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Inicio Farmacia Hospitalaria (English Edition) Meta-analysis of the effectiveness of the strategy of monotherapy with boosted p...
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Vol. 34. Issue 5.
Pages 237-244 (January 2010)
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Vol. 34. Issue 5.
Pages 237-244 (January 2010)
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Meta-analysis of the effectiveness of the strategy of monotherapy with boosted protease inhibitors in HIV+ patients
Meta-análisis sobre la eficacia de la estrategia de monoterapia con inhibidores de la proteasa potenciados en pacientes VIH+
J. Saez de la Fuente, A. Such Díaz, C. Sánchez Gil, C. Esteban Alba, I. Escobar Rodríguez
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Servicio de Farmacia, Hospital Infanta Leonor, Madrid, Spain
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The objective of this study is to analyse the available evidence regarding the effectiveness of the strategy of induction maintenance with boosted protease inhibitors with ritonavir in adult HIV patients as compared to conventional treatment.


We performed a meta-analysis of randomised controlled trials in HIV patients to compare the efficacy of a monotherapy strategy of boosted protease inhibitors as compared with conventional antiretroviral therapy. The literature search was conducted in PubMed, EMBASE (September 1999-September 2009) and in conference abstracts of the last 5 years. The Odds Ratio of treatment failure and their 95% confidence intervals were calculated. To combine the results of individual studies selected, a fixed effects model based on the Mantel-Haenszel method or random effects was used, depending on whether or not the results were heterogeneous.


Initially a total of 1510 publications were found, of which just 8 studies met the criteria for inclusion in the meta-analysis. The combined Odds Ratio of the 8 studies is 1.39 (95% CI 1.02–1.90) for the treatment group with conventional antiretroviral treatment, but with a confidence interval close to the limits of statistical non-significance.


The results of the combined effectiveness analysis in the meta-analysis found no significant differences between the conventional strategy and monotherapy. This strategy is considered recommended (level A evidence) in patients with no history of previous failure of protease inhibitor, with undetectable plasma viral load and signs or symptoms of nucleoside/nucleotide toxicity.

HIV protease inhibitors
Boosted ritonavir

El objetivo del presente trabajo es analizar la evidencia disponible sobre la eficacia de la estrategia de inducción mantenimiento con inhibidores de proteasa potenciados con ritonavir en pacientes adultos VIH respecto al tratamiento convencional.


Se realizó un meta-análisis de ensayos aleatorizados y controlados en pacientes VIH para comparar la eficacia de una estrategia de monoterapia con inhibidores de proteasa potenciados frente al tratamiento antirretroviral convencional. La búsqueda bibliográfica se realizó en PubMed, EMBASE (septiembre 1999-septiembre 2009) y en resúmenes de congresos de los últimos 5 años. Se calcularon los Odds Ratio del fracaso terapéutico y sus intervalos de confianza del 95%. Para combinar los resultados de los estudios individuales seleccionados, se empleó un modelo de efectos fijos basado en el método de Mantel-Haenszel o de efectos aleatorios, en función de que exista o no heterogeneidad en los resultados.


Se localizaron inicialmente un total de 1.510 publicaciones, de las que solo 8 estudios cumplieron los criterios de inclusión en el meta-análisis. El Odds Ratio combinado de los 8 estudios es de 1,39 (IC 95% 1,02–1,90) a favor del grupo de tratamiento con tratamiento antirretroviral convencional, pero con un intervalo de confianza cercano a los límites de la no significación estadística.


Los resultados del análisis de eficacia combinado en el meta-análisis no encuentran diferencias significativas entre la estrategia convencional y la monoterapia. Esta estrategia se considera recomendable (nivel A de evidencia) en pacientes sin historia de fracaso previo a inhibidores de la proteasa, con carga viral plasmática indetectable y signos o síntomas de toxicidad por análogos de nucleósidos/nucleótidos.

