Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients.

BACKGROUND: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. METHODS: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. RESULTS: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29-68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of -0.8kPa in non-RPV-exposed patients (p=0.254) and -1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, -2.8kPa [p<0.001]; non-RPV-exposed, -1.1kPa [p=0.22]). CONCLUSION: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.

Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients / Beneficios de la rilpivirina para la rigidez hepática en pacientes con coinfección por VIH/VHC

Background: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. Methods: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. Results: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29–68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of −0.8kPa in non-RPV-exposed patients (p=0.254) and −1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, −2.8kPa [p<0.001]; non-RPV-exposed, −1.1kPa [p=0.22]). Conclusion: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.(AU)

Antecedentes: La rilpivirina (RPV) es un fármaco antirretroviral caracterizado por una buena tolerabilidad y un perfil de seguridad hepática favorable. Las últimas investigaciones han mostrado que la RPV mejora la fibrosis hepática en modelos animales de varias enfermedades hepáticas crónicas. Nuestro estudio tenía como objetivo analizar el efecto de la RPV en la fibrosis hepática mediante la evaluación de cambios en la rigidez hepática utilizando una elastografía transitoria. Métodos: Estudio de cohortes retrospectivo de pacientes infectados por VIH expuestos y no expuestos a RPV. Se analizó el cambio en la rigidez hepática durante el período entre dos mediciones mediante elastografía transitoria y se comparó entre pacientes expuestos y no expuestos a RPV. Resultados: Seleccionamos a 118 pacientes infectados por VIH expuestos a RPV y 118 pacientes infectados por VIH no expuestos a RPV. La mediana del tiempo entre las mediciones mediante elastografía transitoria (ET) fue de 50 (29-68) meses. Un modelo lineal general de medidas repetidas basado en las principales características clínicas reveló una reducción significativa en el valor de ET, −0,8kPa en el grupo de pacientes no expuestos a RPV (p=0,254) y de −1,6kPa en el grupo de pacientes expuestos a RPV (p<0,001). El análisis de subgrupos mostró una reducción significativa en el valor de ET solo en pacientes curados de hepatitis C (expuestos a RPV, −2,8kPa [p<0,001]; no expuestos a RPV, −1,1kPa [p=0,22]). Conclusión: Las pautas antirretrovirales basadas en RPV redujeron significativamente la rigidez hepática, evaluada por las mediciones de ET, en los pacientes que se habían curado de hepatitis C crónica.(AU)

Eficacia en vida real del cambio a bictegravir/ emtricitabina/tenofovir alafenamida en pacientes previamente tratados con pautas triples que contienen rilpivirina / Real-world efficacy of switching to bictegravir/ emtricitabine/tenofovir alafenamide in pretreated patients with triple therapy containing rilpivirine

Objetivo. Analizar la eficacia y tolerabilidad de la estrategia de cambio desde regímenes basados en rilpivirina (RPV)a bictegravir/emtricitabina/tenofovir alafenamida (B/F/TAF) enla vida real.Métodos. Estudio unicéntrico, observacional y retrospectivo. Se seleccionaron pacientes que cambiaron de un régimencon RPV a B/F/TAF antes de febrero del 2020 analizándose losresultados después de 24 y 48 semanas. Se determinó el porcentaje que permanecía con carga viral indetectable, así comolos cambios en linfocitos CD4+, parámetros metabólicos y función renal.Resultados. Se incluyeron en el estudio 42 pacientes. 32de los 35 (91,4%) que completaron las 48 semanas de seguimiento tenían carga viral indetectable. El recuento de linfocitos CD4+ permaneció estable a las 24 y a las 48 semanas. Eltipo de análogos recibidos previamente no influyó en la respuestaConclusión. El cambio desde una triple terapia con RPV aB/F/TAF es una estrategia segura y eficaz en la vida real. (AU)

Objective. To analyze the efficacy and tolerability of thestrategy to change from rilpivirine (RPV) based regimens tobictegravir / emtricitabine / tenofovir alafenamide (B/F/TAF).Methods. Single-center, observational and retrospectivestudy. Patients who made the change to B/F/TAF before February 2020 were selected, analyzing the results after 24 and48 weeks. The percentage that remained with an undetectableviral load was determined, as well as the changes in CD4 +lymphocytes, metabolic parameters and renal function.Results. A total of 42 patients were included. Thirty-twoof the 35 patients (91.4%) who completed the 48 weeks offollow-up had an undetectable viral load. The CD4 + lymphocyte count remained stable at 24 and 48 weeks. The responseto B/F/TAF was not influenced by the two analogs previouslyreceived.Conclusion. Switching from triple therapy with RPV toB/F/TAF is a safe and effective strategy in real life. (AU)

Contribución de cabotegravir + rilpivirina de acción prolongada al tratamiento de la infección por VIH-1 / Contribution of cabotegravir + rilpivirine long-acting for the treatment of HIV-1 infection

Objetivo: Determinar la contribución de valor de cabotegravir + rilpivirina, el primer tratamiento antirretroviral inyectable de acción prolongada,utilizando metodología de análisis de decisión multicriterio.Método: El estudio se desarrolló en dos fases: una prueba piloto y unafase de extensión, con un grupo multidisciplinar más grande. Se seleccionaron siete regímenes de comprimido único orales diarios recomendadosen las guías GeSIDA como comparadores. Se utilizó el marco EVIDEM,compuesto por 12 criterios cuantitativos y 5 contextuales. Los criterioscuantitativos se analizaron calculando la media y desviación estándar, ylos cualitativos se analizaron mediante el porcentaje de expertos que consideraron el impacto positivo, neutro o negativo para el Sistema Nacionalde Salud.Resultados: Un total de 35 expertos participaron en el estudio. Lainfección por virus de la inmunodeficiencia humana 1 se consideró grave(media ± desviación estándar: 3,0 ± 1,0), con un tamaño de poblaciónafectada (2,7 ± 1,2) y unas necesidades no cubiertas (2,8 ± 1,0) moderadas. Las diferencias fueron mínimas en los criterios comparativos deeficacia/efectividad (0,1 ± 0,5), seguridad/tolerabilidad (–0,5 ± 0,7) ycoste: coste del tratamiento (0,5 ± 2,0), otros costes médicos (0,2 ± 1,8)y costes no-médicos/indirectos (0,5 ± 1,6). Los expertos observaron una mejora con cabotegravir + rilpivirina de acción prolongada en los resultados reportados por los pacientes (2,7 ± 1,4). El beneficio terapéutico(3,5 ± 1,2) se consideró moderado-alto. La evidencia de cabotegravir+ rilpivirina de acción prolongada fue considerada robusta (4,3 ± 0,8),con elevado consenso sobre su futura recomendación en las guías(3,2 ± 1,0). En los criterios contextuales, el impacto fue positivo en loscriterios de prioridades de acceso (91%), objetivo común (63%) y contextopolítico (60%). (AU)

Objective: To determine the value contribution of cabotegravir + rilpivirine, the first injectable every two months long-acting antiretroviral regimen, using multi-criteria decision analysis.Method: The study was developed in two phases. After a small pilot,a field work study with a larger number of multidisciplinary experts wascarried out. Seven single-tablet regimens, currently recommended by theGeSIDA guidelines, were selected as comparators. EVIDEM methodology was followed, with a framework composed by 12 quantitative and5 contextual criteria. Mean and standard deviations were calculated forquantitative criteria (1 to 5 scale; comparative criteria –5 to +5), whereasqualitative criteria were analyzed as percentages of experts that considered a positive, neutral or negative impact for the National Health System.Results: 35 experts participated in the study. Human immunodeficiencyvirus-1 infection was considered severe (mean ± standard deviation:3.0 ± 1.0), with moderate size of affected population (2.7 ± 1.2) andunmet needs (2.8 ± 1.0). Minimal differences were found in comparative efficacy/effectiveness (0.1 ± 0.5), safety/tolerability (–0.5 ± 0.7),and cost criteria: cost of the intervention (0.5 ± 2.0), other medical costs(0.2 ± 1.8) and non-medical/indirect costs (0.5 ± 1.6). Experts perceived an improvement with cabotegravir + rilpivirine long-acting, compared to current daily oral single-tablet regimens, in patient-reported outcomes(2.7 ± 1.4). Therapeutic benefit of the long-acting regimen was considered moderate-to-high (3.5 ± 1.2). (AU)

