Abstract
OBJECTIVE:
Hepatitis B is an important public health concern. Currently, the COVID-19 pandemic is a major challenge for health systems, and the access to pharmacologic and non-pharmacologic treatment of chronic diseases, such as hepatitis B, may have been affected due to the contingency measures. This study aimed to evaluate the access to antiviral therapy during the ongoing pandemic.
METHODS:
This was a descriptive analysis of the access to treatment for chronic hepatitis B at a tertiary-level university hospital in São Paulo, integrated with the Brazilian health system. The study was conducted from April to December 2020.
RESULTS:
Access to antiviral therapy for 225 patients was assessed. The majority of the population was male (59%). The main type of service was the Programa Medicamento em Casa (Home Medication Delivery Program), which was availed by 144 (64%) patients. Women had poorer access to antiviral therapy (56%, p<0.05), and patients registered in the HMDP (68%, p<0.05) had better access. The age group of >48 years represented 70% of the group without access to antiviral therapy. Twenty-two pharmaceutical appointments were conducted through phone calls with patients without access to antiviral therapy.
CONCLUSION:
This study contributes to the rationalization of efforts in a public health crisis through the identification of groups with the highest risk of poor access to antiviral therapy and the demonstration of the benefits of a medication delivery system.
KEYWORDS: Hepatitis B, Antiviral agents, COVID-19, Public health
INTRODUCTION
Hepatitis B is an important public health issue with significant morbidity and mortality rates. Since the beginning of the century, mortality due to viral hepatitis has increased by 22%, which is expected to increase in the absence of adequate diagnosis and treatment. Globally, hepatitis B is responsible for approximately 800,000 deaths from complications such as cirrhosis and hepatocellular carcinoma, and 3.5% of the world population is estimated to have chronic hepatitis B 1,2 . In Brazil, 9,938 new cases and 1,728 deaths from hepatitis B were recorded in 2018 3 .
The main goal of antiviral therapy against hepatitis B is to achieve viral suppression to slow disease progression and prevent complications, increasing survival and quality of life 4,5 . Currently, the Ministry of Health offers five oral drugs for the treatment of chronic hepatitis B: tenofovir (TDF), entecavir (ETV), and lamivudine (3TC) 6 . Ford et al. reported treatment adherence as one of the main factors that define the success of antiviral therapy and discussed the presence of numerous barriers, such as lack of medication. Adverse reactions can also be a barrier to adherence 2,7 . Abreu et al. identified an unsatisfactory rate of non-adherence (43%) when compared with experimental models, which associated rates below 65% with an additional 2.6 million deaths in a 15-year period. In a prospective study, for 3 consecutive years, a significant increase in the rate of adherence after health education to patients was noted 8,9 .
Since March 2020, the COVID-19 pandemic has become a global challenge to health systems. The restriction measures and mobilization of health professionals may have impaired the management of chronic diseases. Supplying medications for chronic use is a priority of health services and, by extension, of the pharmaceutical service 10,11 . The pharmacist plays an important role in fostering adherence and monitoring the efficacy and safety of current therapy to avoid unnecessary hospital visits 10,12 .
Therefore, according to the recommendations of the official entities in the State of São Paulo, the Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo instituted contingency measures on March 18, 2020, aimed at ensuring medical care to patients through the program “HC at home” with the postponement of in-person medical consultations and extension of the validity of medical prescriptions.
In the midst of the COVID-19 pandemic, access to drugs may be hampered due to the adopted contingency measures and, consequently, impair the treatment of chronic diseases.
Regular and continued use of medications is essential for the success of therapy in hepatitis B. Therefore, it is necessary to investigate the access to antiviral therapy during the pandemic period and the current public health situation.
METHODS
This was a descriptive analysis of patients undergoing treatment for chronic hepatitis B who continued and discontinued antiviral therapy, given the contingency measures adopted secondary to the COVID-19 pandemic.
This study was conducted in a tertiary-level university hospital in São Paulo integrated into the Unified Health System. Patients aged >18 years, diagnosed with chronic hepatitis B, using antiviral therapy (e.g., TDF, ETV, or 3TC), and in outpatient follow-up were included. Patients co-infected with hepatitis C and human immunodeficiency virus were excluded.
