Editorials

Is transmitted drug resistance in HIV on the rise?

It seems so

Papers p 1087

The transmission of drug resistant variants of HIV-1 has the potential seriously to limit the therapeutic options of newly infected patients. The selection of HIV drug resistant variants among individuals who are already receiving treatment also clearly limits both the size and duration of the viral supression induced by drug treatment. ^{1 2} Reports from North America and Europe indicate that up to 14% of recently infected patients have been infected with a strain of virus bearing well characterised drug resistance mutations (in 1-10% of cases) or reduced susceptibility to a particular drug (2-14% of cases).^3-5 Temporal trends in the transmission of drug resistance for these populations are not yet available, but a paper from the United Kingdom in this week's BMJ suggests an increase in the risk of being infected with drug resistant HIV virus between 1994 and 2000 (p 1087).⁶

Estimates of the likelihood of transmission vary depending on the type of exposure and the magnitude of viral load in the HIV infected partner.⁷ An incomplete understanding of the biological factors that influence viral transmission further limits the accuracy of projected estimates of transmitted drug resistance. In order to interpret the relative prevalence rates of drug resistance among recently infected subjects we must consider the route of exposure (mucosal or blood borne), possible geographical variations, detection assay type (genotype v phenotype), susceptibility threshold (for phenotypic assays) or type of mutations considered (for genotypic assays), and perhaps HIV subtype (non-B v B v recombinant subtypes). Available assays generally identify only the resistance profile of the predominant viral variant in the infected subject. In the absence of drug selection pressure, reversion to a more replication competent, perhaps drug susceptible, variant may occur, which may in turn preclude the detection of drug resistant variants. Prevalence estimates of transmitted drug resistance in newly infected patients should not therefore be generalised to patients with established infection who have not yet started treatment with antiretroviral drugs, who may harbour drug resistant variants within archived latent reservoirs of virus that may re-emerge in the presence of drug selection pressure.

In the study this week from the UK Collaborative Group on Monitoring the Transmission of HIV Drug Resistance, 69 subjects who developed HIV infection during 1994-2000 were evaluated for resistance within 18 months of their infection; none had received treatment with antiretroviral drugs at the time of resistance testing.⁶ Genotypic resistance was detected in 14% of the subjects, 3% with mutations conferring drug resistance to all three of the available classes of antiretroviral drugs. These estimates are consistent with previous reports of transmitted drug resistance in recently infected subjects.^3-5 These investigators also identified an increase in the prevalence of transmitted drug resistance during the period of study, with drug resistant variants detected in 27% of subjects identified in 2000. Significant increases in the prevalence of transmitted drug resistance have been reported from North America during this same period.⁸

The clinical importance of transmitted drug resistance, particularly using different thresholds of susceptibility, has not been established. However, among patients already established on treatment there is generally good correlation between genotypic and phenotypic markers of resistance and virological responses to treatment.⁹

Methods to improve drug adherence and targeted HIV prevention messages may ultimately reduce the risk of transmitted drug resistance. However, the study this week from the UK group clearly identifies the urgency that needs to be associated with these steps. Drug resistance testing in all recently infected individuals is needed to monitor changes in the prevalence of transmitted drug resistance among different risk groups and to optimise initial treatment choices.

Susan J Little, assistant professor of medicine. 

University of California Department of Medicine, UCSD Treatment Center, 150 W Washington Street, San Diego, CA 92103-2005, USA (slittle{at}ucsd.edu)