|Year : 2021 | Volume
| Issue : 5 | Page : 586-591
The outcome of intervention, characteristics, and determinants of treatment failure in HIV-infected adolescents on first-line antiretroviral therapy at a tertiary health institution, in South-east Nigeria
Maria-Lauretta Orji, Nnamdi Benson Onyire, James Olisaluka Ojukwu, Cecilia Oluchukwu Oyim-Elechi
Department of Paediatrics, Alex-Ekwueme Federal University Teaching Hospital, Abakaliki, Ebonyi, Nigeria
|Date of Submission||12-May-2021|
|Date of Decision||29-Jun-2021|
|Date of Acceptance||07-Jul-2021|
|Date of Web Publication||11-Oct-2021|
Dr. Maria-Lauretta Orji
Department of Paediatrics, Alex-Ekwueme Federal University Teaching Hospital, P.M.B 102, Abakaliki, Ebonyi
Source of Support: None, Conflict of Interest: None
Background: The adolescent phase of life is characterized by the desire for independence, experimentation, and heightened peer influence. These may affect HIV prevention, care, treatment, and support in adolescents. Objective: This study was aimed at determining the outcome of intervention and factors responsible for treatment failure among adolescents on first-line antiretroviral therapy (ART). Materials and Methods: It was an interventional cohort study that studied 88 adolescents on ART. An interviewer-administered questionnaire was used to collect the data on sociodemographics. Assessment of adherence was done by pill count and self-reports. Reverse transcriptase polymerase chain reaction was used to quantify the amount of HIV RNA in participants. Results: A total of 22 (25.0%) out of 88 adolescents had viral load assays of ≥1000 copies/ml despite being on first-line ART for a mean period of 5.70 ± 3.21 years. After enhanced adherence counselling (EAC) of three months, 10 (44.5%) of the 22 adolescents achieved viral suppression (<1000 copies/ml). Being tired of taking drugs was the major reason (41.1%) for non-adherance to ART. There were significant relationships between treatment failure and age (P = 0.010), gender (P = 0.024), socio-economic class (P = 0.020), orphan status (P = 0.010), type of ART (P = 0.008), HIV status disclosure (P ≤ 0.001), and sexual experience in the adolescent (P ≤ 0.001). Conclusion: Viral suppression rate after EAC was low. There is a need to address modifiable factors that influence viral non-suppression in adolescents through adolescent-friendly and responsive services geared toward counselling, skill acquisition, and empowerment to help adolescents navigate this stage of life.
Keywords: Adolescent, antiretroviral therapy, HIV infection, treatment failure
|How to cite this article:|
Orji ML, Onyire NB, Ojukwu JO, Oyim-Elechi CO. The outcome of intervention, characteristics, and determinants of treatment failure in HIV-infected adolescents on first-line antiretroviral therapy at a tertiary health institution, in South-east Nigeria. Niger J Med 2021;30:586-91
|How to cite this URL:|
Orji ML, Onyire NB, Ojukwu JO, Oyim-Elechi CO. The outcome of intervention, characteristics, and determinants of treatment failure in HIV-infected adolescents on first-line antiretroviral therapy at a tertiary health institution, in South-east Nigeria. Niger J Med [serial online] 2021 [cited 2021 Nov 29];30:586-91. Available from: http://www.njmonline.org/text.asp?2021/30/5/586/327966
| Introduction|| |
The introduction of antiretroviral therapy (ART) to HIV care has boosted the survival of children and adolescents living with HIV. Virologic failure is the earliest evidence of treatment failure and occurs when high HIV RNA (≥1000 copies/ml) is detectable in the blood after six months of effective therapy. Delay in detecting treatment failure and prompt switch to second-line ART is responsible for HIV drug resistance. Drug resistance reduces the ability of the ARVs to block or reduce HIV replication and also compromises future drug regimens.
The last “90” in the UNAIDS 90-90-90 strategy for HIV care, connotes 90% viral suppression among people receiving ART. Studies have shown that poor adherence to medication is the most common predictor of viral nonsuppression.,, The World Health Organization (WHO) recommends enhanced adherence counseling (EAC) sessions for 3–6 months for people with initial high viral load assays before diagnosing treatment failure., Nasuuna et al. noted that out of the 345 participants with unsuppressed viral load count, only (23.0%) achieved viral suppression following intensive adherence counselling program for children and adolescents with viral failure. HIV-infected people with persistently unsuppressed viral loads after the EAC sessions are tagged as having treatment failure and as such switched to the second-line regimen.
