417. Low Prevalence of Transmitted Reverse Transcriptase Mutation K65R Across Different HIV-1 Subtypes
Session: Poster Abstract Session: HIV - Antiretroviral Therapy
Friday, October 21, 2011
Room: Poster Hall B1
Background: Tenofovir containing regimens have demonstrated potential efficacy as pre-exposure prophylaxis (PREP) in preventing HIV-1 infection. Transmitted drug resistance is an increasing global concern affecting treatment success in HIV-1 infected individuals as well as potentially impacting PREP in uninfected individuals. The reverse transcriptase (RT) mutation K65R, reported at higher rates in subtype C, is associated with decreased efficacy of tenofovir and its transmission may limit tenofovir-based PREP success. The worldwide prevalence of transmitted K65R in HIV-1 subtypes is unknown.

Methods: We performed a literature review of studies involving HIV-1 infected, treatment naïve individuals through July 31st, 2010. RT sequences from those studies were obtained from GenBank, Stanford, and Los Alamos Databases. Additional data collected included country of origin, year of study, and subtype which was determined by the Stanford HIV Database. One member of all sequence-pairs with 100% identity was excluded. Existence of K65R was identified using Stanford HIV Database tools. Mutation proportions were compared among subtypes using the chi square test. 

Results: 23,054 RT sequences were available form 203 reported studies, of which 21,268 were unique. (N=1,637 subtype A; 10,370 subtype B; 3,110 subtype C; 477 subtype D; 403 subtype F; 605 subtype G; 41 subtype H; 29 subtype J; 200 subtype K; 1,819 CRF01_AE; 1,721 CRF02_AG; 848 other recombinant forms and 8 Group O). The prevalence of K65R was low across all HIV-1 variants. The overall prevalence was 0.09% (N=19, 95% CI 0.05-0.13). Subtype B was found to have the highest prevalence (0.13%, 13/10,370) followed by subtype C (0.10%, 3/3,110), CRF01_AE (0.11%, 2/1,819) and CRF02_AG (0.06%, 1/1,721). All K65R mutations in subtype C were reported before 2000 and during 2000 or after in the other subtypes. There was no statistically significant difference in K65 prevalence among subtype B compared to non-subtype B populations (p=0.14).

Conclusion: The prevalence of K65R transmission across HIV-1 subtypes is low in this worldwide survey, suggesting that at the current time, resistance related to this mutation may have a minimal effect on tenofovir PREP effectiveness.


Subject Category: H. HIV/AIDS and other retroviruses

Philip A. Chan, MD, MS, Infectious Diseases, Alpert Medical School of Brown University, The Miriam Hospital, Providence, RI, Austin Huang, PhD, Computer Science, Brown University, Providence, RI and Rami Kantor, MD, Alpert Medical School of Brown University, The Miriam Hospital, Providence, RI

Disclosures:

P. A. Chan, None

A. Huang, None

R. Kantor, None

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