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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e3181a56de5
Clinical Science

Lopinavir-Ritonavir Monotherapy Versus Lopinavir-Ritonavir and 2 Nucleosides for Maintenance Therapy of HIV: 96-Week Analysis

Arribas, Jose R MD*; Delgado, Rafael MD†; Arranz, Alberto MD‡; Muñoz, Rosa MD, PhD*; Portilla, Joaquin MD§; Pasquau, Juan MD‖; Pérez-Elias, María J MD¶; Iribarren, Jose A MD#; Rubio, Rafael MD**; Ocampo, Antonio MD††; Sánchez-Conde, Matilde‡‡; Knobel, Hernando MD§§; Arazo, Piedad MD‖‖; Sanz, Jesús MD‡¶¶; López-Aldeguer, José MD##; Montes, María L MD*; Pulido, Federico MD***; for the OK04 Study Group

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Author Information

From the *Servicio de Medicina Interna, Hospital La Paz, Universidad Autónoma de Madrid, Madrid, Spain; †Laboratorio de Microbiología Molecular, Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain; ‡Hospital Príncipe de Asturias, Alcalá de Henares, Spain; §Hospital General de Alicante, Alicante, Spain; ‖Hospital Virgen de las Nieves, Granada, Spain; ¶Hospital Ramón y Cajal, Madrid, Spain; #Hospital Donostia, San Sebastián, Spain; **Unidad VIH, Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain; ††Complexo Hospitalario Universitario de Vigo, Pontevedra, Spain; ‡‡Hospital Gregrorio Marañón, Madrid, Spain; §§Internal Medicine and Infectious Disease Department, Hospital del Mar, Barcelona, Spain; ‖‖Hospital Miguel Servet, Zaragoza, Spain; ¶¶Hospital La Princesa, Madrid, Spain; and ##Hospital La Fe, Valencia, Spain.

Supported by unrestricted grants from Abbott Laboratories and the Fundación de Investigación Médica Mutua Madrileña (MUTUA 2005-066). F.P. is the recipient of a Beca de Ampliación de Estudios (BAE) grant from the Instituto de Salud Carlos III, Spanish Ministry of Health (BA06/90001).

The funding source had no role in the study design, data collection, analysis and interpretation of the data, preparation of the article, or the decision to submit the article for publication.

Disclosure: Drs. F.P. and J.R.A. reports receiving consulting and lecture fees from Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, and Roche. Dr. R.D. reports having received grant support and lecture fees from Abbott. Dr. M.J.P.E. was occasional speaker and advisor for Abbott, Bristol-Myers Squibb, Boeringher Ingelheim, Gilead, GlaxoSmithKline, Roche, and Tibotec. Dr. J.P. has received lecture fees from Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Roche, and Schering-Plough y Boehringer Ingelheim. J.R.A. is an investigator from the Programa de Intensificación de la Actividad Investigadora en el SNS (I3SNS) 2008. INT07/147. No other potential conflict of interest relevant to this article was reported.

J.R.A. and F.P. contributed equally to this study.

Correspondence to: Jose R. Arribas, MD, Consulta Medicina Interna 2, Hospital La Paz. Paseo de la Castellana 261, 28046 Madrid, Spain (e-mail: jrarribas.hulp@salud.madrid.org).

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Abstract

Background: The OK04 trial has shown that 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy with 2 nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, it is still uncertain if this experimental strategy can maintain suppression in the long term.

Methods: Patients entered this noninferiority trial (upper limit 95% confidence interval: +12%) with no history of virological failure while receiving a protease inhibitor and receiving 2 nucleosides plus lopinavir/ritonavir, with HIV RNA <50 copies per milliliter for more than 6 months. Primary end point was percent of patients without therapeutic failure, defined as confirmed HIV RNA >500 copies per milliliter with exclusion of monotherapy patients who resuppressed to <50 copies per milliliter after resuming baseline nucleosides, or loss to follow-up, or change of randomized therapy other than reinduction.

