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


METHODS
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Goudsmit
J
J
Department of Human Retrovirology, Academic Medical Centre, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands.
Weverling
G J
GJ
van der Hoek
L
L
de Ronde
A
A
Miedema
F
F
Coutinho
R A
RA
Lange
J M
JM
Boerlijst
M C
MC
D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002353:Carrier State / Q000821:virology*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000635:transmission* / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D018451:Homosexuality, Male; D006801:Humans; D015994:Incidence; D008297:Male; D008957:Models, Genetic; D015233:Models, Statistical; D009426:Netherlands / Q000453:epidemiology; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase; D016333:HIV Protease