Hippokratia 2020, 24(3): 114-119
Goma F1,2, Papazisis G2, Karakiulakis G, Papakonstantinou E2
1National Public Health Organization, 2 Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Greece
Background: Adherence to HIV antiretroviral therapy (ART) is of great importance for reducing viral load and the eventual treatment of the patients and minimizing infectivity. This study aimed to investigate adherence to ART among people living with HIV in northern Greece and investigate the factors influencing adherence to ART.
Methods: A correlational study was performed on a cohort of 112 seropositive individuals (100 men and 12 women) with a mean age of 37.14 years. The simplified medication adherence questionnaire (SMAQ) was used to assess adherence. In addition, the perceived available support questionnaire (PAS) for social support assessment was utilized to evaluate the perceived social support.
Results: Approximately 60% of patients were found to be nonadherent to ART. Important factors affecting adherence are educational level, social support, and use of substances.
Conclusions: The results show that a significant proportion of the cohort of patients investigated from northern Greece does not show adherence to ART. Several factors were identified to be of significant influence, which should be taken into consideration by the Greek healthcare providers. HIPPOKRATIA 2020, 24(3): 114-119.
Keywords: HIV, AIDS, adherence, antiretroviral therapy, determinants of adherence, social support
Corresponding author: Eleni Papakonstantinou, MD, Ph.D., Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece, tel: +302310999304, e-mail: firstname.lastname@example.org
HIV infection is a major health issue around the world. Antiretroviral therapy (ART) as a suitable and effective treatment for HIV infection is well documented1. Besides the effectiveness of the antiretroviral drugs themselves, the efficacy of ART is significantly affected by adherence to therapy throughout the life of the HIV seropositive patients2. A high level of adherence to ART (>95 %) is necessary to achieve and maintain complete and sustained viral depression to prevent disease and to minimize infectivity3,4. However, many HIV seropositive patients have failed to achieve or maintain the adequate levels of adherence required to ensure sustained viral suppression, even though current ART regimens are considered easier to conform to than those of the past5. Poor adherence can jeopardize the effectiveness of treatment because it reduces the immunological benefit, increases the hazards of hospital admissions, and increases the hazard οf longer duration of hospitalization6.
Adherence is acknowledged as a complex behavior influenced by a wide range of factors that can be categorized into socio-demographic, health-related, patient-related, treatment-related, and interpersonal factors7,8. Healthcare providers need information on these factors that significantly affect adherence to ART to prepare and support patients to obtain and maintain good levels of adherence2. Adherence to ART, a crucial determinant and success or failure predictor of treatment outcomes, has become a public health issue9. Adherence has been shown to be a predictor of drug resistance2, recovery of CD4+ cell count10, and survival11. In addition, it has been shown that important factors associated with deterioration of adherence are poor social support12, use of drugs13 and individual characteristics, such as age14 and level of education15.
Although there is considerable information in the literature regarding adherence to HIV ART, there is no available data for Greece. This information is of particular interest due to the recent socio-economic burden experienced by Greek citizens. The purpose of the present study was to investigate in a cohort of HIV patients from northern Greece: i) the proportion of patients who adhere to ART, ii) the characteristics of patients associated with reduced levels of adherence, and iii) the influence of several socio-economic parameters on adherence.
In the present study, the fundamental principles of an observational cross-sectional study were implemented, as the aim was to record the level of adherence and to investigate the relationship of adherence with perceived social support for seropositive individuals. Independent variables were socio-demographic characteristics of patients and perceived social support of seropositive individuals, while adherence to antiretroviral treatment was considered a dependent variable. The survey was conducted from November 2018 to November 2019. The study’s research protocol was approved by the Bioethics and Ethics committee of the School of Medicine of Aristotle University of Thessaloniki (decision No 158, date: 21/11/2018).
Study population and sample
One hundred and twelve HIV seropositive individuals, residents in northern Greece, were selected to participate in the study. The sampling method used in the present study was convenience sampling. The HIV seropositive patients who participated were users of the health care services of Special Infections Units in hospitals of Athens, in the Special Infections Unit of the AHEPA University Hospital, and the National Public Health Organization. The selection of individuals was made randomly during their visit to an appointment for counseling information and/or support. Through a consent form, the patients were informed about the type and purpose of the study, as well as about the anonymity and confidentiality of participants. The inclusion criteria of participants in the study were: a) age ≥18 years, b) no prior diagnosis of mental disorder, and c) sufficient knowledge of writing and reading of the Greek language.
The simplified medication adherence questionnaire (SMAQ) was utilized to evaluate adherence to ART16. The questionnaire consists of six questions with predetermined short answers that patients should answer. Based on individual responses, each patient was classified as either adherent or non-adherent to ART. The SMAQ scale has been translated and validated in the Greece sample and showed a high reliability and validity17. Perceived available support questionnaire (PAS), a scale of the Berlin Social Support Scales18, was used to evaluate the perceived social support of people with HIV. The scale consists of seven questions, four of which describe perceived emotional, social support, and the remaining three indicate the material support that individuals perceive to be derived from their social environment. The PAS scale has been translated and validated in a Greek sample and showed high reliability and validity19. Questionnaires, due to their practicality and flexibility, are able to identify the concerns of patients. Although patient self-report overestimates 20 % the level of adherence, this method still has significant interpretive ability regarding viral load measurements20. Self-reported non-adherence is significantly associated with virological failure21.
IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY) was used for the analysis of the data. Indicators such as frequency (n) and relative frequency (%) were used to represent the results of the SMAQ tool to illustrate the degree of adherence to antiretroviral therapy. Both univariate analyses, using the non-parametric chi-square test, and multivariate analysis, using logistic regression analysis, were used to investigate which characteristics predict the adherence to antiretroviral therapy. Also, logistic regression analyses were used to investigate the effect of social support on antiretroviral therapy adherence. The significance level of the research was set at α =0.05. Results are presented as mean ± standard deviation.
The demographic characteristics of the 100 (89.3 %) male and 12 (10.7 %) female participants are presented in Table 1. The mean age of the 112 participants was 37.14 ± 7.7 years with the sample’s age ranging from 25 to 63 years. The majority of the sample resided in a large urban area (n = 79, 70.5%) and were single (n =78, 69.6 %). Regarding the participants’ educational level, 40.2 % (n =45) were high school graduates and 33 % (n =37) were university graduates. A smaller number were either primary/middle school graduates (n =8, 7.22 %) or Masters/Ph.D. holders (n =22, 19.7 %). Regarding the employment status of patients, 65.2 % (n =73) of them were working at the time of the survey.
Analysis of the data showed that 45.5 % (n =51) of patients received regimens of Integrase Inhibitors (IIs) + Nucleoside Reverse Transcriptase Inhibitors (NRTIs), and 30.4 % (n =34) NRTIs + Non-NRTIs (NNRTIs). A smaller proportion of patients received Protease Inhibitors (PIs) + NNRTIs (n =15, 13.4 %), IIs + NNRTIs (n =8, 7.1 %), IIs + PIs (n =3, 2.7 %) and PIs + NTRIs (n =1, 0.9 %). The mean time from diagnosis was 65.45 ± 53.42 months, with a range from eight to 378 months. The majority of the patients had been diagnosed during the preceding ten years (less than 120 months). The average time from ART initiation was 48.63 ± 50.58 months, ranging from six to 372 months. The majority of the sample had commenced treatment during the preceding eight years (less than 96 months). Also, 71.7 % (n =43) of patients had changed their antiretroviral medication once, 16.7 % (n =10) twice and 10 % (n =6) three times.
Use of substance and smoking
Analysis of the responses revealed that 48.2 % (n =54) of patients had used marijuana, 25 % (n =28) cocaine, 14.3 % (n =16) ketamine, and 13.4 % (n =15) amphetamines. With respect to tobacco, 47.3 % (n =53) did not smoke, 19.6 % (n =22) reported smoking up to ten cigarettes daily, and 26.8 % (n =30) ten to 20 cigarettes per day.
Adherence to ART
Analysis of the data from SMAQ for adherence to ART is presented in Table 2. Results indicate that 59.6 % (n =62) of patients had forgotten to take their medication at least once; 14.3 % (n =15) were careless at times about taking their medication; 18.8 % (n =21) did not take their medication over the last weekend; 27.7 % (n =31) of patients reported that they had not taken their medication for three or more days. A patient was categorized as non-compliant should a non-compliance answer was given to any of the questions, and (in quantification terms) should the patient had missed more than two doses in the preceding week or had not taken any medication for more than two days during the preceding three months. The results showed that 58.93 % (n =66) of patients were found to be nonadherent to ART.
The analysis of the data of the PAS questionnaire, for the evaluation of the Social Support Scales, revealed that the average of the dimension assessing emotional support was 3.11 ± 0.66 [95 % confidence interval (CI): 2.98-3.23] and the mean value of dimension assessing instrumental support was 3.20 ± 0.74 (95 % CI: 3.06-3.34). The mean of the individual score can range from one to four; the higher the score, the higher the level of social support they perceive to be. These results show that participants had from high to very high emotional and instrumental support.
Influence of demographic parameters on adherence to ART
Analysis of the data from the investigation regarding the influence of the demographic parameters on adherence to ART is presented in Table 3. It was revealed that there was a significant dependence of adherence to ART related to the place of residence, χ2 (2) =7.561, p =0.023, and the educational level, χ2 (3) =12.131, p =0.007. The results show that patients residing in a provincial town are more likely to fail to comply with ART. Moreover, results showed that most post-doctoral/Ph.D. patients were adherent to ART compared to primary, middle school, high school, and university graduates. Results from the logistic regression analysis revealed a significant effect of educational level, b =0.487, p <0.019 More specifically, those with a higher educational level have a 1.068 (95% CI: 1.309-2.646) higher likelihood of adhering to ART than those with a lower educational background (Table 4).
Influence of the use of narcotic substances on adherence to ART
Analysis of the chi-square independence test data from the investigation of the influence of narcotic substances on adherence to ART are presented in Table 5. It was revealed that there was a negative dependency between adherence to ART and use of marijuana: χ2 (1) =12.447, p <0.001; cocaine: χ2 (1) =8.313, p =0.004; ketamine: χ2 (1) =3.843, p =0.05; all of the above narcotics in general: χ2 (1) =12.613, p <0.001. The frequency of marijuana use during the preceding 12 months also had a negative dependency effect on adherence to ART: χ2 (4) =18.656, p <0.001 (Table 5).
The role of social support on adherence to ART
Analysis of the data by the logistic regression analysis from the investigation of the influence of social support on adherence to ART is presented in Table 6. It was revealed that there is a significant effect of actual support, b =1.630, p =0.005, on adherence to ART. In contrast, no significant effect of emotional support on adherence to ART was observed: b =-0.795, p =0.169. More precisely, the augmentation of the instrumental support by one unit resulted in a 5.1 increase (95% CI: 1.634-15.938) in the likelihood of adherence to ART.
The challenge for treating HIV patients is adherence to ART22. Adherence is the extent to which a patient takes a drug in the manner recommended by the healthcare provider1 and has been recognized as an essential factor associated with the success of antiretroviral treatment11. The results showed that a considerable proportion of participants in the cohort from northern Greece were found to be nonadherent to ART. More specifically, it was observed that approximately six out of ten participants were nonadherent to ART. Individual statements from the SMAQ tool indicated that the most common reason for non-adherence as reported by participants was forgetting to receive ART. The rate of non-adherence is exceptionally high compared to similar studies in the international field, which have shown that the rate of non-adherence in North America is 48 %, in Africa 17 %, in Asia 17 %, in Europe 38 %, and in south America 38 %7,23,24. This difference may be attributed to the recent socio-economic burden imposed on the Greek citizens over the last decade. Analysis of the data showed that factors related to adherence to ART were the place of residence, the educational level, the use of narcotic substances, and social support. An important finding of the study was to highlight the relationship between narcotics and adherence to ART. The results showed that the use of marijuana, cocaine, and ketamine, as well as the increase in the frequency of marijuana use, significantly reduced the likelihood of adherence to ART. The influence of narcotics on adherence to ART has been confirmed in several studies13,25,26. Research results have shown that increased social (emotional and practical) support is associated with increased adherence to ART. Similar results have been found in studies investigating the role of social support in enhancing adherence12,27,28. Social and psychological variables are among the most important factors affecting adherence to a treatment27.
