1. THE EFFICIENCY OF THE TANNIN EXTRACTED FROM THE Guazuma ulmifolia IN THE REVERSE TRANSCRIPTASE INHIBITION OF THE HIV VIRUS DR. PAULO ANTÔNIO RODRIGUES GOUVEIA

2. INTRODUCTION AIDS ; The HIV virus; Antiretroviral therapy; Natural compounds; Tannin.

3. GUIDING QUESTIONS Does the tannin extracted from the Guazuma ulmifolia show the best inhibitors pharmacokinetic profiles of the HIV reverse transcriptase with fewer side-effects? Which molecular weight of the taninn has the retroviral inhibitor action of the HIV reverse transcriptase with fewer toxicity?

4. OBJECTIVES

5. General: To identify the efficiency of the Guazuma ulmifolia plant substracted as a viral duplication inhibitor of the HIV reverse transcriptase with a lower toxicity risk.

6. Especific: To identify the taninn molecular weight that has retroviral inhibitor action of the HIV reverse transcriptase with lower toxicity risk. To promote the reduction of the viral load preservating the function of the immunologic system. To postpone the illness evolution changing the HIV natural history.

7. JUSTIFICATIVE JUSTIFICATIVE

8. METHODOLOGY Research nature; Research scene; Collection of data; Term of consent: RESOLUTION N° 196/96 FROM THE BRAZILIAN DEPARTMENT OF HEALTH that regulates the research involving human beings.

9. THEORETICAL FUNDAMENTS Virus; Prevalence; HIV morphology; Protease inhibitors; Natural source compounds; Guazuma ulmifolia. *Properties; * Dosing; * Molecular weight; * Capacity of forming complexes with the proteins.

10. The cell infection occurs when the HIV virion connects itself to a cellular receptor, generally the CD4, through the gp120 protein; thus, the virus merges to the cell membrane and the capsid content is liberated in the cell cytoplasm. PHYSIOPATHOLOGY

11. CLINICAL CASE I Patient D.B.D.S., 47 years old, male, carrier of HIV for about 10 years, began the treatment with Guazuma ulmifolia (mutamba), in january 2011. He used the extract for 30 days and realized the following exams:

12. COMPLETE BLOOD COUNT (CBC) (02/03/11) Haematocrit (Hct): 46,0% Red Blood Cells (RBC): 5,04 Haemoglobins: 16,10 Platelets: 126.000 Leukocytes: 3.000 segmented: 62 Total lymphocytes: 34 Relative lymphocytes: 1020 Rod cells: 3

13. COMPLETE BLOOD COUNT (02/24/11) Haematocrit (Hct): 44,2% Red Blood Cells (RBC): 4,69 Haemoglobins: 15,2 Platelets: 114.000 Leukocytes : 4.630 Segmented: 41 Total lymphocytes: 52 Relative: 2408

14. COMPLETE BLOOD COUNT (03/24/11) Haematocrit (Hct): 40,8% Red Blood Cells (RBC): 4,65 Haemoglobins: 14 Platelets: 166.000 Leukocytes: 5.300 Total lymphocytes: 40 Relative: 2120 Monocytes: 4 Segmented: 5104/02/2011 Qualitative PCR (Hermes Pardini): positive

15. COMPLETE BLOOD COUNT (05/16/11) Haematocrit (Hct): 42,3% Red Blood Cells (RBC): 4,7 Haemoglobin : 14,4 Platelets: 124.000 Leukocytes: 4.210 Segmented: 39 Total lymphocytes: 52 Relative: 2189 Neutrophils: 7

16. COMPLETE BLOOD COUNT (06/02/11) Haematocrit (Hct): 47,2% Red Blood Cells (RBC): 5,48 Haemoglobin: 16,10 Platelets: 180.000 Leukocytes: 6.200 Neutrophils: 52 Total lymphocytes: 45 Relative: 279006/21/2011 Viral load (LACEN-TO): 288.886

17. COMPLETE BLOOD COUNT (07/21/11) Haematocrit (Hct): 48% Red Blood Cells (RBC): 5,4 Haemoglobin: 16 Platelets: 164.000 Leukocytes: 6.000 Segmented: 37 Total lymphocytes: 50 Relative: 3.000 Neutrophils: 9

