of South Africa’s 2011 expansion of treatment guidelines – starting
antiretroviral therapy (ART) at or below 350 cells/mm3 – will not
increase patient loss to follow-up, researchers report in this first study from
a routine clinical setting published in the advance online edition of AIDS.
findings, however, showed considerable variation by gender. The link between
starting ART at higher CD4 counts and reduced risk of loss to follow-up was greatest
among non-pregnant women, and men.
one year of starting ART at 201-350 cells/mm3, there was a 42%
(adjusted hazard ration [aHR]: 0.58, 95% CI:0.37-0.91) and 26% (aHR: 0.74, 95%
CI: 0.44-1.23) reduced risk of loss to follow-up among non-pregnant women and
men, respectively, compared to those starting ART below 200 cells/mm3.
to follow-up among pregnant women starting ART was the highest of any gender
group; starting ART at higher CD4 counts had no effect on the risk of loss to
follow-up in this group.
with other findings, this “is particularly concerning since HIV is the largest
cause of maternal mortality in South
Africa” the authors note.
in other studies, risk of death and tuberculosis was much lower during the
first year among those starting treatment at higher CD4 counts.
a patient starts treatment before s/he sees a clinical need, the risk of the
patient being lost to follow-up may increase, so potentially reversing the clinical
gains of starting treatment earlier, the authors note.
loss is a major challenge to providing effective HIV care and our results
suggest that expanding ART eligibility to patients with higher baseline CD4
values can be done without increasing loss”, the authors comment.
mid-2011 an estimated 1.8 million people in South Africa had started ART since
the launch of its national programme in 2004, the world’s largest.
national guidelines set ART eligibility at under 200 cells/mm3 or
the World Health Organization (WHO) clinical stage IV.
2009, WHO revised its guidelines, raising the threshold for ART eligibility to
at or below 350 cells/mm3 in resource-poor settings. In August 2011, South Africa
officially adopted this as policy. This change resulted in an estimated
additional 1 million treatment-naive adults with CD4 counts between 200 and 349
cells/mm3 becoming eligible.
it is known that starting ART at higher CD4 cell counts reduces the risk of
death and disease, the effect of earlier treatment on loss to follow-up has not been measured.
authors cite the only study within sub-Saharan Africa (in Lesotho) reporting on
the effect of starting ART at higher counts on loss to follow-up, which found a
39% reduced risk when starting ART at CD4 counts above 200 compared to starting
treatment at or below 200 cells/mm3.
Witkoppen Health and Welfare Centre, an NGO-operated clinic in northern Johannesburg serving a
mostly poor population from formal and informal settlements, provided a unique
opportunity to examine this within the context of routine care. Wittkoppen
began providing ART to all adults with CD4 counts at or under 350 cells/mm3
in March 2010, over a year before the national policy was formalised.
this observational cohort the authors created a retrospective study of all
ART-naive adults (over 18 years of age) starting ART at or above 350 cells/mm3
between April and December 2010. Data were taken from the clinic’s electronic
patient record system in May 2012 to allow for all patients to have a 12-month
starting ART, monthly clinic visits are scheduled until a patient is considered
stable and adherent, which usually takes five to six months. After this point, visits
are scheduled every three to six months.
authors compared loss to follow-up, defined as not returning to clinic within
three months of the last missed scheduled visit, death and incident
tuberculosis within one year of starting ART between those at or under 200
cells/mm3 and those with 201 to 350 cells/mm3.
the 1430 patients, at the start of ART, almost half (48%) had a higher CD4 count
(201-350) with a median of 268 (IQR: 239-307) cells/mm3. Among those
(52%) with a CD4 count under 200 the median was 105 (IQR: 55-154) cells/mm3.
greater proportion of women had a higher CD4 count (75.7% compared to
63.4%). This is in part because more pregnant women were in the higher group
(19.2% compared to 10.6%) due to routine antenatal testing, the authors note.
was more prevalent at the start of ART in the lower CD4 group (16.7% compared
the first year of starting treatment, loss to follow-up was highest among those
in the lower CD4 group, with 15.5% (95% CI: 13.0-18.2%) compared to 12.7% (95% CI:
authors found that loss to follow-up among men in both groups was considerably
higher than among non-pregnant women starting ART at the higher CD4 count.
Consistent with other studies the higher loss among men would suggest, the
authors note, the need for specific retention interventions targeted to men.
line with a number of other studies in resource-poor settings these findings
contribute to the evidence of significant reduced risk of death and
opportunistic infections when starting ART at higher CD4 cell counts, lending
further support to South
Africa’s decision to revise its guidelines
in accordance with WHO recommendations.
The unique study site meant the issue could be examined within the
context of routine clinical care.
relate to a single site so they may not be generalizable to all public health
sectors in South Africa
or healthcare centres in other regions.
authors caution not to interpret these findings as evidence for when to start
ART. “Our results only pertain to what happens to patients once they are
diagnosed and initiate ART at their initial presentation CD4 value.”
authors conclude, “As data becomes available from more sites that adopted the
policy of initiating ART at higher CD4 cell counts, it will be important to
perform similar evaluations... Such information will be invaluable to national
HIV/AIDS programmes looking for guidance about the implications of earlier ART
initiation, and may inform future expansions of the ART treatment criteria in South Africa.”