Factors associated with non-adherence to Antiretroviral Therapy among HIV infected adolescents at Guji zone Health Facilities, South Ethiopia

DOI: https://doi.org/10.21203/rs.3.rs-108419/v1

Abstract

Background: Suboptimal adherence results in inadequate drug exposure and increases the likelihood of viral replication and resistance, limit future therapeutic options. A high level of adherence is very crucial to maximize the usefulness of antiretroviral therapy. This study aimed to examine factors associated with non-adherence to antiretroviral therapy among adolescents in Guji Zone, South Ethiopia.

Methods: Institution based case-control study design was employed on adolescent clients on antiretroviral therapy in the ART clinic of Guji zone health facilities from 26 February to 20 April 2018. Cases and controls were recruited by a consecutive sampling method. Bivariate and multivariable logistic regression was done using SPSS version 20 at 95% Confidence Interval (CI) and a precision of 5%.

Results: A total of 297(101 cases and 196 controls) adolescents on ART participated in this study. Being rural residents AOR 1.9(1.1-3.6), Living with unmarried/widowed and separated caregivers AOR 2.1(1.2-3.8), living with unemployed caregivers AOR 4.2(2.0-8.9), not disclosing HIV Status AOR 5(2.8-9.4), having symptom of depression for adolescents AOR 2.7(1.5-4.9), not using reminding methods AOR 2.4(1.2-4.8) and Uses of other drugs besides ART AOR 2.6(1.5-5.0) were found to be independent factors associated with non-adherence to ART among adolescents.

Conclusion: -Residence area, caregiver marital status, sources of income for the family, disclosure status, depression status, uses of reminding methods, and uses of other drugs besides ART were factors associated with non-adherence to antiretroviral therapy among adolescents. Support from peers and family can promote adolescent's adherence, as it buffers the stress associated with the illness, encourages optimism, reduces depression, and improves healthful behaviors. The provision of health education on the importance of treatments and needs for adherence should be encouraged. Uses of reminding methods, continuous monitoring of clients on ART regarding the uses of medications other than antiretroviral therapy is important.

Background

WHO defines adherence as the extent to which a patient’s behavior coincides with medical or patient follows medical instructions (1). Poor adherence to treatment in HIV is extremely complex both in its causes and its capacity to negatively affect patient outcomes, treatment options, and healthcare costs. Achieving such high rates of adherence is very challenging to such patients, because their regimens include multiple, often expensive medications that have complex dosing schedules and may cause food interactions and side effects that result in poor tolerability (2).

Globally, an estimated 2.1 million adolescents are living with HIV in 2016, among which 150 adolescents dying from AIDS-related causes every day. This report emphasizes that between 2000 and 2015, annual AIDS-related deaths declined for all age groups except adolescents, where mortality more than doubled from 18,000 to 41,000 per annual (3).

AIDS is the leading cause of death among adolescents in Africa and the second most common cause of death among adolescents globally (4) Adolescents (10–19 years) continued to be vulnerable, both socially and economically, to HIV infection despite efforts to date. This is particularly true for adolescents especially girls who live in settings with a generalized HIV epidemic or who are members of key populations at higher risk for HIV acquisition or transmission through sexual transmission (5).

In sub-Saharan Africa (SSA), adolescent girls and young women accounted for 25% of new HIV infections among adults. The reason for the vulnerability in sub Saharan region were  Harmful gender norms and inequalities, insufficient access to education and sexual and reproductive health services, poverty, food insecurity and violence, are at the root of the increased HIV risk of adolescent girls(6). Two out of three newly infected adolescents aged 15-19 years were girls in SSA. As a reason of successful scale up and effectiveness of antiretroviral therapy (ART), children living with HIV are surviving and growing into adolescence. This increasing population requires ongoing support to remain in care and adhere to ART, as well as to manage the changes related to adolescence (7).

Ethiopian adolescent communities today face many health-related challenges, and their lives vary considerably from those of their parents, grandparents and other relatives. A number of behaviors lead to increased risk of getting HIV/AIDS among adolescents in Ethiopia, were unprotected sexual intercourse and multiple sexual partners (8). Regarding factors related with occurrence of HIV on adolescents, different factors that can lead to the occurrence of HIV/AIDS in adolescents are biological, transactional sex, violence, limited access to education and lack of access to service  are some  of the factors contributing for acquisition of HIV among adolescents globally (9). Adolescents represented the fastest growing age group of people living with HIV (PLHIV), accounting for 5.9% of the burden of HIV that underscores the need for greater understanding and suitable adaptation of HIV care and treatment services. Sustaining optimal ART adherence in adolescents (ALHIV) has emerged as a major healthcare challenge, fundamentally due to regimen complexity and adherence efficacy (10).