Several studies exist on the prevalence of treatment failure in children aged 0–19 years, with prevalence rates ranging from 7.7% to 64.0%.,,,,,, There is however a dearth of data on adolescents living with HIV. The adolescent stage of development is heralded by an increase in decision-making, experimentation process, increased peer pressure, and search for self. This phase of life is also met with deviations from expected or prescribed behavior. These developments may complicate the attitude of adolescents to their health and treatment. Some studies have reported poor adherence to ART among adolescents leading to viral non-suppression and subsequent treatment failure.,
Ebonyi et al. reported male gender, treatment interruption, and follow-up by a general practitioner as the significant predictors of treatment failure. Yihun et al. noted that poor adherence to ART, orphan status, and drug regimen were the significant predictors of treatment failure among the study population. While Emmett et al. reported that full disclosure of HIV status at age of seven years and above was protective against treatment failure; Sisay et al. noted that late disclosure of HIV status was significantly related to treatment failure.
Adolescents have an increased risk for horizontal HIV infection because of their low rates of condom use, high rates of sexually transmitted diseases (STDs), and alcohol or drug use., Unprotected sexual activity among adolescents on ART may increase the viral load or introduce drug-resistant strains of HIV which can complicate treatment.
There is a paucity of data on the effects of EAC and determinants of treatment failure in the HIV-infected adolescent. Hence, this study was aimed at determining the outcome of EAC and factors that influence treatment failure in adolescents.
| Materials and Methods|| |
A hospital-based interventional cohort study conducted between July 2018 and June 2019.
The study was conducted in the paediatric ART clinic of Alex Ekwueme Federal Teaching Hospital Abakaliki, Ebonyi state.
Adolescents aged 10–19 years seen in the Pediatric ART clinic were consecutively recruited into the study following informed written consent obtained from caregivers and verbal assent from adolescents. All study participants had routine viral load measurements carried out as per the patient management protocol. All participants with high viral load received EAC as per guideline for managing suspected treatment failure in line with WHO recommendation, and were continually followed up for a period of 3 months. During the follow-up period, participants with high viral load assay continued on their previous antiretroviral medications. After the three-month period, a repeat viral load was done. Reverse transcriptase-polymerase chain reaction was used to quantify the amount of HIV RNA in the participants.
Treatment failure can be virologic, immunologic, and clinical. Viral load of participants was used to classify the participants into two groups: Suppressed (viral load <1000 cells/mm3) and non-suppressed (viral load ≥1000 cells/mm3). CD4 count of <100 cells/mm3 for a child five years of age or older is an immunologic failure while the WHO clinical staging of HIV/AIDS was used to group subjects into Stages 1–4. Stages 3 and 4 diseases of HIV defined clinical failure. The participants should have been on medication for at least six months and adherence to therapy assessed and ensured.
An interviewer-administered questionnaire was used to obtain the information about the adolescent's bio-data, socioeconomic class of caregiver, place of dwelling, sexual history, status disclosure, ART regimen, and adherence to ART. Adherence to ART was obtained by pill count and direct questioning of the adolescents and information obtained was used to classify the participants into poor <95% (for a participant taking medication twice daily, omitting more than one dose in 10 days implies <95% adherence) and good ≥95% with reference to the national guideline. The socioeconomic class was grouped into upper and lower classes as described by Oyedeji.
Ethical approval from the Health Research and Ethical Committee of FETHA was sought and obtained before the commencement of the study. The study was explained to parents/guardians and only those who gave written consent were included in the study.
The data were entered into the SPSS version 22 (IBM Corp. Chicago, IL, USA). Tables were constructed as appropriate showing frequencies and percentages of variables. The Chi-square statistics were used to determine the relationship between sociodemographics and treatment failure. Independent variables that were significantly associated with treatment failure in the bivariate analysis were further examined in the multivariate analysis. The statistical significance was achieved at P ≤ 0.05.
| Results|| |
At the initial viral load screening, 22 (25.0%) of the 88 adolescents had high viral load measurements. By the end of the three months intervention period (EAC), 10 (45.5%) of the 22 adolescents achieved viral suppression as shown in [Figure 1] below which depicts the study flow chart. A total of 12 participants remained non-suppressed, giving a prevalence rate of treatment failure of 13.6%. A total of 71 (80.7%) were on zidovudine or abacavir, lamuvidine, and nevirapine or efavirenz combination (AZV/ABC + 3TC + NVP/EFV) and 19.3% on tenofovir, lamivudine, and efavirenz/doltegravir (TDF + 3TC + EFV/DTG). The majority (89.8%) of the adolescents were asymptomatic (WHO clinical Stage 1 of disease) and only 9 of them had skin lesions such as verruca plana, papular dermatitis, and tinea coporis depicting WHO clinical Stage 2 disease. None was in WHO clinical Stage 3 or 4. All the participants were on co-trimoxazole prophylaxis.
The majority (52.3%) of the adolescents were in the early adolescent age bracket (10–13 years). The mean age of the participants was 13.37 ± 3.10 with a male-to-female ratio of 1.4:1 and the majority (72.7%, 64/88) had caregivers in the lower socioeconomic class. Fifty participants (56.8%) were urban dwellers and about half (48.9%) of the subjects were orphans having lost at least a caregiver, as shown in [Table 1].
|Table 1: Baseline characteristics of adolescents attending the antiretroviral therapy clinic|
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A total of 71 (80.7%) out of the 88 were adherent on ART based on pill count and self-report. Poor adherence to ART was the main reason for viral non-suppression among adolescents as 17 (77.3%) of the 22 adolescents with initial high viral load assays were non-adherent to medication. After the three-month enhanced adherence intervention, 6 (27.3%) adolescents remained nonadherent to ART. Adolescents within the 14–16 years age bracket, male gender, those in lower socioeconomic class, sexually exposed and orphaned constituted the majority of the non-adherant group [Table 2].
|Table 2: Relationship between adherence to antiretroviral therapy (pre- and post-enhanced adherence counseling) and sociodemographics|
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The different reasons why adolescents were non-adherant to drugs are shown in [Figure 2]. A total of 41.1% of the adolescents were tired of taking drugs, 11.8% forget to take drugs while 17.6% were ill and did not take drugs, 11.8% were not adherent because of drug side effects and 5.9% lacked transport fare to the facility of care as reason, while 11.8% of the adolescents had no reason.
[Table 3] shows the relationship between sociodemographic variables and HIV treatment failure after the three-month EAC. A total of 12 (13.6%) out of the 88 adolescents had sustained viral load assays ≥1,000 copies/ml and had failed on first-line ART and were then switched to second-line ART. There were significant relationships between treatment failure and age (P = 0.010), gender (P = 0.024), socioeconomic class (P = 0.020), orphan status (P = 0.010), and sexual experience in the adolescent (P ≤ 0.001).
|Table 3: Relationship between post-intervention treatment failure and sociodemographics|
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A total of 8 (66.7%) out of the 12 adolescents that had treatment failure were on AZT (ABC)/3TC/NVP (EFV) regimen with 9 (75.0%) of them having been on ART for more than five years. Ten (83.3%) of the 12 adolescents knew their HIV status and 9 (90.0%) of the disclosure was done when they were between 10 and 15 years of age [Table 4].
|Table 4: Relationship between human immunodeficiency virus care and post-intervention treatment failure among adolescents on antiretroviral therapy|
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| Discussion|| |
Viral suppression following EAC was 45.5%. This is low when compared to the WHO target of 90% viral suppression for participants on ART. The reasons for this finding are multi-factorial. It may be related to patient's characteristics such as treatment fatigue, depression, and stigma, antiretroviral drug resistance, antiretroviral regimen related factors such as pill burden, frequency, and potency, and health-care provider related such as inadequate and ineffective counseling. It was however higher than that reported by Nasuuna et al. who reported 23% in a study among children and adolescents. This difference may be related to the differences in age bracket studied and factors influencing adherence. Poor adherence to ART limits the efficacy of the drug and increases the chances of failure. The majority of the adolescents reported being tired of taking drugs as their reason for poor adherence and most of the adolescents have had ART for more than five years. This long duration of drug intake may have caused treatment fatigue and possible depression among adolescents. This is contrary to reasons for poor adherence to ART in children that revolved around their caregivers.
A total of 12 (13.6%) out of the 88 adolescents with unsuppressed viral load counts after EAC failed on their first-line ART. This rate of treatment failure was lower than previously documented rates observed in children by Yihun et al., Sebunya et al., and Cissé et al. that reported prevalence rates of 26.4%, 48.98%, and 64.0%, respectively. The difference in prevalence rates may be attributed to the age groups of participants used and differences in sample size used. While these previous studies were carried out in children 0–19 years of age, the index study was on adolescents aged 10–19 years.
