HIV type 1 genotypic resistance in a clinical database correlates with antiretroviral utilization.
We established a database of HIV-1 reverse transcriptase (RT) and protease (PR) sequences and mutations to monitor the prevalence of antiretroviral drug resistance and mutational patterns in clinical samples submitted for testing to a major U.S. reference laboratory. At the end of 1998, 80% of the clinical samples tested harbored HIV strains with genotypically predicted resistance to at least one antiretroviral (ARV) drug. By the third quarter of 2002, the frequency of genotypically predicted resistance declined to 65% of samples tested. The prevalence of both PR and nucleoside RT inhibitor resistance declined over this period, while an increase in resistance to nonnucleoside RT inhibitors was found. These genotypic results strongly correlated with a nationwide decrease in the prescription of PR and nucleoside RT inhibitors, and an increase in the prescription of nonnucleoside RT inhibitors over the time period. The increased number of strains that were genotypically sensitive to all classes of ARV probably indicates an increase in genotypic assay use in ARV-naive individuals, however, the trends and correlations in this data set were similar when evaluated after removal of genotypically sensitive strains. Continued monitoring of ARV resistance prevalence, patterns, and utilization trends in clinical databases provides insight into the evolving relationship between clinical practice and ARV resistance.
Kagan
Ron
R
Department of Infectious Diseases, Quest Diagnostics Nichols Institute, San Juan Capistrano, California 92690, USA. kaganr@questdiagnostics.com
Winters
Mark
M
Merigan
Thomas
T
Heseltine
Peter
P
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D030541:Databases, Genetic; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D009154:Mutation; D010818:Practice Patterns, Physicians'; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease