HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance.
OBJECTIVE
Monitoring regional levels of transmitted HIV-1 resistance informs treatment guidelines and provides feedback on the success of HIV-1 prevention efforts. Surveillance programs for estimating the frequency of transmitted resistance are being developed in both industrialized and resource-poor countries. However, such programs will not produce comparable estimates unless a standardized list of drug-resistance mutations is used to define transmitted resistance.


METHODS
In this paper, we outline considerations for developing a list of drug-resistance mutations for epidemiologic estimates of transmitted resistance. First, the mutations should cause or contribute to drug resistance and should develop in persons receiving antiretroviral therapy. Second, the mutations should not occur as polymorphisms in the absence of therapy. Third, the mutation list should be applicable to all group M subtypes. Fourth, the mutation list should be simple, unambiguous, and parsimonious.


RESULTS
Applying these considerations, we developed a list of 31 protease inhibitor-resistance mutations at 14 protease positions, 31 nucleoside reverse transcriptase inhibitor-resistance mutations at 15 reverse transcriptase positions, and 18 non-nucleoside reverse transcriptase inhibitor-resistance mutations at 10 reverse transcriptase positions.


CONCLUSIONS
This list, which should be updated regularly using the same or similar criteria, can be used for genotypic surveillance of transmitted HIV-1 drug resistance.
Shafer
Robert W
RW
Division of Infectious Diseases, Stanford University, Stanford, California, USA. rshafer@stanford.edu
Rhee
Soo-Yon
SY
Pillay
Deenan
D
Miller
Veronica
V
Sandstrom
Paul
P
Schapiro
Jonathan M
JM
Kuritzkes
Daniel R
DR
Bennett
Diane
D
D019380:Anti-HIV Agents / Q000494:pharmacology; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease