In the current study, the prevalence of nonadherence to CPT was found to be very common (65.5%), almost double that of nonadherence to ART. The main reasons for nonadherence to CPT were side effects, pill fatigue and forgetting to take. Gastrointestinal side effects followed by rash were the most commonly reported side effects. CD4 count, adherence to ART, and side effects were significant predictors of nonadherence to CPT. PLHIV who had a CD4 count above 350, were nonadherent to ART and experienced side effects were more likely to be nonadherent to CPT.
CPT is a widely used standard of care for PLHIV for the prevention of OIs in resource-limited settings.13,15 However, the current study has shown a significant gap in the uptake of CPT as an intervention among PLHIV. The prevalence of nonadherence to CPT in this study was twice that reported by Mekonnen and Addis from the University of Gondar Compressive Specialized and Teaching Hospital (32.2%).16 The reason for this difference could be due to the difference in levels of nonadherence measurement. In this study, the assumption of near optimal ART adherence (≥ 95%) was considered for calculating nonadherence to CPT (missing at least two doses from 30 doses), whereas in the study by Mekonnen and Addis, nonadherence was measured if a participant had missed three doses or more per 30 doses of cotrimoxazole. Moreover, a similar nonadherence prevalence was reported in a study by Nigatu17, where approximately 60% of the respondents reported that they had missed at least two doses of CPT in the last month.
Although CPT is considered a feasible, cost-effective and well-tolerated intervention13, side effects were a predictor and one of the main reasons for nonadherence to CPT in this study. PLHIV who experienced side effects were 3.85 times more likely to be nonadherent to CPT than those who did not experience side effects (p value = 0.001; AOR, 3.849; 95% CI, 1.789–8.284). The impact of medication side effects on adherence to long-term ART is well documented by other studies.18,Error! Reference source not found. Similar to the findings in this study, Mekonnen and Addis16 also reported forgetting to take a pill and the development of side effects as the main reasons for missing doses of CPT. Discontinuation of CPT due to tolerable side effects, pill fatigue and being forgetful indicates the presence of gaps in the implementation of the program in the study setting, highlighting the need for continued medication counseling for PLHIV with regard to the benefit of CPT.
PLHIV with CD4 counts > 350 were 3.48 times more likely to interrupt CPT by themselves than those with CD4 counts ≤ 350 (p value = 0.002; AOR, 3.481; 95% CI, 1.555–7.792). This could be because PLHIV may receive information on when to discontinue CPT from their health care providers and/or from other PLHIV receiving care in the ART clinic. Similarly, having a CD4 above 350 was the main reason for CPT interruption in a retrospective evaluation of cotrimoxazole use performed by Misganaw et al.20 PLHIV adherent to ART were 72.1% less likely to be nonadherent to CPT compared with those nonadherent to ART (p value = 0.001; AOR, 0.279; 95% CI, 0.128–0.608), indicating that adherence to ART and CPT were directly related. However, it is not clear whether CPT nonadherence resulted in nonadherence to ART or vice versa.
Patients’ knowledge of their diagnosis and the expected course of their illness or the benefit of treatments have been associated with significant improvement of adherence.16, 18 Likewise, low levels of knowledge on CPT have been linked with nonadherence to CPT.21, 22 In contrast to these findings, univariate binary logistic analysis of the current study indicates that participants who knew the benefits of CPT were more likely to be nonadherent to CPT than those who did not know. However, in the final multivariable regression, knowledge and attitude about the benefit of CPT had no statistically significant association with nonadherence to CPT. Despite the majority of PLHIV in this study having knowledge about the benefits of CPT, a significant number of participants believed CPT is less important than ART. These negative beliefs might be a driving factor for the high level of nonadherence to CPT.
HIV infection is a potential cause of social isolation; thus, social isolation may be a risk factor for decreased adherence in HIV-infected individuals.23 Studies have identified that a lack of family support has a negative impact on adherence to chronic medication use.18, 21 However, in this study, family support had no significant association with CPT nonadherence.
Although CPT is relatively available in every setup of resource-limited settings, the current study has shown the presence of gaps in its uptake and barriers to cotrimoxazole prophylaxis adherence. PLHIV seem to have a negative belief about the importance of CPT compared to ART. They were more reluctant to maintain adherence to CPT for reasons related to side effects, pill fatigue and being forgetful, indicating the need for continued medication counseling. However, the study has some limitations. Being a cross-sectional study, it was not possible to see causal relationships between some variables. For instance, it was difficult to know if CPT nonadherence resulted in nonadherence to ART or vice versa. Future studies should focus on the impact of CPT nonadherence on ART outcomes. Moreover, longitudinal studies are necessary to illustrate CPT nonadherence across a continuum of care and the contributing factors from multiple perspectives.