Nurse Media Journal of Nursing, 8(2), 2018, 79-85
Available Online at http://ejournal.undip.ac.id/index.php/medianers

Antiretroviral Side Effects on Adherence in People Living
with HIV/AIDS
Gede Arya Bagus Arisudhana1, Muchlis Achsan Udji Sofro2, Untung Sujianto3
1

Postgraduate Program in Nursing, Department of Nursing, Diponegoro University, Indonesia
2
Faculty of Medicine, Diponegoro University, Indonesia
3
Department of Nursing, Faculty of Medicine, Diponegoro University, Indonesia
Corresponding Author: Gede Arya Bagus Arisudhana (aryabagus08@gmail.com)

ABSTRACT
Background: Antiretroviral therapy is a lifelong treatment in people living with
HIV/AIDS (PLWHA). Adherence is the key to the effectiveness of antiretroviral therapy.
The administration of antiretroviral has some side effects that may affect patient
adherence.
Purpose: This study aimed to examine the impacts of antiretroviral side effects on
adherence in PLWHA.
Methods: This study used a correlational research design. The samples were 78 patients
receiving antiretroviral therapy at the tropical disease and infection polyclinic in a
hospital in Semarang. Purposive sampling was used to recruit the samples. Data on side
effects of antiretroviral were obtained based on the patients’ reports, while data on
adherence of pill consumption were obtained through the calculation of pills using pill
count adherence rate. The collected data were analyzed using the Fisher’s exact test.
Results: Results showed that the side effects of antiretroviral therapy influenced the
antiretroviral adherence (p<0.001). Most of the side effects of antiretroviral reported by
participants were nausea and dizziness. Some participants also reported weakness,
difficult to concentrate, and diarrhea.
Conclusion: The side effects of antiretroviral had negative impacts on patients’
antiretroviral therapy adherence. Therefore, nurses and health care providers of PLWHA
should be able to recognize and give concern on antiretroviral side effect management.
Keywords: Adherence; antiretroviral; PLWHA; side effect

BACKGROUND
HIV/AIDS is still a global health problem since it was discovered. The report of Joint
United Nations Program on HIV/AIDS (UNAIDS) in 2015 shows that the number of
people living with HIV/AIDS (PLWHA) in the world reaches 36.7 million people with
2.1 million newly infected with HIV and 1.1 million deaths due to AIDS (UNAIDS,
2016). Indonesia is among the 12 countries in the Asia Pacific region with the fastest
spread of HIV cases since 2001 up to 2015 (UNAIDS, 2016). In Indonesia PLWHA
receiving antiretroviral therapy reached 130,577 people, consisting of adults (93.5%) and
children (6.5%). Most of them were still on antiretroviral therapy (50.5%), while 2.6%
were unknown, 15.6% were died, 8.7% were out, 2% stopped, 20.6% were lost to follow
up (Directorate General of Disease Control and Environmental Health, 2016). The

Copyright © 2018, NMJN, p-ISSN 2087-7811, e-ISSN 2406-8799

Nurse Media Journal of Nursing, 8(2), 2018, 80

number of PLWHA in Semarang City was 2,926 who were eligible for antiretroviral
therapy and 987 people were still on antiretroviral therapy (Semarang City Health Office,
2015).
Antiretroviral can reduce the risk of HIV transmission, inhibit worsening of opportunistic
infections, reduce the amount of virus (viral load) to be undetectable (Directorate General
of Disease Control and Environmental Health, 2011). Treatment with antiretroviral is
associated with a number of adverse events that have short-term and long-term
consequences. The patients’ perception that the medication has side effects may cause
patients to be non-adherent to the treatment. Factors affecting non-adherence to
medication among patients are complex. Few studies found that the side effects of
treatment were associated with poor adherence and inspite of antiretroviral benefit,
adverse effects are commonly the main reasons for skipping medication (Al-Dakkak et
al., 2013).
Some studies reported high incidence of antiretroviral side-effects primarily at initial
initiation of ART (Masenyetse, Manda, & Mwambi, 2015; Teklay, 2013). Other studies
have shown that patients reporting higher adverse reactions to antiretroviral are more
likely to be non-adherent to their antiretroviral regimen. This suggests that adverse
reactions may cause treatment interruption and replacement in the prescribed regimen.
High adherence (>95%) in antiretroviral is needed to avoid viral resistance to
antiretroviral drugs, treatment failure, and lost to follow up (Ministry of Health Republic
of Indonesia, 2012; UNAIDS, 2016).
Adherence is an important determinant of successful antiretroviral therapy (Teklay,
2013). Most patients get first-line antiretroviral which can be obtained freely while the
type of antiretroviral given is based on the patient’s condition. The side effects
experienced by the patients are various with varying levels of adherence. Severe side
effects of antiretroviral may have significant impacts on adherence. Even though nursing
interventions have been given but there are still many inadequacies in the consumption
of antiretroviral drugs due to the side effects of therapy. It is critical to understand the
impacts of antiretroviral side effects on adherence in PLWHA.
PURPOSE
This study aimed to examine the impacts of antiretroviral side effects on adherence in
PLWHA.
METHODS
Design and sample
This study used a correlational research design. The samples were 78 participants who
were recruited by purposive sampling. The inclusion criteria were; patients aged >18
years, at 1st and 2nd clinical stages, use first-line antiretroviral therapy, and CD4 cell count
>200 cells/mm3 when initiating therapy. Upon enrollment and during follow-up visits,
data on socio-demographic factors were collected, including the number and doses of
antiretroviral, durations of antiretroviral used, age, and employment status. Antiretroviral
side effect symptoms were collected using the questionnaires. Participants were asked to
bring their medication bottles to each study visit. Using a pill-count form, data on the

