Carrier rate of zidovudine-resistant HIV-1: the impact of failing therapy on transmission of resistant strains

Because maintenance of treatment success in HIV-1 infection requires viruses to remain therapy sensitive in drug-naive seropositive persons, we looked at the primary infections caused by drug-resistant HIV-1 over time. Furthermore, to study the coverage rate of therapy and therapy failure in relation to the transmission of resistant viruses a mathematical model was developed. The reverse transcriptase and protease genes of viruses were analysed in newly infected people in the period 1990-1998 in the Amsterdam Cohort Study on HIV infection and AIDS in homosexual men. The mathematical model was based on the coverage of drug regimens selecting zidovudine (ZDV) resistance, the lag time in which resistance is gained or lost, the death rate of people infected with resistant virus, and the replacement of resistance-selecting regimens by more potent treatments that substantially reduce viral load and mortality. Of 43 individuals with a primary HIV-infection, three (7%) harboured ZDV-resistant viruses. The first of the ZDV-resistant strains was transmitted in 1995, the last two in 1996. The build-up of ZDV resistance was described by the mathematical model indicating that the equilibrium level of resistance due to treatment depends only on the treatment rate and the outflow rate of patients with resistance virus. Our model indicates that the frequency of viral resistance in a population is determined largely by the number of individuals on insufficient or failing therapy and is influenced only modestly by secondary transmission of ZDV-resistant strains