Pursuing use of optimal formulations for paediatric HIV epidemic control - a look at the use of LPV/r oral pellets and oral granules.

INTRODUCTION: Despite a significant reduction in mother-to-child transmission of HIV, an estimated 180,000 children were infected with HIV in 2017, and only 52% of children under 15 years of age living with HIV (CLHIV) are on life-saving antiretroviral therapy (ART). Without effective treatment, half of CLHIV die before the age of two years and only one in five survives to five years of age. DISCUSSION: Over the past four years, the United States Food and Drug Administration tentatively approved new formulations of lopinavir/ritonavir (LPV/r) in the form of oral pellets and oral granules. However, the slow uptake of the aforementioned formulations in the low- and middle-income countries with the highest paediatric HIV burden is largely due to three challenges: limited manufacturing capacity; current unit cost of the pellets and granules; and slow uptake of these new formulations by policy makers and health care workers. CONCLUSIONS: Solutions to overcome these barriers include ensuring availability of an adequate supply of LPV/r oral pellets and oral granules, considering all programmatic and clinical factors when selecting paediatric ART formulations, and leveraging current resources to decrease paediatric HIV morbidity and mortality.

Initiatives to challenge patent barriers and their relationship with the price of medicines procured by the Brazilian Unified National Health System. / Iniciativas de enfrentamento da barreira patentária e a relação com o preço de medicamentos adquiridos pelo Sistema Único de Saúde.

Since 1996, when antiretroviral (ARV) treatments started being guaranteed to people living with HIV in Brazil, the government has faced the challenge of ensuring sustainability of this policy within a context of incorporating patented medicines. This article sought to analyze the historical series of the price of lopinavir/ritonavir (LPV/r) in Brazil and in the international market also considering the initiatives to challenge patent barriers between 2001 and 2012. The methods used were mapping initiatives to challenge LPV/r patent barriers and the analysis of historical series of its price in Brazil and in the international market. Results show that, between 2001 and 2003, there were efforts to use compulsory licensing as a threat. From 2005 to 2007, initiatives by different satkeholders were identified: declaration of public interest, pre-grant opposition ("support to examination") and civil action. From 2006 to 2008, compulsory licensing initiatives in other countries resulted in a price reduction in Brazil. Between 2009 and 2012, there was a 30% reduction in the Brazilian purchasing price.

Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with lopinavir/ritonavir plus lamivudine for initial ART in HIV infected adults.

INTRODUCTION: The National AIDS Plan and the Spanish AIDS study group (GESIDA) proposes "preferred regimens" (PR) of antiretroviral treatment (ART) as initial therapy in HIV-infected patients. In 2013, the recommended regimens were all triple therapy regimens. The Gardel Study assessed the efficacy of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) plus lamivudine (3TC). Our objective is to evaluate the GESIDA PR and the DT regimen LPV/r+3TC cost/efficacy ratios. METHODS: Decision tree models were built. EFFICACY: probability of having viral load <50 copies/mL at week 48. ART regime cost: costs of ART, adverse effects, and drug resistance tests during the first 48 weeks. RESULTS: Cost/efficacy ratios varied between 5,817 and 13,930 euros per responder at 48 weeks, for the DT of LPV/r+3TC and tenofovir DF/emtricitabine+raltegravir, respectively. CONCLUSIONS: Taking into account the official Spanish prices of ART, the most efficient regimen was DT of LPV/r+3TC, followed by the triple therapy with non-nucleoside containing regimens.

