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Vol. 14. Núm. 2.
Páginas 132-142 (junio 2010)
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Vol. 14. Núm. 2.
Páginas 132-142 (junio 2010)
Open Access
Inhibidores de la integrasa y raltegravir en el manejo de la infección por virus de la inmunodeficiencia humana en la era de la resistencia a múltiples medicamentos
Integrase Inhibitors and raltegravir use in the management of HIV infection in the era of multidrug resistance
Visitas
9324
Fredy Guevara1,
Autor para correspondencia
freddyorlando79@gmail.com

Departamento de Medicina Interna, Fundación Santafé de Bogotá, Calle 119 N° 7-75, piso 2, Bogotá, D.C., Colombia. Teléfono: 603-0303, extensión 5191.
, Francisco Blanco2, Miguel Arredondo2,3
1 Departamento de Medicina Interna, Fundación Santafé de Bogotá, Residente en Infectología, Universidad Nacional de Colombia, Bogotá, D.C., Colombia
2 Sección de ensayos clínicos, Departamento de VIH y Enfermedades Infecciosas, Hospital Carlos III, Madrid, España
3 Sección de Biología Molecular, Departamento de VIH y Enfermedades Infecciosas, Hospital Carlos III, Madrid, España
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La infección por el virus de la inmunodeficiencia humana ha generado un impacto mundial que ha sobrepasado los cálculos iniciales previstos para esta enfermedad. En la actualidad, se hace necesaria la búsqueda de nuevos medicamentos antirretrovirales dentro de las familias de medicamentos conocidas, pero, aún más importante, es la búsqueda de nuevos blancos terapéuticos sobre los cuales incidan los fármacos a los que no ha estado expuesto el virus y, asimismo, ante los cuales no presentan resistencia natural.

Los inhibidores de la integrasa constituyen la familia de medicamentos antirretrovirales más recientemente aprobada para uso clínico. El raltegravir es un medicamento nuevo, con atributos importantes que lo hacen una herramienta que se debe tener en cuenta en esquemas de rescate, terapia de cambio y acorde con la consideración de paciente naive, es decir, sin tratamiento previo con este fármaco.

Palabras clave:
MK 0518
inhibidores de la integrasa
terapia antirretroviral
Abstract

Immunodeficiency virus infection in humans (HIV) has generated a worldwide impact exceeding initial estimates for this disease. At present, it is necessary to search for new antiretroviral drugs within the families of known medication, but the search for new therapeutic objectives under the effect of medication which has not been exposed to the virus and, therefore without natural resistance to it, is even more important. Integrase inhibitors are the family of antiretroviral medication most recently approved for clinical use; raltegravir is a new drug with important attributes that make it a tool to be considered in rescue regimens, change therapies, and naïve patient particular cases.

