Obstacles to successful antiretroviral treatment of HIV-1 infection: problems & perspectives.
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.
Potter
Simon J
SJ
Retroviral Genetics Laboratory, Centre for Virus Research, Westmead Millennium Institute, Sydney, NSW, Australia.
Chew
Choo Beng
CB
Steain
Megan
M
Dwyer
Dominic E
DE
Saksena
Nitin K
NK
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018450:Disease Progression; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D019427:HIV Integrase / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D011480:Protease Inhibitors / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D019562:Viral Load; D016335:Zinc Fingers
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019427:HIV Integrase