HIV-1 pol mutation frequency by subtype and treatment experience: extension of the HIVseq program to seven non-B subtypes

Objective:HIVseq was developed in 2000 to make published data on the frequency of HIV-1 group M protease and reverse transcriptase (RT) mutations available in real time to laboratories and researchers sequencing these genes. Because most published protease and RT sequences belonged to subtype B, the initial version of HIVseq was based on this subtype. As additional non-B sequences from persons with well-characterized antiretroviral treatment histories have become available, the program has been extended to subtypes A, C, D, F, G, CRF01, and CRF02. Methods:The latest frequency of each protease and RT mutation according to subtype and drug-class exposure was calculated using published sequences in the Stanford HIV RT and Protease Sequence Database. Each mutation was hyperlinked to published reports of viruses containing the mutation. Results:As of September 2005, the mean number of protease sequences per non-B subtype was 534 from protease inhibitor-naive persons and 133 from protease inhibitor-treated persons, representing 13.2% and 2.3%, respectively, of the data available for subtype B. The mean number of RT sequences per non-B subtype was 373 from RT inhibitor-naive persons and 288 from RT inhibitor-treated persons, representing 17.9% and 3.8%, respectively, of the data available for subtype B. Conclusions:HIVseq allows users to examine protease and RT mutations within the context of previously published sequences of these genes. The publication of additional non-B protease and RT sequences from persons with well-characterized treatment histories, however, will be required to perform the same types of analysis possible with the much larger number of subtype B sequences.

[1]  A. Vandamme,et al.  Different substitutions under drug pressure at protease codon 82 in HIV-1 subtype G compared to subtype B infected individuals including a novel 182M resistance mutation , 2005 .

[2]  J. Schapiro,et al.  Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C , 2004, AIDS.

[3]  Tommy F. Liu,et al.  HIV-1 Protease and reverse-transcriptase mutations: correlations with antiretroviral therapy in subtype B isolates and implications for drug-resistance surveillance. , 2005, The Journal of infectious diseases.

[4]  Robert W. Shafer,et al.  Human immunodeficiency virus type 1 reverse transcriptase and protease mutation search engine for queries , 2000, Nature Medicine.

[5]  B. J. Betts,et al.  High Degree of Interlaboratory Reproducibility of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Sequencing of Plasma Samples from Heavily Treated Patients , 2001, Journal of Clinical Microbiology.

[6]  M. Wainberg,et al.  A V106M mutation in HIV-1 clade C viruses exposed to efavirenz confers cross-resistance to non-nucleoside reverse transcriptase inhibitors , 2003, AIDS.

[7]  B. Korber,et al.  HIV sequence compendium 2002 , 2002 .

[8]  Bryan Chan,et al.  Human immunodeficiency virus reverse transcriptase and protease sequence database , 2003, Nucleic Acids Res..

[9]  K. Lole,et al.  Full-Length Human Immunodeficiency Virus Type 1 Genomes from Subtype C-Infected Seroconverters in India, with Evidence of Intersubtype Recombination , 1999, Journal of Virology.

[10]  Lynn Morris,et al.  Impact of HIV-1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration , 2005, PLoS medicine.

[11]  J. Schapiro,et al.  Antiretroviral Drug Resistance in Non-Subtype B HIV-1, HIV-2 and Siv , 2004, Antiviral therapy.

[12]  T. Speed,et al.  Biological Sequence Analysis , 1998 .