Rates of transmission of antiretroviral drug resistant strains of HIV-1

Background: it is clear that transmission of drug resistant HIV-1 is possible and occurs regularly. However, there is a lack of clarity concerning the true rate of this transmission in a given population, the impact of combination therapies on this rate, and the contribution of transmitted resistant virus to treatment failure either in an individual or on a population basis. Objectives: To provide a review of our current understanding of rates of transmission of drug resistant HIV-1 in various populations and to report the results of a study conducted to determine this rate in Sydney, Australia in the years 1992-2000. Study design: A review of the literature combined with a prospective study of antiretroviral drug resistance in 130 individuals who were diagnosed with symptomatic primary infection at St. Vincent's Hospital, Sydney, Australia between 1992 and 2000. Sequencing of reverse transcriptase (RT) and protease (PR) was performed by the TruGene HIV-1 genotyping kit (Visible Genetics Inc.). Results: The results found in the Sydney population contrast with much of the literature. The prevalence of mutations that conferred primary resistance to protease inhibitors (PIs) was only 0.8% at position V82I. Secondary mutations/polymorphisms were seen in the PR at position LI0I/V, K20R, M36I, L63P, A71T/V, or V77I in 60%. L63P was the most frequently found mutation (46.3%). The incidence of protease-resistant strains of HIV in primary HIV-1 infection did not change after the introduction of PIs in 1996. The distribution of the most common resistance mutations in the RT was as follows; M41L (8.5%) and T215Y (8.5%) and K70R (4.8%). The frequency of mutations associated with NRTI resistance was significantly lower in the post 1995 samples (43.9 vs. 19.1%, P < 0.05). Moreover, both M41L and K70R, but not T215Y, occurred with significantly decreased frequency in the post 1995 samples. Conclusions., In contrast to other studies we found no increase in the rate of PR resistance and a decrease in the rate of RT resistance in recently transmitted virus over the period 1992-2000. 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 in this country. (C) 2002 Elsevier Science B.V. All rights reserved.