Iniciativas de enfrentamento da barreira patentária e a relação com o preço de medicamentos adquiridos pelo Sistema Único de Saúde / Iniciativas para enfrentarse a la barrera patentaria y su relación con el precio de medicamentos adquiridos por el Sistema Único de Salud / Initiatives to challenge patent barriers and their relationship with the price of medicines procured by the Brazilian Unified National Health System

Resumo: Desde 1996, com a consolidação da oferta do tratamento antirretroviral (ARV) às pessoas vivendo com HIV no Brasil, o governo tem como desafio assegurar a sustentabilidade desta oferta num contexto de incorporação de medicamentos patenteados. O artigo teve como objetivo analisar a série histórica do preço do lopinavir/ritonavir (LPV/r) no Brasil e no mercado internacional à luz de iniciativas de enfrentamento da barreira patentária no período de 2001 a 2012. A metodologia consistiu em mapeamento de iniciativas de enfrentamento da barreira patentária para o LPV/r e análise da série histórica do preço no Brasil e no mercado internacional. Os resultados encontrados apontam que, entre 2001 e 2003, identificaram-se esforços de ameaça de licença compulsória. De 2005 a 2007, identificaram-se iniciativas por diferentes atores: declaração de interesse público, subsídios ao exame e ação civil pública. De 2006 e 2008, iniciativas internacionais de licença compulsória resultaram na redução do preço no Brasil. Entre 2009 e 2012, observa-se uma redução do preço de aquisição pelo Brasil de 30%.

Resumen: Desde 1996, con la consolidación de la oferta de tratamiento antirretroviral (ARV) para las personas viviendo con VIH, el Gobierno de Brasil tiene el desafío de asegurar la sostenibilidad de dicha oferta en un contexto de incorporación de medicamentos patentados. El objetivo de este artículo es analizar la serie histórica del precio del lopinavir/ritonavir (LPV/r) en Brasil y en el mercado internacional, a la luz de iniciativas para enfrentar la barrera patentaria durante el período de 2001 a 2012. La metodología consistió en un mapeo de iniciativas para hacer frente a la barrera patentaria del LPV/r y el análisis de la serie histórica de sus precios de adquisición por el SUS y en el mercado internacional. Entre 2001 y 2003 se identificaron esfuerzos por obtener reducciones de precio de LPV/r, mediante la amenaza de expedición de licencia obligatoria. De 2005 a 2007, se identificaron varias iniciativas de diferentes actores, tales como, la expedición de declaración de interés público, preseentación de subsidios para el examen de solicitudes de patente de este medicamento y la interpesición de acción civil pública. Entre 2006 y 2008, la expedición de licencias obligatorias en el marco de iniciativas internacionales, propiciaron reducciones de precio de LPV/r en Brasil. La reducción promedio del precio de adquisición por parte SUS fue de 30% entre 2009 y 2012.

Abstract: Since 1996, when antiretroviral (ARV) treatments started being guaranteed to people living with HIV in Brazil, the government has faced the challenge of ensuring sustainability of this policy within a context of incorporating patented medicines. This article sought to analyze the historical series of the price of lopinavir/ritonavir (LPV/r) in Brazil and in the international market also considering the initiatives to challenge patent barriers between 2001 and 2012. The methods used were mapping initiatives to challenge LPV/r patent barriers and the analysis of historical series of its price in Brazil and in the international market. Results show that, between 2001 and 2003, there were efforts to use compulsory licensing as a threat. From 2005 to 2007, initiatives by different satkeholders were identified: declaration of public interest, pre-grant opposition ("support to examination") and civil action. From 2006 to 2008, compulsory licensing initiatives in other countries resulted in a price reduction in Brazil. Between 2009 and 2012, there was a 30% reduction in the Brazilian purchasing price.

Cost-effectiveness of first-line antiretroviral therapy for HIV-infected African children less than 3 years of age.