Grado de satisfacción y conocimiento de pacientes positivos para HIV ante el cambio de tenofovir a tenofovir-alafenamida en tratamientos con emtricitabina y rilpivirina / Satisfaction and knowledge among patients with HIV after switching from tenofovir to tenofovir alafenamide in regimens containing emtricitabine and rilpivirine

Introducción. La satisfacción y el conocimiento del cambio de tenofovir por tenofovir- alafenamida en pacientes con HIV no se han estudiado aún. Estos dos parámetros se relacionan con mejores resultados en salud y, por lo tanto, es importante medirlos durante la práctica clínica habitual. Objetivo. Evaluar el grado de conocimiento y satisfacción de los pacientes positivos para HIV ante el cambio de tratamiento antirretroviral con rilpivirina, emtricitabina y tenofovir (RPV-FTC-TDF) por rilpivirina, emtricitabina y tenofovir-alafenamida (RPV-FTC-TAF). Materiales y métodos. Se llevó a cabo un estudio prospectivo en un hospital de tercer nivel entre los meses de septiembre y noviembre de 2018. Se incluyeron pacientes previamente tratados con RPV-FTC-TDF que acudían por segunda vez a consulta para recibir el tratamiento con RPV-FTC-TAF. La satisfacción y el grado de conocimiento se analizaron mediante nueve preguntas, usando una escala de tipo Likert de 5 puntos para evaluar el grado de acuerdo. Resultados. Se incluyeron 116 pacientes en el estudio. El 75 % de ellos se mostró satisfecho con el cambio y se consideró que el 64 % conocía lo que implicaba. Los pacientes jóvenes se mostraron menos satisfechos con el modo en que se les explicó el cambio (p=0,0487). Los pacientes estaban mejor informados sobre las ventajas renales (85 % de conocimiento) y óseas (82 %) de la nueva medicación, que sobre sus inconvenientes para el perfil lipídico (40 %). Conclusiones. En general, los pacientes se mostraron satisfechos con el cambio de medicación y conocían la posología del medicamento y las ventajas de la tenofovir- alafenamida frente al tenofovir, pero no sus posibles efectos adversos.

Introduction: Satisfaction and knowledge among patients with HIV after switching from tenofovir to tenofovir/alafenamide remain unexplored. Given that both parameters are associated with better health outcomes it is relevant to measure them in patients during routine clinical practice. Objective: To evaluate the degree of knowledge and satisfaction in patients who had their antiretroviral regimen switched from rilpivirine (RPV)/emtricitabine (FTC)/TDF to RPV/FTC/TAF. Materials and methods: We conducted a prospective study in a third-level hospital between September, 2018, and November, 2018. We included patients who had previously been treated with RPV/FTC/TDF and collected their RPV/FTC/TAF treatment in the second visit. A 5-point Likert-type agreement/disagreement scale was used to assess satisfaction and knowledge regarding the medication switch. Results: We included 116 patients in the study of whom 75% were satisfied and 64% had a high-level of knowledge. Young patients were less satisfied with the way in which the change was explained (p=0.0487). Concerning the new medication, the patients were better informed about its renal (85% of them) and bone benefits (82%) than about its adverse effects on the lipid profile (40%). Conclusions: The patients were generally satisfied with the change in medication and well informed about the dosage and advantages of TAF over TDF, but less well informed about the possible adverse effects of TAF.

Resistencia primaria de HIV en el área metropolitana de Buenos Aires

La vigilancia de resistencia primaria de HIV es fundamental para optimizar el tratamiento antirretroviral (TARV) de la infección. Las mutaciones a vigilar están definidas en una lista de referencia de la Organización Mundial de la Salud (OMS), que no incluye mutaciones para drogas nuevas como la rilpivirina. Revisamos retrospectivamente las historias clínicas de pacientes naive de TARV asistidos en 2011-2013 en un centro privado de derivación de HIV/Sida, pesquisando mutaciones según criterios de OMS y mutaciones específicas de resistencia a rilpivirina. Incluimos 91 pacientes; 71 (78.0%) eran hombres y 46 (50.5%) eran hombres que tenían sexo con hombres; 34 (37.4%) presentaban infección temprana y 60 (65.9%) estaban asintomáticos. Los valores medianos de edad, carga viral y recuento de CD4 fueron 33 años, 62 100 copias/ml y 548 células/μl, respectivamente. Encontramos mutaciones de lista OMS en 11 (12.1%) pacientes, dos de ellos presentaron mutaciones a dos familias de drogas. Siete mutaciones correspondieron a inhibidores no nucleosídicos de la retrotranscriptasa, cuatro a análogos nucleosídicos y dos a inhibidores de la proteasa; las más frecuentes fueron K103N y M41L. No hubo mayor frecuencia de mutaciones en pacientes con infección temprana, ni diferencias según sexo, orientación sexual o recuento de CD4. Tres pacientes (3.3%) presentaron mutaciones asociadas a bajos niveles de resistencia a rilpivirina (E138A, E138G). Los niveles de resistencia primaria observados en este estudio evidencian la importancia de determinar resistencia previo al inicio de TARV en la población asistida en nuestro centro. La prevalencia observada de resistencia primaria a rilpivirina fue baja.(AU)

Surveillance of primary drug resistance is critical to optimize antiretroviral therapy (ART) for HIV. Mutations to be monitored are defined in a reference list of the World Health Organization (WHO), which does not include mutations for new drugs, such as rilpivirine. We undertook a retrospective analysis of medical records of ART naive patients treated at a specialized HIV/AIDS center, evaluating the prevalence of WHO mutations and mutations specific for rilpivirine. Ninety-one patients were included during 2011-2013, being male 71 (78.0%), and men who have sex with men 46 (50.5%). The median values for age, viral load, and CD4 counts were 33 years, 62 100 copies/mL, and 548 cells/l, retrospectively; 34 (37.3%) had early infection and 60 (65.9%) were asymptomatic. WHO mutations were found in 11 (12.1%) patients, two of whom presented multiple mutations. Seven mutations corresponded to non-nucleoside reverse transcriptase inhibitors, four to nucleoside analogues, and two to protease inhibitors. The most frequent mutations were K103N and M41L. No differences in mutation frequencies were found when compared by time post-infection, gender, sexual orientation, or CD4 count. Mutations conferring low-level resistance to rilpivirine were found in 3 (3.3%) patients; such mutations were E138A and E138G. The overall moderate primary resistance levels found in this study highlight the value of performing a resistance test before ART initiation in the served population. The observed prevalence of primary resistance to rilpivirine was low.(AU)

Resistencia primaria de HIV en el área metropolitana de Buenos Aires

La vigilancia de resistencia primaria de HIV es fundamental para optimizar el tratamiento antirretroviral (TARV) de la infección. Las mutaciones a vigilar están definidas en una lista de referencia de la Organización Mundial de la Salud (OMS), que no incluye mutaciones para drogas nuevas como la rilpivirina. Revisamos retrospectivamente las historias clínicas de pacientes naive de TARV asistidos en 2011-2013 en un centro privado de derivación de HIV/Sida, pesquisando mutaciones según criterios de OMS y mutaciones específicas de resistencia a rilpivirina. Incluimos 91 pacientes; 71 (78.0%) eran hombres y 46 (50.5%) eran hombres que tenían sexo con hombres; 34 (37.4%) presentaban infección temprana y 60 (65.9%) estaban asintomáticos. Los valores medianos de edad, carga viral y recuento de CD4 fueron 33 años, 62 100 copias/ml y 548 células/μl, respectivamente. Encontramos mutaciones de lista OMS en 11 (12.1%) pacientes, dos de ellos presentaron mutaciones a dos familias de drogas. Siete mutaciones correspondieron a inhibidores no nucleosídicos de la retrotranscriptasa, cuatro a análogos nucleosídicos y dos a inhibidores de la proteasa; las más frecuentes fueron K103N y M41L. No hubo mayor frecuencia de mutaciones en pacientes con infección temprana, ni diferencias según sexo, orientación sexual o recuento de CD4. Tres pacientes (3.3%) presentaron mutaciones asociadas a bajos niveles de resistencia a rilpivirina (E138A, E138G). Los niveles de resistencia primaria observados en este estudio evidencian la importancia de determinar resistencia previo al inicio de TARV en la población asistida en nuestro centro. La prevalencia observada de resistencia primaria a rilpivirina fue baja.