In Ethiopia studies done on ART Adherence reported different level of adherence ranging from 0-100%) (11–15) in study done in Addis Ababa, revealed that accounting for average nonadherence  rate of 26.5%(11).Another study in the same area among adolescent reported a self-reported nonadherence level as 20.9% (12).  Although the potential negative effects of poor adherence are known, in patients with HIV, adherence takes on particular importance as adherence may impact not only viral suppression, but also the emergence of permanent treatment resistance. Treatment-related factors, patient-related factors, provider-related factors, and healthcare system–related factors may all impact adherence (13).  Therefore, the aim of this study was to assess factors associated with non-adherence to ART among adolescents patients in Guji zone Oromia Region,Ethiopia.

Methods

A case-conrol study was conducted from  February 26 up to April 20/2018 at Guji zone Public health facilities which is found at south eastern part of Ethiopia 600km away from Addis Ababa. The total estimated  population of  the Guji  zone is approximately 1,432,527, of whom 358,131 are adolescents aged (10-19). In Guji zone there are 4566 peoples receiving ART among these 463 are adolescents aged 10-19 years of age accounting 10.14% of the total peoples on ART services at ART centers in the zone during study period.  Both first line and second line treatment were available in the zone ART centers. Total number of peoples newly infected and enrolled to ART in 2016/7 (2009 E.C) were 753 from these 6.4% were adolescents of which 89.6% were girls (14).

Study sample

Those Adolescent clients on ART for at least three months at the selected ART Care Centers were included in the study.. The sample size of the study was calculated by Epi-Info™ 7 software Statcalc program. Variables that are used to calculate sample size are disclosure status, felt depressed, gender, types of health facility, WHO staging ( 3 and 4), experienced ART side effect, distance of health facility. Sample size was calculated by using double population proportion formula. The expected prevalence of exposure among controls felt depressed 3.3% and prevalence of cases with exposure felt depressed 13.1% from study conducted in Malawi considering 5% level of significance, 80% power of the study and 2:1 controls to case ratio. Accordingly, the the largest sample size selected for this study involved case 101 and control 196, total 297  adolecents taking ART from documentation durind the study period. Purposively Sampled 6 government health facilities (2 hospitals and 4 health centers) based on number of adolescent on ART at health facilities (those having >5 clients) were included in this study. From  purposively selected health facilities,  the total adolescents  on  ART were four hundred twenty one. Then the calculated sample size were distributed to the selected health facilities using proportional to population size based on total adolescent on ART at each selected clinic. In this allocation, adolescents visited to ART clinic at respective health facilities during data collection period were approached.  Based on these the recruited health facilities were Shakiso Health Center with 275 clients(case=67, control=128),  Megado Health Center with 54 clients(case=7, control=14), Adola General Hospital with 35 clients(case=8, control=17), Negelle General Hospital with 30 clients(case=13, control=24), Adola Health Center with 21 clients(case=5,control=10) and Haraqalo Health Center with 6 clients(case=1, control=3) were included based number of adolescents on ART in these facilities during data collection period. Cases: Adolescents taking  ART doses those who missed doses completely or single missed dose of 3 or 7 days recall or those who  have less than 95% adherence ( missing >2 doses of 30 doses) (15,16)  

Control: Adolescents taking ART doses those who take doses (95% or more adherence = missing ≤2 doses of 30 days doses or no missed  dose on 3 or 7 days recall (15,16)