Palabras clave:
Inhibidores de proteasa
Ritonavir potenciado
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Panel de expertos de Gesida y Plan Nacional sobre el Sida. Recomendaciones de Gesida/Plan Nacional sobre el Sida respecto al tratamiento antirretroviral en adultos infectados por el virus de la inmunodeficiencia humana (updated January 2010). 2009. [accessed 15/1/2010]. Available from: http://www.gesida.seimc.org/
R. Polo, H. Knobel, I. Escobar, Coordinators of PNS/SEFH/GESIDA expert.
Mejorar la adherencia al tratamiento antirretroviral. Recomendaciones de la SPNS/SEFH/GESIDA.
Farm Hosp, 32 (2008), pp. 349-357
S.R. Hammer, J.J. Eron, P. Reiss, R.T. Schooley, M.A. Thompson, S. Walmsley, et al.
Antiretroviral treatment of adult HIV infection: 2008 recommendations of the international AIDS Society USA-panel.
JAMA, 300 (2008), pp. 555-570
Pannel of antiretroviral guidelines fotr adults and adolescents. Guideline for the use of antiretroviral agents in HIV-infected adults and adolescents. Department of Health and Human Services. January 29, 2008 [accessed 15/11/2009]. Available from: http://AIDSinfo.nih.gov/
A. Carr, D.A. Cooper.
Adverse effects of antiretroviral therapy.
Lancet, 356 (2000), pp. 1423-1430
D.V. Havlir, I.C. Marschner, M.S. Hirsch, A.C. Collier, P. Tebas, R.L. Bassett, et al.
AIDS Clinical Trials Group Study 343 Team Maintenance antiretroviral therapies in HIV infected patients with undetectable plasma HIV RNA after triple-drug therapy.
N Engl J Med, 339 (1998), pp. 1261-1268
P. Flandre, F. Raffi, D. Descamps, V. Calvez, G. Peytavin, V. Meiffredy, et al.
Final analysis of the Trilege induction-maintenance trial: results at 18 months.
AIDS, 16 (2002), pp. 561-568
M.H. Reijers, G.J. Weverling, S. Jurriaans, F.W. Wit, H.M. Weigel, R.W. Ten Kate, et al.
Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study.
Lancet, 352 (1998), pp. 185-190
J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman.
Measuring inconsistency in meta-analyses.
J.A. Sterne, D. Gavaghan, M. Egger.
Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature.
J Clin Epidemiol, 53 (2000), pp. 1119-1129
J.A. Sterne, M. Egger.
Funnel plots for detecting bias in metaanalysis: guidelines on choice of axis.
J Clin Epidemiol, 54 (2001), pp. 1046-1055
F. Pulido, J. Arribas, R. Delgado, E. Cabrero, J. González-García, M.J. Pérez-Elias, et al.
Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV.
AIDS, 22 (2008), pp. F1-F9
J.R. Arribas, R. Delgado, A. Arranz, R. Muñoz, J. Portilla, J. Pasquau, et al.
Lopinavir–ritonavir monotherapy versus lopinavir–ritonavir and 2 nucleosides for maintenance therapy of HIV: 96-week analysis.
J Acquir Immune Defic Syndr, 51 (2009), pp. 147-152
J.F. Delfraissy, P. Flandre, C. Delaugerre, J. Ghosn, A. Horban, P.M. Girard, et al.
Lopinavir/ritonavir monotherapy or plus zidovudine and lamivudine in antiretroviral-naive HIV-infected patients.
J.R. Arribas, F. Pulido, R. Delgado, A. Lorenzo, P. Miralles, A. Arranz, et al.
Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48-week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK Study).
J Acquir Immune Defic Syndr, 40 (2005), pp. 280-287
Nunes EP, Oliveira MS, Almeida MMTB, Pilotto JH, Ribeiro JE, Faulhaber JC, et al. 96-week efficacy and safety results of simplification to single agent lopinavir/ritonavir (LPV/r) regimen in patient suppressed below 80 copies/mL on HAART−the KalMoStudy. 11th European AIDS Conference, European AIDS Clinical Society, 2007: Madrid, Spain. AbstractP75/04.