Results: Through 96 weeks, percentage of patient without therapeutic failure was 87% (monotherapy, n = 100) vs. 78% (triple therapy, n = 98; 95% confidence interval: −20% to +1.2%). Percentage with HIV RNA <50 copies per milliliter (intention to treat, missing = failure, reinduction = failure): 77% (monotherapy) vs. 78% (triple therapy). Low-level viral rebound was more frequent in the monotherapy group. Twelve patients in the monotherapy group (12%) needed reinduction with nucleosides. Discontinuations due to adverse events were significantly more frequent in the triple therapy group (8%) than in the monotherapy group (0%); P = 0.003.

Conclusions: At 96-week lopinavir/ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy. Incidence of adverse events leading to treatment discontinuation was significantly lower with monotherapy. (ClinicalTrials.gov number, NCT00114933).

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INTRODUCTION

Boosted protease inhibitor monotherapy is a new strategy to treat patients infected with HIV.1-5 By decreasing the number of drugs needed to treat HIV infection, boosted protease inhibitor monotherapy has the potential to decrease the cost of treatment6 and to minimize long-term side effects of HAART.4 Several trials have already evaluated lopinavir-ritonavir monotherapy as initial therapy5 in antiretroviral-naive patients and as maintenance treatment once viral suppression has been achieved.2-4 The largest of these trials is the OK04 trial. The OK04 trial has already shown that 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy with 2 nucleosides and lopinavir-ritonavir in patients with prior stable suppression.3

One very important clinical and scientific question is if patients receiving lopinavir-ritonavir monotherapy can maintain viral suppression in the long term. It might be argued that because patients are receiving treatment with just 1 antiretroviral, the probability of long-term control of HIV replication is lower than with triple therapy. To try to answer this question, we report here the results of the OK04 trial through 96 weeks of follow-up.

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METHODS

Design of the Study

Details of the OK04 study design and methodology have been previously reported.3 Patients entered this trial with no history of virological failure while receiving a protease inhibitor and receiving 2 nucleosides plus lopinavir-ritonavir soft gel capsules, with plasma HIV RNA <50 copies per milliliter for more than 6 months. Patients were randomized to continue triple therapy or to stop the nucleosides and receive lopinavir-ritonavir monotherapy followed by reinduction with 2 nucleosides if virological rebound occurred without genotypic resistance to lopinavir-ritonavir.

Patients were assessed at baseline, week 4, week 12, and every 12 weeks thereafter until week 96. At study visits, clinical data were collected and labs were drawn after an overnight fast. Laboratory analyses included CD4 cell count, measurement of plasma HIV-1 RNA, haematology, plasma chemistry profiles, and a fasting lipid panel.

Plasma HIV-1 RNA and RNA HIV-1 genotyping were performed at the Laboratory of Molecular Microbiology from Hospital 12 de Octubre in Madrid. All other laboratory determinations were performed locally at each site. Adherence was analyzed by self-report using the GEEMA adherence questionnaire.7

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Resistance Analysis

Viral genotyping was performed in all samples with viral load >500 copies per milliliter. Genotypic and phenotypic resistance analyses were performed as previously detailed.3

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Objectives

The primary objective of the OK04 trial was to assess the noninferiority of the monotherapy group compared with the triple therapy group as measured by the proportion of patients without therapeutic failure at week 48. The secondary objectives were to assess at week 48 and 96 the proportion of patients with viral suppression by an HIV RNA level of 50 copies per milliliter, the proportion of patients developing resistance to protease inhibitors, and to assess changes in CD4 cell counts.

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Statistical Analysis

The primary end point was proportion of patients without therapeutic failure at week 48, defined as confirmed HIV RNA higher than 500 copies per milliliter (with exclusion of patients receiving monotherapy who resuppressed to <50 copies per milliliter after resuming baseline nucleosides), loss to follow-up, or change of randomized therapy other than reinduction. Per protocol noninferiority would be demonstrated if the upper limit of the 95% confidence interval (CI) of the difference in percentage of patients without therapeutic failure (triple therapy-monotherapy) was <12%. Secondary efficacy outcomes included the proportion of patients with virological failure (HIV RNA >50 copies/mL) through week 96. For these secondary outcomes, we used the US Food and Drug Administration algorithm for time to loss of virologic response. This algorithm requires consecutive confirmation of a value before assigning failure. Missing data, early termination of participation in the study, or reinduction with nucleosides in the monotherapy group were considered to be failures in these analyses.

