Eric (Nord) Coordinateur Laboratoire: PEETERS Martine (MPL) AGHOKENG Avelin (Cameroon) COUMBA Toure Kane (Sénégal) BADO Guillaume (Burkina) Coordination Méthodologie: LEMOING Vincent (MPL) IZARD Susanne (MPL) EYMARD DUVERNAY Sabrina (MPL) COURNIL Amandine (MPL) CIAFFI Laura (Chef de Projet) Coordinateurs Administratifs: BUNIOWSKI Annie (IBB) URENA Katia (IBB) WOOMER Barbara (IBB) LAPLACE Sophie (IRD) Site Cameroun IP : KOULLA SHIRO Sinata ARC : ABESSOLO ABESSOLO Hermine MECs : MBEN Jean Marc, TOBY Roselyne, MANGA Nestor, AYANGMA Liliane, TAMAN Bernadette Phar : ESSOMBA Claudine, MANIRAKIZA Geraldine, MBARGA Therese, EPANDA Solange INF : BIKIE Angeline, NKE Thimotee ASSO : MASSAHA Nathalie, NKE Eveline, NGALLE Micheline DB : NGONO BIKOBO Dominique, ABOLOGO Larissa METABODY: AMBANI Landry Agnes et LOWE Tatiana Site Sénégal IP : NDOUR Tediane Cheik ARC : FORTES Louise MECs : NGOM Ndeye Fatou, DIALLO Mouhamadou TEC : DIOP Aïssatou, DIOUF Badara Pharmacie : BARA Ndiaye, KOITA FALL Mame Basty Lab : SECK FALL Bineta Lab (MPL): SERRANO Laëtitia Asso : BA Seydou, NJANTOU Philoméne (DB) DB et METABODY: NDYAYE Amady Site Burkina IP : SAWADOGO Adrien ARC : HEMA Arsene MECs : KABORE M. Firmin, KAMBOULE B. Euloges, ZOUNGRANA Jacques Pharmacie : OUEDRAGO Patricia et TRAORE Richard INF : SANOU Yachinte Lab : BADO Guillaume, COULIBALY Monique Asso : SOME Edwige et KAMBOU Alima SOME Jacqueline DB : TAPSOBA Achille, SOMBIE Diamasso ADM : SANOU Sidia METABODY: PODA 14

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