Background: Clinical trials frequently enroll subjects from different study sites. Few
such studies provide analysis by individual site. Between 2004-2007, the South African Military
Health System (SAMHS) established 6 research sites (3 urban, 3 rural) to build capacity for clinical
research and HIV care. We explore differences in clinical, virologic and CD4 outcomes by site in
the context of a randomized controlled trial.
Methods: Phidisa-II is the first randomised controlled trial conducted in the South African military
setting, which compared 4 antiretroviral regimens in treatment-naïve advanced HIV subjects. Primary
study outcome was first AIDS event or death. Kaplan-Meier curves for AIDS events and mortality
were compared across sites. Hazard rates were adjusted for baseline risk factors to assess the
independent effect of site. Secondary outcomes of CD4 count and viral responses are also compared
across study sites.
Results: 1,771 subjects [average age=35.4 ± 5.5 years old, 68% male, with median CD4 count=105
(IQR 41, 157) cells/mm3 and HIV RNA=144,000 (IQR 53,900-305,000)copies/mL] enrolled in 3
urban and 3 rural sites. Sites varied considerably in resources and diagnostic capacities. After adjusting
for baseline characteristics, study site was found to be a factor significantly associated with
mortality (p=0.008), with Urban 2 and Rural 2 sites had the lowest mortality. Site was also associated
with the adjusted hazard for AIDS events (p=0.038). At 24 months, CD4 count was similar
across sites, but HIV suppression rate varied considerably (range 40-70%).
Conclusion: Site heterogeneity was found in primary clinical outcomes of mortality and AIDS
event rates, but there were no clear patterns for differences between the rural versus urban sites. Site
differences were also found in the proportion of confirmed AIDS events. Factors within study sites
that may have contributed to poorer outcomes need further investigation.