Keywords:
MK 0518
HIV intregrase inhibitors
antiretroviral therapy
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Referencias
[1.]
UNAIDS. 2005. AIDS epidemic update: December 2005. UNAIDS and WHO. Geneve, Switzerland. Disponible en: http://www.unaids.org/epi/2005/doc/EPIupdate2005_pdf_ en/epi-update2005_en.pdf.
[2.]
Pneumocystis pneumonia – Los Angeles. MMWR Morb Mortal Wkly Rep. 1981;30:250-2.
[3.]
Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men – New York City and California. MMWR Morb Mortal Wkly Rep. 1981;30:305-8.
[4.]
Follow-up on Kaposi's sarcoma and Pneumocystis pneumonia. MMWR Morb Mortal Wkly Rep. 1981;30:409-10.
[5.]
M.S. Cohen, N. Hellman, J.A. Levy, K. DeCock, J. Lange.
The spread, treatment and prevention of HIV-1: evolution of a global pandemic.
J Clin Invest, 118 (2008), pp. 1244-1254
[6.]
F. Barre-Sinoussi, J.C. Chermann, F. Rey, M.T. Nugeyre, S. Chamaret, J. Gruest, et al.
Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS).
Science, 220 (1983), pp. 868-871
[7.]
J.M. Guardiola, V. Soriano.
Tratamiento de la infección por VIH-SIDA fármacos y combinaciones.
Décima edición. Madrid: Publicaciones Permanyer, (2007),
[8.]
Y. Pommier, A. Jonson, C. Marchand.
Integrase inhibitors to treat HIV/AIDS.
Nature Reviews, 4 (2005), pp. 236-248
[9.]
P. Tripathi, S. Agrawal.
Immunobiology of human immnunodeficiency virus infection.
Indian J Med Microbiol, 25 (2007), pp. 311-322
[10.]
A. Engelman, P. Cherepanov.
The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication.
PLoS Pathog, 4 (2008), pp. e1000046
[11.]
Zeinalipour-LE, C. Nicolaou, A. Nicolaides, L.G. Kostrikis.
HIV- 1 integrase: from biology to chemotherapeutics.
Curr HIV Res, 5 (2007), pp. 365-388
[12.]
R. Craigie, K. Mizuuchi, F.D. Bushman, A. Engelman.
A rapid in vitro assay for HIV DNA integration.
Nucleic Acids Res, 19 (1991), pp. 2729-2734
[13.]
Y. Goldgur, R. Craigie, G.H. Cohen, T. Fujiwara, T. Yoshinaga, T. Fujishita, et al.
Structure of the HIV-1 integrase catalytic domain coplexed with an inhibitor: a platform or antiviral drug design.
Proc Natl Acad Sci USA, 95 (1999), pp. 4831-4836
[14.]
D.J. Hazuda, P. Felock, M. Witmer, A. Wolfe, K. Stillmock, J.A. grobler, et al.
Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells.
Science, 287 (2000), pp. 646-650
[15.]
D.J. Hazuda, S.D. Young, J.P. Guare, N.J. Anthony, R.P. Gómez, J.S. Wai, et al.
Integrase inhibitors and cellular immunity suppress retroviral replication in rhesus macaques.
Science, 305 (2004), pp. 528-532
[16.]
T.H. Evering, M. Markowitz, Raltegravir.
an integrase inhibitor for HIV-1.
Expert Opin Investig Drugs, 17 (2008), pp. 413-422
[17.]
M. Markowitz, J.O. Morales-Ramírez, B.Y. Nguyen, C.M. Kovacs, R.T. Steigbigel, D.A. Cooper, et al.
Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals.
J Acquir Immune Defic Syndr, 43 (2006), pp. 509-515
[18.]
M. Markowitz, B.Y. Nguyen, E. Gotuzzo, F. Mendo, W. Ratanasuwan, C. Kovacs.
and Protocol 004 Part II Study Team. Rapid and durable antiretroviral effect of the HIV-1 Integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study.
J Acquir Immune Defic Syndr, 46 (2007), pp. 125-133
[19.]
B. Grinsztejn, B.Y. Nguyen, C. Katlama, J.M. Gatell, A. Lazzarin, D. Vittecoq.
and the Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomized controlled trial.
Lancet, 369 (2007), pp. 1261-1269
[20.]
D. Cooper, J. Gatell, J. Rockstroh, C. Katlama, P. Yeni.
Lazzarin A and for the BENCHMRK-1 Study Group. Results of BENCHMRK-1, a phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, in patients with triple-class resistant virus.
14th Conference on Retroviruses and Opportunistic Infections,
[21.]
R. Steigbigel, P. Kumar, J. Eron, M. Schechter, M. Markowitz, M. Loufty.
and for the BENCHMRK-2 Study Group. Results of BENCHMRK-2, a phase III study evaluating the efficacy and safety of MK-0518, a novel HIV-1 integrase inhibitor, inpatients with triple-class resistant virus.
14th Conference on Retroviruses and Opportunistic Infections,
[22.]
R. Steigbigel, P. Kumar, J. Eron, M. Schechter, M. Markowitz.
Loutfy M and for the BENCHMRK-2 Study Group. 48-week results from BENCHMRK-2, a phase III study of Raltegravir in patients failing ART with triple-class resistant HIV-1.
15th Conference on Retroviruses and Opportunistic Infections,
[23.]
R. Steigbigel, D. Cooper, P. Kumar, E. Joseph, M. Schechter, M. Markowitz, et al.
Raltegravir with optimized background therapy for resistant HIV-1 infection.
N Engl J Med, 359 (2008), pp. 339-354
[24.]
R. Steigbigel, D. Cooper, D. Teppler, Long-term efficacy and safety of raltegravir combined with optimized background therapy in treatment experienced patients with drug resistant HIV infection: Week 96 result of the BENCHMRK 1 and 2 phase III trials.
for the BENCHMRK study teams.
Clin Infect Dis, 50 (2010), pp. 605-612
[25.]
K. Kassahun, I. McIntosh, D. Cui, D. Hreniuk, S. Merschman, K. Lasseter, et al.
Metabolism and disposition in humans of Raltegravir (MK-0518), an anti AIDS drug targeting the human immunodeficiency virus integrase enzime.
