Viral load monitoring of antiretroviral therapy in low-resource settings: Design and implementation of a cluster-randomized clinical trial

Potential benefits and cost-effectiveness of viral load monitoring of antiretroviral therapy (ART) require investigation using an approach that is directly relevant to rapidly expanding treatment programs associated with the US President's Emergency Plan for AIDS Relief (PEPFAR). The primary aim of the ongoing Viral Load Study in Zambia is to determine whether routine viral load testing of patients on ART improves survival. The trial is powered for mortality; target enrollment is 2100 adults initiating ART to be followed for 18 months. Ministry of Health clinics in Lusaka were cluster-randomized to one of two strategies to monitor ART response: (1) standard care, i.e., monitoring treatment response with clinical criteria, CD4+ cell counts every six months, and rare viral load testing, or (2) standard care enhanced with viral load testing at 0, 3, 6, 12, and 18 months. The study is nested within the national ART program to optimize external validity and feasibility assessment. As of January 2008, the study has been successfully implemented in 12 Lusaka clinics with 1968 participants enrolled. After a median of 9.2 months of follow-up, 132 participants had died, and 120 had been discontinued due to voluntary withdrawal (n=37), loss to follow-up (n=31), and transfer out of Lusaka (n=52). The Viral Load Study is assessing whether regular viral load testing is beneficial and, if so, practical and cost-effective, or causes harm by wasting resources and/or prematurely exhausting limited drug options in developing country settings. This large pragmatic clinical trial demonstrates successful implementation of a scientifically rigorous study overload on usual PEPFAR-related ART practice.