In this study, we examined factors associated with ART adherence in Lao PDR. Non-adherence usually means skipping one dose of medicine. Based on the self-report questionnaire, the study results indicated that more than half of the PLHIV had good adherence to ART defined as ≥95%. Nevertheless, 40% of respondents reported poor ART adherence. This is a concern given poor adherence severely compromises effectiveness and is linked with the likelihood of the drug resistance. Non-adherence to ART in this study was associated with socio-demographic characteristics, illicit drug use, and history of taking ART. In the final model in our sample, the variables educational level at secondary school, having used illicit drugs, having started ART within the last 31–60 months and forgetfulness played a significant role in predicting adherence to ART.
The finding of 60% ART adherence among PLHIV in our study is similar to that found in a study in Zambia and one in India
[22, 23], but lower than studies China
, and Vietnam
. It is also lower than reported in studies conducted in developed countries using similar self-report measures
[26, 27]. Some caution is needed in comparing adherence rates across studies however, as the methods of measuring adherence (self-report vs. pill counts or medication electronic monitoring system (MEMS) and settings such as free ART vs. non-free, rural vs. urban, plasma donor vs. injecting drug users or other risk groups) can affect findings. Measurement of ART adherence is also problematic as patients may overestimate their adherence due to recall bias, the demand characteristics of patient-provider consultation and the desire to avoid criticism
In our study, reasons given for non-adherence related to being busy, forgetfulness and distance to the clinic. Other reasons given included running out of medication, having too many pills to take, the taste of the medication, severe side effects, difficulties in maintaining the medication regiment and self-stigma. Self-stigma may lead to patients being unwilling or fearful of taking medicine when other people are present
. A qualitative study in Vietnam identified self-stigma as a pervasive barrier to ART adherence with patients concerned that taking medications in the presence of others could lead to unplanned disclosure of their HIV status
. Forgetfulness was identified in our study as a significant variable in predicting adherence to ART. This is similar to a study in rural China
. In the present study, we found a statistically significant association between non-adherence and secondary school educational level. Other studies have shown low levels of education as an important factor associated with non-adherence and a general barrier for medical care
[29, 30]. In contrast, a study in Bangalore, India found education had no effect on adherence
. This difference in findings may be due to our participant group in general being relatively well educated and thus more aware about the problems of sub-optimal treatment.
Illicit drug use has been associated with depression and anxiety, either as part of the withdrawal process or because of repeated use. This is particularly relevant in the treatment of HIV infection because depression is one of the strongest predictors of poor adherence and poor treatment outcomes
. Our study found that illicit drug use was a contributing factor to non-adherence based on the 95% threshold. Illicit drug use has been reported to reduce the level of adherence in many studies
[32–34]. Various studies have documented that widespread illicit drug use among PLHIV makes their treatment complicated and hinders their quality of life
[4, 35]. It has also been suggested that less than 95% adherence when combined with illicit drug may lead to viral suppression
Being on ART for 31–60 months was significantly associated with non-adherence to ART in this study. This finding is supported by Andreo C. et al. who found that where patients had been on ART medication for more than two years, increased non-adherence was observed
. This could be because the longer patients are on treatment they become complacent and find it harder to follow the strict regimen. Research in Vietnam also identified that over time, family members who had initially played a supportive role in helping patients take their medication, assumed the PLHIV was taking their medication as prescribed and followed up with the patient less regularly
. This factor may also be a contributing factor in decreased adherence over time.
Some studies have identified side effects of ART medications as significant barriers to good adherence
. In this study, although half of the patients (52.3%) reported signs and symptoms of adverse reactions to their treatment, further analysis did not identify these factors as being significantly related to non-adherence. However, this might be due to the limitations of the methods used as both non-adherence and the adherence group reported having trouble with side effects. Nevertheless, it would seem to be a priority that ART programs should where possible, increase the availability of regimens with fewer adverse reactions.
In the present study, no difference in adherence levels based on the duration of taking ART and WHO clinical stages was observed. In addition, the CD4 count at the start of treatment did not significantly correlate with non-adherence to ART. A study in India demonstrated an association between self-reported adherence and improvement in CD4 counts
. According to Sarna et al.,
 lower improvement in CD4 counts during the early stages of taking ART medication may be due to a delay between virologic and immunologic failure.
The present study suggests that to increase ART compliance a number of strategies are required. There has been limited research however on the effectiveness of strategies to enhance adherence in low-income settings. Directly observed therapy (DOT) as used in tuberculosis treatment, has been used with ART with some effect but is resource intensive
. In Vietnam, perceptions of stigma prevented home-based DOT being viewed as acceptable
. Other interventions include limiting the size, number, side effects and frequency of pills taken per day. Such regimens are likely to be more attractive to patients trying to conceal their HIV status for fear of stigma
Mobile phones can provide an inexpensive and convenient means of communication to support treatment compliance. Randomized controlled trials have found mobile phones to be an effective adherence support tool in in low-resource settings
. A trial in Kenya for example found a weekly mobile phone text asking in the local language “how are you?” improved viral suppression outcomes when compared with care
. In focus group interviews patients reported that the weekly messages made them feel that someone cared. Another trial found that short weekly one-way text messaging improved medication adherence whereas daily messaging did not
. A study in Vietnam however, found that while there was overall acceptance of the use of mobile phones, stigma and fear of HIV disclosure were a barrier to use
. In Lao PDR, mobile phones are sometimes used to contact the patients when they miss appointments but texting or other mobile phone functions are not currently used to encourage compliance. Given in the present study stigma was a barrier to optimal ART compliance and some HIV patients were also illegal drug-users, further research into the appropriateness of mobile phone use as a form of adherence support in Lao PDR is needed. Issues of confidentiality would also need to be addressed. Research would also be needed to identify the preferred types of mobile phone functions for adherence maintenance. Provider attention to developing a good relationship with the patient, taking time to address concerns about the medications and side-effects can improve adherence. Counseling, education and peer support are other interventions which have been identified as being effective
. In Vietnam a randomized controlled trial found peer support improved quality of life and adherence after 12 months among ART patients presenting at clinical stages 3 and 4 at baseline, but had no impact on quality of life among ART patients enrolled at clinical stages 1 and 2
Limitations of study
The findings of this study must be interpreted in the light of its limitations. The study was conducted at only two sites in the country and the findings may not be generalizable to other clinical settings. There is no gold standard for measuring adherence and our measurement of adherence is based on PLHIV self-reports of missed doses which may be subject to social desirability and recall biases. The literature for example, suggests that PLHIV tend to overestimate adherence
. However, many other studies document that well collected self-reported data clearly correlate with virologic change and is more practical in most settings
. A meta-analysis of several studies demonstrated a good correlation between self-reported medication adherence and virologic outcomes and that self-reported lower non-adherence to be more reliable than self-reported higher adherence
[45, 46]. Further, in the present study, adherence information was collected by the non-clinical research staff so there was less reason for participants to over-report adherence. We were also unable to relate the obtained adherence rate to CD4 cell count due to financial and logistical barriers to frequent laboratory monitoring, a limitation common in low and low-middle income countries.
It is also possible that selection bias occurred, as only those PLHIV who were on ART at the time of data collection were included, whereas those who were lost-to-follow up or could not attend the clinic to collect medication were excluded. The cross-sectional design of this study means we could only estimate levels of adherence at one point in time while adherence to medication is a dynamic process and participants’ behavior may change over time. In addition, the design means that casual relationships between ART non-adherence and other correlates cannot be identified and we can only demonstrate association between levels of education, illicit drug use, duration since the initiation of ART and non-adherence. Additionally, we collected PLHIV consecutively attending the care units over a limited time. Finally, the focus of this research was on individual patient factors affecting adherence. Additional research is needed to better understand heath care provider and health care system determinants of treatment adherence.