BACKGROUND: The International Maternal, Pediatric, and Adolescent Clinical Trials P1060 trial demonstrated superior outcomes for HIV-infected children less than 3 years old initiating antiretroviral therapy (ART) with lopinavir/ritonavir compared to nevirapine, but lopinavir/ritonavir is four-fold costlier. DESIGN/METHODS: We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model, with published and P1060 data, to project outcomes under three strategies: no ART; first-line nevirapine (with second-line lopinavir/ritonavir); and first-line lopinavir/ritonavir (second-line nevirapine). The base-case examined South African children initiating ART at age 12 months; sensitivity analyses varied all key model parameters. Outcomes included life expectancy, lifetime costs, and incremental cost-effectiveness ratios [ICERs; dollars/year of life saved ($/YLS)]. We considered interventions with ICERs less than 1× per-capita gross domestic product (South Africa: $7500)/YLS as 'very cost-effective,' interventions with ICERs below 3× gross domestic product/YLS as 'cost-effective,' and interventions leading to longer life expectancy and lower lifetime costs as 'cost-saving'. RESULTS: Projected life expectancy was 2.8 years with no ART. Both ART regimens markedly improved life expectancy and were very cost-effective, compared to no ART. First-line lopinavir/ritonavir led to longer life expectancy (28.8 years) and lower lifetime costs ($41 350/person, from lower second-line costs) than first-line nevirapine (27.6 years, $44 030). First-line lopinavir/ritonavir remained cost-saving or very cost-effective compared to first-line nevirapine unless: liquid lopinavir/ritonavir led to two-fold higher virologic failure rates or 15-fold greater costs than in the base-case, or second-line ART following first-line lopinavir/ritonavir was very ineffective. CONCLUSIONS: On the basis of P1060 data, first-line lopinavir/ritonavir leads to longer life expectancy and is cost-saving or very cost-effective compared to first-line nevirapine. This supports WHO guidelines, but increasing access to pediatric ART is critical regardless of the regimen used.

[Lack of bioavailability of generic lopinavir/ritonavir not prequalified by WHO marketed in Africa (Congo Brazzaville)]. / Absence de bio-équivalence d'un générique du lopinavir/ritonavir non préqualifié par l'OMS commercialisé en Afrique (Congo Brazzaville).

Although second-line generic antiretroviral drugs are of great value in developing countries there are concerns regarding their quality and safety. This study is a case report and pharmacological study in healthy volunteers. A French subject of sub-saharan origin who visited Republic of Congo received a post-exposure treatment with AZT+3TC and LPV/r (200/50 mg, Arga-L®, India) following unprotected sexual intercourse. Two days later, in France, tests showed that plasma concentrations of lopinavir and ritonavir were undetectable. The WHO prequalification list showed Arga-L® was not prequalified. A pharmacological study in healthy volunteers evaluated oral bioavailability: plasma concentrations of generic LPV/r Arga-L® and LPV/r Kaletra® (400/100 mg) were measured after one single dose at 7 days apart in four healthy volunteers. Concentrations of Arga-L® at 12 h after intake were considerably lower than those of Kaletra®, revealing very low oral bioavailability of generic lopinavir and ritonavir (<10%) compared to the brand-name drug. We found that Arga-L®, despite having adequate qualitative and quantitative drug contents, had very poor bio availability compared to Kaletra®. In order to avoid the selection and the spread of drug-resistant HIV strains, rigorous pharmacological monitoring of generic antiretroviral drugs that are not pre-qualified by WHO, but are marketed in Africa, must be a priority for health authorities.

Cost effectiveness of darunavir/ritonavir combination antiretroviral therapy for treatment-naive adults with HIV-1 infection in Canada.

OBJECTIVE: The AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects (ARTEMIS) clinical trial examined the efficacy and safety of two ritonavir-boosted protease inhibitors (PI/r), darunavir/r 800/100 mg once daily (QD) and lopinavir/r 800/200 mg daily, both used in combination with tenofovir disoproxil fumarate/emtricitabine. This study aimed to assess the cost effectiveness of the darunavir/r regimen compared with the lopinavir/r regimen in treatment-naive adults with HIV-1 infection in Canada. METHODS: A Markov model with a 3-month cycle time and six CD4 cell-count-based health states (>500, 351-500, 201-500, 101-200, 51-100, and 0-50 cells/mm(3)) followed a cohort of treatment-naive adults with HIV-1 infection through initial darunavir/r or lopinavir/r combination therapy and a common set of subsequent regimens over the course of their remaining lifetimes. Population characteristics and transition probabilities were estimated from the ARTEMIS clinical trial and other trials. Costs (in 2014 Canadian dollars), utilities, and mortality were estimated from Canadian sources and published literature. Costs and health outcomes were discounted at 5% per year. One-way and probabilistic sensitivity analyses were performed, including a simple indirect comparison of the darunavir/r initial regimen with an atazanavir/r-based regimen. RESULTS: In the base-case lifetime analysis, individuals receiving initial therapy with the darunavir/r regimen experienced 0.25 more quality-adjusted life-years (QALYs) with lower antiretroviral drug costs (-$14,246) and total costs (-$18,402) than individuals receiving the lopinavir/r regimen, indicating that darunavir/r dominated lopinavir/r. In an indirect comparison with an atazanavir/r-based regimen, the darunavir/r regimen remained the dominant choice, but with lower cost savings (-$2,303) and QALY gains (0.02). Results were robust to a wide range of other changes in input parameter values, population characteristics, and modeling assumptions. The probabilistic sensitivity analysis demonstrated that the darunavir/r regimen was cost effective compared with the lopinavir/r regimen in over 86% of simulations for willingness-to-pay thresholds between $0 and $100,000 per QALY gained. CONCLUSIONS: Darunavir/r 800/100 mg QD may be a cost-effective PI/r component of initial antiretroviral therapy for treatment-naive adults with HIV-1 infection in Canada.

Does a significant reduction in malaria risk make lopinavir/ritonavir-based ART cost-effective for children with HIV in co-endemic, low-resource settings?

BACKGROUND: HIV infection and malaria co-infection is not uncommon among children in co-endemic regions, and evidence suggests that HIV is a risk factor for severe malaria among children. HIV protease inhibitors (PIs) are highly effective in pediatric HIV treatment regimens, however, their effectiveness against malaria has been mixed, with some PIs demonstrating in vitro activity against Plasmodium falciparum. Recent findings suggest lopinavir/ritonavir (LPV/r)-based treatment regimens reduce the incidence of malaria infection by over 40% in pediatric HIV patients compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. METHODS: We assessed whether a significant reduction in malaria risk makes LPV/r-based ART regimens cost-effective compared to NNRTI-based regimens in co-endemic, low-resource settings. We modeled the difference in unit cost per disability adjusted life year (DALY) gained among two theoretical groups of HIV+ children under 5 years old receiving ART in a resource-limited setting co-endemic for malaria. The first group received standard NNRTI-based antiretrovirals, the second group received a standard regimen containing LPV/r. We used recent cohort data for the incidence reduction for malaria. Drug costs were taken from the 2011 Clinton Health Access Initiative Antiretroviral (ARV) ceiling price list. DALYs for HIV and malaria were derived from WHO estimates. RESULTS: Our model suggests a unit cost of US$147 per DALY gained for the LPV/r-based group compared to US$37 per DALY gained for the NNRTI-based group. CONCLUSION: In HIV and malaria co-endemic settings, considerations of PI cost effectiveness incorporating known reductions in malaria mortality suggest a nominal increase in DALYs gained for PIs over NNRTI-based regimens for HIV positive children under five on ART. Our analysis was based on several assumptions due to lack of sound data on malaria and HIV DALY attribution among pediatric populations. Further study in this area is required.

Cost-minimization comparison of darunavir plus ritonavir and lopinavir/ritonavir in HIV-1 infected treatment-naïve women of childbearing age.

BACKGROUND: Guidelines from the Department of Health and Human Services in the US recommend ritonavir-boosted lopinavir (LPV/r) as a preferred protease inhibitor (PI) for HIV-positive antiretroviral-naїve pregnant women. These guidelines also cite ritonavir-boosted darunavir (DRV + RTV) as an alternative PI in this clinical scenario. The purpose of this analysis was to compare economic outcomes for regimens based on these two treatments. STUDY DESIGN: An existing discrete event simulation (DES) model was adapted to conduct a cost-minimization analysis comparing the two regimens in HIV-infected women of childbearing age (WOCBA), from the perspective of a healthcare payer in the US. METHODS: The DES model was used to represent disease states, health events, healthcare encounters, pregnancy, and treatment choices in HIV-infected WOCBA starting treatment with regimens based on either LPV/r or DRV + RTV. It also incorporated parameters for individual patient characteristics, and for antiretroviral (ARV) treatment effectiveness, treatment sequencing, clinical progression, and resource use. Potential events included scheduled physician visits; viral suppression; viral rebound; AIDS-related complications; CHD events; treatment discontinuation and switching; ARV treatment side-effects (SE); and death. The primary outcomes were discounted 5-year and 10-year healthcare costs. Alternative scenarios considered different rates of switching from DRV + RTV to LPV/r upon conception. RESULTS: Compared with DRV + RTV, LPV/r was associated with similar clinical outcomes while offering savings at the 5- and 10-year horizons (of $24,904 and $43,502 per patient, respectively), and in extensive sensitivity analyses. The main driver of the savings was the difference in cost between PIs. CONCLUSIONS: Starting HIV-infected ARV-treatment-naїve WOCBA on an LPV/r-based regimen is cost-saving and provides similar patient outcomes compared to a DRV + RTV-based regimen.

Lopinavir/ritonavir versus darunavir plus ritonavir for HIV infection: a cost-effectiveness analysis for the United States.

BACKGROUND: The ARTEMIS trial compared first-line antiretroviral therapy (ART) with lopinavir/ritonavir (LPV/r) to darunavir plus ritonavir (DRV + RTV) for HIV-1-infected subjects. In order to fully assess the implications of this study, economic modelling extrapolating over a longer term is required. OBJECTIVE: The aim of this study was to simulate the course of HIV and its management, including the multiple factors known to be of importance in ART. METHODS: A comprehensive discrete event simulation was created to represent, as realistically as possible, ART management and HIV outcomes. The model was focused on patients for whom clinicians believed that LPV/r or DRV + RTV were good options as a first regimen. Prognosis was determined by the impact of initial treatment on baseline CD4+ T-cell count and viral load, adherence, virological suppression/failure/rebound, acquired resistance mutations, and ensuing treatment changes. Inputs were taken from trial data (ARTEMIS), literature and, where necessary, stated assumptions. Clinical measures included AIDS events, side effects, time on sequential therapies, cardiovascular events, and expected life-years lost as a result of HIV infection. The model underwent face, technical and partial predictive validation. Treatment-naive individuals similar to those in the ARTEMIS trial were modelled over a lifetime, and outcomes with first-line DRV + RTV were compared with those with LPV/r, both paired with tenofovir and emtricitabine. Up to three regimen changes were permitted. Drug prices were based on wholesale acquisition cost. Outcomes were lifetime healthcare costs (in 2011 US dollars) from the US healthcare system perspective and quality-adjusted life-years (QALYs) (discounted at 3 % per annum). RESULTS: Choice of LPV/r over DRV + RTV as initial ART resulted in nearly identical clinical outcomes, but distinctly different economic consequences. Starting with an LPV/r regimen potentially results in approximately US$25,000 discounted lifetime savings. Accumulated QALYs for LPV/r and DRV + RTV were 12.130 and 12.083, respectively (a 19-day difference). In sensitivity analyses, net monetary benefit ranged from US$12,000 to US$31,000, favouring LPV/r (base case US$27,762). CONCLUSIONS: A comprehensive simulation of lifetime course of HIV in the USA indicated that using LPV/r as first-line therapy compared with DRV + RTV may result in cost savings, with similar clinical outcomes.

Cost-utility analysis of lopinavir/ritonavir versus atazanavir + ritonavir administered as first-line therapy for the treatment of HIV infection in Italy: from randomised trial to real world.

