Mutations in
human immunodeficiency virus type 1 (
HIV-1) are a major impediment to successful
highly active antiretroviral therapy (
HAART) and the design of anti-
HIV vaccines. Although
HAART has made long-term
suppression of
HIV a reality,
drug resistance,
drug toxicity,
drug penetration, adherence to
therapy, low levels of continued
viral replication in cellular
reservoirs and augmentation of host
immune responses are some of the most important challenges that remain to be sorted out. Continuing
viral replication in the
face of
HAART leads to the accumulation of
drug resistance mutations, increase in viral loads and eventual
disease progression.
Patients who fail
therapy have minimal options for their clinical management. Therefore, a clear
understanding of the pathogenesis of
drug-resistant
HIV-1, and all of the issues that influence the success of
HAART is urgently needed. In the present article, we discuss various obstacles to
HIV therapy, and provide perspectives relating to these issues that are critical in determining the success or failure of
HAART.