Robustillo-Cortés Mª de las A1, Tortajada Goitia B2, Ríos Sánchez E3, Talero Barrientos E4,
Álvarez de Sotomayor Paz M4, Morillo Verdugo R1
1 Facultativo Especialista de Área de Farmacia Hospitalaria. Hospital Universitario de Valme.
Servicio de Farmacia Hospitalaria. Sevilla (España)
2 Facultativo Especialista de Área de Farmacia Hospitalaria. Agencia Sanitaria Costa del Sol. Servicio de Farmacia
Hospitalaria. Marbella. Málaga (España)
3 Facultativo Especialista de Área de Farmacia Hospitalaria. Hospital Universitario de Puerto Real.
Servicio de Farmacia Hospitalaria. Puerto Real. Cádiz (España)
4 Doctora en Farmacia. Departamento de Farmacología. Facultad de Farmacia. Universidad de Sevilla. Sevilla (España)
Rev. OFIL 2016, 26;4:251-257
Fecha de recepción: 15/03/2016 – Fecha de aceptación: 02/04/2016
María de las Aguas Robustillo
Avda. Grecia, 35 – Bloque 6 1 C
Correo electrónico: firstname.lastname@example.org
Objective: To determine the compliance of quality care indicators (GESIDA) for adult patients living with HIV infection in PSITAR cohort.
Methods: Multi-center, prospective observational study. All adult naive patients, that began treatment during 2011 belonging to the PSITAR cohort, were selected. We recorded demographic data, virological parameters at baseline and 48 weeks of treatment and pharmacotherapy variables. The selected indicators were: The compliance of initial antiretroviral therapy with the Spanish national treatment guidelines (GESIDA) for treatment-naive HIV-infected patient (95%), undetectable viral load at 48 weeks (80%), treatment initiation with Abacavir without screening for HLA-B*5701 (0%), treatment modifications within the first year (<30%), adherence treatment measure (95%), study of resistance in the virologic failure (90%) and average expenditure per patient in the first treatment (GESIDA median).
Results: In total 108 HIV+ naive patients were included, 83.3% men. The median age was 40.5 years (21-75). The most frequent combination was tenofovir-emtricitabine-efavirenz with 61.0%. 28 patients (29.7%) modified their treatment during the first year. Focusing on indicators compliance, starting of treatment with a recommended regimen had 95.4% of compliance, undetectable viral load indicator 74.1%, treatment initiation without Abacavir test 0%, treatment modifications within the first year 25.9%, adherence treatment measure 86.3%, study of resistance in the virologic failure 80% and average expenditure per patient was 8,846 euros.
Conclusion: Quality care follow up indicators were fulfilled in their vast majority. The worst accomplished indicators such as undetectable viral load at 48 weeks, evaluation of adherence and study of resistance must be study to examine the possible improvement points.
Key Words: HIV, quality indicators, health care, drug therapy.
Highly activity antiretroviral therapy (HAART) has substantially reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV) since its introduction in 1996. This has changed the natural history of disease1,2. Over the past few years, drug development has evolved to achieve, in most cases, a partial restoration of the immune system3 and an approach to the life expectancy of the general population4.
Both treatment and monitoring of HIV-infected patients are gradually becoming more complex. This and the fact that, HIV disease is considered as a chronic disease, leads to an increased demand for standardize the care for these patients5. In order to determine the quality of clinical practice and to implement the appropriate improvements, in 2010, GESIDA (Spanish Study Group on AIDS) quality care indicators for adult patients living with HIV infection were published6.
Of these, drug therapy management indicators play a key role, as evidenced by the fact that four of these indicators are included among the most relevant indicators and eight among indicators of basic accreditation.
In addition, pharmacotherapy follow-up is a basic pillar of achieving the goals of pharmacotherapy patients. On the other hand, in general, hospital pharmacist role has changed in our working frame. Simple concept of pharmacist as “drugs dispenser” has been replaced by more active and dynamic role. Pharmacist has become co-responsible, with the other members of the multidisciplinary team, for clinical outcomes of drug prescribed to each patient. All this shows the importance of pharmacist dedicated to VIH patient’s health care and they are a key element of therapy management and rational drug use.
In order to facilitate pharmacotherapy follow-up and to obtain useful outcomes indicators such as drug effectiveness and safety, PSITAR cohort was developed with its specific registry tool.
PSITAR is a prospective HIV naive patient’s cohort. This cohort collects information from patients over 18 years of age belonging to seven hospitals in Andalusia. Patients were included in PSITAR cohort from 2011 to the present.
This new tool is meant to solve one of the main problems faced by health professionals: dispensing heterogeneous software and they are not geared towards drug pharmacotherapy management patients.
This online platform allows easily introducing and exploiting demographic, analytical and pharmacological parameters of patients at baseline and it allows monitoring their development over time.
The aim of this study is to assess the compliance of quality care indicators (GESIDA) for adult patients living with HIV infection in PSITAR cohort.
