Atazanavir sulfate + cobicistat for the treatment of HIV infection.

INTRODUCTION: During last two decades several drugs were developed to offer long-term benefits in terms of virologic efficacy, favourable tolerability and toxicity profiles in treatment of HIV infection. Pharmacokinetics boosting of protease inhibitor allows a higher genetic barrier, as few or no drug-resistant mutations are detected in patients with virologic failure. Areas covered: Atazanavir sulfate + cobicistat (ATV/c) was recently approved for the treatment of HIV-1 infection. Bioequivalence between cobicistat (COBI) and ritonavir (RTV) as a pharmacoenhancer of ATV was established. Additionally, randomized clinical trials demonstrated that ATV/c and ATV/ritonavir had comparable efficacy and safety profiles. Low rates of virologic failure and no ATV resistance mutations were observed in these clinical trials. Therefore, COBI shows increased advantages over RTV, such as no activity against HIV, fewer drug-drug interactions and better solubility, which promotes coformulation strategies with less pill burden, better tolerability, and, potentially, higher life-long treatment adherence. Expert commentary: ATV/c regimen supports its useas an effective treatment option for HIV-1 infected patients with increased cardiovascular disease and chronic kidney disease risk associated with aging. In addition, ATV/c is a new opportunity to expand the strategy of switch to a dual therapy to lower the risk of long-term toxicities as well as the advantage of its cost-benefit.

Economic and Public Health Impacts of Policies Restricting Access to Hepatitis C Treatment for Medicaid Patients.

BACKGROUND: Interferon-free hepatitis C treatment regimens are effective but very costly. The cost-effectiveness, budget, and public health impacts of current Medicaid treatment policies restricting treatment to patients with advanced disease remain unknown. OBJECTIVES: To evaluate the cost-effectiveness of current Medicaid policies restricting hepatitis C treatment to patients with advanced disease compared with a strategy providing unrestricted access to hepatitis C treatment, assess the budget and public health impact of each strategy, and estimate the feasibility and long-term effects of increased access to treatment for patients with hepatitis C. METHODS: Using a Markov model, we compared two strategies for 45- to 55-year-old Medicaid beneficiaries: 1) Current Practice-only advanced disease is treated before Medicare eligibility and 2) Full Access-both early-stage and advanced disease are treated before Medicare eligibility. Patients could develop progressive fibrosis, cirrhosis, or hepatocellular carcinoma, undergo transplantation, or die each year. Morbidity was reduced after successful treatment. We calculated the incremental cost-effectiveness ratio and compared the costs and public health effects of each strategy from the perspective of Medicare alone as well as the Centers for Medicare & Medicaid Services perspective. We varied model inputs in one-way and probabilistic sensitivity analyses. RESULTS: Full Access was less costly and more effective than Current Practice for all cohorts and perspectives, with differences in cost ranging from $5,369 to $11,960 and in effectiveness from 0.82 to 3.01 quality-adjusted life-years. In a probabilistic sensitivity analysis, Full Access was cost saving in 93% of model iterations. Compared with Current Practice, Full Access averted 5,994 hepatocellular carcinoma cases and 121 liver transplants per 100,000 patients. CONCLUSIONS: Current Medicaid policies restricting hepatitis C treatment to patients with advanced disease are more costly and less effective than unrestricted, full-access strategies. Collaboration between state and federal payers may be needed to realize the full public health impact of recent innovations in hepatitis C treatment.

Cost Effectiveness of Protease Inhibitor Monotherapy Versus Standard Triple Therapy in the Long-Term Management of HIV Patients: Analysis Using Evidence from the PIVOT Trial.

