Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration

Kantor, Rami; Katzenstein, David A; Efron, Brad; Carvalho, Ana Patricia; Wynhoven, Brian; Cane, Patricia; Clarke, John; Sirivichayakul, Sunee; Soares, Marcelo A; Snoeck, Joke; Pillay, Candice; Rudich, Hagit; Rodrigues, Rosangela; Holguin, Africa; Ariyoshi, Koya; Bouzas, Maria Belen; Cahn, Pedro; Sugiura, Wataru; Soriano, Vincent; Brigido, Luis F; Grossman, Zehava; Morris, Lynn; Vandamme, Anne-Mieke; Tanuri, Amilcar; Phanuphak, Praphan; Weber, Jonathan N; Pillay, Deenan; Harrigan, P Richard; Camacho, Ricardo; Schapiro, Jonathan M; Shafer, Robert W; Ho, David D

doi:10.1371/journal.pmed.0020112

Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse transcriptase genotype: results of a global collaboration

Author:

Kantor, Rami

Katzenstein, David A ; Efron, Brad ; Carvalho, Ana Patricia ; Wynhoven, Brian ; Cane, Patricia ; Clarke, John ; Sirivichayakul, Sunee ; Soares, Marcelo A ; Snoeck, Joke ; Pillay, Candice ; Rudich, Hagit ; Rodrigues, Rosangela ; Holguin, Africa ; Ariyoshi, Koya ; Bouzas, Maria Belen ; Cahn, Pedro ; Sugiura, Wataru ; Soriano, Vincent ; Brigido, Luis F ; Grossman, Zehava ; Morris, Lynn ; Vandamme, Anne-Mieke ; Tanuri, Amilcar ; Phanuphak, Praphan ; Weber, Jonathan N ; Pillay, Deenan ; Harrigan, P Richard ; Camacho, Ricardo ; Schapiro, Jonathan M ; Shafer, Robert W ; Ho, David D

Keywords:

Amino Acid Sequence, Anti-Retroviral Agents, DNA Mutational Analysis, Drug Resistance, Viral, HIV Infections, HIV-1, Humans, Molecular Sequence Data, Peptide Hydrolases, RNA-Directed DNA Polymerase, World Health, Science & Technology, Life Sciences & Biomedicine, Medicine, General & Internal, General & Internal Medicine, IMMUNODEFICIENCY-VIRUS TYPE-1, NON-B SUBTYPES, DRUG-RESISTANCE, MUTATION PATTERNS, COTE-DIVOIRE, CLADE-C, HIV-1-INFECTED ADULTS, V106M MUTATION, SUSCEPTIBILITY, SEQUENCE, Global Health, 11 Medical and Health Sciences, 32 Biomedical and clinical sciences, 42 Health sciences

Abstract:

BACKGROUND: The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. METHODS AND FINDINGS: To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. CONCLUSION: Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations.