Rationale and uses of a public HIV drug-resistance database

Abstract

Knowledge regarding the drug resistance of human immunodeficiency virus (HIV) is critical for surveillance of drug resistance, development of antiretroviral drugs, and management of infections with drug-resistant viruses. Such knowledge is derived from studies that correlate genetic variation in the targets of therapy with the antiretroviral treatments received by persons from whom the variant was obtained (genotype-treatment), with drug-susceptibility data on genetic variants (genotype-phenotype), and with virological and clinical response to a new treatment regimen (genotype-outcome). An HIV drug-resistance database is required to represent, store, and analyze the diverse forms of data underlying our knowledge of drug resistance and to make these data available to the broad community of researchers studying drug resistance in HIV and clinicians using HIV drug-resistance tests. Such genotype-treatment, genotype-phenotype, and genotype-outcome correlations are contained in the Stanford HIV RT and Protease Sequence Database and have specific usefulness.

Figure 1

Examples of 3 published intersubtype differences in the genetic mechanisms of HIV-1 drug resistance, as demonstrated by Profile Queries on the Stanford HIV RT and Protease Sequence Database (http://hivdb.stanford.edu/pages/genotype-rx.html). A, Association of the RT mutation V106M with nonnucleoside RT inhibitor therapy in subtype C viruses [12, 13]. B, Association of the protease mutation V82T and V82M with protease inhibitor therapy in subtype G viruses [14]. C, Decrease in the D30N:L90M ratio during nelfinavir therapy in subtype C compared with subtype B [15, 16]. For each section, the top line contains the consensus B reference amino acids. The number in parenthesis under the reference amino acid contains the number of persons in the database (meeting the query’s criteria) with sequences encompassing that position. The entries beneath the number in parenthesis indicate reported differences from the reference amino acid. Superscripts indicate the proportion of persons in whom the superscripted amino acid is found.

Figure 2

Stanford HIV RT and Protease Sequence Database query for results concerning stavudine (D4T) susceptibility on isolates containing the RT mutations M41L, L210W, and T215Y, using the PhenoSense (Monogram Biosciences) and Antivirogram (Virco) assays. When this query is performed on the Web (http://hivdb.stanford.edu/cgi-bin/RT_Phenotype.cgi), these summary figures are followed by a table containing a line-by-line listing of each result and its associated publication.