BACKGROUND: Protease inhibitor (PI) monotherapy can maintain virological suppression in the majority of patients once it has been established on triple therapy and may also have the potential for substantial cost savings arising from the use of fewer drugs. However, the cost effectiveness of PI monotherapy has yet to be demonstrated. OBJECTIVES: In this study we examine the cost effectiveness of PI monotherapy with prompt return to combination therapy in the event of viral load rebound compared with ongoing triple therapy (OT) in patients with suppressed viral load on combination antiretroviral therapy (ART) in the UK. METHODS: The analysis used data from the PIVOT trial in which HIV-positive adults with suppressed viral load for ≥24 weeks on combination ART were randomised to maintain OT or to a strategy of PI monotherapy with prompt return to combination therapy if viral load rebounded. A cost-effectiveness analysis including long-term modelling was conducted. Main outcomes included UK National Health Service (NHS) costs and quality-adjusted life-years (QALYs) with comparative results presented as incremental cost-effectiveness ratios. RESULTS: PI monotherapy was cost saving as a result of large savings in ART drug costs while being no less effective in terms of QALYs in the within-trial analysis and marginally less effective with lifetime modelling. In the base-case analysis over 3 years, the incremental total cost per patient was -£6424.11 (95 % confidence interval -7418.84 to -5429.38) and incremental QALYs were 0.0051 (95 % CI -0.0479 to 0.0582), resulting in PI monotherapy 'dominating' OT. Multiple scenario analyses found that PI monotherapy was cost saving with no marked differences in QALYs. Modelling of lifetime costs and QALYs showed that PI monotherapy was associated with significant cost savings and was marginally less effective; PI monotherapy was cost effective at accepted cost-effectiveness thresholds in all but one scenario analysis. CONCLUSIONS: Under most assumptions, PI monotherapy appears to be a cost-effective treatment strategy compared with OT for HIV-infected patients who have achieved sustained virological suppression.

[Challenges of lopinavir/ritonavir in the chronicity of human immunodeficiency virus infection]. / Desafíos de lopinavir/ritonavir en la cronicidad de la infección por virus de la inmunodeficiencia humana.

Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs.

Health technology assessment in the HIV setting: the case of monotherapy.

Despite the success of multiple-drug therapy regimens, the idea of treating human immunodeficiency virus (HIV) infection with fewer drugs is captivating due to issues of convenience, long-term toxicities and costs. This study investigated the impact on a local health budget of the introduction of a protease inhibitor (PI)-based antiretroviral monotherapy. An analysis of 23,721 administrative records of HIV-infected patients and a health technology assessment (HTA) were performed to assess cost-effectiveness, budget, organizational, ethics, and equity impact. Data showed that monotherapy had a annual cost of € 7,076 (patient with undetectable viral load) and € 7,860 (patient with detectable viral load), and that its implementation would realise economic savings of between 12 and 24 million euro (between 4.80% and 9.72% of the 2010 total regional budget expenditure for HIV management) in the first year, with cumulated savings of between 48 and 145 million euro over the following five years. Organizational, ethical and equity impact did not indicate any significant differences. The study suggests that for specific categories of patients monotherapy may be an alternative to existing therapies. Its implementation would not result in higher operating costs, and would lead to a reduction in total expenditure.

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.

Antiretroviral treatment-based cost saving interventions may offset expenses for new patients and earlier treatment start.

OBJECTIVES: Combination antiretroviral therapy (cART) has become the main driver of total costs of caring for persons living with HIV (PLHIV). The present study estimated the short/medium-term cost trends in response to the recent evolution of national guidelines and regional therapeutic protocols for cART in Italy. METHODS: We developed a deterministic mathematical model that was calibrated using epidemic data for Lazio, a region located in central Italy with about six million inhabitants. RESULTS: In the Base Case Scenario, the estimated number of PLHIV in the Lazio region increased over the period 2012-2016 from 14 414 to 17 179. Over the same period, the average projected annual cost for treating the HIV-infected population was €147.0 million. An earlier cART initiation resulted in a rise of 2.3% in the average estimated annual cost, whereas an increase from 27% to 50% in the proportion of naïve subjects starting cART with a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen resulted in a reduction of 0.3%. Simplification strategies based on NNRTIs co-formulated in a single tablet regimen and protease inhibitor/ritonavir-boosted monotherapy produced an overall reduction in average annual costs of 1.5%. A further average saving of 3.3% resulted from the introduction of generic antiretroviral drugs. CONCLUSIONS: In the medium term, cost saving interventions could finance the increase in costs resulting from the inertial growth in the number of patients requiring treatment and from the earlier treatment initiation recommended in recent guidelines.

