Resistant viral variants in cellular reservoirs of human immunodeficiency virus infection

Since the advent of antiretroviral therapy (ART), morbidity and mortality rates in those infected with human immunodeficiency virus type 1 (HIV-1) have been significantly reduced. However, HIV-1 is known to persist in several types of cells and tissues, and will usually return to pretreatment levels when therapy is stopped, even in those individuals who have been on suppressive ART for a long time. The discovery of drug sanctuaries and viral reservoirs in the body, in which HIV may persist, has helped to explain why therapeutic eradication of HIV-1 has proved so difficult. Several studies have indicated that the latent reservoir is an archive, composed of a mixture of wild-type and drug-resistant strains. Archived variants are assumed to remain life-long, thereby precluding the successful recycling of any drug towards which resistance has arisen. Several studies have underlined the value of pro-viral DNA as an additional source of information on the total burden of resistance in an individual. The HIV mutation patterns detected in plasma do not necessarily reflect those found in the cell-associated compartment, and may not be the same as those in different anatomical compartments. Although assessment of drug resistance in plasma is of direct and immediate importance for treatment, examination of the genotypic pattern of HIV-1 in cellular compartments might also provide information allowing a more sustainable response to therapy and better disease management.