In conclusion, this study identified important factors such as place of residence, level of education, use of narcotic substances, and social support that affect short-term adherence for a cohort of HIV patients from northern Greece.
Limitations of the study and future work
The study was conducted using a convenience sample, and the findings may not be generalizable to other clinical settings or a broader range of patients receiving ART. In addition, this study was based on a cross-sectional study design. Therefore, the time relationship between the variables studied is unknown, so that no causal relationship can be established. In addition, cross-sectional research in this study could only measure the level of adherence at one-time point, while medication adherence is dynamic and participants’ behavior may change over time. A patient who has been identified today as having complied with ART may not be compliant tomorrow. Care must be taken in interpreting the direction of causality.
The present study results, taking into account the study’s limitations, are the first reported for Greece and are in close agreement with those reported in the literature for most other countries. It is necessary to investigate factors related to long-term adherence to ART and its long-term maintenance (e.g., use of reminder tools, telemedicine). The impact of these factors on treatment outcomes may be subject to potential bias. Therefore, it would be useful to evaluate the impact of these factors using randomized controlled trials to obtain more reliable data before applying these findings to clinical practice.
Conflict of interest
Authors declare no conflict of interest.
1. Günthard HF, Saag MS, Benson CA, del Rio C, Eron JJ, Gallant JE, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel. JAMA. 2016; 316: 191-210.
2. Iacob SA, Iacob DG, Jugulete G. Improving the Adherence to Antiretroviral Therapy, a Difficult but Essential Task for a Suc-cessful HIV Treatment-Clinical Points of View and Practical Considerations. Front Pharmacol. 2017; 8: 831.
3. Bangsberg DR, Acosta EP, Gupta R, Guzman D, Riley ED, Harrigan PR, et al. Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness. AIDS. 2006; 20: 223-231.
4. Golin CE, Liu H, Hays RD, Miller LG, Beck CK, Ickovics J, et al. A prospective study of predictors of adherence to combi-nation antiretroviral medication. J Gen Intern Med. 2002; 17: 756-765.
5. Vervoort SC, Grypdonck MH, de Grauwe A, Hoepelman AI, Borleffs JC. Adherence to HAART: processes explaining adher-ence behavior in acceptors and non-acceptors. AIDS Care. 2009; 21: 431-438.
6. Mai HT, Le GM, Tran BX, Do HN, Latkin CA, Nguyen LT, et al. Adherence to antiretroviral therapy among HIV/ AIDS pa-tients in the context of early treatment initiation in Vietnam. Patient Prefer Adherence. 2018; 12: 2131-2137.
7. Kim J, Lee E, Park BJ, Bang JH, Lee JY. Adherence to antiretroviral therapy and factors affecting low medication adherence among incident HIV-infected individuals during 2009-2016: A nationwide study. Sci Rep. 2018; 8: 3133.
8. Mbengue MAS, Sarr SO, Diop A, Ndour CT, Ndiaye B, Mboup S. Prevalence and determinants of adherence to antiretroviral treatment among HIV patients on first-line regimen: a cross-sectional study in Dakar, Senegal. Pan Afr Med J. 2019; 33: 95.
9. Erah PO, Arut JE. Adherence of HIV/AIDS patients to antiretroviral therapy in a tertiary health facility in Benin City. Afr J Pharm Pharmacol. 2008; 2: 145-152.
10. Seng R, Goujard C, Krastinova E, Miailhes P, Orr S, Molina JM, et al. Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ cell count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy. AIDS. 2015; 29: 595-607.
11. Lima VD, Harrigan R, Murray M, Moore DM, Wood E, Hogg RS, Montaner JS. Differential impact of adherence on long-term treatment response among naive HIV-infected individuals. AIDS. 2008; 22:2371-2380.