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.

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.

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

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Potential for simplification of HIV treatment with boosted protease inhibitor monotherapy.

BACKGROUND: Previous studies have evaluated the simplification of HIV treatment with ritonavir-boosted protease inhibitor monotherapy, demonstrating acceptable efficacy and advantages such as avoidance of the adverse effects of reverse transcriptase inhibitors. To achieve the best results, patients should be appropriately selected for this therapy. OBJECTIVE: The purpose of this study was to estimate the proportion of HIV patients suitable for boosted protease inhibitor monotherapy according to clinical trial criteria. Setting The study was conducted in the outpatient hospital pharmacy service of the Complejo Hospitalario de Navarra in northern Spain. METHOD: A retrospective analysis was performed on data from 635 adults on antiretroviral therapy. The eligibility criteria were: (1) >18 years of age; (2) prior triple-drug antiretroviral regimen; (3) durability of current treatment >18 months; (4) viral load <400 copies/mL over the 18 months before evaluation and <50 copies/mL over the last 6 months; (5) CD4 count ≥250 cells/µL; (6) CD4 count nadir >100 cells/µL; (7) no previous virological failure under prior protease inhibitor-based regimen; (8) absence of co-infection with hepatitis B virus; (9) absence of HIV-related neurological disease; and (10) adherence >95 %. The average cost of the current treatment was calculated for patients who met all criteria, as well as the potential economic impact of simplification to monotherapy. MAIN OUTCOME MEASURE: Number of patients meeting all criteria for simplification to monotherapy according to clinical trial standards. RESULTS: One hundred and three patients (16.5 %) met the clinical trial criteria for protease inhibitor monotherapy. One hundred and fifty patients (24 %) failed to fulfil only one of the conditions. Fifty-four percent of the patients who met all of the criteria had been treated for more than 10 years. The average saving per patient per year was 2,850-3,400. CONCLUSION: This treatment strategy represents a realistic, albeit minority, option. Fulfilment of the above conditions should be the basis for simplification to protease inhibitor monotherapy, though the final decision depends on clinical criteria and patient preferences assessed by the attending physician. Further studies are needed to confirm long-term safety and efficacy.

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.

Protease inhibitor-containing antiretroviral treatment and tuberculosis: can rifabutin fill the breach?

OBJECTIVE: To assess how to best manage co-administration of rifabutin (RFB) and human immunodeficiency virus 1 (HIV-1) protease inhibitor (PI) containing antiretroviral treatment (ART). Recommended for initial anti-tuberculosis treatment, rifampicin (RMP) lowers PI concentrations below therapeutic levels, posing significant challenges for ART. As RFB has little effect on PI concentrations, it could be an alternative to RMP. METHODS: A review of the scientific literature on the safety and efficacy of RFB for adult tuberculosis (TB) treatment was conducted, focusing on ART-TB co-therapy. A cost comparison was performed between treatment regimens, and estimates of the burden of TB disease in patients on ART were used to model RFB demand in low- and middle-income countries (LMICs). RESULTS: Eleven clinical studies were identified, comprising 1543 TB patients treated with RFB; 980 (64%) were living with HIV. RFB was as safe and effective as RMP, including in 313 patients receiving co-administered ART (unboosted PIs included indinavir, nelfinavir or saquinavir; a minority received ritonavir [RTV] boosted amprenavir or saquinavir). The total cost for 6 months of all HIV and TB treatment containing RTV-boosted lopinavir (LPV) and RFB is US$410, compared to US$455 if RMP is used with LPV super-boosted with RTV. Our model suggests that demand for RFB in LMICs could be between 10,000 and 18,000 courses by 2012. CONCLUSION: RFB is effective and safe in combination with the PIs studied, cost-saving for co-therapy with currently recommended boosted PIs, and may have a pivotal role in the roll-out of ART. Further research into a daily dose of RFB to simplify dosing regimens and developing fixed-dose combinations can enhance the public sector roll-out of ART.

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.