AZT resistant HIV mutations can persist for three years or more after infection, according to evidence presented to the 2002 Scientific Conference of the Public Health Laboratory Service for England and Wales on 10 September.
Dr Pat Cane of the Antiviral Susceptibility Reference Unit presented evidence to delegates showing that between 25% and a third of people identified as newly infected with HIV in the UK had been infected with virus resistant to at least one of the currently available HIV antiretroviral drugs. Although AZT resistance was most common, there were rarer cases of non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor-resistant HIV being transmitted, and some individuals recently infected with HIV resistant to all three classes of drugs had been identified.
Data were presented on five cases to illustrate how long drug-resistant mutations might persist in the absence of selective pressure from HAART by Dr Cane. One case showed that AZT resistance mutations were still present three years after initial infection, and a second that ddC resistance was present a year after infection.
However, Dr Cane also presented evidence which suggested that resistant HIV may be less “fit” and still susceptible to treatment with HAART, even with combinations containing drugs to which a person had evidence of genotypic resistance (specific mutations associated with resistance to a drug). In particular, Dr Cane drew attention to one case where a person was infected with HIV resistant to drugs from all the three main classes of HAART drugs, including AZT (which, along with 3TC and efavirenz, made up his first-line therapy) and achieved an undetectable viral load. However, after a nine month treatment interruption, HIV resistant to AZT was still found to be present. A case of nevirapine resistant HIV which reverted to wild-type within a year was also reported to the conference.
Even when resistant virus further mutated to be less fit or reverted to wild-type, treatment options could be limited. Dr Cane suggested that “fossil markers” could be left in a person’s viral reservoirs which could re-emerge if a person was treated with a drug to which resistance had previously been present.
Cane PA et al. Determination of stability of resistance-associated mutations in HIV-1 following primary infection with resistant virus. PHLS Annual Conference, oral presentation, 10 September, 2002.