In the original OK04 trial, protocol investigators were allowed to intensify with 2 nucleosides the antiretroviral treatment of patients in the monotherapy group if patients experienced a confirmed HIV RNA >500 copies per milliliter. Based on the first year results, protocol was amended to also allow intensification with nucleosides if patients developed sustained HIV RNA >50 HIV RNA copies per milliliter but <500 HIV RNA copies per milliliter that was confirmed in 3 other samples within the following 8 weeks.

Additional secondary end points were the development of HIV resistance and changes in the CD4+ cell count. Comparisons between the 2 treatment groups were also made with respect to the frequency and severity of treatment-related adverse events, the incidence of laboratory abnormalities, and changes from baseline in laboratory values. All randomized and dosed patients were included in the safety analysis. The severity of adverse events and laboratory abnormalities was graded according to the National Institutes of Allergy and Infectious Diseases Division of AIDS table for grading the severity of adult and pediatric adverse events.8

Treatment groups were compared using the Fisher exact test and χ2 test for categorical variables and the Mann-Whitney U test for continuous variables. Time-to-event analyses were performed using Kaplan-Meier survival curves and the log rank test. All reported P values are 2 sided and were not adjusted for multiple testing.

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RESULTS

Detailed characteristics of the study population have been published previously3 and were similar in the monotherapy (n = 100) and triple therapy treatment (n = 98) groups, with an overall median age of 41 years, proportion male of 80%, median time with HIV RNA <50 copies per milliliter of 18 months, and median CD4 count of 474 cells per microliter. Before randomization, the most common nucleoside combinations used along with lopinavir-ritonavir were zidovudine plus lamivudine and stavudine plus lamivudine.

At week 96, similar numbers of patients were still receiving randomized therapy. Main reason to change randomized therapy was adverse events in the triple therapy group and reinduction with nucleosides in the monotherapy group (Table 1). As shown in Figure 1, at week 96, there were not statistically significant differences between the monotherapy and the triple therapy groups with regard to time to HIV RNA >50 copies per milliliter. The lack of statistically significant differences were found both in the intention to treat and in the observed treatment analysis. By an intention to treat analysis in which missing data and reinduction with nucleosides are considered failures, 77.6% (76 of 98) of patients receiving triple therapy had an HIV RNA <50 copies per milliliter compared with 77% (77 of 100) of patients receiving monotherapy (P = 0.865; log rank). At week 96, by observed treatment analysis in which missing data or change in therapy is censored and reinduction with nucleosides is considered failure, 94.4% of patients receiving triple therapy had an HIV RNA <50 copies per milliliter compared with 86.4% of patients receiving monotherapy (P = 0.06; log rank).

Table 1
Table 1
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Figure 1
Figure 1
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Episodes of low-level viremia (between 50 and 500 HIV RNA copies/mL) were more common in the monotherapy group than in the triple therapy group (Fig. 2). During the first 48 weeks of the trial, 6 patients in the monotherapy group were reinduced with nucleosides (5 due to an HIV RNA >500 copies/mL and 1 due to HIV RNA >50 but <500 copies/mL). From week 48 to week 96, 6 additional patients in the monotherapy group had to be reinduced with nucleosides (all because HIV RNA >50 but <500 copies/mL). Of the 12 (12%) patients needing reinduction with baseline nucleosides, 10 remain with HIV RNA <50 copies per milliliter and 2 have experienced subsequent virologic rebound after reinduction. At week 96, proportion of patients without therapeutic failure according to our primary end point definition (for which the 10 patients with successful reinductions are not considered failures) was 78% in the triple therapy group and 87% in the monotherapy group (difference: −9%; 95% CI: −20% to +1.2%, P = 0.09). The upper limit of the CI for the difference (+1.2%) fulfilled the preestablished criteria for noninferiority of the monotherapy group.

Figure 2
Figure 2
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The mean increase from baseline in CD4 cell counts at week 96 was 71 cells per microliter in the monotherapy group and 47 cells per microliter in the triple therapy group (difference not statistically significant).

Using the GEEMA adherence questionnaire, 35% of patients in the monotherapy group and 38% of patients in the triple therapy group were categorized as fully adherent both to daily number and timing of doses in all visits up to week 96. If the item in GEEMA adherence questionnaire related to timing of doses was excluded from the analysis, then 52% of patients in the monotherapy group and 50% of patients in the triple therapy group were classified as fully adherent to the daily number of doses through week 96. The proportion of patients missing at least 1 day of medication since the prior visit were 33% in the monotherapy group and 31% in the triple therapy group. The proportion of patients with at least 1 missed dose of medication during the week before study visits was 38% in the monotherapy group and 37% in the triple therapy group. None of these comparisons were statistically significant.

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Genotypic Analysis

At week 96, 29 samples from 16 patients in the monotherapy group had been examined by genotypic resistance testing compared with 9 samples from 4 patients in the triple therapy group. During the first year of follow-up, 2 patients in the monotherapy group and 1 patient in the triple therapy group had loss of virological suppression with HIV isolates containing major protease inhibitor mutations. Details of these 3 patients had been previously described.3 From week 48 to week 96, resistance genotyping did not show new isolates containing major protease inhibitor mutations in the monotherapy group. In the triple therapy group, 1 new patient had an isolate with major protease inhibitor mutations. For this patient, ultrasenstitive genotypic and phylogenetic analysis could not rule out superinfection with a resistant virus. In total, after 2 years of follow-up, proportion of patients rebounding with isolates containing major protease inhibitor mutations was 2% in the monotherapy group and 2% in the triple therapy group.

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Safety and Tolerability

At week 96, 8 patients had discontinued randomized therapy due to adverse events in the triple therapy group vs. none in the monotherapy group (P = 0.003). Detailed types of adverse events and the nucleoside combinations received by patients who discontinued triple therapy are shown in Table 2.

Table 2
Table 2
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In both treatment groups, there were no statistically significant changes from baseline in fasting total cholesterol, high-density lipoprotein cholesterol, or triglycerides. Grade 3 or 4 hypertriglyceridemia was seen in 8 patients (8%) in the monotherapy group and in 6 patients (6%) in the triple therapy group.

Grade 3 hypercholesterolemia was seen in 11 patients (11%) in the monotherapy group and 7 patients (7%) in the triple therapy group. Grade 3 or 4 aspartate aminotransferase or alanine aminotransferase elevations were seen in 7 patients (7%) in the monotherapy group and in 4 patients (4%) in the triple therapy group. Of the 11 patients with grade 3 or 4 aspartate aminotransferase/alanine aminotransferase elevations, 10 were coinfected with hepatitis C virus. No patient discontinued the study because of elevated lipid or aminotransferase levels.

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DISCUSSION

After 2 years of follow-up, the OK04 study shows that lopinavir-ritonavir monotherapy can maintain HIV viral suppression in a very large proportion of patients. Of the 100 patients initially randomized to lopinavir-ritonavir monotherapy, 77% remain on monotherapy with an HIV viral load of less than 50 HIV RNA copies per milliliter at week 96. This result support the durability of lopinavir-ritonavir monotherapy and is consistent with the long-term follow-up of our pilot clinical trial in which 66.7% of patients randomized to lopinavir-ritonavir monotherapy remain on monotherapy and with HIV RNA <50 copies per milliliter after 4 years of follow-up.9 The durability of lopinavir-ritonavir monotherapy might be explained by the fact that residual replication below 50 HIV RNA copies per milliliter does not seem to be increased in patients receiving this single-drug regimen.10

As it happened during the first 48 weeks of the trial, episodes of low-level viral rebound were more frequent in patients receiving monotherapy than in patients receiving triple therapy. This difference is better appreciated in the on-treatment analyses (Fig. 1B) in which successful reinductions, missing data, or changes (for toxicity or other reasons) are censored. In this analysis, there is a trend toward better virologic control in the triple therapy group. The most likely explanation for these episodes of low-level viremia is suboptimal adherence. In the 2 OK trials11 and in the M03-613 trial,12 treatment adherence was a significant risk factor for loss of virological suppression in patients receiving lopinavir-ritonavir monotherapy. For example, total days without medication between 2 consecutive visits in the OK trials were 1 for patients maintaining suppression and 6 for patients who experienced loss of virological suppression.11

The more frequent incidence of episodes of low-level viremia in patients receiving monotherapy is not incompatible with the long durability of the regimen. With the data, we have so far, we believe that the forgiveness of lopinavir-ritonavir monotherapy could be lower than the forgiveness provided by lopinavir-ritonavir and 2 nucleosides. Consequently, there is a higher risk of episodes of low-level viremia in patients with suboptimal adherence to monotherapy. However, we hypothesize that for the adherent patient, the probability of remaining suppressed on monotherapy might be similar than the probability of patients receiving triple therapy.

A critical aspect of the lopinavir-ritonavir monotherapy strategy is the possibility of regaining virological control by reinduction with nucleosides without loosing therapeutic options. The original protocol allowed reinduction with baseline nucleosides for patients with confirmed viral rebound >500 copies per milliliter if no major protease inhibitor resistance mutation was detected. However, after the first year of follow-up, we identified several patients who experienced sustained viral rebound between 50 and 500 HIV RNA copies per milliliter. To manage these patients, we decided to amend the protocol to allow reinduction after viral rebound between 50 and 500 HIV RNA copies per milliliter that lasted at least 8 weeks. Following this strategy, 6 patients randomized to monotherapy had to be reinduced during the second year of follow-up. It should be highlighted that we have not detected any additional case of protease inhibitor resistance development during the second year of follow-up and that the great majority of patients needing reinduction (83%) have regained viral suppression. Similarly, in our pilot clinical trial, patients reinduced with nucleosides were able to maintain long-term virological suppression up to 4 years after reinduction.9 Taken together, these findings support the safety of the strategy of using lopinavir-ritonavir as maintenance monotherapy followed by reintroduction of nucleosides as needed.

One important finding during the second year of follow-up is that discontinuations of randomized therapy due to adverse events were significantly more frequent in the triple therapy group than in the monotherapy group. Of note, 6 of the 8 patients who discontinued therapy suffered adverse events that are characteristic of nucleoside-induced toxicity. It might be argued that nucleoside combinations for these patients were not the ones recommended by international guidelines as preferred combinations.13,14 However, our clinical trial allowed enrolling patients with nucleoside resistance. Once HIV has already developed the M184V mutation that confers resistance to lamivudine, the ability of clinicians to prescribe “safe” nucleoside combinations is already compromised. We believe that these patients who are receiving a nucleoside combination that is considered toxic might be good candidates to explore the strategy of lopinavir-ritonavir monotherapy.

One important limitation of our findings is that we did not have an objective assessment of lipoatrophy. It is possible that the incidence of lipoatrophy was the same in the monotherapy group, but because those patients were already not receiving nucleosides, clinicians opted to continue monotherapy. Nevertheless, the M03-613 study has already shown that the risk of lipoatrophy is reduced in patients who receive lopinavir-ritonavir monotherapy.4

In summary, the 96 results of the OK04 trial continue to support the efficacy and safety of the lopinavir-ritonavir monotherapy strategy. Although episodes of low-level viremia were more frequent in the monotherapy group, we did not observe an increased risk of resistance development and most of these patients could be resuppressed restarting nucleosides. The toxicity of the monotherapy regimen was lower than the toxicity of the triple regimen.

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ACKNOWLEDGMENTS

We are grateful to the patients who participated in the study. In addition of the authors, the study OK04 group includes the following: Hospital Doce de Octubre, Madrid: S. Fiorante, C. Cepeda, V. Moreno, A. Hernando, and J. R. Costa; Hospital La Paz, Madrid: Juan González-García, N. Perez Valero, and F. Gaya; Hospital Ramón y Cajal, Madrid: F. Dronda, A. Antela, and S. Moreno; Hospital Príncipe de Asturias, Alcalá de Henares: J. Sanz, J. De Miguel, and E. Casas; Hospital General de Alicante, Alicante: V. Boix, E. Merino, and S. Reus; Hospital Virgen de las Nieves, Granada: M. A. López, M. C. Hidalgo, M. R. Javier, A. Tapia, and M. López; Hospital Donostia, San Sebastián: X. Camino, M. A. von Wichmann, J. Arrizabalaga, and F. J. Rodríguez-Arrondo; Hospital Xeral Cíes, Vigo: A. López, C. Miralles, and P. Vázquez; Hospital Gregorio Marañón, Madrid: P. Miralles, J. Berenguer, J. C. López, and J. Cosín; Hospital del Mar, Barcelona: G. Vallecillo; Hospital de la Princesa, Madrid: R. Carrillo and I. Santos; Hospital La Fe, Valencia: M. Salavert, J. Lacruz, M. Blanes, and V. Navarro; Hospital Miguel Servet, Zaragoza: J. M. Aguirre, M. A. Pascual; Fundación Jiménez Díaz, Madrid: M. Górgolas and A. Goyeneche; Hospital de Tenerife, Tenerife: J. L. Sirvent, R. Alemán, A. M. López and M. M. Alonso; Hospital Civil de Basurto, Bilbao: J. M. Santamaría, R. Teira, and O. Ferrero; Z. Zubero, J. Muñoz, and J. Baraiaetxaburu; Hospital de Valme, Sevilla: F. Lozano, J. Gómez, J.A. Pineda, J. Corzo, E.M. León, and G. Sebastián; Hospital Santa Creu I Sant Pau, Barcelona: P. Domingo, M. Gutiérrez, G. Mateo, M. Fuster, M. A. Sambeat, J. Cadafalch, and M. Gurgí; Hospital Germans Trias i Pujol, Badalona: B. Clotet, A. Tuldrá, A. Ballesteros, J. Moltó, J. R. Santos, and A. Bonjoch; Hospital de Bellvitge, Hospitalet de Llobregat: D. Podzamczer, P. Robres, E. Ferrerr, and M. Olmo; Hospital Clinic Universitari, Barcelona: J. M. Gatell, A. Milinkovic, J. Mallolas, and E. Martínez; Hospital San Carlos, Madrid: V. Estrada, M. Fuster, M. J. Téllez, and J. Vergas; Hospital de Elche, Elche: F. Gutiérrez, M. Masía, S. Padilla, and E. Bernal; Hospital Clínico de Valencia, Valencia: G. García and M. J. Galindo; Hospital Insular de Canarias, Las Palmas: A. Francés; Hospital Virgen Macarena, Sevilla: M. A. Muniaín, J. Gálvez, L. Orbea, J. Rodríguez, A. Domínguez, D. Morales, and G. Ollero; Hospital General de Valencia: V. Abril, E. Ortega, and A. Martín.

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REFERENCES

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3. Pulido F, Arribas JR, Delgado R, et al. Lopinavir-ritonavir monotherapy versus lopinavir-ritonavir and two nucleosides for maintenance therapy of HIV. AIDS. 2008;22:F1-F9.

4. Cameron DW, Da Silva BA, Arribas JR, et al. Ninety-six week results of a randomized comparative trial of lopinavir/ritonavir plus lamivudine/zidovudine followed by deintensification to lopinavir/ritonavir monotherapy versus efavirenz plus lamivudine/zidovudine therapy in antiretroviral-naive subject. J Infect Dis. 2008;198:234-240.

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6. Escobar I, Pulido F, Perez E, et al. Análisis farmacoeconómico de una estrategia de mantenimiento con lopinavir-ritonavir como monoterapia en pacientes con infección por el VIH. Enferm Infecc Microbiol Clin. 2006;24:490-494.

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10. McKinnon JE, Arribas JR, Pulido F, et al. The level of persistent plasma viremia does not increase after simplification of antiretroviral therapy to lopinavir-ritonavir alone. AIDS. 2006;20:2331-2335.

11. Pulido F, Arribas JR, González-Garcia J, et al. Risk factors for loss of virological suppression at 48 weeks in patients receiving lopinavir/ritonavir monotherapy in 2 clinical trials comparing LPV/rmMonotherapy vs triple therapy with LPV/r (OK and OK04 Trials). Presented at Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, CA. Abstract 513.

12. Campo R, Cotte L, Gathe J, et al. Predictors of loss of virologic response in subjects who deintensified to lopinavir/ritonavir monotherapy after achieving plasma HIV-1 RNA <50 copies/mL on lopinavir/ritonavir Plus zidovudine/lamivudine. Presented at: Program and abstracts of the 14th Conference on Retroviruses and Opportunistic Infections; February 25-28, 2007; Los Angeles, CA. Abstract 514.

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Keywords:

HIV; lopinavir/ritonavir; monotherapy

© 2009 Lippincott Williams & Wilkins, Inc.

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