D.W. Cameron, B.A. Da Silva, J.R. Arribas, R.A. Myers, N.C. Bellos, N. Gilmore, et al.
A 96-week comparison of lopinavir-ritonavir combination therapy followed by lopinavir-ritonavir monotherapy versus efavirenz combination therapy.
J Infect Dis, 198 (2008), pp. 234-240
Arribas JR, Horban A, Gerstoft J, Fätkenheuer G, Nelson M, Clumeck N, et al. The MONET trial: darunavir/ritonavir monotherapy shows non-inferior efficacy to standard HAART, for patients with HIV RNA<50 copies/mL at baseline. In: V IAS Conference; Cape Town, South Africa; July 19-22, 2009. Abstract TUAB106-LB.
Katlama C, Valantin MA, Algarte-Genin M, Duvivier C, Lambert- Niclot S, Girard GR, et al. A randomized multicenter study to compare the efficacy of a monotherapy of darunavir to a triple therapy with 2 nucleosides analogues combined to darunavir/r in HIV infected patients with full viral suppression. In: V IAS Conference; Cape Town, Soth Africa; Juy 19-22, 2009. Abstract WELBB102.
J. Molto, J.R. Santos, E. Negredo, C. Miranda, S. Videla, B. Clotet.
Lopinavir/ritonavir monotherapy as a simplification strategy in routine clinical practice.
J Antimicrob Chemother, 60 (2007), pp. 436-439
C. Delaugerre, P. Flandre, M.L. Chaix, J. Ghosn, F. Raffi, P. Dellamonica, et al.
Protease inhibitor resistance analysis in the MONARK trial comparing first-line lopinavir-ritonavir monotherapy to lopinavir-ritonavir plus zidovudine and lamivudine triple therapy.
Antimicrob Agents Chemother, 53 (2009), pp. 2934-2939
F. Pulido, I. Pérez-Valero, R. Delgado, A. Arranz, J. Pasquau, J. Portilla, et al.
Risk factors for loss of virological suppression in patients receiving lopinavir/ritonavir monotherapy for maintenance of HIV suppression.
Antivir Ther, 14 (2009), pp. 195-201
R.E. Campo, B.A. Da Silva, L. Cotte, J.C. Gathe, B. Gazzard, C.B. Hicks, et al.
Predictors of loss of virologic response in subjects who simplified to lopinavir/ritonavir monotherapy from lopinavir/ritonavir plus zidovudine/lamivudine.
AIDS Res Hum Retroviruses, 25 (2009), pp. 269-275
B. Spire, F. Marcellin, I. Cohen-Codar, P. Flandre, F. Boue, P. Dellamonica, et al.
Effect of lopinavir/ritonavir monotherapy on quality of life and self-reported symptoms among antiretroviral-naive patients: results of the MONARK trial.
Antivir Ther, 13 (2008), pp. 591-599
J.M. Libre Codina, M.A. Casado Gómez, R. Sánchez de la Rosa, M.J. Pérez Elías, J. Santos González, C. Miralles Álvarez, et al.
Costes de la toxicidad asociada a los análogos de nucleósidos inhibidores de la transcriptasa inversa en pacientes con infección por el VIH-1.
Enferm Infecc Microbiol Clin, 25 (2007), pp. 98-107
I. Escobar, F. Pulido, E. Pérez, J.R. Arribas, M.P. García, A. Hernández.
Análisis farmacoeconómico de una estrategia de mantenimiento con lopinavir/ritonavir como monoterapia en pacientes con infección por el VIH.
Enferm Infecc Microbiol Clin, 24 (2006), pp. 490-494
Arribas JR, Pulido F, Méndez I, Lázaro P, Norton M, Cabrero E, et al. 96 wks pharmacoeconomic outcome of lopinavir/r monotherapy as maintenance strategy in HIV+ patients with suppressed viral load. OK04-PharmECO analysis. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, November 9–13, 2008 [abstract P308].
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