Surveillance of primary drug resistance is critical to optimize antiretroviral therapy (ART) for HIV. Mutations to be monitored are defined in a reference list of the World Health Organization (WHO), which does not include mutations for new drugs, such as rilpivirine. We undertook a retrospective analysis of medical records of ART naive patients treated at a specialized HIV/AIDS center, evaluating the prevalence of WHO mutations and mutations specific for rilpivirine. Ninety-one patients were included during 2011-2013, being male 71 (78.0%), and men who have sex with men 46 (50.5%). The median values for age, viral load, and CD4 counts were 33 years, 62 100 copies/mL, and 548 cells/l, retrospectively; 34 (37.3%) had early infection and 60 (65.9%) were asymptomatic. WHO mutations were found in 11 (12.1%) patients, two of whom presented multiple mutations. Seven mutations corresponded to non-nucleoside reverse transcriptase inhibitors, four to nucleoside analogues, and two to protease inhibitors. The most frequent mutations were K103N and M41L. No differences in mutation frequencies were found when compared by time post-infection, gender, sexual orientation, or CD4 count. Mutations conferring low-level resistance to rilpivirine were found in 3 (3.3%) patients; such mutations were E138A and E138G. The overall moderate primary resistance levels found in this study highlight the value of performing a resistance test before ART initiation in the served population. The observed prevalence of primary resistance to rilpivirine was low.

[Mechanism of action and pharmacokinetics of rilpivirine]. / Mecanismo de acción y farmacocinética de rilpivirina.

Rilpivirine is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) with high efficacy in the treatment of HIV infection in treatment-naïve patients. This drug is active against both wild-type HIV-1 and a wide variety of first-generation NNRTI. Rilpivirine has a highly favorable pharmacokinetics profile, but, because its absorption depends on gastric pH, it should be administered with food to ensure correct absorption. Rilpivirine is metabolized by cytochrome P450 (CYP) 3A and consequently potential interactions should be considered when it is administered with P450 (CYP) 3A inducers or inhibitors. Although higher doses can behave as enzyme inducers, at a dose of 25mg/day, rilpivirine is unlikely to alter the concentrations of other drugs metabolized through this pathway. Because of its prolonged half-life, rilpivirine can be administered orally once daily.

[Safety profile of rilpivirine: general and neuropsychiatric tolerability, safety in patients with hepatitis B or C viruses, and lipid profile]. / Perfil de seguridad de rilpivirina: tolerabilidad general y neuropsiquiátrica, seguridad en pacientes coinfectados con virus de la hepatitis B/virus de la hepatitis C, y perfil lipídico.

Currently available data on the safety and tolerability of rilpivirine come from the product information document, a phase IIb, dose-finding clinical trial (TMC278-C204), the phase III ECHO and THRIVE clinical trials, and the preliminary data from the STaR and SPIRIT clinical trials, with a total of 1,728 patients. The comparator has usually been efavirenz. All studies have found a lower incidence and severity of neuropsychiatric adverse effects, a better lipid profile, and a lower number of patients with subclinical transaminase elevation in patients treated with rilpivirine. However, because of the relatively low number of patients coinfected with hepatitis B or C virus, definitive conclusions cannot be drawn. Similarly, experience in patients with mild or moderate liver failure is limited and there are no safety data in patients with advanced liver failure.

[Pharmacokinetic interactions]. / Interacciones farmacocinéticas.

Rilpivirine (RPV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been approved for use in treatment-naïve patients and which has potent antiviral activity. Its adverse effects profile differs from that of first-generation NNRTs. The pharmacological interactions produced by RPV are due to its effects on the CYP450 system; RPV is a substrate and mild inducer of CYP3A4. Moreover, in vitro, RPV inhibits glycoprotein-P. RPV has clinically significant pharmacological interactions, especially with protease inhibitors (except boosted darunavir and lopinavir) and the NNRTIs efavirenz and nevirapine. Coadministration of RPV with drugs that increase gastric pH, such as omeprazole, or those inducing CYP3A4, such as rifampicin, can significantly reduce RPV concentrations and is contraindicated. The concomitant use of RPV with a CYP3A4 inhibitor (such as clarithromycin) can increase RPV concentrations. Administration of PRV with food is recommended to obtain better absorption and adequate plasma values.

[Data on rilpivirine in treatment-naïve patients. Lessons from ECHO, THRIVE and STaR]. / Datos de rilpivirina en pacientes naïve. Lecciones de los estudios ECHO, THRIVE y STaR.

