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Background:  Transmission of HIV-1 drug resistance is well documented. The public health impact of this phenomenon will be further determined by the stability of these viruses as the majority population within such individuals. We have therefore undertaken prospective monitoring of primary infections for drug resistance, and follow-up in those infected with such viruses. 

Methods:  Primary infection was defined as an evolving serology response or, seroconversion within an 18-month period; 16 patients experienced primary infection with evidence of resistance-associated mutations and were followed for up to 3 years.  Genotypes were determined using an in-house assay.  One patient received 1 year of treatment post diagnosis.

Results:  Drug resistance persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within RT, and multi-drug resistance demonstrated little reversion to/outgrowth of wild type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months respectively.   Multi-drug resistance  (NRTI, NNRTI, and PI) in 3 patients  was found to be stable for up to 2 years, the maximum period studied, and to be associated with low viral loads, except for 1 patient showing a change from T215Y to T215C associated with a marked increase in viral load.  An additional patient was found to have virus showing M41L and T215S 10 years after known seroconversion, although she had received 5 months of AZT after 2 years, so complicating interpretation of this result in the absence of a seroconversion sample.

Conclusions:  Certain resistance-associated mutations are highly stable long term, and could be utilized as indicators of infection with drug resistant virus. Persistence of multi-drug-resistance viruses is of concern, and lack of reversion may be due to the presence of compensatory mutations within these viruses.  However, other mutations may disappear rapidly, possibly due to the fitness gain of reversion.  These data demonstrate that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.  The long-term  persistence of primary resistance indicates a significant risk of transmission of resistant virus from patients who are not necessarily antiretroviral experienced.

Keywords: primary resistance; persistence; mutations