A Paradigm Shift to Prevent HIV Drug Resistance

Abstract

Standard care for HIV antiretroviral treatment in resource-rich regions of the world includes HIV RNA monitoring every three to four months for viral rebound (i.e., an increase in HIV RNA to detectable levels following suppression). Viral rebound confirmed by two HIV RNA determinations prompts adherence counseling, and a change in regimen based on prior antiretroviral treatment and antiretroviral resistance testing. Because of the prohibitive cost of viral RNA monitoring, standard care for resource-limited regions of the world includes clinical monitoring, together with CD4 monitoring if it is available. A new WHO (World Health Organization) Stage IV opportunistic infection, a 50% decline from peak CD4 level, failure to increase CD4 levels to 50–100 cells/mm3 after one year, or a fall in CD4 cell count to pretreatment levels after one year prompts a change to second-line therapy if available [1]. The major limitation of CD4 and clinical monitoring alone is that clinical deterioration and CD4 decline often occur well after virologic failure and the accumulation of resistance mutations that may compromise the efficacy of limited second-line treatment options [16]. Conversely, CD4 and clinical decline can occur in the absence of virologic failure, which can prompt a premature switch to second-line therapy. This limitation has prompted a search for low-cost approaches to HIV RNA monitoring, including new surrogates of HIV RNA [2]. This search, however, has yet to yield a reliable, inexpensive, and scalable approach for resource-limited regions of the world. Linked Research Article This Perspective discusses the following new study published in PLoS Medicine: Bisson GP, Gross R, Bellamy S, Chittams J, Hislop M, et al. (2008) Pharmacy refill adherence compared with CD4 count changes for monitoring HIV-infected adults on antiretroviral therapy. PLoS Med 5(5): e109. doi:10.1371/journal.pmed.0050109 Analyzing pharmacy and laboratory records from 1,982 patients beginning HIV therapy in southern Africa, Gregory Bisson and colleagues find medication adherence superior to CD4 count changes in identifying treatment failure.