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On the protease gene , no major mutation was detected. However, many minor mutations, feature

HIV-1 drug resistance among naives patients in Senegal. Leye N. 1 , Diop-Ndiaye H. 1 , Kebe K. 1 , Guindo P.M. 1 , Watara B. 3 , Ngom Guèye N.F. 2 , Diouf E B 2 .., Diallo S. 1 , Diop-Diongue O. 1 , Diaw-Diouf N.A. 1 , Gaye-Diallo A. 1 , Sembène M. 3 , Touré-Kane C 1 . and Mboup S. 1

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On the protease gene , no major mutation was detected. However, many minor mutations, feature

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  1. HIV-1 drug resistance among naives patients in Senegal Leye N.1, Diop-Ndiaye H.1, Kebe K.1, Guindo P.M.1, Watara B.3, Ngom Guèye N.F.2, Diouf E B2.., Diallo S.1, Diop-Diongue O.1, Diaw-Diouf N.A.1, Gaye-Diallo A.1, Sembène M.3, Touré-Kane C1. and Mboup S.1 1Laboratory Bactériology-Virology, University of Dakar N.3, - 2CTA OPALS, CHU de Fann, Sénégal- 3 Center of halth of Roi Baudouin Background HAART has dramatically improved survival and quality of life among people living with HIV and AIDS globally.However, drug resistant mutations of HIV are a great challenge to the benefits of HAART In Senegal, HAART is available in the capital city since 1998 and gradually in the decentralized settings since 2001. Secondary resistance can be compared with the rich countries. But, circulating of primary resistance is no studies. • Methodology • 104 naive HIV-1 patients were recruited in 2 main • clinical care center in 2003, 2005 and 2007 • In 2003-2005, they were chosen on the basis of a rate • of LTCD4/mm3 superior or equal to 350. • In 2007, criteria are TCD4 superior or equal to 500 • and/or age under 25 years. • 2003- 2005 : a 1850 pb fragment including PR gene et 420 first AA of RT gene was amplified by a nested RT-PCR • 2007-2008 : nested RT-PCR was done separatly for PR and RT gene Objectives - To analyze the presence of mutations associated to ARV among newly diagnosed immunocompetent HIV positive patients. - To study strains polymorphism in both Protease (PR) and RT gene Detection of drug resistance mutations On RT gene,1 sample presents major mutation (G190E) conferred a high level resistance to EFV and NVP. Ten samples present minor resistance mutations of which 4 associated to the NRTIs, 2 (E44D, V108I, K238KN and T215ST) and 6 to the non nucleoside (V179E, T69PT, K103EK, E138A A62V and V118I). According to the Stanford the K238N and the K103EK conferred an intermediate resistance to the DLV and the NVP. The T215ST conferred an intermediate resistance to the ZDV and the D4T.  . Results Characteristic of population and strains 87 (83, 65%) of 104 patients, were women and 17 were men. Age is only known for 97 patients with an average of 32 years. The median of LTCD4 was of 562 cellules/mm3. Phylogenetic analysis showed a predominance of the recombinant CRF02_AG with 64 strains (61,5%) but also the presence of other strains : A(n=1), A3, (n=2), B (n=4), C (n=8), D’ (n=1), CRF06 (n=2), CRF11_cpx (n=2), of the recombinants unique CFR02/A3 (n=5), F/U (n=1), G/U/G (n=1) CRF36_cpx /CRF02_AG (n=2), U/ CRF02_AG (n=4), U/ CRF37_cpx (n=1), ERxample of set of primers used for the long fragment and the DNA analyzer : Applied Biosystems 3100 Avent • Phylogenetic analysis were done by neighbour-joining method and sequences • were submitted on Stanford HIVdb and were compared • with the ANRS v2006.7 and Rega v6.4.1algorithms and • the IAS Resistance Testing-USA panel (09/2007) Table 2: Drug resistance mutations on RT gene 2005 On the protease gene, no major mutation was detected. However, many minor mutations, feature of the non B strains, were present and the most important are: M36I, K20I/R/T, H69K, I13V, L63P/T/H/S/G, I93L, L10I/V, G16E and V77I. A: 2005 B: 2007-2008 Figure 1: Characterization of strains Table 3: Drug resistance mutations on RT gene of 2007-2008 Figure 4 : Drug resistance mutations on PR gene 2008 Conclusion ARV reduces morbidity and mortality of HIV infected patients but resistance can occur Risk of transmission of resistants virus This study showed an emergence of drug resistance strains in HIV naïve patients (2%). Resistance surveillance and genetic diversity study are necessary and strategies to preserve the first line drugs are needed. . Figure 2: Phylogenetic tree of 2005 Références Derache A, Maiga A., et coll. Evolution of genetic diversity and drug resistance mutation HIV-1 among untreated patients from Mali Between 2005-2006. PMID: 18556706 Laurent C, Ngom Gueye NF, Ndour CT et coll. Long-term benefits of highly active antiretroviral therapy in Senegalese HIV-1-infected adults. J Acquir Immune Defic Syndr. 2005 Jan 1;38(1):14-7 Nicaise Ndembi, Awet Abraha, et coll. Molecular Characterization of Human Immunodeficiency Virus Type 1(HIV-1) and HIV-2 in Yaounde´, Cameroon: Evidence of Major Drug Resistance Mutations in Newly Diagnosed Patients Infected with Subtypes Other than Subtype B. CLINICAL MICROBIOLOGY, Jan. 2008, p. 177–184 Toni T, Masquelier B et coll. HIV-1 ANTIRETROVIRAL drug resistance in recently infected patients in Abidjan, Cote Ivoire: A 4-years survey 2002-2006. PMID: 1799113 Acknowledgments ANRS 1257 financial project ANRS 12134 financial project Contact : leyenafissatou@hotmail.com, halimatoudiop@yahoo.fr Figure 3: Phylogénétic tree Viral Check Workshop 21th-27thJune Dakar Senegal

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