You are here
Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance.
| Title | Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Smith, RA, Anderson, DJ, Pyrak, CL, Preston, BD, Gottlieb, GS |
| Journal | J Infect Dis |
| Volume | 199 |
| Issue | 9 |
| Pagination | 1323-6 |
| Date Published | 2009 May 1 |
| ISSN | 0022-1899 |
| Keywords | Acquired Immunodeficiency Syndrome, Africa, Western, Amino Acid Substitution, Anti-HIV Agents, Antiviral Agents, Drug Resistance, Viral, Genetic Predisposition to Disease, HIV Infections, HIV-1, HIV-2, Humans, Mutagenesis, Site-Directed, Phenotype, Reverse Transcriptase Inhibitors, RNA-Directed DNA Polymerase, Zidovudine |
| Abstract | Genotypic surveys suggest that human immunodeficiency virus type 1 (HIV-1) and HIV-2 evolve different sets of mutations in response to nucleoside reverse-transcriptase inhibitors (NRTIs). We used site-directed mutagenesis, culture-based phenotyping, and cell-free assays to determine the resistance profiles conferred by specific amino acid replacements in HIV-2 reverse transcriptase. Although thymidine analogue mutations had no effect on zidovudine sensitivity, the addition of Q151M together with K65R or M184V was sufficient for high-level resistance to both lamivudine and zidovudine in HIV-2, and the combination of K65R, Q151M, and M184V conferred classwide NRTI resistance. These data suggest that current NRTI-based regimens are suboptimal for treating HIV-2 infection. |
| DOI | 10.1086/597802 |
| Alternate Journal | J. Infect. Dis. |
| PubMed ID | 19358668 |
