Antiretroviral resistance among HIV-infected persons who have died in British Columbia, in the era of modern antiretroviral therapy.
BACKGROUND
The prevalence of antiretroviral resistance among persons enrolled in the centralized HIV/AIDS Drug Treatment Program in British Columbia, Canada, who had died between July 1997 and December 2001, was investigated, to determine the degree to which antiretroviral resistance contributed to mortality.


METHODS
During this period, 637 deaths had occurred. The last plasma sample obtained during therapy was genotyped retrospectively for treated individuals who had died of a nonaccidental cause. Samples with plasma human immunodeficiency virus (HIV) loads <500 copies/mL were not genotyped. Drug resistance among 1220 living HIV-infected persons who had experienced virologic therapy failure during the study period also was examined.


RESULTS
Of 554 individuals who had died of nonaccidental causes, 58 (10.4%) were antiretroviral naive, and 99 (17.9%) had very brief exposure to antiretroviral therapy (median, 2 months). The majority of isolates from the remaining 397 individuals harbored either no major resistance mutations or represented samples with plasma HIV suppression of <500 copies/mL. Resistance to >/=1, >/=2, or 3 drug classes was observed in 76%, 42%, and 11% of individuals, respectively, in the group of 1220 living individuals experiencing virologic therapy failure, compared with only 44%, 23%, and 5% of individuals, respectively, who had died (P<.001).


CONCLUSIONS
Only a relatively low prevalence of multidrug resistance was observed in this cohort, indicating that the exhaustion of treatment options because of drug resistance was not a significant contributor to mortality.
Recsky
Magdalena A
MA
British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital, Vancouver, British Columbia, Canada.
Brumme
Zabrina L
ZL
Chan
Keith J
KJ
Wynhoven
Brian
B
Yip
Benita
B
Dong
Winnie W Y
WW
Heath
Katherine V
KV
Montaner
Julio S G
JS
Levy
Adrian R
AR
Hogg
Robert S
RS
Harrigan
P Richard
PR
D000328:Adult; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001955:British Columbia; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D006678:HIV / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000821:virology*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D054303:HIV Reverse Transcriptase / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D019562:Viral Load
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D016333:HIV Protease