12. Enriquez M, Mercier DA, Cheng AL, Banderas JW. Perceived Social Support Among Adults Struggling With Adherence to HIV Care and Treatment. J Assoc Nurses AIDS Care. 2019; 30: 362-371.
13. Camargo CC, Cavassan NRV, Tasca KI, Meneguin S, Miot HA, Souza LR. Depression and Coping Are Associated with Fail-ure of Adherence to Antiretroviral Therapy Among People Living with HIV/AIDS. AIDS Res Hum Retroviruses. 2019; 35: 1181-1188.
14. Marcus EN. The silent epidemic–the health effects of illiteracy. N Engl J Med. 2006; 355: 339-341.
15. Buscher A, Hartman C, Kallen MA, Giordano TP. Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naive HIV patients. Int J STD AIDS. 2012; 23: 351-355.
16. Knobel H, Alonso J, Casado JL, Collazos J, González J, Ruiz I, et al. Validation of a simplified medication adherence ques-tionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS. 2002; 16: 605-613.
17. Alikari V, Matziou V, Tsironi M, Kollia N, Theofilou P, Aroni A, et al. A Modified Version of the Greek Simplified Medica-tion Adherence Questionnaire for Hemodialysis Patients. Health Psychol Res. 2017; 5: 6647.
18. Schulz U, Schwarzer R. Soziale Unterstützung bei der Krankheitsbewaltigung: Die Berliner Social Support Skalen (BSSS). Diagnostica. 2003; 49: 73-82.
19. Tsimtsiou Z. Physician – patient relationship and communication: a study of attitudes and expectations in physician and pa-tients. Ph.D. thesis, School of Medicine, Aristotle University of Thessaloniki, 2008. Available at: https://thesis.ekt.gr/thesisBookReader/id/19369#page/1/mode/2up, date accessed: 4/3/2020.
20. Kabore L, Muntner P, Chamot E, Zinski A, Burkholder G, Mugavero MJ. Self-Report Measures in the Assessment of An-tiretroviral Medication Adherence: Comparison with Medication Possession Ratio and HIV Viral Load. J Int Assoc Provid of AIDS Care. 2015; 14: 156-162.
21. Bazabhe WM, Chalmers L, Bereznicki LR, Peterson GM. Adherence to Antiretroviral Therapy and Virologic Failure: A Me-ta-Analysis. Medicine (Baltimore). 2016; 95: e3361.
22. Mini KV, Ramesh A, Parthasarathi G, Mothi SN, Swamy VT. Impact of pharmacist provided education on medication adher-ence behaviour in HIV/AIDS patients treated at a non-government secondary care hospital in India. J AIDS HIV Res. 2012; 4: 94-99.
23. Kim SH, Gerver SM, Fidler S, Ward H. Adherence to antiretroviral therapy in adolescents living with HIV: systematic review and meta-analysis. AIDS. 2014; 28: 1945-1956.
24. Holstad MM, Dilorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to an-tiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav. 2011; 15: 885-896.
25. King RM, Vidrine DJ, Danysh H, Fletcher FE, McCurdy S, Arduino RC, et al. Factors associated with nonadherence to an-tiretroviral therapy in HIV-positive smokers. AIDS Patient Care STDS. 2012; 26: 479-485.
26. González-Álvarez S, Madoz-Gúrpide A, Parro-Torres C, Hernández-Huerta D, Ochoa Mangado E. Relationship between al-cohol consumption, whether linked to other substance use or not, and antiretroviral treatment adherence in HIV+ patients. Adicciones. 2017; 31: 8-17.
27. Oliveira RDS, Primeira MR, Santos WMD, Paula CC, Padoin SMM. Association between social support and adherence to antiretroviral treatment in people living with HIV. Rev Gaucha Enferm. 2020; 41: e20190290.
28. Huynh AK, Kinsler JJ, Cunningham WE, Sayles JN. The role of mental health in mediating the relationship between social support and optimal ART adherence. AIDS Care. 2013; 25: 1179-1184.