The Role of Immunosuppression in Treatment Outcomes

Project Description

Throughout the developing world, the CD4 count threshold to initiate antiretroviral therapy (ART) is 200 for most programs. However, recent evidence suggests that delaying treatment until advanced immunosuppression occurs may lead to increased mortality and higher rates of first-line treatment failure and to poorer immune recovery.

In response, the WHO has recently recommended increasing the CD4 count threshold for treatment initiation to 350 and many countries are currently making this change.To date, however, few countries have done so. In order to contribute to the evidence base on when to initiate ART, the CGHD, in collaboration with the Clinical HIV Research Unit, conducted a study to determine whether initiating at higher CD4 counts led to significant gains in terms of mortality, virologic failure, incident tuberculosis, and loss to follow-up.

The study initiated ART in 294 patients with a CD4 count greater than 200 and 518 patients below 200. Death was much more common among those initiated below 200 compared to those initiated above 200 (3.7% vs. 0.7% respectively) as was virologic failure (12.2% vs. 6.8% respectively). Development of tuberculosis was also more common among those started at lower CD4 counts (8.0% vs. 3.1% respectively) but drop-outs from care were more common among those initiated at higher CD4 counts compared to those initiated at lower CD4 counts (10.0% vs. 14.3%).

This study is one of the first from a resource-limited setting to show that starting patients at higher CD4 counts likely has benefits in terms of better treatment outcomes and survival. However, as patients with higher CD4 counts may also be more likely to leave care and will be required to be on treatment for longer periods of time than those initiated later, it will be critical to monitor loss to follow-up in future cohorts as changes in CD4 initiation thresholds are implemented.

This project is one activity of the CGHD’s Economics and Epidemiology of HIV/AIDS Care and Treatment (South Africa Associate Award).

Project Details

Principal Investigator Matthew Fox
Country(ies) South Africa
Dates of Research 2009 – present