healthmedicinet

When attempting to estimate survival in a large HIV primary care-based sample of patients
diagnosed with KS spanning five countries in sub-Saharan Africa, we found that almost
half were lost to follow-up by the end of 2 years. Because the fraction of those lost
is so large and the disposition of the lost is unknown, it was therefore not possible
to estimate with any certainty a fundamental parameter in cancer epidemiology — survival
— using data from available clinical and administrative systems. As noted earlier,
for a technique like the Kaplan-Meier method to yield an estimate of survival in the
face of loss to follow-up, it requires an assumption that those who are lost to follow-up
have the same outcomes as those who remain under observation. Since this “non-informative
censoring” assumption is likely implausible in our context given that a higher portion
of the lost patients may in fact have died 28], our Kaplan-Meier estimate of survival is essentially uninterpretable.

The substantial loss to follow-up that we observed is consistent with findings from
other cancers in sub-Saharan Africa 29], 30], as well as KS specifically. Although the methodologic approaches and metrics vary,
reported loss to follow-up for KS at 1 year or less after diagnosis in Africa has
ranged from 15 to 23 % 18], 19], 21] and was 26 % at 2 years in another report 20]. Our work, which found an even higher incidence of lost to follow-up, bolsters these
earlier findings in several ways. First, the IeDEA consortium is a large and diverse
population, which for this project included patients from East, West, Central and
Southern Africa, thus enhancing the generalizability of the findings. Second, the
patients were not selected from oncology clinics, clinical trials, registries or a
tightly monitored research cohort. Instead, they were — by design — identified at
the time of their initial diagnosis in real-world community-based HIV primary care
settings and their subsequent observation was entirely without research influence.
Indeed, because we identified patients directly from HIV primary care clinics, irrespective
of whether they had a confirmatory biopsy, our population is likely different than
many registry-based cancer populations which primarily identify KS diagnoses from
pathology laboratories. Since we do not know which types of patients with KS in Africa
obtain a biopsy diagnosis (e.g., they may have more severe disease, or higher socioeconomic
status), it is unclear if patients who receive biopsies are representative of the
larger population of all incident KS. Therefore, if the target is to encompass all
new KS diagnoses in Africa, we believe that our estimate of the incidence of loss
to follow-up among persons with KS is among the least biased to date.

We were unable to determine survival due to the high loss to follow-up and the unknown
disposition of those that are lost to follow-up. In prior work from East Africa that
assessed a consecutive sample of HIV-infected adults attending HIV clinics (including
two clinics participating in this project), we actively sought after those who were
lost by searching for them in the community 31]. We found that three possible outcomes occur in considerable proportions: death,
previously undocumented transfer to another facility, or alive but discontinued care
32], 33]. Specifically, in this prior work, the cumulative incidence of mortality at 1 year
among those that were lost was ultimately found to be 36 %, once the patients had
been tracked 32], 33]. Such vital status estimates, derived from a general HIV cohort, are useful but cannot
be relied upon to accurately estimate mortality rates in selected sub-populations
such as patients with KS. Likewise, it is not likely that nomogram approaches to correct
survival in the face of lost to follow-up that were developed for all HIV-infected
patients on ART (irrespective of KS) 34] will perform adequately amongst patients with KS. Work from South Africa demonstrates
that loss to follow-up is higher in KS patients compared to other HIV-infected patients
starting on ART 21]. We speculate that this is because a larger fraction of patients with KS die, their
deaths go unrecognized by their primary care clinics, and, hence, they are deemed
lost to follow-up. Indeed, the higher incidence of loss among those with CD4???50
cells/mm
³
, while not statistically significant unless restricted to those with biopsy-proven
diagnosis, does suggest that those who were lost became lost because of death. Therefore,
the nominal estimate of survival we observed using available data is likely a substantial
overestimate. Without ascertaining the outcomes of those who are lost, we will never
understand true survival after a diagnosis of KS in sub-Saharan Africa.

A limitation of this work is that many of the KS diagnoses are based on clinical suspicion
only. The high frequency of clinical diagnosis of KS has been documented by others
35] and is largely due to the limited biopsy infrastructure in sub-Saharan Africa 36]. Work from East Africa has shown that there are many conditions that can clinically
mimic KS 37]; it is possible that our study population, therefore, includes patients with conditions
other than KS. Because we suspect that many more clinical mimickers of KS have more
favorable (as opposed to less favorable) prognosis compared to true KS, we again believe
that our nominal estimate of survival is an overestimate of truth. In addition, due
to atypically rigorous tracking of the lost at one of our sites (Lighthouse Clinic
in Malawi), we may actually underestimate the proportion of lost as it compares to
a general African clinic population. Finally, although not a threat to the internal
validity of the overall findings, the sites contributed sizably different numbers
of KS cases, which is in a large part a reflection of underlying differences in KS
epidemiology across sub-Saharan Africa.