Earlier treatment in South African cohort did not increase loss to follow-up

Implementation 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.

The 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.

Within 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.

Loss 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.

Consistent with other findings, this “is particularly concerning since HIV is the largest cause of maternal mortality in South Africa” the authors note.

As in other studies, risk of death and tuberculosis was much lower during the first year among those starting treatment at higher CD4 counts.

If 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.

“Patient 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.

By 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.

Initially, national guidelines set ART eligibility at under 200 cells/mm³ or the World Health Organization (WHO) clinical stage IV.

In 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.

While 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.

The 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.

The 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.

From 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 outcome.

After 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.

The 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.

Of 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.

A 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.

Tuberculosis was more prevalent at the start of ART in the lower CD4 group (16.7% compared to 5.7%).

Within 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: 10.3-15.3%).

The 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.

In 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.

Findings 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.

The 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.”

The 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.”

Clouse K et al. Initiating ART when presenting with higher CD4 counts results in reduced loss to follow-up in South Africa. Advance online edition AIDS 26, doi: 10.1097/QAD.0b013e32835c12f9, 2012.