Drug Metab Dispos, 35 (2007), pp. 1657-1663
[26.]
M. Iwamoto, L. Wenning, A. Petry, T. Laethem, Desmet, J.T. Kost, et al.
Minimal effect of ritonavir and efavirenz on the pharmacokinetics of MK-0518. 46th Interscience.
Conference on Antimicrobial Agents and Chemotherapy,
[27.]
L. Wenning, E. Friedman, J. Kost, S. Merschman, K. Lasseter, N. Azrolan.
Lack of a significant drug interaction between MK-0518 and tenofovir disoproxil fumarate. 46th Interscience.
Conference on Antimicrobial Agents and Chemotherapy,
[28.]
M. Anderson, T. Kakuda, J. Miller, M. Simonts, D. Miller, Hanley, et al.
Pharmacokinetic evaluation of non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC 125 and integrase inhibitor (InSTI) raltegravir (RAL) in healthy subjects.
4th International AIDS Society (IAS) Conference,
[29.]
L. Wenning, H. Hanley, J. Stone, J. Moreau, J. Kost, E. Mangin, et al.
Effect of tipranavir + ritonavir on pharmacokinetics of MK-0518. 46th Interscience.
Conference on Antimicrobial Agents and Chemotherapy,
[30.]
C. Garrido, C. De Mendoza, V. Soriano.
Resistencias a los inhibidores de la integrasa.
Enferm Infecc Microbiol Clin, 26 (2008), pp. 40-46
[31.]
S. Arponen, J. Benito, S. Lozano, F. Blanco, C. Garrido, C. de Mendoza, et al.
More pronounced effect of integrase inhibitor raltegravir on proviral DNA reduction that other antiretroviral drugs in patients achieving undetectable viremia. 15th.
Conference on Retroviruses and Opportunistic Infections,
[32.]
D.J. Hazuda, M.D. Miller, B.Y. Nguyen, J. Zhao.
Resistance to the HIV-integrase inhibitor Raltegravir analysis of protocol 005. A phase II study in patients with triple-class resistant HIV-1 infection. 16th International HIV Drug Resistance Workshop, Barbados, West Indies.
June, 12–16 (2007),
[33.]
D. Hazuda, M. Miller, B. Nguyen, J. Zhao.
Resistance to the HIV integrase inhibitor raltegravir.
16th International HIV Drug Resistance Workshop. Barbados, 12–16 June, (2007),
[34.]
C. Garrido, A.M. Geretti, C. De Mendoza.
Polymorphism at the integrase gene in distintc HIV populations may influence the susceptibility to integrase inhibitors.
6th European HIV Drug Resistance Workshop. Budapest, 26–28 March, (2008),
[35.]
S.M. Hammer, M.S. Saag, M. Schechter, J.S. Montaner, R.T. Schooley, D.M. Jacobsen, et al.
Treatment for adult HIV infection, 2006 recommendations of the International AIDS Society-USA Panel.
JAMA, 296 (2006), pp. 827-843
[36.]
N. Clumeck, A. Pozniak, F. Raffi.
and EACS Executive Committee.
Guidelines for the clinical management and treatment of HIV infected adults. HIV Medicine, 9 (2008), pp. 65-71
[37.]
Panel on antiretroviral guidelines for adults and adolescents. Guidelines for the use of antiretroviral agents in HIV- 1-infected adults and adolescents. Department of Health and Human Services. December, 2009. Disponible en: http://www.aidsinfo.nih.gov/contentFiles/adultandadolescentG L.pdf. Accesed Abr 2009.
[38.]
B. Gazzard, A.J. Bernard, M. Boffito, D. Churchill, S. Edwards, N. Fisher, and the Writing Committee.
British HIV Association. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy.
[39.]
B. Gazzard, A.J. Bernard, M. Boffito, D. Churchill, S. Edwards, N. Fisher, and the Writing Committee.
British HIV Association. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy.
[40.]
J. Gatell, C. Katlama, B. Grinsztejn, J.J. Eron, A. Lazzarin, D. Vittecoq, et al.
Long-term efficacy and safety of the HIV integrase inhibitor raltegravir in patients with limited treatment options in a phase ii study.
J Acquir Immune Defic Syndr, 53 (2010), pp. 456-463
[41.]
R. Steigbigel, D. Cooper, H. Teppler.
for the BENCHMRK Study Teams Long-term efficacy and safety of raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: Week 96 results of the BENCHMRK 1 and 2 phase III trials.
Clinical Infectious Diseases, 50 (2010), pp. 605-612
[42.]
J. Eron, D. Cooper, T. Steigbigel, B. Clotet.
for the BENCHMRK- 1 and 2 Study Groups. Sustained antiretroviral effect of raltegravir at week 156 in the BENCHMRK studies, and exploratory analysis of late outcomes based on early virologic responses.
17th CROI, February 16-19,
[43.]
E. Gotuzzo, Y. Nguyen, M. Markowitz, F. Mendo.
and the Protocol 004 Part II Study Team. Sustained antiretroviral efficacy of raltegravir after 192 weeks of combination ART in treatment-naive HIV-1 infected patients.
17th CROI, February 16-19,
[44.]
J.J. Eron, B. Young, D.A. Cooper.
and SWITCHMRK 1 and 2 investigators Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomized controlled trials.
[45.]
E. Martínez, M. Larrousse, J.M. Libre.
for the SPIRAL Study Group.
Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS. 2010 (en prensa), (2010), pp. 1697-1707
[46.]
F. Guevara, F. Blanco, M. Arredondo.
Terapia de cambio a raltegravir en pacientes VIH positivos con viremia plasmática indetectable y que presentan toxicidad con otros medicamentos antirretrovirales LO-19.
Infectio, 14 (2010), pp. 54
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