We performed a multi-center, prospective observational study. All adult naive patients, that began treatment during 2011 and were treated in outpatient pharmacy hospitals belonging to the PSITAR cohort, were selected. Also, they must complete a full year of follow-up. Patients participating in clinical trials or expanded access to antiretroviral drugs were excluded.
We recorded demographic data: Age at treatment initiation and sex; Virological parameters at baseline and 48 weeks of treatment as CD4 cells (Cel/mL) count and viral load (copies/mL) and pharmacotherapy variables: First HAART regimen, primary antiretroviral resistance (before treatment initiation), discontinuation in the first 48 weeks of treatment and their causes based on Swiss HIV Cohort7. The main reason for treatment modification was classified as treatment failure, intolerance and/or toxic effects, the patient’s choice, the physician’s decision, and other reasons.
Finally, treatment adherence was recorded by SMAQ questionnaire and recording drug dispensations.
The costs of each regimen were calculated from the laboratory sales price plus 4%. The costs of each HAART were calculated from drug price they include. In case there are combinations, the price would be based on price of the combo. Prices were obtained from consensus GESIDA/National AIDS Plan 20118.
Quality care indicators (GESIDA) for adult patients living with HIV infection are described in the document, with the same name, published in 20116.
In the final document, 66 indicators were included as follows: Structural conditions, diagnosis and evaluation, follow-up and preventive interventions, follow-up of patients under treatment, specific aspects in women, comorbidities, hospitalization, mortality rates, training and research.
The indicators which were chosen belong to follow-up of patients under treatment section. The following indicators were selected:
The compliance of initial antiretroviral therapy (ART) with the Spanish national treatment guidelines (GESIDA Guidelines) for treatment-naive HIV-infected patient. The guidelines’ recommendations for initiating antiretroviral treatment are shown in table 1. Undetectable viral load was defined as a viral load of <50 HIV-1 RNA copies/ml at 48 treatment weeks, treatment initiation with Abacavir without screening for HLA-B*5701, treatment modifications within the first year, adherence treatment measure, study of resistance in the virologic failure and average expenditure per patient in the first treatment. Features of each indicator are shown in table 2.
The main variables are taken from the data collection platform PSITAR. The data have been introduced by the heads of each hospital centre through review of dispensations in the outpatient program and review of medical history. The quantitative variables are expressed as median and interquartile range and the qualitative values as percentages. All statistical analyses were performed using SPSS v.20.0.
In total 108 HIV+ naive patients from seven hospitals were included in the study, 83.3% of them were men. The median age was 40.5 years. At the time of initiation of therapy, few patients, 24.1% had an advanced immune deficiency (CD4 cells below 200/ml). The rest of baseline socio-demographic and clinical characteristics are listed in table 3.
Regarding the initial therapy, the most frequent combination in naive patients was tenofovir-emtricitabine with efavirenz with 61.0% of the patients, followed by tenofovir-emtricitabine with atazanavir/ritonavir 15.8%, tenofovir-emtricitabine with darunavir/ritonavir 12.0% and another combinations 11.2%.
Information on primary resistance was available in 73 patients; including three patients had primary drug resistance: one patient developed resistance to protease-inhibitor (PI) and two patients to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).
Of 108 individuals starting ART, 28 (29.7%) modified their treatment during the first year. The most frequent reasons for treatment modification were toxic effects (60.7%), followed by a physician’s decision (14.3%), treatment failure (17.8%) and other reasons (7.2%).
Finally, in relation to adherence to antiretroviral therapy, 22.2% of the patients were non-adherent to one year after treatment initiation.
Quality care indicators
The most accomplished quality indicators were treatment initiation with Abacavir without screening for HLA-B*5701 with 100% compliance (no patient) and the start of treatment with a recommended regimen as GESIDA guidelines with 95.4% compliance. Antiretroviral therapy discontinuation in the first 12 months was above the reference value with 25.9% of cases.
At the opposite end, quality indicators with poorer outcomes were study of resistance in the virologic failure with 80.0% compliance, not exceeding the minimum value, as well as undetectable viral load indicator with 74.1%. Adherence recording didn’t reach the reference value with 86.3% either.
Finally, focusing on cost, mean health expenditure per patient per year was 8,846.0 euros (11,796$). This figure is below the median of rates published in 2011 by GESIDA, with a value of 9,403.8 euros (12,540$).
Our study shows that the compliance of drug therapy management indicators (GESIDA) for adult patients living with HIV infection in PSITAR cohort was elevated.
Currently, there are no studies examining the compliance of quality care indicators (GESIDA) for adult patients since its publication in 2010. There are studies that scan the adherence to guidelines and one paper studies these quality indicators in pediatric population. In this study, quality indicators were adapted to pediatrics patients9. All indicators in the follow-up section exceeded standards values less undetectable viral load. In spite of having this document, it is necessary to use the consensus GESIDA/National AIDS Plan 20118 to analyze our results.
