The effect of injection-drug use on human immunodeficiency virus type 1 (HI
V-1) env genetic evolution was examined in 15 seroconverting injection-drug
users followed up for 4 years. After adjustment for non-drug-related indep
endent variables significantly associated with genetic diversity (time sinc
e seroconversion and progressor status), injection frequency was positively
and highly significantly associated with HIV-1 env genetic diversity (P =
.003). The mutation rate in those who had injected at least once a day duri
ng the previous 6 months was estimated to be 62% greater than the rate in t
hose who had not injected at all. If the positive effect of drug-injection
frequency on env genetic diversity extends to the HIV-1 pol gene, the risk
of emergence of resistance to antiretroviral drugs may be enhanced by incre
ased drug-injection frequency, especially under the selection pressure of a
ntiretroviral therapy.