OBJECTIVE: To estimate the lifetime cost utility of two antiretroviral regimens (once-daily atazanavir plus ritonavir [ATV+r] versus twice-daily lopinavir/ritonavir [LPV/r]) in Italian human immunodeficiency virus (HIV)-infected patients naïve to treatment. DESIGN: With this observational retrospective study we collected the clinical data of a cohort of HIV-infected patients receiving first-line treatment with LPV/r or ATV+r. METHODOLOGY: A Markov microsimulation model including direct costs and health outcomes of first- and second-line highly active retroviral therapy was developed from a third-party (Italian National Healthcare Service) payer's perspective. Health and monetary outcomes associated with the long-term use of ATV+r and LPV/r regimens were evaluated on the basis of eight health states, incidence of diarrhoea and hyperbilirubinemia, AIDS events, opportunistic infections, coronary heart disease events and, for the first time in an economic evaluation, chronic kidney disease (CKD) events. In order to account for possible deviations between real-life data and randomised controlled trial results, a second control arm (ATV+r 2) was created with differential transition probabilities taken from the literature. RESULTS: The average survival was 24.061 years for patients receiving LPV/r, 24.081 and 24.084 for those receiving ATV+r 1 and 2 respectively. The mean quality-adjusted life-years (QALYs) were higher for the patients receiving LPV/r than those receiving ATV+r (13.322 vs. 13.060 and 13.261 for ATV+r 1 and 2). The cost-utility values were 15,310.56 for LPV/r, 15,902.99 and 15,524.85 for ATV+r 1 and 2. CONCLUSIONS: Using real-life data, the model produced significantly different results compared with other studies. With the innovative addition of an evaluation of CKD events, the model showed a cost-utility value advantage for twice-daily LPV/r over once-daily ATV+r, thus providing evidence for its continued use in the treatment of HIV.

The potential cost and benefits of raltegravir in simplified second-line therapy among HIV infected patients in Nigeria and South Africa.

BACKGROUND: There is an urgent need to improve the evidence base for provision of second-line antiretroviral therapy (ART) following first-line virological failure. This is particularly the case in Sub-Saharan Africa where 70% of all people living with HIV/AIDS (PHA) reside. The aim of this study was to simulate the potential risks and benefits of treatment simplification in second-line therapy compared to the current standard of care (SOC) in a lower-middle income and an upper-middle income country in Sub-Saharan Africa. METHODS: We developed a microsimulation model to compare outcomes associated with reducing treatment discontinuations between current SOC for second-line therapy in South Africa and Nigeria and an alternative regimen: ritonavir-boosted lopinavir (LPV/r) combined with raltegravir (RAL). We used published studies and collaborating sites to estimate efficacy, adverse effect and cost. Model outcomes were reported as incremental cost effectiveness ratios (ICERs) in 2011 USD per quality adjusted life year ($/QALY) gained. RESULTS: Reducing treatment discontinuations with LPV/r+RAL resulted in an additional 0.4 discounted QALYs and increased the undiscounted life expectancy by 0.8 years per person compared to the current SOC. The average incremental cost was $6,525 per treated patient in Nigeria and $4,409 per treated patient in South Africa. The cost-effectiveness ratios were $16,302/QALY gained and $11,085/QALY gained for Nigeria and South Africa, respectively. Our results were sensitive to the probability of ART discontinuation and the unit cost for RAL. CONCLUSIONS: The combination of raltegravir and ritonavir-boosted lopinavir was projected to be cost-effective in South Africa. However, at its current price, it is unlikely to be cost-effective in Nigeria.

[Comparative cost-effectiveness analysis between darunavir/ritonavir and other protease inhibitors in treatment-naive human immunodeficiency syndrome type 1-infected patients in Spain]. / Análisis comparativo de coste-eficacia entre darunavir/ritonavir y otros inhibidores de la proteasa en el tratamiento de la infección por el virus de la inmunodeficiencia humana de tipo 1 en pacientes naïve en España.

INTRODUCTION: GESIDA (AIDS Study Group) has proposed preferred regimens of antiretroviral treatment as initial therapy in HIV infected patients. The objective of this analysis is to compare the costs and effectiveness of darunavir/r QD and other ritonavir-boosted (/r) protease inhibitors (PIs) currently recommended in GESIDA guidelines for treatment-naïve patients. METHODS: A cost-efficacy model compared the boosted PIs recommended as preferred or alternative treatment choices, each used with a nucleoside reverse transcriptase inhibitor backbone. Efficacy was measured by 48-week virological response (viral load < 50 copies/mL) adjusted by baseline viral load and CD4 cell count. To generate efficiency frontiers and cost-efficacy ratios, one-year antiretroviral therapy costs in Spain, and 48-week efficacy values were used. RESULTS: The model estimated that starting treatment with darunavir/r QD was the most cost-effective choice compared with the other preferred PI/r based therapies. The average cost per patient with a virological response was lower for darunavir/r QD (13,420€) than for atazanavir/r QD (14,000€), or lopinavir/r BID (13,815€). Among the preferred PI/r-based therapies, darunavir/r QD also was estimated to be the most efficient option for treatment-naïve patients. Atazanavir/r QD and lopinavir/r BID were found to be «dominated¼ by darunavir/r) and, consequently, were outside the efficiency frontier of PI/r-based first-line treatment. Given a fixed budget of 10 million euros for PI/r-based first-line therapy, the model estimated that darunavir/r QD would yield more responders (745) than atazanavir/r QD (714), or lopinavir/r BID (724). At the same time, darunavir/r QD would reduce the number of individuals failing treatment (150) compared with atazanavir/r QD (172) and lopinavir/r BID (286). CONCLUSIONS: In this model, darunavir/r QD was found to be the most cost-effective choice, among the preferred PI/r-based therapies recommended in the Spanish guidelines for treatment-naïve patients.

Utilización de lopinavir/ritonavir en monoterapia / Use of lopinavir/ritonavir monotherapy

No disponible

Economic and health-related quality-of-life (HRQoL) comparison of lopinavir/ritonavir (LPV/r) and atazanavir plus ritonavir (ATV+RTV) based regimens for antiretroviral therapy (ART)-naïve and -experienced United Kingdom patients in 2011.

BACKGROUND: Using a United Kingdom (UK)-based National Health Services perspective for 2011 this study first estimated the cost-effectiveness and budget impact implications for lopinavir/ritonavir (LPV/r) vs atazanavir plus ritonavir (ATV+RTV) treatment of antiretroviral therapy (ART)-naïve patients and secondly examined the long-term health-related quality-of-life (HRQoL) and economic implications for LPV/r vs ATV+RTV treatment of ART-experienced patients. METHODS: A previously published Markov model that integrates epidemiological data of human immunodeficiency virus (HIV) with predictors of coronary heart disease (CHD) was modified under a clearly specified set of assumptions to reflect viral load (VL) suppression profiles and other differences for these two regimens, applying results from the CASTLE study in ART-naïve patients and using data from BMS-045 in ART-experienced patients. ART costs were referenced to current (2011) pricing guidelines in the UK. Medical care costs reflected UK treatment patterns and relevant drug pricing. Costs and outcomes were discounted at 3.5% per year. Costs are expressed in British pounds (£) and life expectancy in quality-adjusted life years (QALYs). RESULTS: In the ART-naïve subjects, the model predicted a marginal improved life expectancy of 0.031 QALYs (11 days) for the ATV+RTV regimen as a result of predicted CHD outcomes based on lower increases in cholesterol levels compared with the LPV/r regimen. The model demonstrated cost savings with the LPV/r regimen. The total lifetime cost savings was £4070 per patient for the LPV/r regimen. LPV/r saved £2133 and £3409 per patient at 5 and 10 years, respectively. Referenced to LPV/r, the incremental cost-effectiveness ratio (ICER) for ATV+RTV was £149,270/QALY. For ART-experienced patients VL suppression differences favored LPV/r, while CHD risk associated with elevated total cholesterol marginally favored ATV+RTV, resulting in a net improvement in life expectancy of 0.31 QALYs (106 days) for LPV/r. Five-year costs were £5538 per patient greater for ATV+RTV, with a discounted lifetime saving of £1445 per LPV/r patient. LPV/r was modestly dominant economically, producing better outcomes and cost savings. LIMITATIONS: The limitations of this study include uncertainty related to how well the model's assumptions capture current practice, as well as the validity of the model parameters used. This study was limited to using aggregated data in the public domain from the two clinical trials. Thus, some of the model parameters may reflect limitations due to trial design and data aggregation bias. This study has attempted to illuminate the effect of these limitations by presenting the results of the comprehensive sensitivity analysis. CONCLUSIONS: Based on 2011 costs of HIV in the UK and the published efficacy data from the CASTLE and BMS-045 studies, ATV+RTV-based regimens are not expected to be a cost-effective use of resources for ART-naïve patients similar to patients in the CASTLE study, nor for ART-experienced patients based on the only published comparison of ATV+RTV and LPV/r.

