US researchers have established that resistance to non-nucleoside reverse transcriptase inhibitors acquired at the time of HIV infection can persist for more than one year. Their findings were presented on Wednesday at the Ninth Annual Retroviruses Conference in Seattle.
Thirty seven patients were identified by Dr Susan Little and colleagues from the University of California out of a cohort of 301 seroconverters identified by multicentre surveillence in the US. Patients were identified within an average of 52 to 68 days of infection, and a sub-group of six patients with NNRTI resistance were tracked over one year to deteremine whether NNRTI resistance disappeared.
After 400 days, virus with reduced sensitivity to NNRTIs still made up 20-30% of the virus population, and resistance mutations associated with NNRTIs were still detectable. In at least one case, the K103N mutation associated with nevirapine resistance was detected after 500 days of infection.
These findings suggest that a sample taken during the first year after seroconversion can be used to determine the risk of NNRTI resistance when individuals start treatment in later years, since the NNRTI-resistant virus may no longer be detectable but will still be archived, ready to re-emerge under the selective pressure of drug therapy, particularly in the context of sub-optimal adherence or drug levels.
Dr Little noted that the persistence of NNRTI resistance may have implications for secondary transmission of resistance; if resistant virus persists for more than a year, it is possible that a large proportion of drug-resistant new infections could be generated by highly infectious individuals who have already acquired drug resistant virus, and who are experiencing acute HIV infection.
Dr Joep Lange, President of the International Society, suggested that the findings should give pause to proponents of short course nevirapine treatment for prevention of mother to child transmission.
"If we are seeing this degree of persistence, we should think carefully about what this means for adult treatment in resource limited countries" he said.
Little S et al. Persistence of transmitted drug resistance among subjects with primary HIV infection not receiving antiretroviral therapy. Ninth Conference on Retroviruses and Opportunistic Infections, Seattle, abstract 95, 2002.