PMID- 15995959 OWN - NLM STAT- MEDLINE DCOM- 20050923 LR - 20181113 IS - 0022-1899 (Print) IS - 1537-6613 (Electronic) IS - 0022-1899 (Linking) VI - 192 IP - 3 DP - 2005 Aug 1 TI - HIV-1 Protease and reverse-transcriptase mutations: correlations with antiretroviral therapy in subtype B isolates and implications for drug-resistance surveillance. PG - 456-65 AB - Background. It is important, for drug-resistance surveillance, to identify human immunodeficiency virus type 1 (HIV-1) strains that have undergone antiretroviral drug selection.Methods. We compared the prevalence of protease and reverse-transcriptase (RT) mutations in HIV-1 sequences from persons with and without previous treatment with protease inhibitors (PIs), nucleoside RT inhibitors (NRTIs), and nonnucleoside RT inhibitors (NNRTIs). Treatment-associated mutations in protease isolates from 5867 persons and RT isolates from 6247 persons were categorized by whether they were polymorphic (prevalence, >0.5%) in untreated individuals and whether they were established drug-resistance mutations. New methods were introduced to minimize misclassification from transmitted resistance, population stratification, sequencing artifacts, and multiple hypothesis testing.Results. Some 36 established and 24 additional nonpolymorphic protease mutations at 34 positions were related to PI treatment, 21 established and 22 additional nonpolymorphic RT mutations at 24 positions with NRTI treatment, and 15 established and 11 additional nonpolymorphic RT mutations at 15 positions with NNRTI treatment. In addition, 11 PI-associated and 1 NRTI-associated established mutations were polymorphic in viruses from untreated persons.Conclusions. Established drug-resistance mutations encompass only a subset of treatment-associated mutations; some of these are polymorphic in untreated persons. In contrast, nonpolymorphic treatment-associated mutations may be more sensitive and specific markers of transmitted HIV-1 drug resistance. FAU - Rhee, Soo-Yon AU - Rhee SY AD - Division of Infectious Diseases, Department of Medicine, Stanford University, CA 94301, USA. FAU - Fessel, W Jeffrey AU - Fessel WJ FAU - Zolopa, Andrew R AU - Zolopa AR FAU - Hurley, Leo AU - Hurley L FAU - Liu, Tommy AU - Liu T FAU - Taylor, Jonathan AU - Taylor J FAU - Nguyen, Dong Phuong AU - Nguyen DP FAU - Slome, Sally AU - Slome S FAU - Klein, Daniel AU - Klein D FAU - Horberg, Michael AU - Horberg M FAU - Flamm, Jason AU - Flamm J FAU - Follansbee, Stephen AU - Follansbee S FAU - Schapiro, Jonathan M AU - Schapiro JM FAU - Shafer, Robert W AU - Shafer RW LA - eng GR - R01 AI068581/AI/NIAID NIH HHS/United States GR - R01 AI068581-03/AI/NIAID NIH HHS/United States GR - R01 AI046148/AI/NIAID NIH HHS/United States GR - AI46148-01/AI/NIAID NIH HHS/United States GR - R01 AI046148-08/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20050705 PL - United States TA - J Infect Dis JT - The Journal of infectious diseases JID - 0413675 RN - 0 (Anti-HIV Agents) RN - 0 (HIV Protease Inhibitors) RN - 0 (Reverse Transcriptase Inhibitors) RN - EC 3.4.23.- (HIV Protease) SB - IM MH - Anti-HIV Agents/*pharmacology MH - HIV Infections/drug therapy/transmission MH - HIV Protease/chemistry/drug effects/*genetics MH - HIV Protease Inhibitors/*therapeutic use MH - Humans MH - *Mutation MH - Polymorphism, Genetic MH - Reverse Transcriptase Inhibitors/*therapeutic use PMC - PMC2597526 MID - NIHMS65108 EDAT- 2005/07/05 09:00 MHDA- 2005/09/24 09:00 PMCR- 2008/12/08 CRDT- 2005/07/05 09:00 PHST- 2004/11/01 00:00 [received] PHST- 2005/03/04 00:00 [accepted] PHST- 2005/07/05 09:00 [pubmed] PHST- 2005/09/24 09:00 [medline] PHST- 2005/07/05 09:00 [entrez] PHST- 2008/12/08 00:00 [pmc-release] AID - JID33885 [pii] AID - 10.1086/431601 [doi] PST - ppublish SO - J Infect Dis. 2005 Aug 1;192(3):456-65. doi: 10.1086/431601. Epub 2005 Jul 5.