Although the majority of the adolescents were in the early adolescent age group (10–13 years), treatment failure was the highest in the mid-adolescent age group (14–16 years) with a total of 66.7% of all the adolescents that failed on ART. The mid-adolescent age bracket is the period of self-discovery, independence, and heightened experimentation on sex, drugs, friends, and risk. This phase of life may have influenced their decision-making and behaviour.
More males (58.3%) than females had treatment failure in this study. This may be explained by the fact that more males were enrolled in the study. Ebonyi et al. and Sisay et al. also reported similar findings, although no reason was attributed to such observation in their study.
In the index study, none of the participants had a clinical failure. This underscores the importance of early diagnosis of treatment failure using viral load assay. Detecting virologic failure enables prompt decisions on interventions such as EAC and switch of the treatment regimen for those with persistently high viral loads to avoid the occurrence of drug resistance very early in the management of such subjects. This was corroborated by Yihun et al. that noted that of the overall prevalence rate of 12.19%, virologic failure contributed 48.98% while immunologic failure accounted for 28.57% and no clinical failure.
Many adolescents do not believe that HIV is a threat to them, and many do not know how to protect themselves or are unable to protect themselves due to forced sex. A third of the adolescents that failed on their ART regimen were sexually active. This could be attributed to the possibility of contracting STDs that may worsen HIV care and acquisition of drug-resistant strain of the virus from an infected but undiagnosed partner leading to treatment failure.
Orphaned adolescents had higher treatment failure compared to their colleagues. The unmet emotional and psychosocial needs of the adolescent with HIV due to the death of one or both parents may be the reason for this finding. Similarly, the majority of the adolescents from lower socioeconomic class failed the most on their ART. This may be attributed to the fact that lack of basic needs places the adolescents at the risk of sex for money with its attendant sexually transmitted infections, substance abuse, poor health and malnutrition, and low access to the health facility which may have a negative influence on the treatment and care of HIV., This was corroborated by Yihun et al. who noted orphan status as a significant predictor of treatment failure.
Adolescents who were on zidovudine/abacavir, lamivudine, and nevirapine/efavirenz-based combinations failed more on ART compared to those on tenofovir, lamivudine, and doltegravir combination. This finding may be attributed to the fixed-dose combination of the later regimen allowing it to be taken as a single dose, thus reduces pill burden and increases adherence. In addition, the non-nucleoside reverse transcriptase inhibitors are associated with the development of mutations that can quickly induce high drug resistance, low clinical potency, and serious adverse effects compared to doltegravir containing regimen. This was corroborated by Nasuuna et al, that reported a low viral suppression rate among children and adolescents that were mostly (71%) on a nevirapine-based ART regimen.
Status disclosure to HIV-infected children is thought to be of immense benefit in adherence to ARVs and overall care of subjects. Age at disclosure is however as important as the disclosure itself. It was observed in this study that the majority of the adolescents that failed on their first-line ARVs (90%) had received full disclosure of their HIV status, by the age of 10 years and over. This late disclosure may explain the high rate of treatment failure despite knowing their HIV status. This is corroborated by Emmett et al. who noted that full disclosure of HIV status from the age of seven years was protective against treatment failure and Sisay et al. that observed that late disclosure of HIV status was significantly related to treatment failure. Early disclosure of HIV status to an infected child helps to build and maintain trust between child and caregiver. It becomes rather difficult to build such trust in an adolescent who had been on medication for a disease unknown to him/her and over time becomes suspicious of the caregiver and may even develop a defiant attitude toward the caregiver and medications.
| Conclusion|| |
A three-month EAC improved viral suppression by 45.5%. Treatment failure in adolescents is influenced by age, gender, socioeconomic class, orphan status, sexual exposure, type of ART, and status disclosure. The factors that influence treatment failure among adolescents could be tackled in a well-organized adolescent-friendly centre where adolescents are equipped with information that will enable them to become responsible for their health and treatment.
Financial support and sponsorship
The present study was funded by the authors
Conflicts of interest
There are no conflicts of interest.
| References|| |
Federal Ministry of Health. HIV/AIDS Prevention and Care. Guidelines for Paediatric and Adolescent HIV/AIDS Care and Treatment. Ebonyi State, South-east, Nigeria: Federal Ministry of Health; 2007. p. 102-76.
World Health Organization. WHO Consultation on ART Failure in the Context of Public Health. Montreux Switzerland: World Health Organization Monthly Report; 2008. p. 26-7.
