Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil

Robson Pierre Nascimento da Silva1, Luana M. S. Marins1, Lusiele Guaraldo2, Paula M. Luz1, Sandra Wagner Cardoso1, Ronaldo I. Moreira1, Vanessa G. Oliveira3, Valdiléa G. Veloso1, Beatriz Grinsztejn1, Rita de Cássia Elias Estrela4, Thiago S. Torres5
1Laboratório de Pesquisa Clínica em DST/AIDS, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz), Rio de Janeiro, Brazil
2Laboratório de Pesquisa Clínica em Doenças Febris Agudas, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz), Rio de Janeiro, Brazil
3Serviço de Farmácia (Sefarm), Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI-Fiocruz), Rio de Janeiro, Brazil
4Laboratório de Farmacometria, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil
5Av Brasil 4365 Manguinhos, 21045-360, Rio de Janeiro, Brazil

Tóm tắt

Abstract Background

The increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil.

Methods

Cross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy.

Results

A total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4–54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2–17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2–52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy.

Conclusions

We found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients’ therapeutic regimens should be implemented.

Từ khóa


Tài liệu tham khảo

UNAIDS, Global HIV. & AIDS statistics — Fact sheet [Internet]. 2022 [cited 2023 May 30]. Available from: https://www.unaids.org/en/resources/fact-sheet.

Ministério da Saúde, Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis. Boletim Epidemiológico HIV/Aids 2021 [Internet]. Brasília/DF: Ministério da Saúde. ; 2021 Dec. Available from: http://www.aids.gov.br/pt-br/pub/2021/boletim-epidemiologico-hivaids-2021.

Santos GS. dos. Monitoramento imunológico na história da infecção pelo HIV-1 [Internet]. [São Paulo]: Sec. Est. Saúde SP; 2019 [cited 2020 May 27]. Available from: http://docs.bvsalud.org/biblioref/2019/08/1010326/tcc-graziele-santos-2019.pdf.

Brazil, Ministry of Health. Prevenção Combinada [Internet]. 2022 [cited 2022 Jun 24]. Available from: http://www.aids.gov.br/pt-br/publico-geral/previna-se.

Kanters S, Vitoria M, Zoratti M, Doherty M, Penazzato M, Rangaraj A, et al. Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400 mg among antiretroviral therapies for first-line HIV treatment: a systematic literature review and network meta-analysis. EClinicalMedicine. 2020;28:100573.

Smiley CL, Rebeiro PF, Cesar C, Belaunzaran-Zamudio PF, Crabtree-Ramirez B, Padgett D, et al. Estimated life expectancy gains with antiretroviral therapy among adults with HIV in Latin America and the Caribbean: a multisite retrospective cohort study. Lancet HIV. 2021;8:e266–73.

Althoff KN, McGinnis KA, Wyatt CM, Freiberg MS, Gilbert C, Oursler KK, et al. Comparison of risk and age at diagnosis of myocardial infarction, end-stage renal disease, and Non-AIDS-Defining Cancer in HIV-Infected Versus Uninfected adults. Clin Infect Dis. 2015;60:627–38.

Cardoso SW, Torres TS, Santini-Oliveira M, Marins LMS, Veloso VG, Grinsztejn B. Aging with HIV: a practical review. Braz J Infect Dis Off Publ Braz Soc Infect Dis. 2013;17:464–79.

Guaraldi G, Orlando G, Zona S, Menozzi M, Carli F, Garlassi E, et al. Premature age-related Comorbidities among HIV-Infected persons compared with the General Population. Clin Infect Dis. 2011;53:1120–6.

De Francesco D, Wit FW, Bürkle A, Oehlke S, Kootstra NA, Winston A, et al. Do people living with HIV experience greater age advancement than their HIV-negative counterparts? AIDS. 2019;33:259–68.

Guo M-L, Buch S. Neuroinflammation & pre-mature aging in the context of chronic HIV infection and drug abuse: role of dysregulated autophagy. Brain Res. 2019;1724:146446.

de Oliveira PC, Silveira MR, Ceccato M, das GB, Reis AMM, Pinto IVL, Reis EA. Prevalência e Fatores Associados à Polifarmácia em Idosos Atendidos na Atenção Primária à Saúde em Belo Horizonte-MG, Brasil. Ciênc Saúde Coletiva. 2021;26:1553–64.

Vallejo Maroto I, Fernández Moyano A. Continuidad asistencial en el paciente pluripatológico. Med Clínica. 2012;139:206–7.

Fernández Cañabate S, Ortega Valín L. Polypharmacy among HIV infected people aged 50 years or older. Colomb Med Cali Colomb. 2019;50:142–52.

Okoli C, de Los Rios P, Eremin A, Brough G, Young B, Short D. Relationship between polypharmacy and quality of life among people in 24 countries living with HIV. Prev Chronic Dis. 2020;17:E22.

Pontelo BM, Greco DB, Guimarães NS, Rotsen N, Braga VAR, Pimentel PHN et al. Profile of drug–drug interactions and impact on the effectiveness of antiretroviral therapy among patients living with HIV followed at an infectious Diseases Referral Center in Belo Horizonte, Brazil. Braz J Infect Dis. 2020;S1413867020300301.

WHOCC - ATC/DDD Index [Internet]. [cited 2021 May 26]. Available from: https://www.whocc.no/atc_ddd_index/.

López-Centeno B, Badenes-Olmedo C, Mataix-Sanjuan Á, Mcallister K, Bellón JM, Gibbons S et al. Polypharmacy and Drug–Drug Interactions in People Living With Human Immunodeficiency Virus in the Region of Madrid, Spain: A Population-Based Study. Clin Infect Dis. 2019;ciz811.

IBGE. Cor ou raça | Educa | Jovens - IBGE [Internet]. [cited 2022 Jan 5]. Available from: https://educa.ibge.gov.br/jovens/conheca-o-brasil/populacao/18319-cor-ou-raca.html.

R: The R Project for Statistical Computing [Internet]. [cited 2021 May 26]. Available from: https://www.r-project.org/.

PROTOCOLO CLÍNICO E DIRETRIZES TERAPÊUTICAS PARA PROFILAXIA PÓS-EXPOSIÇÃO PEP DE RISCO À INFECÇÃO PELO HIV, IST E HEPATITES VIRAIS. | Departamento de Doenças de Condições Crônicas e Infecções Sexualmente Transmissíveis [Internet]. [cited 2022 Jan 5]. Available from: http://www.aids.gov.br/pt-br/pub/2021/protocolo-clinico-e-diretrizes-terapeuticas-para-profilaxia-pos-exposicao-pep-de-risco.

Torres TS, Cardoso SW, Velasque L, de Marins S, de Oliveira LMS, Veloso MS. Aging with HIV: an overview of an urban cohort in Rio de Janeiro (Brazil) across decades of life. Braz J Infect Dis. 2013;17:324–31.

Justice AC, Goetz MB, Stewart CN, Hogan BC, Humes E, Luz PM, et al. Delayed presentation of HIV among older individuals: a growing problem. Lancet HIV. 2022;9:e269–80.

Barbaro G. Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy. Curr Drug Targets Cardiovasc Haematol Disord. 2005;5:337–43.

Christo PP. Alterações cognitivas na infecção pelo HIV e Aids. Rev Assoc Médica Bras. 2010;56:242–7.

Ford N, Shubber Z, Pozniak A, Vitoria M, Doherty M, Kirby C, et al. Comparative safety and neuropsychiatric adverse events Associated with Efavirenz Use in First-Line antiretroviral therapy: a systematic review and Meta-analysis of Randomized trials. JAIDS J Acquir Immune Defic Syndr. 2015;69:422–9.

Paul R. Neurocognitive phenotyping of HIV in the era of antiretroviral therapy. Curr HIV/AIDS Rep. 2019;16:230–5.

Tedaldi EM, Minniti NL, Fischer T. HIV-associated neurocognitive disorders: the relationship of HIV infection with physical and social comorbidities. BioMed Res Int. 2015;2015:641913.

Hoare J, Sevenoaks T, Mtukushe B, Williams T, Heany S, Phillips N. Global systematic review of common Mental Health Disorders in adults living with HIV. Curr HIV/AIDS Rep. 2021;18:569–80.

