370-M. No Increase in Protease Resistance and a Decrease in Reverse Transcriptase Resistance Mutations in Primary HIV-1 Infection: 1992-2001 Sydney, Australia

Abstract

E-mail Abstract Author

Add To Itinerary

Session

Search Abstracts

Program

Session 56 Poster Session
Acute Infection: Resistance, Fitness, and Transmission
Session Time: 4:30-6:30 pm
Room 4E-F

370-M.

No Increase in Protease Resistance and a Decrease in Reverse Transcriptase Resistance Mutations in Primary HIV-1 Infection: 1992-2001 Sydney, Australia
P. Ammaranond*¹, P. Cunningham², R. Oelrichs³, K. Suzuki¹, C. Harris² , L. Leas², A. Grulich¹, A. D. Kelleher¹, and D. A. Cooper¹
¹NCHECR, Univ. of New South Wales, Sydney; ²St. Vincent's Hosp., Univ. of New South Wales, Sydney; and ³Macfarlane Burnet Ctr. for Med. Res., Fairfield, Australia

Background: Our objective was to describe epidemiological correlates of changes in prevalence of drug resistance mutations in patients with acute HIV-1 primary infection in Sydney, Australia.
Methods: 135 patients who had acute primary infection diagnosed between April 1992 and October 2001 and who had sterile plasma sample stored prior to therapy were studied. Plasma viral RNA was extracted and automated DNA sequencing was used to genotype the HIV-1 protease (PR) and reverse transcriptase (RT) regions. Maximum likelihood phylogenetic analysis and bootstrapping of a neighbor joining analysis using 100 replicate data sets were performed.
Results: All samples were successfully sequenced. Median time from onset of symptoms to sampling was 22 days. Only 1 individual (0.7%) had any primary mutation in the PR (V82I). At least 1 of these secondary PR mutations: L10I/V, K20R, M36I, L63P, A71T/V, and V77I/V, was observed in 60%, with L63P being the most frequent (40.0%). The prevalence of secondary mutations in PR was not different before (58.6%) and after (58.4%) the introduction of protease inhibitors (pre and post December 31, 1995). Mutations associated with RT resistance were seen in 30.4%. The most common were M41L (8.9%) and T215Y (8.1%) and K70R (4.4%). The frequency of mutations associated with NRTI resistance was significantly lower in post 1995 samples (43.9% vs 19.1%, p < 0.05). Both M41L and K70R (p < 0.05), but not T215Y, occurred less frequently in the post 1995 samples. Phylogenetic analysis showed that 53 of the sequences fell into 20 clusters with highly significant bootstrap values (>70%), 74 sequences were unclustered. This distribution indicates the population surveyed is likely to be representative of overall transmission patterns in Sydney. Apparent transmission of virus with resistance mutations was seen in 7 clusters.
Conclusions: In contrast to other studies no increase in the rate of PR resistance and a decrease in the rate of RT resistance was found in recently transmitted virus over the period 1992-2001. The data indicate that many of the secondary resistance mutations in the PR gene are naturally occurring polymorphisms. The reasons for the differences between these results and those reported from elsewhere may relate to treatment regimens used in the transmitting population and may have implications for treatment policies.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections