title: Resistance to reverse transcriptase inhibitors used in the treatment and prevention of HIV-1 infection.
abstract: Inhibitors that target the retroviral enzyme reverse transcriptase (RT) have played an indispensable role in the treatment and prevention of HIV-1 infection. They can be grouped into two distinct therapeutic groups, namely the nucleoside and nucleotide RT inhibitors (NRTIs), and the non-nucleoside RT inhibitors (NNRTIs). NRTIs form the backbones of most first- and second-line antiretroviral therapy (ART) regimens formulated for the treatment of HIV-1 infection. They are also used to prevent mother-to-child transmission, and as pre-exposure prophylaxis in individuals at risk of HIV-1 infection. The NNRTIs nevirapine (NVP), efavirenz and rilpivirine also used to form part of first-line ART regimens, although this is no longer recommended, while etravirine can be used in salvage ART regimens. A single-dose of NVP administered to both mother and child has routinely been used in resource-limited settings to reduce the rate of HIV-1 transmission. Unfortunately, the development of HIV-1 resistance to RT inhibitors can compromise the efficacy of these antiviral drugs in both the treatment and prevention arenas. Here, we provide an up-to-date review on drug-resistance mutations in HIV-1 RT, and discuss their cross-resistance profiles, molecular mechanisms and clinical significance.
authors.affiliation: University of Pittsburgh School of Medicine, Division of Infectious Diseases, Department of Medicine S817 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sluis-Cremer
authors.affiliation: McGill University AIDS Center, Lady Davis Institute, Jewish General Hospital, 3755 Côte Ste-Catherine Road, Montreal, QC, H3T 1E2, Canada.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wainberg
authors.affiliation: Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University, Health Sciences Research Building, Room E-418, 1760 Haygood Drive, Atlanta, GA 30322, USA.|Veterans Affairs Medical Center, 1670 Clairmont Rd, Atlanta, GA 30033, USA.
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
mesh_terms: D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018562:Disease Transmission, Infectious / Q000517:prevention & control; D024882:Drug Resistance, Viral; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000517:prevention & control; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D020125:Mutation, Missense; D065129:Pre-Exposure Prophylaxis / Q000379:methods; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase
keywords: HIV; mutations; non-nucleoside; nucleoside; resistance; reverse transcriptase