Copyright © 2018, NMJN, p-ISSN 2087-7811, e-ISSN 2406-8799

Nurse Media Journal of Nursing, 8(2), 2018, 81

name, number of remaining pills in the bottle, and number of prescribed pills of each
antiretroviral medication were collected at each visit.
Ethical consideration
The study was conducted at the tropical and infection disease polyclinic in a hospital in
Semarang for 5 weeks in 2017. This study was reviewed and approved by the medical
research ethics committee of the Faculty of Medicine, Diponegoro University, and Dr.
Kariadi General Referral Hospital in Semarang.
Measurements
Pill counts were calculated as the number of pills taken (the number of pills dispensed –
the number of pills counted). Pill Counts Adherence Rate (PCAR) was done by counting
the number of pills or drugs that have been consumed divided by the number of
medications prescribed for a certain period and then multiplied by 100% (Wu et al., 2015).
The number of pills expected to have been taken was calculated by multiplying the daily
dose (1/2, 1 or 2 tablets) by the number of days since the date dispensed (Achieng et al.,
2013). Previous studies have found that pill count adherence assessment was able to show
different adherence in treatment and indicated the rate of adherence so that it can detect
non-adherence (Achieng et al., 2013). Adherence can be categorized into optimal
adherence in which PCAR is ≥95% and suboptimal adherence in which PCAR is <95%
(Joshi et al., 2014).
Data analysis
The univariate and bivariate analyses were applied. The univariate data were presented in
frequency and percentage for categorical data, mean and SD for numerical data. Fisher’s
exact test was used as the bivariate analysis.
RESULTS
Participants characteristics
In the first table, the average age of the participants was 37.63 years with an average
antiretroviral treatment duration of 4.13 years. Participants in this study were dominated
by men as many as 51 (65%) people, and 51 (65%) participants had jobs. The side effects
of antiretroviral experienced by participants were mostly dizziness (52.9%) and nausea
(47.1%).
Table 1. Participants’ characteristics (n=78)
Variable
Age
Durations of antiretroviral used
Level of adherence
Gender
Male
Experienced side effects
Not experienced side effects

Frequency (%)
78 (100)
78 (100)

Mean±SD
37.63 ± 10.075
4.13±3.188
88.77±3.35

51 (65)
22 (28)
29 (37)
27 (35)

Copyright © 2018, NMJN, p-ISSN 2087-7811, e-ISSN 2406-8799

Nurse Media Journal of Nursing, 8(2), 2018, 82

Variable
Female
Experienced side effects
Not experienced side effects
Employment Status
Working
Not Working
Kind of side effects (SE)
Gantrointestinal SE
Nausea
Vomiting
Diarrhea
Abdominal bloating
Central nervous SE
Dizziness
Insomnia
Difficult to concentrate
Others SE
Limp
Rash
Drowsiness

Frequency (%)
12 (15
15 (20)

Mean±SD

51 (65)
27 (35)

16 (47.1)
10 (29.4)
3 (8.8)
3 (8.8)
18 (52.9)
6 (17.6)
7 (20.6)
6 (17.6)
8 (23.5)
7 (20.6)

Side effects on antiretroviral adherence
Table 2 explains the number of participants who experienced antiretroviral side effects as
many as 34 (44%). Two participants had optimal compliance (2.5%) and 32 participants
(42%) had suboptimal compliance. Participants who did not experience antiretroviral side
effects but had optimal adherence were 35 (45%) and suboptimal were 9 (11.5%). The
correlation between drug side effects and adherence to antiretroviral medication showed
a p-value <0.001; with a coefficient correlation 0.590 (59%).
Table 2. Side effects on antiretroviral adherence (n=78)
Side Effect
Experienced (%)
Not experienced (%)
Total

Adherence
Optimal (%)
Suboptimal (%)
2 (2.5)
32 (41.0)
35 (45.0)
9 (11.5)
37 (47.5)
41 (52.5)

Total (%)
34 (44)
44 (56)
78 (100)

r

p

0.590

<0.001

DISCUSSION
The results of this study indicate there were 34 participants who experienced side effects
after taking antiretroviral, 12 females and 22 males. A consistent finding explains that
female sex has been shown to be at a higher risk factor for clinically relevant adverse drug
reactions (Anderson, 2008). To assess the side effect of antiretroviral drugs, the patients’
own report on adverse effects was used. After initialization of antiretroviral treatment
subjects reported experiencing side effects such as dizziness and nausea. The mean level
of adherence is reported to be in value 88.77% (Table 1). High adherence (>95%) is
needed to prevent treatment failure (Ministry of Health Republic of Indonesia, 2012);
UNAIDS, 2016).

Copyright © 2018, NMJN, p-ISSN 2087-7811, e-ISSN 2406-8799

Nurse Media Journal of Nursing, 8(2), 2018, 83

This study showed correlations between side effects and nonadherence to antiretroviral.
The correlations between side effects on adherence of antiretroviral was shown in Fisher’s
exact test with p-value <0.001. The level of correlation shown by a coefficient correlation
0.590. This suggests that drug side effects may explain its effect on non-adherence
consuming ARV as much as 59%. Severity of medication adverse effects was related to
an increased nonadherence. This is consistent with other studies that identified adverse
effects as a predictor of nonadherence (Okoronkwo, Okeke, Chinweuba, & Iheanacho,
2013; Rudy, Murphy, Harris, Muenz, & Ellen, 2009; Wakibi, Ng, & Mbugua, 2011). The
result of this study is consistent with the conceptualization of adherence as a multifaceted
construct and influenced by a wide range of dynamic factors. This current study
contributes to the understanding of the correlations between side effects and adherence to
antiretroviral by identifying specific adverse effects related to nonadherence.
Drug-induced side effects are more common in PLWHA than in the general population.
Side effects can be caused by immune hyperactivation factors, changes in metabolism in
the body, cytokine profile, oxidative stress, and genetic predisposition (Latif, Maria, &
Syafar, 2014). Antiretroviral side-effects generally occur within the first three months of
treatment, but not all PLWHA will experience adverse effects after taking antiretroviral
drugs (Latif et al., 2014). This is in line with a study conducted in Nigeria suggesting that
drug side effects are more likely to occur in the first six months of treatment than with
long-standing antiretroviral therapy (Eluwa, Badru, & Akpoigbe, 2012). Another study
which is not in line with the results of this study explains that the period of time needed
to undergo therapy and the time to suffer from the disease can increase the high risk of
decreasing the level of adherence (Kammerer, Garry, Hartigan, Carter, & Erlich, 2007).
It can be caused by the patient’s perception about the medication side effects.
Thus, developing clinical interventions that address the self-management of side effects
is needed. Interventions focus on psychosocial factors and reduce risk behaviors. Studies
have shown that symptom management interventions have been effective at increasing
self-care ability in managing medication side effects with HIV+ individuals (Chen et al.,
2013). This study had certain limitation. It was performed in a small sample size, which
might influence the significant differences in the level of adherence based on patient
characteristics.
CONCLUSION
The results of this study showed that antiretroviral side effects have an impact on patient’s
antiretroviral therapy poor adherence. Antiretroviral adverse reactions were the single
most common reason for poor adherence. Therefore, healthcare providers especially
nurses should be able to recognize and give concern on antiretroviral side effect
management. Identifying risk factors for the occurrence of non-adherence is of crucial
importance to optimize the initial choice of antiretroviral regimen before initiating the
therapy.

Copyright © 2018, NMJN, p-ISSN 2087-7811, e-ISSN 2406-8799

Nurse Media Journal of Nursing, 8(2), 2018, 84

REFERENCES
Achieng, L., Musangi, H., Billingsley, K., Onguit, S., Ombegoh, E., Bryant, L., … Keiser,
P. (2013). The use of pill counts as a facilitator of adherence with antiretroviral
therapy in resource limited settings. PLoS ONE, 8(12), 1-6.
Al-Dakkak, I., Patel, S., McCann, E., Gadkari, A., Prajapati, G., & Maiese, E. M. (2013).
The impact of specific HIV treatment-related adverse events on adherence to
antiretroviral therapy: A systematic review and meta-analysis. AIDS Care Psychological and Socio-Medical Aspects of AIDS/HIV, 25(4), 400-414.
Anderson, G. D. (2008). Gender differences in pharmacological response. International
Review of Neurobiology, 83(8), 1-10.
Chen, W. T., Shiu, C. S., Yang, J. P., Simoni, J. M., Fredriksen-Goldsen, Karen I., Lee,
T. S. H., & Zhao, H. (2013). Antiretroviral therapy (ART) side effect impacted on
quality of life, and depressive symptomatology: A mixed-method study. Journal of
AIDS and Clinical Research, 4(3), 218-234.
Directorate General of Disease Control and Environmental Health. (2011). National
guidelines for clinical management of HIV infection and antiretroviral therapy in
adults (2011th ed.). Jakarta: Ministry of Health Republic of Indonesia.
Directorate General of Disease Control and Environmental Health. (2016). Statistics of
HIV / AIDs case in Indonesia first quarter of 2016 (2016th ed.). Jakarta: Ministry
of Health Republic of Indonesia.
Eluwa, G. I., Badru, T., & Akpoigbe, K. J. (2012). Adverse drug reactions to antiretroviral
therapy (ARVs): incidence, type and risk factors in Nigeria. BMC Clinical
Pharmacology, 12(7), 1-9.
Joshi, B., Chauhan, S., Pasi, A., Kulkarni, R., Sunil, N., Bachani, D., & Mankeshwar, R.
(2014). Level of suboptimal adherence to first line antiretroviral treatment & its
determinants among HIV positive people in India. Indian Journal of Medical
Research, 140(JUL), 84-95.
Kammerer, J., Garry, G., Hartigan, M., Carter, B., & Erlich, L. (2007). Adherence in
patients on dialysis: Strategies for success. Nephrology Nursing Journal: Journal
of the American Nephrology Nurses’ Association, 34(5), 479-486.
Latif, F., Maria, I. L., & Syafar, M. (2014). Efek samping obat terhadap kepatuhan
pengobatan antiretroviral orang dengan HIV / AIDS [Drug Side Effects on
Adherence to Antiretroviral Treatment among People Living with HIV/AIDS].
Jurnal Kesehatan Masyarakat Nasional, 9(2), 101-106.
Masenyetse, L. J., Manda, S., & Mwambi, H. G. (2015). An assessment of adverse drug
reactions among HIV positive patients receiving antiretroviral treatment in South
Africa. AIDS Research and Therapy, 12(1), 6.
Ministry of Health Republic of Indonesia. (2012). Guidelines for sustainable
implementation of HIV-IMS services (2012th ed.). Jakarta: Ministry of Health
Republic of Indonesia.
Okoronkwo, I., Okeke, U., Chinweuba, A., & Iheanacho, P. (2013). Nonadherence factors
and sociodemographic characteristics of hiv-infected adults receiving antiretroviral
therapy in Nnamdi Azikiwe University Teaching Hospital, Nnewi, Nigeria.
International Scholarly Research Notices AIDS, 2013, 1-8.

Copyright © 2018, NMJN, p-ISSN 2087-7811, e-ISSN 2406-8799

Nurse Media Journal of Nursing, 8(2), 2018, 85

Rudy, B. J., Murphy, D. A., Harris, D. R., Muenz, L., & Ellen, J. (2009). Patient-related
risks for nonadherence to antiretroviral therapy among HIV-infected youth in the
United States: A study of prevalence and interactions. AIDS Patient Care and STDs,
23(3), 185-194.
Semarang City Health Office. (2015). Health profile of Semarang City 2015 (2015th ed.).
Semarang: Semarang City Health Office.
Teklay, G. (2013). Adverse effects and regimen switch among patients on antiretroviral
treatment in a resource limited setting in Ethiopia. Journal of Pharmacovigilance,
1(4), 1-5.
UNAIDS. (2016). Prevention Gap Report 2016. Geneva. Retrieved from
http://www.unaids.org/sites/default/files/media_asset/2016-prevention-gapreport_en.pdf
Wakibi, S. N., Ng, Z. W., & Mbugua, G. G. (2011). Factors associated with nonadherence to highly active antiretroviral therapy in Nairobi, Kenya. AIDS Research
and Therapy, 8(43), 1-8.
Wu, P., Johnson, B. A., Nachega, J. B., Wu, B., Ordóñez, C. E., Hare, A. Q., … Marconi,
V. C. (2015). The combination of pill count and self-reported adherence is a strong
predictor of first-line ART failure for adults in South Africa. Current HIV Research,
27(4), 1251-1265.

Copyright © 2018, NMJN, p-ISSN 2087-7811, e-ISSN 2406-8799