The study investigated the factors associated with virological failure among adolescents on ART and revealed that poor adherence to treatment, taking alcohol and non-disclosure of HIV status increased the odds of virological failure. The less likelihood factors included having a support group and being on 2nd line treatment. Correct and consistent use of a condom was a protective factor.
The study demonstrated that adolescents who were not adhering to ART were less likely to achieve viral suppression as compared to those who were adhering to ART. This is biologically plausible as poor adherence result in drug dosages below the level necessary to produce a therapeutic effect, thereby enabling development of drug resistance [15]. Our results are in line with those of Evans et al., 2013 in South Africa suggesting that poor adherence is associated with a higher risk of virological failure [16, 17]. The benefits of a combination therapy like Tenolam E (a 3 drug regimen -Tenofovir + Lamivudine+ Efavirenz) in this study could be due to its once-daily regimen which has less pill burden as compared to other regimens.
In this study, adolescents who reported being on other medications apart from ART were more likely to develop virological failure as compared to those who were on ART only. Although the study did not assess why adolescents on other medications were more likely to develop virological failure, this could be due to several explanations like by the pill burden that would be encountered by adolescents that would be on other medications. Other studies demonstrated that pill burden among adolescents is associated with poor adherence [18]. This could possibly be as a result of drug to drug interaction or the disease severity of those on other medications.
The odds of virological failure increased with disease severity at ART initiation. Virologic failure was more likely in advanced disease (WHO stage 3 and 4, CD4 < 350 cells/mm3). This shows delay in ART initiation among adolescents. Chimbetete et al., 2011 also found that patients initiated on ART after developing AIDS related illness (WHO stage 3 & 4), and those who had low baseline CD4 counts had higher risk of treatment failure as compared to those in WHO stage 1 or 2 and those with high CD4 [8]. However the 2015 WHO guidelines expanded ART initiation to treat all. This will minimize the delays on ART initiation but delayed diagnosis would remain a significant problem. Similar findings from other studies suggest that adolescents who delay ART initiation are more likely to have resistant mutations [19, 20].
The independent association of alcohol consumption and virological failure is not surprising since alcohol use among adolescents has been associated with lower treatment adherence, disease progression and failed viral suppression. One study by Matare et al., 2014 examined the association of alcohol with viral suppression and found that those who consumed alcohol were more likely to develop virological failure compared to those who did not [7]. In another study by Adrovandi et al., 2014, alcohol use was associated with poor adherence [21]. In contrast, Chimbetete et al., 2011 found no difference in treatment failure among those who were alcohol drinkers [8]. This could be explained by the levels of drinking alcohol in that study, which had no effect on their drug adherence levels.
Disclosure has been shown to be a protective factor as far as viral suppression is concerned. This could be due to the association between disclosure of HIV status and adherence. Some studies have found delayed or nondisclosure of HIV status to be associated with virological failure [22]. Attention should be focused on increased involvement of the child and family in medical treatment after disclosure. Disclosed children have better access to social support and tend to be less depressed over the long-term, thereby adhering to their medication well [22].
In this study, belonging to a support group was a less likelihood factor. Ayer et al., 2016 also found that belonging to a support group was associated with viral suppression [23]. Our study also demonstrated that older adolescents were more likely to develop virological failure as compared to the younger adolescents. This is consistent with Cowan et al., 2009 on viral load suppression among adolescents in sub-Saharan Africa, who also found that older adolescents were more likely to have virological failure as compared to the younger adolescents [24]. The increased risk of virological failure among older adolescents could be explained by the developmental milestones gone through by older adolescents in transition to their adulthood as compared to the younger adolescents. These include social, emotional and cognitive changes [25].
Those who were on second line treatment were less likely to develop virological failure as compared to those on first line treatment regimen. However, the additional counselling among adolescents on second-line treatment might have somewhat biased this study finding. Those who are on second line treatment receive enhanced adherence unlike those on first line treatment.
The strengths of this study included the triangulation of information given by the study participants with the information included in the clinical records. However, our study had some limitations. The Information provided on exposure differed between cases and controls. Cases could accurately recall past exposures better than controls resulting in recall bias. However some of the given information were verified with medical records. Some of the questions included in the questionnaires were sensitive and this could have introduced social desirability bias. Also adherence was assessed using pill count method which not a perfect method of assessing adherence. Despite these shortcomings, this study fills a gap in research on factors associated with virological failure in Harare city, Zimbabwe.
