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Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda

Reynolds, Steven Ja,b; Nakigozi, Gertrudec; Newell, Kevind; Ndyanabo, Anthonyc; Galiwongo, Ronaldc; Boaz, Igac; Quinn, Thomas Ca,b; Gray, Rone; Wawer, Mariae; Serwadda, Davidf

doi: 10.1097/QAD.0b013e3283262a78
Clinical Science: Concise Communications

Objective: Most antiretroviral treatment program in resource-limited settings use immunologic or clinical monitoring to measure response to therapy and to decide when to change to a second-line regimen. Our objective was to evaluate immunologic failure criteria against gold standard virologic monitoring.

Design: Observational cohort.

Methods: Participants enrolled in an antiretroviral treatment program in rural Uganda who had at least 6 months of follow-up were included in this analysis. Immunologic monitoring was performed by CD4 cell counts every 3 months during the first year, and every 6 months thereafter. HIV-1 viral loads were performed every 6 months.

Results: A total of 1133 participants enrolled in the Rakai Health Sciences Program antiretroviral treatment program between June 2004 and September 2007 were followed for up to 44.4 months (median follow-up 20.2 months; IQR 12.4–29.5 months). WHO immunologic failure criteria were reached by 125 (11.0%) participants. A virologic failure endpoint defined as HIV-1 viral load more than 400 copies/ml on two measurements was reached by 112 participants (9.9%). Only 26 participants (2.3%) experienced both an immunologic and virologic failure endpoint (2 viral load > 400 copies/ml) during follow-up.

Conclusion: Immunologic failure criteria performed poorly in our setting and would have resulted in a substantial proportion of participants with suppressed HIV-1 viral load being switched unnecessarily. These criteria also lacked sensitivity to identify participants failing virologically. Periodic viral load measurements may be a better marker for treatment failure in our setting.

aNational Institute of Allergy and Infectious Diseases, Bethesda, USA

bJohns Hopkins School of Medicine, Baltimore, USA

cRakai Health Sciences Program, Kalisizo, Uganda

dSAIC-Frederick directorate, SAIC-Frederick, Inc., NCI-Frederick, Frederick, USA

eJohns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA

fMakerere University School of Public Health, Kampala, Uganda.

Received 18 September, 2008

Revised 10 November, 2008

Accepted 11 December, 2008

Correspondence to Steven J. Reynolds, MD, MPH, 2190 Kampala Place, Washington, DC 20521, USA. E-mail:

© 2009 Lippincott Williams & Wilkins, Inc.