O Halloran M, Boyle C, Kehoe B, Bagkeris E, Mallon P, Post FA, et al. Polypharmacy and drug–drug interactions in older and younger people living with HIV: the POPPY study. Antivir Ther. 2019;24:193–201.

Marzolini C, Elzi L, Gibbons S, Weber R, Fux C, Furrer H, et al. Prevalence of comedications and effect of potential drug–drug interactions in the swiss HIV Cohort Study. Antivir Ther. 2010;15:413–23.

Courlet P, Livio F, Guidi M, Cavassini M, Battegay M, Stoeckle M, et al. Polypharmacy, drug–drug interactions, and inappropriate drugs: New Challenges in the Aging Population with HIV. Open Forum Infect Dis. 2019;6:ofz531.

Lima MAC, Cunha GH da, Galvão MTG, Rocha RP, Franco KB, Fontenele MSM et al. Hipertensão arterial sistêmica em pessoas vivendo com HIV/aids: revisão integrativa. Rev Bras Enferm. 2017;70:1309–17.

Vos Alinda G, Barth Roos E, Klipstein-Grobusch Kerstin, Tempelman Hugo A, Devillé Walter LJ, Caitlin D, et al. Cardiovascular Disease Burden in Rural Africa: does HIV and Antiretroviral Treatment play a role? J Am Heart Assoc. 2020;9:e013466.

Crum-Cianflone NF. Human immunodeficiency virus and the gastrointestinal tract. Infect Dis Clin Pract. 2010;18:283–5.

Pupulin ÁRT, Carvalho PG, Nishi L, Nakamura CV, Guilherme ALF. Enteropatógenos relacionados à diarréia em pacientes HIV que fazem uso de terapia anti-retroviral. Rev Soc Bras Med Trop. 2009;42:551–5.

Coelho L, Cardoso SW, Amancio RT, Moreira RI, Campos DP, Veloso VG, et al. Trends in AIDS-defining opportunistic illnesses incidence over 25 years in Rio de Janeiro, Brazil. PLoS ONE. 2014;9:e98666.

Siefried KJ, Mao L, Cysique LA, Rule J, Giles ML, Smith DE, et al. Concomitant medication polypharmacy, interactions and imperfect adherence are common in australian adults on suppressive antiretroviral therapy. AIDS. 2018;32:35–48.

Zhao J, Nguyen LNT, Nguyen LN, Dang X, Cao D, Khanal S, et al. ATM Deficiency accelerates DNA damage, Telomere Erosion, and premature T cell aging in HIV-Infected individuals on antiretroviral therapy. Front Immunol. 2019;10:2531.

McNicholl IR, Gandhi M, Hare CB, Greene M, Pierluissi E. A pharmacist-led program to evaluate and reduce polypharmacy and potentially inappropriate prescribing in older HIV-Positive patients. Pharmacother J Hum Pharmacol Drug Ther. 2017;37:1498–506.

Sales AS, Sales MGS, Casotti CA. Perfil farmacoterapêutico e fatores associados à polifarmácia entre idosos de aiquara, Bahia, em 2014*. Epidemiol E Serviços Saúde. 2017;26:121–32.

Loikas D, Wettermark B, von Euler M, Bergman U, Schenck-Gustafsson K. Differences in drug utilisation between men and women: a cross-sectional analysis of all dispensed drugs in Sweden. BMJ Open. 2013;3:e002378.

Manteuffel M, Williams S, Chen W, Verbrugge RR, Pittman DG, Steinkellner A. Influence of patient sex and gender on Medication Use, Adherence, and prescribing alignment with guidelines. J Womens Health. 2014;23:112–9.

Zhang N, Sundquist J, Sundquist K, Ji J. An increasing Trend in the prevalence of polypharmacy in Sweden: a Nationwide Register-Based study. Front Pharmacol. 2020;11:326.

Silva IR, Giatti L, Chor D, Fonseca M, de Mengue JM, de Acurcio SS et al. A,. Polypharmacy, socioeconomic indicators and number of diseases: results from ELSA-Brasil. Rev Bras Epidemiol. 2020;23:e200077.