Data were collected from patients regarding the prescribed antiviral therapy (e.g., TDF, ETV, or 3TC) between October 1, 2019, and April 1, 2020, and medications were dispensed by the pharmacy from April 1 to 30, 2020, through an institutional computerized system of medical records. After confirming the withdrawal or delivery of drugs, two groups were identified: group with access to antiviral therapy and group without access to antiviral therapy (Figure 1).
Figure 1. Flowchart of the patient enrollment process.
The members of the group without access to antiviral therapy were evaluated for possible failures in the dispensing process and were the candidates for distanced pharmaceutical consultation through phone calls. The distance pharmaceutical consultation form was applied individually and recorded in electronic medical records. After 30 days from the date of consultation and registration in the institutional system, a favorable (i.e., dispensation of treatment and continuity of antiviral therapy) or unfavorable outcome (i.e., probable treatment abandonment) was assessed.
Quantitative variables are presented as absolute values and mean±standard deviation, and qualitative variables are presented as absolute frequency (n) and relative frequency (%). The association between qualitative variables was assessed by the chi-square statistical test, with a significance set at p<0.05.
According to the opinion no. 4.157.514 of the Research Ethics Committee of the institution, the study was exempt from the requirement of the informed consent form.
RESULTS
The study analyzed 225 patients who were prescribed antiviral therapy regarding their access to the prescribed medication in the proposed period. A total of 182 (80.9%) patients were identified to have access to the prescribed treatment, whereas 43 (19.1%) patients did not have access to the drug.
The general characteristics of the study participants are shown in Table 1. The largest percentage of the population is male (59%). The mean age was 55.11±14.20 years. The most prescribed drug was tenofovir, being given to 181 (80.4%) patients. The main type of care in the pharmacy was the Home Medication Delivery Program (HMDP), an institutional program for the delivery of medicines at home, to 144 (64%) patients.
Table 1. General characteristics of patients with chronic hepatitis B treated with antiviral therapy at an outpatient gastroenterology clinic.
| Characteristics | Total (N=225) | |
|---|---|---|
| Sex, n (%) | ||
| Female | 93 (41.33) | |
| Male | 132 (58.67) | |
| Age (years), mean±SD | 55.11±14.20 | |
| Medications, n (%) | ||
| Tenofovir | 184 (81.78) | |
| Entecavir | 36 (16.00) | |
| Lamivudine (tablet) | 3 (1.33) | |
| Lamivudine (suspension) | 2 (0.89) | |
| Care offered by pharmacy, n (%) | ||
| In-person | 81 (36) | |
| Home medicine program | 144 (64) | |
SD: standard deviation.
When analyzing the association between gender and access to antiviral therapy (Table 2), we confirmed that women had less access than men to antiviral therapy (56 vs. 44%, p<0.05) during the study period.
Table 2. Comparison of groups with and without access to antiviral therapy by sex.
| Sex | With access to antiviral therapy | Without access to antiviral therapy | p-value | ||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Female | 69 | 38 | 24 | 56 | 0.031 |
| Male | 113 | 62 | 19 | 44 | 0.031 |
Similarly, when comparing the groups with and without access to antiviral therapy regarding the type of care, access was higher in the group that received the drug through the HMDP, corresponding to 68% (p<0.05) among those who had guaranteed access to antiviral therapy (Table 3).
Table 3. Comparison of groups with and without access to antiviral therapy by care offered.
| Care provided by pharmacy | With access to antiviral therapy | Without access to antiviral therapy | p-value | ||
|---|---|---|---|---|---|
| N | % | N | % | ||
| In-person | 58 | 32 | 23 | 53 | 0.007 |
| Home medicine program | 124 | 68 | 20 | 47 | 0.007 |
The analysis of the group without access to antiviral therapy revealed that 30% experienced access failure due to the inefficiency of the measures during the pandemic. The remaining 70% was attributed to patient non-adherence. The age group of 48–77 years corresponded to 70% of the patients in the group without access to antiviral therapy.
The pharmaceutical consultations conducted from August to December 2020 recorded the reasons reported by 22 (47%) of the 43 patients without access to antiviral therapy (Table 4): 9 (41%) did not reside in São Paulo (capital); 15 (68%) mainly used public transportation; 14 (64%) had remaining medications at home; and 5 (23%) had a “fear of leaving home.”
Table 4. Distance pharmaceutical consultations and responses from patients in the without access to antiviral therapy group (n=22).
| Remote pharmaceutical consultations | n | % | |
|---|---|---|---|
| Performed | 22 | 51 | |
| Not performed | 21 | 49 | |
| In which city do you currently live? | Sao Paulo | 11 | 50 |
| Other | 11 | 50 | |
| How long does it take you to travel to the Hospital das Clínicas? | 30 min | 1 | 5 |
| 1 h | 11 | 50 | |
| >1 h | 10 | 45 | |
| What means of transportation do you use to travel to the Hospital das Clínicas? | Own | 7 | 32 |
| Public | 15 | 68 | |
| Do you live alone? | Yes | 10 | 45 |
| No | 12 | 55 | |
| What medication are you using for the treatment of chronic hepatitis B? | TDF | 13 | 59 |
| ETV | 6 | 27 | |
| 3TC | 0 | 0 | |
| Don’t know | 3 | 14 | |
| Are you responsible for your pharmacotherapy? | Yes | 22 | 100 |
| No | 0 | 0 | |
| You were not given the drug in April for the treatment of chronic hepatitis B.Why did you not come to the Hospital das Clínicas to receive the drug? | Fear of leaving home | 5 | 23 |
| Strictly complied with the social isolation recommendations | 2 | 9 | |
| I didn’t know the pharmacy was open | 0 | 0 | |
| I used leftover drug at home | 14 | 64 | |
| Distance from hospital | 0 | 0 | |
| Lack of transportation | 1 | 5 | |
| Other | 0 | 0 | |
| Did you have to seek emergency medical care with symptoms of COVID-19? | Yes, needed hospitalization for >24 h | 1 | 5 |
| Yes, but did not need hospitalization | 2 | 9 | |
| No | 19 | 86 | |
| Remote post-consultation situation | Continue antiviral therapy | 20 | 91 |
| Failure to access/likely abandonment | 2 | 9 |
DISCUSSION
The data from this study were collected at the beginning of the COVID-19 pandemic, in which there were numerous changes in social mobility due to the establishment of control measures, particularly social distancing 13 . The results indicate the difficulty of access to medications for a significant proportion of patients.
In a survey conducted between May and June 2020 in Nigeria among study participants with chronic conditions, there was an increase from 10.6 to 35.2% in patients who had difficulty obtaining access to medications 14 . In Italy, the impact of COVID-19 on the management of liver diseases, including viral hepatitis, was reported, and in 23% of the patients, the onset of viral hepatitis treatment was postponed 15 .
Medication access hampered by the COVID-19 pandemic is an additional challenge to the WHO’s target of eliminating viral hepatitis 1 . Mobility restrictions and suspension of medical care during this pandemic may have contributed to poor access. In a survey by the World Hepatitis Alliance, 52% of frontline health professionals reported that patients undergoing treatment for viral hepatitis did not have access to the drug 16 .
Levorato et al. reported that women, in general, more frequently seek health services 17 . In the United States and other English-speaking European countries, men exhibit less compliance than women on the recommendations for social distancing, and those aged >45 years exhibited greater adherence to social distancing measures during this pandemic 18 . In this study, females and patients aged >48 years were predominant in the group without access to antiviral therapy, which may be related to better adherence to pandemic measures.
The difficulty of access was greater in those who receive the drug in person at the pharmacy, as well as in the age groups of 41–50 and 61–70 years. These data may be related to the context of the pandemic and restriction measures. The study does not exactly provide the reasons for not accessing the drug but suggests that the number of reduced medical visits and strict compliance with social distancing may have influenced the findings. The generalizability of our results is subject to limitations such as the limited study duration and lack of data regarding the consequences of the COVID-19 pandemic on disease progression. Further investigations involving the same study population are required.
CONCLUSION
The findings from this study can contribute to the identification and monitoring of high-risk populations and those with potential difficulty in accessing treatment during a public health crisis. The efficiency of the established pandemic contingency plans was not evaluated; however, beneficial results were evident in the drug delivery system that can be expanded in similar contexts to ensure access to all patients.
ACKNOWLEDGMENTS
MRB thanks the Ministry of Health for the residency grant (Hospital and Clinical Pharmaceutical Care). SKO thanks the National Council for Scientific and Technological Development—CNPq (PQ 308609/2018-2).
Footnotes
Funding: none.
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