Social and clinical attributes of patients who restart antiretroviral therapy in central and Copperbelt provinces, Zambia: a retrospective longitudinal study

Antiretroviral therapy (ART) is an essential part of the fight against the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), sustains human lives for people living with HIV (PLHIV) and prevents HIV/AIDS morbidity and mortality [1]. ART though expensive, in the long run saves money and promotes development [2]. While the benefits and successes of ART have been widely acknowledged worldwide [1, 3‐6], about 30 % of the patients are lost to follow-up (LTFU) from treatment in programmes in most developing countries [7‐10]. However, some of the patients who interrupt ART later restart the treatment. This interruption of ART prevents patients from reaping the full benefits of the treatment [2].

LTFU was defined in the 2010 Zambia ART guidelines as missing a scheduled pharmacy pick-up for more than 60 days [11]. Patients who came back to ART after LTFU were considered to have restarted ART. Therefore, treatment resumption in this study was defined as restarting ART after the patient was declared LTFU at the health facility. Defaulting results in treatment interruption, which has negative effects on the CD4 cell response of the patient. Patients who default and restart ART run a higher risk of illness and death because of AIDS-related conditions [3, 4, 10, 12‐18]. Defaulting may, therefore, result in patients restarting ART at an increased viral rebound, acute retroviral syndrome due to immune decomposition and an increased risk of HIV transmission [19].

It has been suggested that patients who restart ART normally resume treatment at a CD4 count level lower to their CD4 count prior to ART defaulting but similar to the CD4 count at first ART initiation [17]. This underscores the potentially negative impact of treatment defaulting that might lead to a reversal of the immunological recovery made while on the initial treatment [20]. Defaulting ART has also been associated with age, gender, residency and self-rate health. In some studies Younger age or female gender or patients with CD4 counts >350 cells/mm³ were found to be more likely to default. Other studies established positive significant associations between restarting ART with older age or female gender or urban residency or shorter time since defaulting [18, 21‐23]. Despite knowing the factors associated with defaulting and restarting ART, the social and clinical characteristics of such patients who default and restart have not been well described and documented in Zambia where the attrition rate of patients is still high [8]. Therefore this study aimed at describing and documenting the socio-demographic and clinical characteristics of patients who defaulted and restarted ART from January, 2009 to December, 2010 in Zambia; and also to determine the socio-demographic and clinical characteristics associated with CD4 count response at 6 and 24 months after restarting ART.

The study demonstrates that different individuals will exhibit different responses in CD4 cell count after restarting ART. Age, occupation, type of treatment, total duration on treatment, duration of LTFU, duration on treatment before LTFU and previous CD4 count were associated with CD4 cell count at 6 months after restarting ART. At 24 months after restarting ART, three (3) variables were significantly associated with CD4 count and these were Age, CD4 count at 6 months and total duration on treatment.

In this study, most of the patients who restarted ART were ≥35 years. The patients in the age group of ≥45 years showed a significant lower CD4 count at 24 months as compared to the age group 15–34 years. Younger age may be associated with better CD4 cell count recovery while older age maybe associated with a weaker immunity system, which makes the immunological recovery slower. The older patients may also be more likely to develop more severe opportunistic infections associated with old age than the younger age group even after they resume ART. This result is consistent with the study done on adults in South Africa, which found that resumption of ART was more likely in patients ≥30 years old than those who are younger [18]. Furthermore, in a cohort study conducted in a hospital setting in Brazil, patients over 40 years of age were reported to present lower increase in CD4 cell count over time compared to the younger age group [25]. This result may have important public health implications in the administration and retention of older patients in ART care.

Patients in formal and self-employment showed a higher CD4 cell count increase as compared to those unemployed and this higher CD4 count was attained in the first year of restarting ART. It is a well-known fact that paid work is good for health and may improve access to health services (including ART care) through employer-sponsored health programmes [26]. The income status of an individual and the family dynamics have been reported to influence the health outcome of the patients on ART. Poor living conditions and failure to meet the indirect cost of ART were factors preventing patients from complying with treatment. As a result, patients with less income have been reported to be 10 times more likely to experience negative life events than patients with high income [26, 27]. This could be the reason why patients in formal and self-employment showed a higher CD4 count increase in this study. In line with this assumption, approaches that aim at improving ART care services must include interventions that deliberately focus on ensuring high levels of adherence and low LTFU. These interventions must be tailored differently and specifically for employed and non-employed patients.