Rilpivirine (RPV) is a new, second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) that has been recently approved for use in the initial antiretroviral therapy (ART) of treatment-naïve HIV-infected patients, combined with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI). The approved dose is 25mg once daily with food. RPV has been assessed in a phase IIb study (TMC278-C204) and in three phase III trials (ECHO, THRIVE and STaR). In all of them, RPV was compared with the gold standard, efavirenz (EFV); these studies enrolled a large number of patients (n=1,349 on RPV). RPV was non-inferior to EFV at 48 and 96 weeks. In all the studies and study arms, the tolerability of RPV was better than that of EFV, especially for neuropsychiatric adverse effects, rash, and lipid profile. An analysis of the combined data from the ECHO and THRIVE trials showed marked differences, depending on baseline viral load. The therapeutic efficacy of RPV was superior to that of EFV in patients with a baseline viral load ≤ 100,000 copies/mL, due to a similar virological efficacy and a better tolerability profile. However, in patients with a baseline viral load ≥ 100,000 copies/mL, virological failure was more frequent in the RPV arm, especially in patients with a viral load ≥ 500,000 copies/mL. Emerging resistance mutations to RPV were commonly detected in patients with virological failure, especially in those with a higher baseline viral load. In view of these results, the European Medications Agency and the US Food and Drug Administration have approved the use of RPV in treatment-naïve patients with a baseline viral load ≤ 100,000 copies/mL. Some treatment guidelines have already included RPV among their recommendations. The guidelines of the US Department of Health and Human Services (DHSS) and the International Antiviral Society-USA ((IAS-USA), while awaiting additional data, consider RPV-based regimens as an alternative regimen. The Gesida guidelines consider RPV to be among the preferred regimens in patients with a viral load ≤ 100,000 copies/mL. Recent data from the STaR trial, which used fixed drug combinations, have shown the non-inferiority of RPV with respect to EFV, less virological failure and less emergence of resistance mutations with RPV use, irrespective of baseline viral load. In summary, efficacy and safety data suggest that RPV plus 2 NRTI is an effective and safe initial antiretroviral regime.

[Potential role of rilpivirine in simplification regimens]. / Potencial papel de rilpivirina en el escenario de simplificación.

Antiretroviral simplification is a useful strategy to improve adherence and quality of life and prevent or reverse adverse effects in patients with HIV infection. The availability of new drugs with high efficacy and better tolerability in once-daily formulations or in fixed-dose combinations may be a better option for prolonged treatment. Rilpivirine, a new nonnucleoside reverse transcriptase inhibitor (NNRTI), has shown high antiviral efficacy in clinical trials with treatment-naïve patients, with a lower incidence of adverse effects and good tolerability. Its use in simplification regimens has been evaluated after the switch from efavirenz, demonstrating that dose adjustment is not required. In a large randomized study in patients who were receiving protease inhibitors, virological efficacy was maintained, with a lower incidence of adverse effects and improved lipid parameters and cardiovascular risk score. Given the ease of administration and good tolerability of this drug, recent communications at congresses have shown the rapid applicability of the results of studies in daily clinical practice in this scenario.

[Resistance profile of rilpivirine]. / Perfil de resistencia de rilpivirina.

Rilpivirine (RPV) is a new second-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) approved for use in combination with two nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) as initial therapy in treatment-naïve HIV-1-infected patients with a baseline viral load ≤100,000 copies/mL. RPV is a diarylpyrimidine derivative with potent in vitro activity against multiple HIV-1 variants with resistance mutations to first-generation NNRTI such as K103N. In vitro studies and phase III clinical trials have allowed the identification of 16 mutations associated with resistance to RPV K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L. The risk of virologic failure in patients receiving RPV plus 2 NRTI with plasma viral load ≤ 100,000 copies/mL is low, but a high percentage of patients failing RPV develop resistance mutations to both RPV and NRTI. The most common resistance mutation that emerges in this setting is E138K. This mutation is usually associated with M184I due to a double compensatory effect of this combination, which confers resistance to RPV, as well as to lamivudine and emtricitabine. The emergence of RPV resistance confers cross-resistance to all NNRTI and, importantly, high percentages of cross-resistance to etravirine.