Determinants of loss to follow-up in patients on antiretroviral treatment, South Africa, 2004–2012: a cohort study

We found a progressive increase in the incidence of LTFU patients with each year after initiation of ART: the patient retention rate was 82 % after 2 years and 55 % after 5 years. This finding is similar to other studies done in sub-Saharan Africa [8‐10]. It is, however, important to keep in mind that different definitions of LTFU may have been used in these studies. Due to limited research, we compare our study findings to the available research literature, bearing in mind that some of these study findings may or may not have been different, if our definition of LTFU would have been applied to their analysis. Our retention rate at 2 years gives the impression that our retention rates are at higher end of the rates that have been reported in some sub-Saharan ART programs (range from 24 to 77 % at 2 years) [8].

South Africa has a goal that at least 70 % of patients that are initiated on ART are alive and on treatment 5 years after ART initiation [11]. Though we appear to have comparatively better programmatic success in retaining patients in care at 2 years after ART initiation when compared to other sub-Saharan programs, we are not achieving this 70 % retention target at 5 years after ART initiation, and more effort is needed to improve patient retention in care at 5 years after ART initiation.

Our study, like other studies that have shown that being single is a risk factor for becoming LTFU [20], found that patients that did not have a committed partner had a higher risk of becoming LTFU. This suggests that having a committed primary relationship is protective against being LTFU. In our study we found that 80 % of patients did not have committed primary relationships. It is therefore important that other systems and programs that lower the rates of LTFU be employed. Integrated patient care, community based adherence support programs, active outreach to patients, the availability of adherence support services as well as facility and community based patient adherence groups on ART have been found to lead to lower rates of LTFU [12, 14‐16, 19, 20]. These findings are well in support of the South African government’s call for integrated patient care and the nationwide rolling out of adherence clubs/groups. It is also important for health facilities to investigate facility specific factors that can impact LTFU rates and implement programs that are tailored specifically to reduce LTFU in their unique settings [19]. Though other studies have also shown that young age, being male and illiteracy are risk factors for becoming LTFU, an association between age, sex or level of education and becoming LTFU was not found our study [9, 17, 20].

The benefits of taking ART were clearly identified: we found that there were significant increases in weight as well as in immune function (evidenced by increasing CD4 cell counts) from the time of ART initiation till the last known measurements both in patients that were LTFU and in those that remained in care. Our findings showed that patients that became LTFU had significantly lower weight and CD4 cell count measurements both at ART initiation and at last known measurement. However, patient weight was not associated with becoming LTFU.

There have been varying findings with regards to the association between baseline CD4 cell count and LTFU, with some studies showing that patients that had CD4 counts between 301 cells/ml and 350 cells/ml had a lower risk of becoming LTFU than those with CD4 counts < 200 cells/ml [13], while others showed that higher baseline CD4 cell count was associated with a higher risk of LTFU [12, 20, 21]. Our findings showed that patients that had a CD4 cell count of > 200 cells/ml at ART initiation were at a higher risk of becoming LTFU. This finding could possibly be explained by the fact that patients with a high CD4 cell count generally do not have the typical clinical symptoms of advanced HIV disease and thus, may not perceive the benefits of the strict patient follow-up schedule. However, we did not find any association between baseline WHO clinical staging and LTFU to further support this explanation. That we did not find any significant association between baseline WHO staging and LTFU was unlike other studies [17]. This could be explained by the fact that eligibility criteria for ART initiation may be based only on WHO staging in resource constrained countries, and may account for the variable study findings regarding the association between LTFU and WHO clinical staging. The use of WHO clinical staging as an ART eligibility criteria, may not necessarily correlate with immune status (CD4 count) or actual disease progress, especially where diagnostic tests for AIDS defining conditions are not readily available.

In our study we were able to demonstrate that patients that were not virologically suppressed (VL > 50 copies/ml) at last clinic visit had a three times higher risk of becoming LTFU than those that had a suppressed VL. Similarly, patients who had advanced clinical disease at last clinic visit (WHO clinical stage three or four) were twice as likely to become LTFU. Similar findings have been reported in other studies [17, 18]. It is important for measures to be put in place that improve retention rates among patients whose viral loads remain high and/or who continue to display advanced clinical stages of HIV disease, despite taking ART.

There is limited literature on the association between ART adverse events and LTFU. Just over half (56 %) of our cohort had a history of at least one ART related adverse event since ART initiation. Less than a quarter of the patients who reported experiencing each of the common ART related adverse event became LTFU. We would have expected that patients experiencing adverse events would likely be discouraged from taking their ART. However we found that these patients had a lower risk of becoming LTFU when compared to patients that had not had ART related adverse events. This result may possibly be due to the perception that patients have of their health status, but further investigation is necessary.

The MNPC is the only structured surveillance cohort that has been set up by the South African National Department of Health to follow up patients that have been initiated on ART. As such, the cohort is the evidence base which provides insight into different aspects of the National ART program. Our study did have limitations that should be taken into account when interpreting the findings. Firstly, we only analysed about 53 % of the patients that were enrolled into the PV surveillance cohort during the period of the study. This could have possibly introduced some selection bias into the study and could have led to an over- or under-estimation of the true incidence of LTFU in our study. We, however, found no significant differences in demographic characteristics when we compared the patients that we included in the study and those that were excluded. Secondly, we were unable to obtain the date of death for some of the patients that died after being LTFU, and thus were not able to confirm whether the patients died 180 days or more after the last clinic appointment. It is therefore possible that some of these patients were misclassified as LTFU, resulting in an over-estimation of the true incidence of LTFU. Thirdly, we assumed that all the patients that were transferred from Tshepang clinic to other ART clinics were still in care at the time of censoring. It is possible that some of these patients became LTFU after being transferred, leading to an under-estimation of the rate of LTFU in our study. Lastly, it is also likely that some of the patients that we classified as LTFU could have self-transferred and continued ART at other sites without notifying Tshepang clinic. This could have led to an over-estimation of the incidence rate of LTFU in our study. Despite these limitations, we believe that our study findings provide an important insight into the magnitude and the factors related to LTFU among patients on ART.