Understanding the impact of losses from HIV treatment programs is critical to accurately evaluating their overall success. In some HIV treatment programs, LTFU may constitute the largest proportion of overall program attrition (Rosen et al. 2007
). In our study, ascertainment of mortality was strongly underestimated in our clinic even though limited active tracing does exist. After matching clinic data with the vital registration system mortality more than double from 4.2% to 10.0%. While this increase is large, other programs without active tracing programs have estimated that their mortality increased as much as five-fold after adjusting for the high rate of death amongst those lost (Geng et al. 2008a
Our study confirms, in a well defined population, the suspicion that there is high mortality amongst those lost from HIV treatment programs in South Africa. We found that the probability of death among those lost to follow-up was nearly 30% at the end of one year. It is encouraging, however, to see that the rate of death in the first year after being lost has steadily fallen since 2004 (test for trend p = 0.0002). While this overall high mortality rate among those lost means that many who are lost are likely not seeking care from another provider, others may be, particularly as more options for care become available. In a recent systematic review, Brinkhof et al. (2009)
estimated that among those lost whose vital status could be determined mortality was as high as 40%, 10% higher than our estimate. Because our study included all patients whose national ID number we had, our study is likely more representative of the clinic population than would be achieved by attempting to contact patients. In addition, as their data was a systematic review it contained results from much earlier in the experience with ART scale up and therefore may reflect higher mortality associated with more limited access to care and fewer options for transferring to another site.
Appropriately evaluating treatment programs means assessing treatment outcomes for all patients. Typically analyses of ART program effectiveness report on both mortality and LTFU because the two are closely linked, but many of those who are lost will have died and are therefore misclassified. It has previously been shown that failure to determine the outcomes in patients lost can cause dramatic underestimation of overall mortality. In a cohort in Botswana missing deaths among those LTFU caused overestimating of one year survival rates by nearly 10% (Bisson et al. 2008
). Despite this, as resources targeted for tracing patients who are lost are limited, outcome assessment remains poor.
A 2007 review concluded that in Africa only South Africa, Mauritius and the Seychelles have well-functioning vital registration systems (Setel et al. 2007
). Outside of these areas, an alternative proposed solution to the problem of poor outcome assessment is to trace randomly sampled subsets of the population and use estimates from the subset whose vital status can be traced to adjust overall estimates of mortality in the cohort (Yiannoutsos et al. 2008
; Geng et al. 2008b
). Another approach uses a nomogram approach to adjust overall mortality (Egger et al. 2009
). When no viable vital registration system exists but resources are available to contact a sample of patients, this approach is likely an improvement over crude approaches which ignore LTFU. However, our study demonstrates that even approaches that sample patients to determine their vital status likely suffer from some bias as they miss patients who cannot be contacted and may miss deaths among patients who go on to die after the sampling.
Despite the benefits of using statistical approaches to adjust for deaths among those lost, this approach is not preferable to directly identifying the vital status of those LTFU. Programs with active tracing have been shown to have substantially lower rates of death than those without (Keiser et al. 2008
). This approach has the added advantage of being able to bring patients back into care and potentially reduce the overall mortality rate. Still when not possible, our results show that matching with vital registration systems can be successfully implemented to better estimate the total mortality of patients in ART programs.
While all patients lost from care are at increased risk for mortality, identifying patients at highest risk for dying after leaving care is of critical importance. In our analysis, those at highest risk of death after being LTFU were predominately those who were sickest when leaving care (low CD4 count, BMI and hemoglobin levels before leaving care) and those on treatment for < 6 months prior to being lost. In cases where limited resources exist for getting patients back into care, these sicker patients should be prioritized for tracing and returned to care.
Our findings must be interpreted in light of their limitations. First, since it is not mandatory for patients to provide a National Identification number when registering for treatment at the clinic we were not able to verify the outcome status of all patients. The clinic in which the study was conducted does not turn away patients regardless of whether or not they have a National ID number. Patients without an ID number could not be included in the analysis and may have been more likely to have died than patients included in the study. If so, our estimates of updated mortality would likely be underestimates. In addition, because stigma still exists around HIV/AIDS some patients may provide a fake identification number for fear of being identified as being HIV positive or of being turned away. Given this, despite dramatically increasing our overall mortality rate to more accurately reflect overall programmatic impact, we are still likely underestimating the true mortality rate amongst those LTFU at the clinic.
In conclusion, we found that mortality was substantially underestimated among patients lost to follow up in an HIV treatment program in Johannesburg, South Africa despite an active tracing program to return patients lost to care. Linking to the national vital registration system proved to be a practical method to more accurately represent mortality in the cohort. Linking to vital registration systems, when feasible can provide a means to more accurately assess the effectiveness of a program and target LTFU patients most at risk for mortality.