ART at CD4 cell counts below 50 cells/mm3 increased the relative
risk of death by approximately 60%, compared to starting at 150 to 249 cells/mm3
or more, and more than tripled the risk of death when compared to starting at a CD4 count above 300 cells/mm3. These findings were reported by Edward J Mills and colleagues in an observational study
of 22,315 patients in ten clinics in Uganda, studied over a ten-year period, and published
in the advance online edition of AIDS.
lower the CD4 cell count at the start of ART, the greater the risk of death.
Death rates were highest in the first year.
a median follow-up period of 31 months ((IQR: 19-45), 6.7% died and 6.4% were
lost to follow-up.
is, note the authors, the largest study to look at the effects of baseline CD4
cell count on mortality
in HIV patients on ART in sub-Saharan Africa, and to quantify the relative risk of very late initiation of antiretroviral therapy.
cell count at the start of ART is one of the most important predictors of
in most resource-poor settings start ART late in the course of their illness,
often with very low CD4 cell counts
World Health Organization guidelines recommend that ART is started at 350 cells/mm3 or below; the International AIDS Society guidelines recommend starting at 500 cells/mm3 or below. Guidance is
based on limited and conflicting data from resource-rich settings.
Data from The AIDS Support Organisation (TASO) clinics in Uganda, from patients aged 14 or over who had started ART between 1 January 2000 and 1 February 2010, were analysed.
were followed until death or the end of the study. Age, gender, and baseline
CD4 cell count (divided by categories: below 50, 50 to 99, 100 to 149, 150 to 249,
250 to 299, and at or above 300 cells/mm3) were noted. Survival was
assessed according to these categories.
age was 37 years (IQR: 31-43) and 70% of patients were female.
CD4 cell count at the start of ART was 142 cells/mm3 (IQR: 70-206
cells/mm3), with more than 70% starting with a CD4 cell count under 200
Sixty per cent of patients started treatment at an advanced stage of their illness (WHO disease stage II
or III). Adherence was maintained at 95%
and over for 85.8% of patients.
authors note that, unlike many programmes in Africa, TASO programmes have a
relatively low loss-to-follow-up rate, as shown in this study. They explain that TASO clinics provide adherence counsellors and database managers at each of their sites. In addition,
peer support groups and psychosocial support have played an important role in
TASO programmes, from the beginnings of the epidemic in Uganda.
mortality rates ranged from 53.8 per 1000 patient-years (95% CI: 48.8-58.8) among
those starting ART with CD4 cell counts below 50 cells/mm3, to 15.7
per 1000 patient-years (95% CI: 12.1-19.3) for those with CD4 cell counts over
for gender, WHO disease stage and year when starting ART, the risk of death
increased significantly as the CD4 cell count decreased. However, the authors
stress that the best time to start ART cannot be determined from this study.
to a CD4 cell count at baseline of under 50 cells/mm3, the risk of
mortality was 0.75 (95% CI: 0.65-0.88)at 50 to 99 cells/mm3; 0.60 (95%
CI: 0.51-0.70) at 100 to 149 cells/mm3; 0.43 (95% CI: 0.37-0.50) at
150 to 249 cells/mm3and 0.41 (95% CI: 0.33-0.51) at more than 250 cells/mm3, p=<0.001.
when taking into account the missing baseline CD4 cell counts of 3817 patients
(17.1%), the differences remained significant.
authors note that the missing data, as in other resource-poor settings, reflect
a lack of resources. In addition, they note that routine patient data
– such as viral
load or resistance testing data
– are not available, so it is not possible to
understand how these factors may have affected mortality in this cohort.
authors caution against drawing conclusions about causality as this was an
authors note their study did not take into account patients, in any of the CD4
cell-count categories, who died before receiving ART.
recommend patients start ART at or below 250 cells/mm3. In the
interests of improved access to treatment and health, the Ugandan Ministry of
Health is considering an increase in the threshold for starting treatment to
authors conclude that starting ART earlier is associated with increased
survival benefits and “may extend beyond mortality alone to decreased
co-infections, decreased resource costs and possibly even prevention efforts”.