Among the indicators with better compliance profile are the following: treatment initiation with Abacavir without screening for HLA-B*5701, treatment initiation with a recommended regimen as GESIDA guidelines and antiretroviral therapy discontinuation in the first 12 months indicator. The cost per patient per year of treatment is less than the value proposed in the indicator description.
By contrast, the worst accomplished quality indicators are the percentage of patients with undetectable viral load, study of resistance in the virologic failure and adherence assessment.
In relation to HLA-B*5701 determination, this procedure is routinely done and has been incorporated into daily clinical practice since 2002, when an association between a diagnosis of hypersensitivity reaction to abacavir and carriage of the major histocompatibility complex class I allele HLA-B*5701 was reported independently by two research group10,11.
In reference to the compliance with clinical practice guidelines for antiretroviral treatment indicator, we knew that most combinations of current drugs achieve undetectable viral load in 70.0% of cases at 48 weeks12. Drugs combinations supported by the largest number of clinical trials with optimal efficiency and durability, acceptable tolerance and ease of use are considered “Preferred regimens”5.
We found that the choice of initial antiretroviral regimen was appropriate in most cases: 95.4% of patients started treatment that was considered recommended by GESIDA guidelines. This is consistent with a study in the Spanish Asociación Médica Vach de Estudios Multicéntricos (VACH) cohort in the years 2004-2006, which found that initial treatment regimens were compliant with the guidelines in 95% of cases13.
Suarez-Garcia et al. study14, carried out in Spanish cohort CORIS, shows a lower adequacy with 91.5% compliance including preferred and alternative regimens. This data may be because in this study patients have been included since 2004. Since then, knowledge about different antiretroviral treatments has strongly developed and most complete guidelines have been elaborated and have been used by many health professionals.
Studies from the USA have found lower percentages of compliance15-17. For example, the Wandeler et al. study which compared initial antiretroviral regimens with American clinical practice guidelines, showed a compliance rate of 73.018. These differences across studies can partly be attributed to different populations and health care systems, use of different guidelines and general differences in the experience of caring for HIV-infected patients.
At last, several studies have focused on the analysis of discontinuations of antiretroviral therapy. Initial ART can be maintained over many years. Discontinuation of ART during first year due to its toxicity can have a negative impact on adherence or virological response. Elzi et al.7 in their study collected all treatment modifications in Swiss cohort of HIV patients between 2005 and 2008 with a percentage of discontinuations during the first year of 41.5%.
The broad availability of new drugs with the possibility of once-daily regimens may have triggered treatment modification, as suggested by the high proportion of patients switched to another antiretroviral regimen in this study19-21.
Recently, a work has been published by The Antiretroviral Therapy Cohort Collaboration (ART-CC)22 where the percentage of treatment discontinuation and its causes has been analyzed in 18 European and American cohorts between 2002 and 2009. Their results were discontinuation percentages close to 50% supporting this idea.
Cost per patient per year of treatment value was below the median cost of the preferred GESIDA regimens8 and at the lower limit of data obtained in the Blasco A et al. study which has been evaluated the costs and the cost effectiveness of initiating treatment following GESIDA guidelines in different situations in 201123.
Among indicators with poorer outcomes, undetectable viral load seems the most important. The aim of ART is to suppress viral replication rapidly and durably to get a figure lower than 50 copies/ml. This goal has been shown to prevent the mutation selection21,22 and to increase virological response23.
In our study 74.1% of patients had undetectable viral load. Such a low number can be explained because recent infections or breakthrough viral load was not specified.
The relationship between resistance mutations and virologic failure has been evidenced with the monitoring of the viral load.
Current treatments have dramatically reduced the frequency of treatment failure and virological failure rates in first-line treatment were between 20-40%24,25.
Prospective randomized studies have shown that the use of genotypic resistances tests in patients with virological failure was associated with a better virological control at three and six months and a better vital prognosis26.
In our study, patients with virological failure was low (limited) and a percentage value may not be indicative of global relevance.
Therapeutic compliance is one of the variables that best predicts virological response. Non-adherence increases the risk of acquiring resistances and morbidity and mortality associated with HIV infection5.
Treatment adherence should be assessed regularly because this allows estimated the patient’s ability to get involved in their own health care and in their disease.
Our study has several limitations. Firstly, we have work in a follow up cohort from a limited geographical area, Andalusia. We think that this cohort was representative because in this area, the national guidelines were followed. Secondly, all pharmacotherapeutic monitoring indicators have not been selected. Some aspects such as the establishment of the first treatment or first medical visit go beyond the pharmaceutical field.
Our new lines of research will focus on determining persistence of therapy in this cohort and on the analysis of time series data.
In conclusion, in our multicentre cohort, quality care follow up indicators (GESIDA) for adult patients living with HIV infection were fulfilled in their vast majority. The worst accomplished indicators such as undetectable viral load at 48 weeks, evaluation of adherence and study of resistance in the virologic failure must be study to examine the possible improvement points.
Conflict of Interest: There is no conflict of interest and source of funding that I should disclose.
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