To our knowledge, this is the first study from sub-Saharan Africa to report on unstructured treatment interruptions in a routine programme setting. Our analysis shows that treatment interruption is a common phenomenon. The probability of ART defaulters to resume therapy within 3 years was 42%. Most ART cohorts report on loss to follow-up defined as not attending the clinic for more than 3 months,8
and assume that loss to follow-up is an irreversible event. Our study shows that patients who fulfil the widely used definition of loss to follow-up at one time point might resume therapy later. In this cohort, the median duration of the first treatment interruption was 7.5 months.
The median CD4 count of those resuming therapy was similar to their initial CD4 count prior to starting treatment, which underscores the potentially negative impact of interruption leading to a reversal in immunological recovery made while on treatment. Data from industrialised settings suggest that treatment interruption has detrimental effects on CD4 count, viral load suppression, and clinical progression.11, 12, 19
Programmes that report patient attrition and the number of patients in care will not account for the potential that up to 14% of patients in care have interrupted treatment at least once.
We were able to determine risk factors for defaulting ART and factors associated with resuming therapy. Male gender, high baseline CD4 count, recency of ART initiation and the first 6 months of treatment were associated with a higher risk of defaulting. Treatment resumption was more likely in women, patients more than 30 years old and within the first year of stopping therapy.
Our finding that men were at higher risk of defaulting treatment and less likely to resume treatment is consistent with studies showing that HIV-infected men are less likely to access treatment25, 26
, have an increased risk for loss to follow-up in the pre-treatment period27
, present with more advanced stages of HIV disease28
and have a higher mortality risk on ART.2, 9, 29-33
Strategies to diagnose HIV in men earlier and to link and to retain them in care might include: i) extending clinic hours into evenings and weekends, ii) training male health care staff and counsellors, iii) offering additional adherence sessions to men and iv) initiating male support groups.
Individuals initiating treatment in more recent years were more likely to default, suggesting that programmatic factors might influence retention in care. A study including data from 15 treatment cohorts from Africa, Asia and South America showed that early patient losses were increasingly common when programs were scaled up.6
Increasing cohort size in an environment of scarce human resources for health has been suggested to influence both the scale-up capacity and the long-term retention in ART programs.34
In the study clinic resources and staffing were further reduced when enrolment for the NIH-funded study finished in 2007. In contrast, year of defaulting was not associated with resumption of treatment, suggesting that patient tracing was less influenced by cohort size (although this would vary according to tracing procedures).
Treatment defaulting was more likely in patients with less advanced immunodeficiency at baseline. This may be explained by the fact that individuals who default treatment and stay alive do so because they feel better on treatment, a phenomenon that has been reported by other studies.35
This finding is particularly important in view of the 2009 WHO guidelines recommending ART initiation at CD4 counts below 350 cells/ μl36
and when considering initiation of ART regardless of CD4 count as proposed in the ‘test and treat’ strategy.37
Initiating ART at the time of HIV diagnosis will result in increased numbers of relatively immunocompetent individuals on ART who may have a higher risk of defaulting treatment. Specific interventions aimed at these individuals need to be developed to ensure optimal retention in care.
This study has several limitations. First, ascertainment of vital status for treatment defaulters was incomplete, which may have led to a misclassification of deaths as defaulters. However, sensitivity analysis excluding individuals with unascertained vital status did not influence our overall findings. Second, resumption of therapy was not ascertained in patients who moved to other communities, possibly resulting in underestimation of treatment resumption. Third, the clinical and immunological consequences of treatment interruption were not analysed due to lack of laboratory data, in particular the lack of capacity to perform routine viral load, and the small number of individuals resuming therapy. However it has been shown in industrialised settings that treatment interruption impacts negatively on CD4 count, viral load suppression and clinical progression.11, 12, 19
We consider that the main finding of this study that a considerable proportion of treatment defaulters return to care is likely to be generalisable to similar settings. Nevertheless, risk factors for defaulting and resuming therapy might differ with regards to eligibility criteria and resources available for patient tracing.
A strength of this study is that the relatively large sample size and follow up time. This allows for an assessment of risk factors for defaulting and treatment interruption that in turn allows for several proposals to be made to limit defaulting and treatment interruption in similar programme settings. In particular, interventions to keep patients in care should be targeted at men, patients with higher CD4 counts and during the first 6 months of ART. Moreover, the finding that the probability of resuming therapy was highest in the first year following treatment defaulting suggests that efforts to bring patients back into care might be most successful early into defaulting treatment.