Análise farmacoepidemiológica e farmacoeconômica do tratamento antirretroviral em dose fixa combinada na perspectiva do Sistema Único de Saúde

Abstract

Background: The combination antiretroviral therapy (cART) is the main strategy to control the Human Immunodeficiency Virus (HIV) infection, preventing the progression of the disease and the transmission of the virus. Its effectiveness, however, depends on high levels of adherence. Single-tablet regimens (STRs) contain three or more antiretrovirals in a singletablet, thus simplifying cART, and potentially providing better clinical outcomes. Since 2015, the STR regimen containing tenofovir disoproxil fumarate, lamivudine and efavirenz is available in the Brazilian National Health System (SUS). However, evidence on the health outcomes and cost-effectiveness with the use of this specific formulation is lacking. Objective: To conduct an epidemiological and pharmacoeconomic analysis of antiretroviral treatment in STR among people living with HIV who initiate cART in SUS. In addition, we evaluated the patterns of use and adherence to cART in the Australian context. Methods: We developed four studies within this thesis. In Study 1, we developed a nonconcurrent prospective cohort to evaluate the efficacy of STR compared to multiple tablet regimens (MTR) in subjects followed at a referral center in Belo Horizonte between January 2014 and December 2016. In this study, the response variable was the effectiveness of ART, defined as viral suppression [viral load (VL) < 50copies/ml] six and twelve months after initiating the treatment. In Study 2, a cost-effectiveness analysis was performed from the SUS perspective and limited to direct medical costs to compare the results of individuals who initiated cART in STR or MTR. We included the same population of Study 1 and compared the proportion of patients achieving viral suppression and associated costs after one year of follow-up between the groups. Results were expressed in United States dollars after conversion by the purchase power parity (US$ 1 = R$ 1,996). Study 3 is a cross-sectional analysis from the baseline of a prospective cohort study conducted at three reference centers in Belo Horizonte, Brazil, which recruited individuals between September 2015 and August 2017. We evaluated the Health-Related Quality of Life (HRQoL) of individuals initiating cART using the WHOQOL-HIV bref and EuroQol-5 Dimensions instruments. The factors associated with this outcome were evaluated by multilevel linear regression models for each instrument. In Study 4, a retrospective cohort of dispensing databases was developed to assess patterns of use and adherence to cART in Australia between July 2013 and June 2017. Adherence was measured by the proportion of days covered (PDC) using a cutoff of PDC ≥ 95% and, secondarily, PDC ≥ 80%. The outcomes were calculated after 12 months of followup and at monthly intervals to allow group-based trajectory modeling. Results: Study 1 included 440 patients, of whom the majority (58%) initiated cART in MTRs. The viral suppression was 74.6% at six months and 83.2% at twelve months, being higher among patients who used STR only at six months (p < 0.05). Factors associated with a lower probability of viral suppression included baseline VL ≥ 100,000 copies/ml, presence of AIDS-defining signs and symptoms, antiretroviral switch, longer interval between diagnosis and cART initiation, and use of tobacco or illicit drugs during the follow-up. Adherence to cART and belonging to the category of risk/exposure of men who have sex with men were associated with a greater probability of effectiveness. Study 2 identified the STR as the optimal choice among the therapies available in Brazil between 2014 and 2016, with an annual cost of US$ 1,101.65 (SD 2,775.68) and a lower cost-effectiveness ratio after one year of follow-up. Study 3 included 366 participants, which showed a median quality of life over 80% for all instruments used. There were no differences between subjects using dolutegravir or efavirenz regimens, both with the backbone tenofovir disoproxil fumarate/ lamivudine. The following factors were associated with poorer HRQoL in at least two of the three models developed: civil status (unmarried), lower educational level, recent cigarette smoking, recent signs and symptoms of anxiety or depression, comorbidities, and occurrence of adverse drug reactions. In Study 4, we included 2,107 participants, most of them using cART regimens containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors + Non-Nucleoside Reverse Transcriptase Inhibitor (44.6%). After one year of follow-up, the mean PDC was 81.0% (SD 21.2) and the proportion of people adherent to ART was 35.7% using the 95% PDC threshold and 60.9% using the 80% PDC threshold. The trajectory analysis revealed three patterns for the probability of adherence over time: good adherence, low adherence, and early non-adherence, and only 51.7% of the participants belonged to the good adherence group. The factors associated with a higher probability of belonging to this group were older age and the use of integrase inhibitors regimens. Similar patterns were obtained for the 80% PDC threshold. Conclusions: The availability of STR in Brazil was beneficial in terms of effectiveness and cost-effectiveness. Therefore, this regimen should be used as a comparator for the purpose of future incorporations of first-line antiretrovirals in the country. To date, newer regimens containing integrase inhibitors have not shown any benefits on HRQoL in the Brazilian context, although longitudinal studies evaluating this and other outcomes should be performed. In general, people living with HIV in Belo Horizonte, who initiated cART, have a high incidence of viral suppression at six and twelve months, as well as high quality of life. However, it is possible to improve these results through early diagnosis and initiation of cART, intensification of health professionals' counseling on adverse events, encouraging patient adherence to cART, increasing the screening and the psychological support for individuals with anxiety or depression, and reducing the use of substances (tobacco and illicit drugs) in this population. Regardless of the cutoff point for optimal adherence, only half of the people on cART maintain good adherence over time in the Australian context, emphasizing the dynamic and complex character of adherence to chronic medications. The results corroborate the use of cART with a lower incidence of adverse drug reactions and regular follow-up of adherence to treatment, especially among younger individuals.