Ebonyi AO, Oguche S, Ejeliogu EU, Okpe SE, Agbaji OO, Sagay SA, et al.
Risk factors for first-line antiretroviral treatment failure in HIV-1 infected children attending jos university teaching hospital, Jos, North Central Nigeria. Br Med Med Res 2014;4:2983-94.
Sisay MM, Ayele TA, Gelaw YA, Tsegaye AT, Gelaye KA, Melak MF. Incidence and risk factors of first-line antiretroviral treatment failure among human immunodeficiency virus-infected children in Amhara regional state, Ethiopia: A retrospective follow-up study. BMJ Open 2018;8:e019181.
Costenaro P, Penazzato M, Lundin R, Rossi G, Massavon W, Patel D, et al.
Predictors of treatment failure in HIV-positive children receiving combination antiretroviral therapy: Cohort data from Mozambique and Uganda. J paediatrics Infect Dis Soc 2015;4:39-48.
WHO. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Geneva: World Health Organization; 2016.
WHO. Adapting and Implementing New Recommendations on HIV Patient Monitoring. Geneva, Switzerland: World Health Organization; 2017.
Nasuuna E, Kigozi J, Babirye A, Muganzi N, Nelson K, Sewankambo K, et al.
Low HIV viral suppression rates following the intensive adherence counselling program for children and adolescents with viral failure in public health in Uganda. BMC Public Health 2018;18:1048.
Davies MA, Moultrie H, Eley B, Rabie H, Van Cutsem G, Giddy J, et al.
Virologic failure and second-line antiretroviral therapy in children in South Africa – The IeDEA Southern Africa collaboration. J Acquir Immune Defic Syndr 2011;56:270-8.
Yihun BA, Kibret GD, Leshargie CT. Incidence and predictors of treatment failure among children on first-line antiretroviral therapy in Amhara Region Referral Hospitals, northwest Ethiopia. 2018: A retrospective study. PLoS One 2019;14:e0215300.
Mee P, Fielding KL, Charalambous S, Churchyard GJ, Grant AD. Evaluation of the WHO criteria for antiretroviral treatment failure among adults in South Africa. AIDS 2008;22:1971-7.
Sebunya R, Musiime V, Kitaka SB, Ndeezi G. Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic. AIDS Res Ther 2013;10:25.
Cissé AM, Laborde-Balen G, Kébé-Fall K, Dramé A, Diop H, Diop K, et al
. High level of treatment failure and drug resistance to first-line antiretroviral therapies among HIV-infected children receiving decentralized care in Senegal. BMC Pediatr 2019;19:47.
Tulloch T, Kaufman M. Adolescent sexuality. Pediatr Rev 2013;34:29-30.
Kirchler E, Palmonari MP. Developmental tasks and the adolescent's relationships with peers and their family. In: Jackson S, Rodriguez-Tome H, editors. Adolescence and Its Social Worlds. Hove: Lawrence Erbaum; 1995.
Belzer ME, Fuchs DN, Luftman GS, Tucker DJ. Antiretroviral adherence issues among HIV-positive adolescents and young adults. J Adolesc Health 1999;25:316-9.
Murphy DA, Sarr M, Durako SJ, Moscicki AB, Wilson CM, Muenz LR, et al.
Barriers to HAART adherence among human immunodeficiency virus-infected adolescents. Arch Pediatr Adolesc Med 2003;157:249-55.
Emmett SD, Cunningham CK, Mmbaga BT, Kinabo GD, Schimana W, Swai ME, et al.
Predicting virologic failure among HIV-1-infected children receiving antiretroviral therapy in Tanzania: A cross-sectional study. J Acquir Immune Defic Syndr 2010;54:368-75.
Redd AD, Quinn TC, Tobian AA. Frequency and Implication of HIV superinfection. Lancet Infect Dis 2013;13:622-8.
Oyedeji GA. Socio-economic and cultural background of hospitalized children in Ilesha. Niger J Paediatr 1985;12:111-7.
Chapp-Jumbo AU, Onyire NB, Orji ML, Onwe OE, Ojukwu JU. Assessment of rate of adherence to highly active antiretroviral therapy (HAART) among HIV infected children attending the infectious disease clinic of federal teaching hospital Abakaliki (FETHA), Ebonyi state, Nigeria. J Child Adolesc Behav 2016;4:1.
Wang Y, De Clercq E, Li G. Current and emerging non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV-1 treatment. Expert Opin Drug Metab Toxicol 2019;15:813-29.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]