In this study, there was no significant association between education level and CD4 count response at both 6 and 24 months after restarting ART. This could be because the definition for highest grade one to twelve (1–12) in the secondary data used was too broad ranging from primary (grade one) to secondary education (grade 12). Patients who had attained grade one level of education may not be different from those with no education.

In addition to the socio-demographic characteristics associated with CD4 count cell response; CD4 count at restart of ART and WHO stage of the patient were associated with CD4 count cell response at 6 and 24 months after restarting ART. The median CD4 count of the patients restarted on ART was <350 cells/mm³ and most of the patients were in WHO stage 4. According to the Zambian National ART Guidelines for 2009 and 2010, patients qualified to be initiated on ART if they presented with CD4 count <350 cells/mm³ and were in WHO stage three or four. However, patients who had defaulted ART were restarted regardless of their CD4 cell count [28‐30]. This eligibility criteria were recommendations for patients who were initiating ART for the first time but not patients who were restarting ART.

As the patients continued on treatment more and more patients moved to WHO stage 1, as a result, over 83.6 % of the patients were in WHO stage 1 and 2 by the end of 24 months. This was expected in the present study as it has been a trend in previous studies [27, 31]. However, results in this study show that despite being on treatment for 24 months, some patients still remained in WHO stage 4 indicating the negative effect of interrupting ART. This may be because treatment interruption in patients may affect the CD4 cell count response negatively after restarting ART [17]. Treatment interruption is also associated with increased risk of disease progression and death [3, 32]. This could explain why the majority of the patients restarting ART were in WHO stage 4 and not the asymptomatic WHO stage 1.

The increment in the number of patients in WHO stage 1 is an indicator that patients who restart ART are likely to respond well to treatment as suggested by the study which was done in rural Zambia and in settings with inadequate HIV treatment available [19, 33]. Similarly, the current study shows that at both 6 and 24 months after restarting ART, the CD4 count of the patients in WHO stage 2, 3 and 4 increased but was inferior to the increase observed in patients who restarted ART in WHO stage 1. This may be due to the reason that baseline CD4 count is one of the most important determinant of subsequent CD4 cell count trajectories in both patients that are initiated on ART for the first time and those that default and restart ART [34]. These results though obtained from two different groups are comparable. It can, therefore, be suggested that there might be no difference in CD4 count responses between patients who restart and those initiated on ART for the first time. However, there is need for further research in this area.

The results in this study are crucial to understand the social and clinical characteristic of patients who default and restart ART in Zambia. The socio-demographic characteristics show that patients that restart are more likely to be aged 35 years and above, married, and must have gone to either primary or secondary level of education. CD4 cell count of the patients who restart ART was associated with age, occupation, type of treatment, CD4 at ART restart and CD4 count at 6 months after restarting ART. These significant associations were observed as early as 6 months after restarting ART and seemed to be confounding.

The finding of this study must be considered in light of the limitations of this study. Firstly, data was collected retrospectively hence some variables had missing information which caused the sample size to vary at each stage of the analysis. However, the variables and patient files with significant missing data were excluded during data analysis. All the main predictors for the dependent variable were also adjusted for at each stage of analysis thereby minimizing potential bias in the main results due to confounding. Furthermore, the reason as to why the patients at Kabwe General Hospital recorded a significantly higher increase in CD4 count as compared to other facilities is not known because the data was collected retrospectively. Secondly, adherence to ART after restarting was based on the records from the pharmacy pick-up of the medication. Finally, this study was conducted at only 5 ART facilities in the Copperbelt and Central provinces of Zambia which were purposively sampled. Therefore, the results can only be generalized to similar settings but not for the country.

The outcome of the research suggest that, ART as the essential and vital medicine used to the fight against HIV/AIDS, sustain human lives and prevent HIV/AIDS morbidity and mortality can only give the full benefits when patients stop defaulting and those who restart adhere to treatment after restarting.