18. COMPLETE BLOOD COUNT (08/11/11) Haematocrit (Hct): 47,8% Red Blood Cells (RBC): 5,4 Haemoglobin: 15,9 Platelets: 175.000 Leukocytes: 6.900 Segmented: 40 Total lymphocytes: 50 (3.450) Anti HIV Serology (Evandro Chagas Institute – Belém – PA 08/12/2011): positive

19. Viral load (LACEN-TO) 09/06/2011: 84,0

20. COMPLETE BLOOD COUNT (09/29/11) Haematocrit (Hct): 42,9% Red Blood Cells (RBC): 4,5 Haemoglobin: 14,8 Platelets: 162.000 Leukocytes: 5.780 Segmented: 38 Total lymphocytes: 54 Relative: 3121 Neutrophils: 5

21. Quantitative PCR by PCR (01/10/2011): RT method – PCR (abbot real time) Result: Method not detected Reference: not detected

22. CLINICAL CASE II Patient P.L.D.O, 46 years old, male, carrier of HIV for about 16 years, began the treatment with Guazuma ulmifolia (mutamba), in january 04th, 2011. He used the extract for 30 days. In February 16th, 2011, he realized the HIV antibody test I and II, and the result was 1st sample 192 and 2nd sample 180 References: Negative: <0,90 Doubtful: 0,90 a 1,00 Positive: >1,00

23. COMPLETE BLOOD COUNT (02/22/11) Haematocrit (Hct): 30,9% Red Blood Cells (RBC): 2,60 Haemoglobin: 11,60 Platelets: 132.000 Leukocytes: 2.800 Segmented: 58 Total lymphocytes: 38 Relative: 1064

24. COMPLETE BLOOD COUNT (08/25/11) Haematocrit (Hct): 39% Red Blood Cells (RBC): 4,3 Haemoglobin: 13 Platelets: 144.000 Leukocytes: 4.200 Segmented: 46 Total lymphocytes: 44 Relative:1848

25. Quantitative PCR by PCR (22/09/2011) – Álvaro Laboratory. RT – PCR method (abbot real time HIV I) Result: not detected Reference: not detected

26. REFERENCES Adesokan, A. A.; Roberts, V. A.; Lee, K. W.; Lins, R. D.; Briggs, J. M.; J. Med. Chem. 2004, 47, 821 Buolamwini, J. K.; Assefa, H.; J. Med. Chem. 2002, 45, 841. Cocuzza, A. J.; Chidester, D. R.; Cordova, B. C.; Jeffrey, S.; Parsons, R. L.; Ko, S..; Bacheler, L. T.; Erickson-Viitanen, S; Trainor, G. L.; Bioorg. Med. Chem. Lett. 2001, 11, 1177. Cocuzza, A. J.; Chidester, D. R.; Cordova, B. C.; Klabe, R. M.; Jeffrey, S.; Diamond, S.; Weigelt, C. A.; Ko, S. S.; Bacheler, L. T.; Erickson- Viitanen, S. K.; Rodgers, J. D.; Bioorg. Med. Chem. Lett. 2001, 11, 1389. Heralth, K. B.; Jayasuriya, H.; Bills, G. F.; Polishook, J. D.; Dombrowski, A. W.; Guan, Z.; Felock, P. J.; Hazuda, D. J.; Singh, S. B.; J. Nat. Prod. 2004, 67, 872. Huang, P.; Farquhar, D.; Plunkett, W.; J. Biol. Chem. 1990, 265, 11914; Ikemoto, T.; Nishiguchi, A.; Mitsudera, H.; Wakimasu, M.; Tomimatsu, K.; Tetrahedron 2001, 57, 1525. Jayasuriya, H.; Guan, Z.; Polishook, J. D.; Dombrowski, A. W.; Felock, P. J.; Hazuda, D. J.; Singh, S. B.; J. Nat. Prod. 2003, 66, 551. Johnson, R.; Chenoweth, D.; J. Biol. Chem. 1989, 260, 7161. Korolkovas, A.; Essentials of Medicinal Chemistry, 2nd ed., Wiley: New York, 1988. Okamoto, H.; Cujec, T. P.; Okamoto, M.; Peterlin, B. M.; Baba, M.; Okamoto, T.; Virology 2000, 272, 402 Tavares, L. C.; Quim. Nova 2002, 27, 631