Background: Incidence of drug resistance in primary HIV infection in North America has approximately doubled in frequency since 4 years ago. Recently, it was claimed that transmission of resistance could plateau within 5 years, as resistant strains have reduced fitness relative to wild type strains. We analyze a model that considers 2 sources of transmitted resistance: patients on therapy with acquired resistance (AR) and subjects infected with transmitted resistance (TR).

Methods: Consensus HIV genotypes for PR and RT were obtained by direct PCR-sequencing. Retrospective analysis of data from a UCSD HIV care clinic was used to estimate virologic failure among patients with established infection.

Results: We define potential transmitters as HIV+ with a plasma viral load (pVL) > 1000. Analyzing patient records from 1997 and 1999, and assuming 50% of HIV+ individuals receive care, we estimate that among subjects with pVL > 1000, 35% represent patients with AR. However, the observed incidence of TR in the same population was only 6.2% in 1997 and 17% in 1999, indicating resistance was transmitted less frequently than expected from patients with AR. Patients with AR harbor both wild type and resistant strains and may transmit either; in contrast individuals with TR harbor and can transmit only resistant strains until a revertant arises. Thus, an increase in numbers of patients with AR causes a linear increase in subjects with TR, which, as these themselves transmit resistant strains, leads to an exponential increase in transmission of resistance, as: ;  (b¢ and    are constants,  is the ratio of the probabilities of transmission of resistant and susceptible strains from individuals with AR).

Conclusions: Based on this model, transmitted drug resistance will continue to increase, and individuals newly infected with TR will become the major source of new resistant infections, indicating an urgent need for interventions to reduce transmission.