Factors Associated with Non-Adherence to Antiretroviral Therapy among HIV-Infected Adolescents at Pediatric Department of Yopougon University Hospital , Côte d ’ Ivoire

Context: The consequences of non-adherence to antiretroviral therapy (ART) are harmful in terms of morbidity and mortality among HIV-infected adolescents. There is a little data in this population in West Africa, about non-adherence to ART. Objective: To identify factors associated with non-adherence to ART in adolescents at the Pediatric Ambulatory Treatment Center (PATC) of the pediatric department of Yopougon University Hospital. Materials and Methods: A cross-sectional study was conducted from May to July 2017 among adolescents aged 10 to 19 years old at PATC of pediatrics department of Yopougon University Hospital. We have considered that adolescent was not adherent to ART when he affirm that he have not taking ART at least once in the week before the survey. A logistic regression model was used to identify factors associated with non-adherence to ART. Results: Overall 166 adolescents were included. The median age was 15 years old [IQI = 13 17 years]. They had a detectable viral load greater than 1000 copies/ml in 41.8% of cases. The rate of non-adherence to ART was 40.4%. The factors associated with non-adherence to ART were male [OR = 2.5 (CI = 1.1 10.0)], having parent widowed [OR = 7.8 (CI = 1.6 39.3)] or divorced [RC= 3.7 (IC=1.1 13.5)], CD4 inclusion rate ≥ 500 cells/ml [OR = 8.5 (CI = 1.6 45.5)] and duration on ART ≥ 10 years [OR = 8.9 (CI = 1.6 50)]. Conclusion: A rigorous therapeutic education taking into account associated factors in this study is necessary to reduce the rate of non-adherence among adolescents at PATC.


Introduction
Significant progress has been made in the fight against HIV infection since the advent of this pandemic.In fact, between 2000 and 2016, the number of new infections fell by 39% and the number of HIV-related deaths fell by a third.Access to antiretroviral treatment (ART) has saved 13 million of life in the world [1] [2].This access to ART has resulted in better survival of HIV-infected children who reach adolescence [3].Adolescents are a vulnerable population.Many physical and emotional changes normally occur during adolescence and many factors can compromise their adherence to ART [4].
Since 2013, to put an end to AIDS epidemic, UNAIDS recommends that 90% of people living with HIV know their HIV serologic status, that 90% HIV infected people receive sustainable ART and that 90% of people receiving ART have viral suppression load by 2020 [5].To achieve the third target of the UNAIDS target (virological suppression), good adherence to ART is indispensable.Adherence to ART remains a challenge in the care of adolescents living with HIV [6] [7] [8] [9].Therapeutic failure is a consequence of poor adherence to ART.It will cause persistence of viral replication.And if nothing is done we will observe the emergence of resistance to ART objectified by genotypic tests of resistance to antiretroviral molecules [9] [10] [11].There is little data in West Africa, about non-adherence to ART among HIV-infected adolescents.In order to undertake effective actions to minimize the consequences of non-adherence in HIV-infected adolescents, it is necessary to identify the barriers to ART adherence.The objective of this study was therefore to identify the factors associated with ART non-adherence in adolescents attending at the Pediatric Ambulatory Treatment Center (PATC) of the pediatric department of Yopougon University Hospital.

Materials and Methods
A cross-sectional study was conducted at the PATC of the pediatric department of Yopougon University Hospital from May to July 2017.Adolescents aged 10 to 19 years old on ART followed for at least 6 months and with updated biological status were included (viral load, CD4 count).Adolescents with severe progressive illness (requiring hospitalization) the day of the survey were excluded.We have selected a convenience sample of adolescents attending at PATC.Eligible adolescents were systematically interviewed using a standardized questionnaire administered face-to-face during the consultation to assess the level of non-adherence.An adherence counciling has been initiated for adolescents who have not good adherence to ART (about difficulty to take ART, management of drugs adverse and reasons of difficulty of adherence to ART).Sociodemographic to antiretroviral treatment we considered the definition of the national guide to pediatric care for HIV infection [12].Good adherence is estimated at 90 to 95%.
So in our study, at least one missed ART intake in the previous week the survey was considered to define non-adherence to ART.Logistic regression was used to identify factors associated with non-adherence to ART.Odd-ratio were estimated with their 95% confidence intervals.A p-value < 0.05 was considered statistically significant.Statistical Analyzes were done with Stata software (Stata™ 12.0 College Station, Texas, USA).

Characteristics of the Study Population
Overall, 449 HIV-infected children on ART are followed at PATC.Undetectable viral load was found in 43.0% of cases.They had a viral load less than 1000 copies in 14.6% of cases.The antiretroviral regimen was based on zidivudine, tenofovir and lopinavir, respectively, in 54.8%, 39.2% and 2.4% of cases.The average duration of ART was 10 years.
Table 1 and Table 2 show the distribution of adolescents by level of adherence to ART.

Factors Associated with Non-Adherence to ART
Factors associated with non-adherence to ART are shown in Table 3 and Table 4.
In multivariate analysis, the factors associated with non-adherence to ART were sex, marital status of parents, baseline CD4 count, and duration of antiretroviral therapy.Girls were less likely to be non-adherence to ART than boys

Adherence to ART
This study specified the rate of non-adherence and the factors associated with non-adhrence to ART in adolescents at the PATC of pediatric department of Yopougon University Hospital.
Good adherence to ART in HIV-infected adolescents is essential to achieve virological suppression.Actually adherence to ART in HIV-infected adolescents remains problematic [4].
The rate of non-adherence to ART is high in this study (40.4% of 166 adolescents interviewed).Because of the method used in this study, we would have expected a lower rate.In fact, the self-assessment method of the compliance measure may overestimate the ART adherence rate [13].To minimize this information bias parents and adolescents have been reassured during obtaining consent.
Several studies in adolescents have shown rates of non-adherence to ART between 20% and 35% [14] [15] [16] [17].Other study in North America and Spain among adolescents and adults estimated the non-adherence rates at 45% and 43% [18] [19].It has been shown that the variation in the rate of non-adherence to ART observed in the studies is related to the use of evaluation method [17] [18].

Factors Associated with Non-Adherence to ART
Our study has identified epidemiological, social and biological factors associated with non-adherence to ART.Girls were likely to be less non-adherent than boys.
This result was also found in a study conducted in Zambia among 15 -19-years old adolescents [20].However, other studies have shown no significant difference between girls and boys [21].This difference in the rate of non-adherence to ART between girls and boys HIV infected varies from one region to another.The environment in which these adolescents live might explain this difference.A qualitative study was necessary to explain this difference of adherence to ART in girl and boys adolescents HIV-infected.
Also, adolescents from divorced, separated, or widowed parents had a higher risk of being non-adherent to ART.In fact, a stable family environment in the presence of the biological parents would be a favorable environment to promote a better adherence to ART.Several studies have found that the presence of a biological parent is a factor frequently associated with good adherence to treatment [22] [23].
The absence of immune depression implying a non-advanced clinical state of the disease is a risk factor for non-adherence to ART in our study.Many studies have shown that in the early stage of the disease, adolescents are less likely to adhere to treatment [24] [25] [26].These adolescents in relatively healthy do not find need to take their drugs.A study conducted in Uganda showed that patients hospitalized at least twice and therefore symptomatic were more likely to adhere to ART [27].There is evidence that the level of adherence tends to decline over time in adolescents on ART and tiredness has often been the reason for non-adherence to ART in adolescents living with HIV in Uganda [28].In our study, a duration of ART beyond 10 years increased the risk of being non-adherent at ART.
Regular compliance counseling and rigorous therapeutic education are needed to minimize the risk of non-adherence in these adolescents who are already weakened by their physical, emotional and psychological state.

Conclusion
This study shows that the level of ART non-compliance among adolescents at the Pediatric Ambulatory Treatment Center of the pediatric department of Yopougon University Hospital is high.Males, adolescents from divorced, separated or widowed parents, lack of immune depression at baseline, and duration of ART beyond 10 years were the main factors associated with non-adherence to ART.Regular compliance counseling and rigorous therapeutic education are needed to minimize the risk of non-adherence.Observational cohort studies need to be undertaken to better understand the determinants of non-adherence to ART in West Africa.
data (age, sex, educational level, type of housing, marital status of parents, vital status of parents), clinical data (clinical stage of the CDC), biological data (viral load and CD4 lymphocyte count) and therapeutic data (ART regimen, duration of on ART) were collected from the patient records.The clinical stage at inclu-T.K. F. Eboua et al.DOI: 10.4236/ojped.2018.83025240 Open Journal of Pediatrics sion was evaluated according to the staging of the CDC Atlanta and the level of immune depression according to the WHO classification.To define adherence

Table 1 .
Sociodemographic characteristics of adolescents according to adherence to ART, n = 166.

Table 2 .
Clinical, immune-virological and therapeutic characteristics according to adherence to ART, n = 166.

Table 3 .
Sociodemographic factors associated with non-adherence to ART.

Table 4 .
Clinical, biological and therapeutic Factors associated with non-adherence with ART.