Economics of switching to second-line antiretroviral therapy with lopinavir/ritonavir in Africa: estimates based on DART trial results and costs for Uganda and Kenya.

BACKGROUND: Substantial immunological improvement has been reported for HIV-infected patients who switch from a failing regimen to a protease inhibitor regimen with Lopinavir/ritonavir (LPV/r). We use decision analysis modeling to estimate health and economic consequences expected from this switch. METHODS: A Markov model combined best evidence for CD4(+) T-cell response, infectious disease events, death rates, and quality of life for African populations with Kenyan and Ugandan data on drug and medical care costs. We estimate the incremental cost-effectiveness ratio of switching to an LPV/r-based regimen versus remaining on a failed first antiretroviral (ARV) regimen or discontinuing all ARV drugs. The model assumes concurrent use of cotrimoxazole, and 4% annual loss to follow-up. Local effects due to prevalence of malaria and tuberculosis are included in the model. Sensitivity analysis examines the effects of varying disease, ARV therapy and CD4(+) T-cell cost, and ART discontinuation assumptions. RESULTS: The base model estimates an improvement of 20 months in average survival for the LPV/r group. The respective LPV/r ICER for Kenya is $1483 per quality-adjusted life year (QALY) compared to $1673/QALY for Uganda. The ICERs increase to $1517 and $1707, respectively, if CD4(+) T-cell tests cost $25. The model comparing switching to LPV/r to discontinuing all ARV drugs decreases both costs and benefits proportionally for the treatment groups. CONCLUSION: The estimates are clearly below the most stringent World Health Organization benchmark for cost-effectiveness for Kenya and within the acceptable range of cost-effectiveness for Uganda. Thus, the switch to second-line therapy with LPV/r in these countries appears to be a cost-effective use of resources.

Simplification of antiretroviral therapy: a good choice for our patients and the sustainability of our health care system.

OBJECTIVE: To describe the efficacy, safety, compliance and cost savings of lopinavir/ritonavir monotherapy. METHOD: Observational, descriptive and retrospective study evaluating monotherapy. Adherence was calculated using an objective method. We estimated the direct costs of dispensing non-triple therapy. RESULTS: We identified 17 patients. Interval adherence was > 95% in 9 patients, 90-95% in 2 patients, 90-85% in 2 patients, and less than 85% in 4 patients. Viral load was undetectable during weeks 12, 24, 36 and 48, except in 2 patients. The CD4 count in most analytical tests remained at > 350 cells/ml, only 1 patient had a lower figure. The average savings was 4819 Euros/patient/year (range 1116 to 8700). CONCLUSIONS: In selected patients, monotherapy can be a cost-effective treatment option.

[Evidence-based therapeutic drug monitoring of lopinavir]. / Niveau de preuve du suivi thérapeutique pharmacologique du lopinavir.

The HIV protease inhibitor lopinavir presents a wide inter-individual variability related to liver and intestinal metabolism involving CYP3A. Published studies were analyzed to establish whether there is evidence that therapeutic drug monitoring of lopinavir could improve patient care. In naïve or pretreated HIV-infected patients, no relationship could be evidenced between virological efficacy and trough lopinavir concentration, most likely because concentrations are above inhibitory concentrations. Although data are limited, patients with elevated triglycerides and cholesterol had trough lopinavir concentrations >8 000 ng/mL. These data suggest that the level of evidence of interest of lopinavir therapeutic drug monitoring is may be recommended in some situations such as children, pregnant women, pretreated patients if the number of mutations is <5, when coadministration with drug with metabolizing enzyme inducing properties is warranted and toxicity.