Data collection Procedures

The data were collected using  Semi- structured questionnaire constituted eight items relating to Socio-demographic related factors, including Sex ,Age , Residence,  Religion, Marital status ,Educational status, Occupational status, Income. The second section constituted seven  questions relating to Psychosocial related factors, including Presence of depression, family member with HIV, Disclosure of HIV status, Stigma and Discriminations, Family support , Alcohol/substance use and perception towards ART. The third section constituted  eight  questions relating to Disease-related factors, including too many pills, Side effect of the drugs, Scheduling problem, Frequency of daily doses, Length of the treatment, CD4 count, WHO stage, Other co-morbidity. The four-section constituted  six  questions relating to Health care delivery systems related factors, including Healthcare facilities (types), Patient provider’s relationship, Health care providers’ experience, Health education/information, Provision of privacy, distance of health facility. The adherence questionnaire was prepared from AIDS Clinical Trial Group (ACTG) and by reviewing different literature conducted in Ethiopia and sub-Saharan Africa. The patient health questionnaire (PHQ9) with 9-items on which score ranges from 0 to 27 was used to assess the depression of the study participants. Individuals up on their response categorized into five categories as (no depression, mild depression, moderate depression, moderately severe depression and severe depression) and then dummy coded as not having symptom of depression and having symptom of depression(17). Data were collected by four BSc Nurses and supervised two BSc nurses after two days trained on the objectives, data col­lection techniques, data quality, and interview techniques for this study. Data collections were conducted on the arrival of the client to service provision point in separate ART room for privacy issue and controls were recruited after case.  The questionnaire was translated into local languages (Afan Oromo and Amharic) then retranslated back to English to maintain consistency by language experts of both languages. The collected data were checked and cleaned for its completeness before entering into Epidata version 3.1.1 software by principal investigator. Missing values and outlier were checked before analysis by running descriptive analysis.

Data analysis procedures

After collecting the data were cleaned, coded, and entered to Epidata version 3.1. Data were checked for completeness and uniformity before entry in to Epidata.  Analysis was by using SPSS version 20 statistical package. Descriptive analysis was conducted and the result was displayed in the form of tables, charts. Then binary logistic analysis was conducted to identify candidate variables for multivariable analysis. Independent variables having p. value < 0.25 were selected as candidate variables for multivariable logistic regression. Multicollinearity between independent variables was checked by logistic regression standard error coefficient (SE) and checking for variance inflation factors and tolerance. Backward stepwise multivariable logistic regression analysis was conducted in order to identify factors independently associated with the non- adherence. The Hosmer and Lemeshow goodness of fitness of the model were also checked. P-value < 0.05 was used to decide whether there was statistical significance or not.

Ethical consideration

The study protocol was reviewed and approved by the Jimma University Research Institutional Review Board(IRB). An official letter of cooperation was obtained from the institute of Health to Zonal Health Offices(Guji Zone) and permission was secured from the Guji Zonal Health Offices directors. Informed verbal consent was obtained and confidentiality was kept by avoiding the patient identifier like name and patient medical record number from questionnaire.

Results

A total of adolescents who are on ART (101 cases and 196 controls) were participated in the study making the response rate 100%. The mean age of control participants was 14.9 years with SD of 2.8 years while the mean age for case participants was 15 years with SD of 2.8 years. About 58(57.4%) cases and 119(60.7%) controls were Females. (table 1) .

Table 1: - Socio-demographic Characteristics of Adolescent on ART in Guji zone health facilities, Ethiopia, 2018.

Variables                               Categories

Cases (%) 

Controls (%)

Sex 

Male

43(42.6%)

77(39.3%)

Female

58(57.4%)

119(60.7%)

Age category

10-14

44(43.6%)

88(44.9%)

15-19

57(56.4%)

108(55.1%)

Residence 

Town 

56(55.4%)

124(63.3%)

Rural 

45(44.6%)

72(36.7%)

 

Religion

Orthodox 

47(46.5%)

92(46.9%)

Muslim

5(5.0%)

27(13.8%)

Protestant

45(44.6%)

72(36.7%)

Catholic

4

5

Caregivers     Marital 

 

status 

Single

17(16.8%)

22(11.2%)

Married

43(42.6%)

111(56.6%)

Divorced

19(18.8%)

40(20.4%)

Widowed

13(12.9%)

19(9.7%)

Separated

9(8.9%)

4(2.0%)

 

 

caregivers Educational

 status 

Can’t read and write

15(15%)

23(11.7%)

Able to read and write

15(15%)

26(13.3%)

 formal     education

 (grade1-8)

58(57%)

113(57.7%)

High school and above

13(4.4%)

34(17.3)

 

 

Ethnicity 

Oromo

48(47.5%)

99(50.5%)

Amhara

21(20.8%)

41(20.9%)

Tegaru

5

6(3.1%)

Sidama

22(21.8%)

41(20.9%)

Others(Gedeo, Guraghe) 

5

9(4.6%)

Caregivers Employment

 status 

Employed 

75(74.3%)

169(86.2%)

Unemployed 

26(25.7%)

 27(13.8%)

Adolescents occupational status 

 

Unemployed 

5

12(6.1%)

Drivers 

10(9.9%)

13(6.6%)

Students 

46(45.5%)

94(48.0%)

Daily laborers

13(12.9%)

33(16.8%)

Merchants

16(15.8%)

24(12.2%)

Commercial sex workers

9(8.9%)

14(7.1%)

Others (shoeshine etc.)

2

6

Adolescents Living 

condition 

Live with family

75(74.3%)

140(71.4%)

Live with other adult or children

9(8.9%)

17(8.7%)

Live alone

17(16.8%)

39(19.9%)


Clinical Characteristics of Adolescents

Majority of cases 88(87.1%) and 164(83.7%) controls were from health centers. Fifty nine (58.4%) cases and 109(55.6%) controls were categorized as WHO clinical stage II. All controls 196(100%) have greater than 95% self/caregiver reported adherence over past one month (table 2).

Table 2: Clinical Characteristics of Adolescent on ART in Guji zone health facilities, Ethiopia, 2018.

Variables(N=297)

Categories

Cases (%)

Controls (%) 

Health Facility Types

Health center

88(87.1%)

164(83.7%)

Hospital 

13(12.9%)

32(16.3%)

WHO Clinical staging

Stage I

27(26.7%)

61(31.1%)

Stage II

59(58.4%)

109(55.6%)

Stage III

13(12.9%)

20(10.2%)

Stage IV

2

6(3.1%)

ART Drug Regimen

First line

99(98.0%)

191(97.4%)

Second line

2

5

Baseline CD4 Count

<350cells/mm

31(56.4%)

60(53.6%)

>350cells/mm

24(43.6%)

52(46.4%)

Latest CD4 count

500ells/mm

26(25.7%)

26(13.3%)

>500cells/mm

72(71.3%)

152(77.5%)

self-reported adherence (30 days)

<95%

98(97%)

0

95%

3

196(100%)























Reason for missing ART drugs Among Adolescents

The reason for missing ART drugs among adolescents about 66(33.7%) controls who have missed < 2 doses in past one month recall as well as who were adherent on their 3 and 7 days recall and all cases were responded on their reason for missing ART drugs.  (figure 1).

Factors Associated with Nonadherence on Binary Logistic Regression

Unmarried/widowed/separated caregivers with COR 1.8(1.1-2.9), source of income (unemployed) with COR 2.2(1.2-3.9) and area of residence (rural) COR 1.4(.85-2.3) were found to be a candidate variables associated with non-adherence status of the adolescents from socio-demographic factors (table 3).

Table 3: Socio-demographic factors associated with non-adherence of Adolescent on ART in Guji zone health facilities, Ethiopia, 2018.

Variables

Categories

Cases (%) 

Controls (%)

COR  (95%CI)

P.Values

Sex

Male

43(42.6%)

77(39.3%)

Reference

 

Female

58(57.4%)

119(60.7%)

0.87(.54- 1.4)

0.584

Age

 

10-14

44(43.6%)

88(44.9%)

Reference

 

15-19

57(56.4%)

108(55.1%)

0.95(.58- 1.5)

0.827

Marital status

 of caregiver

Married

43(42.6%)

111(56.6%)

Reference

 

Single, widowed/separated

58(57.4%)

85(43.4%)

1.8(1.1-2.9)

0.022*

Family living

 together

Both are alive

51(50.4%)

101(51.5%)

Reference 

 

One or both dead

50(49.6%)

95(48.5%)

1.04(0.64-1.7)

0.866

Adolescents Educational status 

Attended formal

 education

71(70.3%)

147(75%)

 Reference 

 

Not attended formal education

30(29.7%)

49(25%)

1.3(0.74-2.2)

.385

Sources of 

Income

Employed

75(74.3%)

169(86.2%)

Reference

 

Unemployed 

26(25.7%)

27(13.8%)

2.2(1.2-3.9)

0.012*

Monthly Income 

<1000ETB

33(32.7%)

72(36.7%)

Reference

 

>=1000ETB

68(67.3%)

124(63.3%)

1.2(0.72-2.0)

0.48

 

Living arrangement

With Family

 

75(74.3%)

140(71.4%)

0.87(.50-1.5)

0.606

Living alone

26(25.7%)

56(28.6%)

Reference

 

Residence 

Town 

56(55.4%)

124(63.3%)

Reference

 

Rural

45(44.6%)

72(36.7%)

1.4(.85-2.3)

0.192*

* P-value less than 0.25

Psychosocial Related Factors Associated with Non-adherence to ART

Psychosocial related variables that were found to be candidate variables were, not disclosing HIV status  COR 4.6(2.7-7.7), adolescents without family support  COR 1.9(1.1-3.4), no satisfaction to family support by adolescents COR .54(0.25-1.19), adolescents/caregivers who are not using method to remind drug taking time COR 1.5(.86-2.7), have experienced  family death by adolescents with COR 1.4 (0.89-2.35), (Table 4).

Table 4: Psychosocial factors associated with non-adherence among of Adolescent on ART in Guji zone health facilities, Ethiopia, 2018.

Variables

Categories 

Cases (%) 

Controls (%) 

COR (95%CI)

P. Values

Disclosure status

Not disclosed

57(56.4%)

 43(22%)

4.6(2.7-7.7)

0.000*

Disclosed 

44(43.6%)

 153(78%)

Reference 

 

Family support

No

31(30.7%)

36(18.4%)

1.9(1.1-3.4)

0.017*

Yes

70(69.3%)

160(81.6%)

Reference 

 

Satisfaction to 

support family

No  

9(8.9%)

 30(15.3%)

 

 

Yes

92(91.1%)

  166(84.7%)

 

 

Reminder method used

Yes 

74(73.3%)

 158(%80.6)

Reference 

 

No

27(26.7%)

  38(19.4%)

1.5(.86-2.7)

0.148*

Experienced family death

One or more

50(49.5%)

  79(40.3%)

1.5 (0.89-2.4)

0.130*

No one died

51(50.5%)

  117(59.7%)

Reference

 

Depression status

Have depression

45(44.5%)

  38(19.4%)

3.3(1.9-5.7)

0.000*

No depression

56(55.5%)

  158(80.6%)

Reference

 

Internalized stigma status

Experienced

61(60.4%)

   97(49.5%)

1.5(0.95-2.5)

0.075*

Not experienced

40(39.6%)

  99(50.5%)

Reference

 

Discrimination status

Experienced

54(53.5%)

   83(42.3%)

1.2(0.72-1.9)

0.491

Not experience

47(46.5%)

   113(57.7%)

Reference 

 

                                       Substance use  in past one month

Alcohol Drinking

Yes

41(40.6%)

 43(21.9%)

2.4(1.4-4.1)

0.001*

No

60(59.4%)

153(78.1%)

Reference

 

Cigarettes Smoking

Yes

11(10.9%)

 10(5%)

2.3(0.9-5.5)

0.071*

No

90(90.1%)

 186(95%)

Reference 

 

Khat chewing

Yes

24(23.7%)

 19(9.6%)

2.9(1.5-5.6)

0.002*

No

77(76.3%)

 177(90.4%)

Reference

 










* P-value less than 0.25

Health Care Delivery System Related Factors Associated with Non-Adherence 

Only adolescents who are following drugs instruction provided by health care provider half of the time or less time with COR 1.9(1.1-3.6) was found to be candidate variable associated with adherence status from health care delivery system related factors(table 5).

Table 5: Health care delivery system related factors associated with non-adherence of Adolescent on ART in Guji zone health facilities, Ethiopia, 2018.

Variables 

Categories 

Cases (%) 

Controls

(%) 

COR (95%CI)

P.Values

Health facility 

distance 

<=5 KM

63(62.4%)

115(62.2%)

Reference 

 

>5 KM

38(37.6%)

74(37.8%)

0.94(0.57-1.5)

0.799

Duration to reach H/F

>60 minutes 

31(30.7%)

51(26%)

1.3(0.74-2.1)

0.394

<=60 minutes

70(69.3%)

145(74%)

Reference 

 

Means of travel to H/F

Vehicles/motor

68(67.3%)

124(63.3%)

Reference 

 

On foot

33(32.7%)

72(36.7%)

0.83(.50-1.4)

0.488

counseled 

No

1

2

 

 

Yes 

100(99%)

194(98.9%)

 

 

Privacy kept

 

No

3

5

 

 

Yes

98(97%)

191(97.4%)

 

 

instruction for

 drug

No

44(43.6%)

81(41.3%)

1.1(0.67-1.8)

0.711

Yes

57(56.4%)

115(68.7%)

Reference 

 

Following instruction

Mostly

76(75.2%)

168(85.7%)

Reference

 

sometimes

25(24.8%)

28(14.3%)

1.9(1.1-3.6)

0.027*

Facility types

HC’s

88(87.1%)

164(83.7%)

Reference 

 

Hospitals 

13(12.9%)

32(16.3%)

1.3(0.66-2.6)

0.432

Health professional experience 

Least experienced

6(6%)

18(9.2%)

 

 

Experienced

95(94%)

178(90.8%)

 

 








* P-value less than 0.25

Disease related factors associated with non-adherence to ART

Two variables; latest CD4 count > 500mm/cells with COR 0.47(0.26-0.87) and adolescent who use other drugs besides ART COR 2.1(1.3-3.5) were identified from disease related factors to be candidate variables  associated with non-adherence status of the adolescents ( Table 6).

Table 6: disease related factors associated with non-adherence of Adolescent on ART in Guji zone health facilities, Ethiopia, 2018.

Variables

Categories

Cases (%)

Controls (%) 

COR(95%CI)

P.Values

ART pills taken at once

1(One)

62(61.4%)

118(60.2%)

Reference

 

>2(Two) 

39(38.6%)

78(39.8%)

0.95(0.58-1.6)

0.843

Daily frequency ART

Once 

52(51.4%)

88(44.9%)

Reference

 

Twice or

 above

49(48.6%)

108(55.1%)

0.77(.47-1.2)

0.282

Duration on 

ART

<2 years

26(25.7%)

51(26%)

Reference 

 

> 2 years

75(74.3%)

145(74%)

1.0(0.57-1.8)

0.959

Baseline CD4count

<350cells/mm

31(56.4%) 

60(53.6%)

Reference 

 

>350cells/mm

24(43.6%)

52(46.4%)

1.1(0.58-2.1)

0.733

Missing

46(45.5%)

87(45.4%)

 

 

Latest CD4 

Count

<500cells/mm

26(25.7%)

26(13.3%)

Reference

 

>500cells/mm

72(71.3%)

152(77.5%)

0.47(.26-0.87)

0.017*

Missing

    3

18(9.2%)

 

 

WHO clinical 

Staging

Stage I & II

86(85.1%)

170(86.7%)

Reference 

 

Stage III & IV 

15(14.9%)

26(13.3%)

1.1(0.57-2.3)

0.707

Other drugs

 besides ART

Yes 

44(43.7%)

52(26.5%)

2.1(1.3-3.5)

0.003*

No 

57(56.3%)

144(73.5%)

Reference 

 

ART regimen

First line

99(98%)

191(97.4%)

 

 

Second line

     2

5(2%)

 

 

 *significant at p. value less than 0.25

Multivariable logistic regression Analysis

After running backward stepwise  multivariable logistic regression; Residence, Marital status of caregiver, sources of income for family, disclosure status,  depression status of adolescents, uses of reminding method and uses of other drugs besides ART were found to be significantly associated with non-adherence to ART among adolescents. Being rural resident is associated with nonadherence to ART among adolescents. Adolescents who resides in rural area have 1.9 times less like to adhere to ART compared to those residing in urban AOR=1.9(1.1-3.6). Adolescents who lives with unemployed caregivers were 4.2 times less likely to adhere to ART compared to those with employed caregivers with AOR 4.2(2.0-8.9 (Table 7).

Table 7: Multivariable Logistic Regression Analysis of factors associated with non- adherence among of Adolescent on ART in Guji zone health facilities, Ethiopia, 2018.

Factors 

Categories (N=297)

Cases (%)

Controls (%)

AOR(95%CI)

P. Values

Residence

Rural 

45(44.6%)

72(36.7%)

1.9(1.1-3.6)

0.026**

Town 

56(55.4%)

124(63.3%)

Reference

 

Uses of 

Other drugs

 besides ART

Yes 

44(43.7%)

52(26.5%)

2.6(1.5-5.0)

0.002**

No 

57(56.3%)

144(73.5%)

Reference 

 

Disclosure status of Adolescent

Disclosed

44(43.6%)

153(78%)

Reference

 

Not disclosed

57(56.4%)

43(22%)

5(2.8-9.4)

0.000**

Caregiver Marital status 

 

Unmarried/widowed/separated

58(57.4%)

85(43.4%)

2.1(1.2-3.8)

0. 012**

Married

43(42.6%)

111(56.6%)

Reference

 

Family income 

Source 

 

Employed

75(74.3%)

169(86.2%)

Reference

 

Unemployed 

26(25.7%)

27(13.8%)

4.2(2.0-8.9)

0.000**

Adolescents Depression status 

No depression

56(55.5%)

158(80.6%)

Reference 

 

Have depression

45(44.5%)

38(19.4%)

2.7(1.5-4.9)

0.002**

 Alcohol use in past one month

Yes 

41(40.6%)

43(21.9%)

1.1(0.5-2.3)

0.9

No 

60(59.4%)

153(78.1%)

Reference 

 

Reminding method

 use 

Yes

74(73.3%)

158(80.6%)

 Reference

 

No

27(26.7%)

38(19.4%)

2.4(1.2-4.8)

0.014**

Internalized stigma 

Not experienced

40(39.6%)

99(50.5%)

Reference

 

Experienced 

61(60.4%)

97(49.5%)

1.8(.98-3.1)

0.060

**factors significantly associated with nonadherence to ART at P. Value < 0.05

 

 

Discussion

The finding of this study anticipated in determining factors associated with non-adherence among adolescents living with HIV who were on ART for greater than or equals to 3 months. We found that rural residence, marital status of the caregivers (unmarried, separated/widowed), unemployed caregivers, having reported symptom of depression, not disclosing HIV status, not using memory aid to remind medication taking time and uses of other drugs besides HAART were significantly associated with non-adherence among adolescents both on binary and multivariable logistic regression analysis.

We found significant association between non-adherence and rural residence that indicates Adolescents from rural area were 1.9 times more likely to not adhere to ART compared to urban residents. This finding has agreement with studies conducted in Uganda and Kenya (18,19) as Adherence was worse among the rural compared to urban living adolescents. This finding of association between non-adherence and rural areas residence may indicate difficulties in access to health services and cost of transportation to refill their medication. Non adherence among adolescent from rural descent might emphasizes the need for more decentralization of ART provision to all facilities at the level of health centers that can be accessible by clients at their nearby health facilities.  This underlines the importance of provision of geographically closer HIV treatment services such as through mobile clinics may offer promising returns for greater ART uptake and adherence among adolescent populations.

We also found that Adolescents whose caregivers were unmarried/widowed/separated among  those who were living with care givers were 2.1 times likely to not adhere to ART compared with adolescents whose caregivers were married and living together. This finding has agreement with study conducted in Mekelle town of northern Ethiopia (20).  while the study conducted in Addis Ababa reported as Adolescents with widowed caregivers were more likely to have the adherence to ART (21). The reason for nonadherence among adolescents with unmarried caregiver might be due to family support from married couples than their counterparts. These also emphasize the potential importance of family structure, caregiver support, and caregiver involvement in adolescent adherence.

A source of income for family was also another independent factor associated with nonadherence among adolescents in our study. Adolescents whose families were unemployed were 4.2 times more likely to become non-adherent compared with adolescents whose caregivers were employed. Contrary to this finding study conducted in eastern Ethiopia reported that  being with employed caregivers increases the likelihood of non-adherence among adolescents (22).  It was not found to be associated with ART adherence status  in studies conducted in Aksum, Mekelle Northern Ethiopia and same study in Addis Ababa (21,17,20) and another systematic review on adolescent in sub-Saharan Africa reported as there were no association between caregivers employment status and adherence status of the adolescents (23,24). The reason for nonadherence among adolescent with unemployed care givers might be related with supports including financial and psychosocial supports provided to adolescents by caregivers. This may arise from lack awareness on the need for support by family to adolescents living with HIV and knowledge gap of unemployed care givers on HIV /AIDS and its treatment.

 

Disclosure of adolescents HIV status had various outcomes at the individual and interpersonal levels. At the same time, it occasionally strained adolescents’ sexual relationships, although it did not always lead to rejection. Our finding highlights the importance of the disclosure status among adolescents was strongly associated with adherence status of the adolescents, adolescent who did not disclosed their HIV status were 5 times more likely to become non-adherent compared to adolescents who had disclosed their sero-status by themselves or by their caregivers. This finding of our study also has agreement with study conducted in south wollo and Aksum northern Ethiopia (17)and study conducted in Nepal southeast Asia 25) reported as not disclosing the HIV status had significantly associated with non-adherence.  In support of our finding two studies conducted in Tanzania indicated that not disclosing HIV status has strongly associated with non-adherence to ART (26,27). In contrary to this study conducted at Tikur Anbessa Hospital Addis Ababa Ethiopia found that clients who were not aware of their HIV sero-status were more likely to adhere to ART (28).  While study conduct in Harari Regional state eastern Ethiopia found as there was no association between disclosure  status and adherence to ART (29) . The possible explanation for this finding might be as due to disclosure creates opportunities for adolescents to access adherence support and other forms of psychosocial support from family members, peers and health care providers.

Depression is common among adolescents living with HIV (ALHIV) worldwide, and has been associated with non-adherence to highly active anti-retroviral therapy (HAART), leading to poor virologic suppression, drug resistance. However, few studies have explored the relationship between depression and ART adherence among adolescents in Ethiopia. We found strong association between depression status and nonadherence as adolescents who have reported as having symptom of depression were 2.7 times likely to become non-adherent compared to adolescents without reported symptoms of depression. different studies found that those patients considered as having depression have low ART medication adherence compared with patients not having the condition, studies conducted in different parts of Ethiopia in Diredawa and Harari town (30) and  study conducted in Aksum town of northern Ethiopia reported as depressed clients have lower ART adherence 17). This finding also supported with other studies  conducted in Rwanda and Uganda that reported as care givers reported depression status of the clients is associated with ART non-adherence (31,32).

This study also revealed that uses of memory aids were also found to be associated with non-adherence. Use of communication devices as reminder tools, for example alarms, pagers, text messages and telephone calls could improve adherence to ART. Adolescents not using memory aids/ reminder methods to take medication were 2.4 times more likely to become non adherent compared to adolescents using reminding methods. This finding has an agreement with prospective study conducted in Jimma University specialized hospital southwest Ethiopia and study conducted in Nekemte referral Hospital of western Ethiopia(33,34). One of the reasons for missing ART drug in our study was simply forgetting. About 31% of the adolescent who missed their medication was due forgetting thus, uses of memory aids help adolescents and care givers to remind the medication taking schedule take/give the drug at recommended time which might in turn foster good adherence.

Another important finding of current study is uses of other drugs besides ART; we found adolescents using other drugs besides ART were 2.6 times more likely to become non-adherent compared to adolescents who were only on ART drugs. The finding is comparable with study conducted in Kenya that reported use of additional drugs beside ART increase the likelihood of non-adherence among adolescents (18). Contrary to this study conducted in Addis Ababa revealed that as uses of additional drugs cotrimoxazole besides ART increases the adherence status (35). While study conducted in south wollo of north eastern Ethiopia reported as there was no association between taking additional drugs besides ART and Adherence status (36). The possible explanation for this particular finding might be drug interaction between ART and other drugs, pill burden from non-ART and ART in combination and also the side effects both non ART and ART drugs on adolescents might lead to non-adherence among adolescents.

Finally unlike previous studies, socio-demographic factors such as sex, age did not show statistically significant associations with non-adherence of ART among adolescents. This might be due to difference in location and difference in socio economic characteristics of the study participants.

Limitation of the Study

We used to measure adolescents adherence to ART by caregivers/ self-report, which may be subject to recall bias and social desirability bias that overestimate/underestimate adherence. Generalizability of our results may be limited to the selected health facilities of the same setup, as our study participants were only those Adolescents on ART who received care during our study period.

Conclusion

We found that, living with unmarried caregivers and being rural residents were associated with non-adherence to ART. Living with unemployed caregivers was found to be strongly associated with nonadherence to ART among adolescents from socio-demographic related factors. This study also demonstrates psychosocial related factors such as having symptom of depression, not disclosing HIV status and not using reminding methods were strongly associated with non-adherence among adolescents on ART. On the other hands uses of other drugs besides ART was found to be strongly associated with non- adherence to ART among adolescents from disease related factors.

Declarations

Conflicts of Interest

The authors state that they conceive no conflicts of interest.

Authors’ Contributions

 ZKE, and LAW designed, reviewed, and analyzed the study and wrote the manuscript. BIJ actively involved in data collection, data analysis, and preparation of the manuscript.  All authors read and approved the final manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Availability of data and materials

The datasets used and/or analyzed during this study is not publicly available, but may be available from the corresponding author upon reasonable request.

Ethical approval and consent to participate

The study protocol was reviewed and approved by the Jimma University Research Institutional Review Board(IRB). Informed consent was sought from the eligible ART patients before participation in the study. Participants were informed of the study objectives, that participation was voluntary, and their right to withdraw from the study at any time.

Consent for publication

Not applicable

Acknowledgments

The authors are thankful to Jimma University,  Guji Zonal Health Office, Public Health facilities and the study participants.

ORCID iD   

Lalisa Ayele:   https://orcid.org/0000-0002-4368-0283

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