BACKGROUND:
Transmission of drug-resistant (DR) strain is associated with treatment
failure in newly infected individuals and represents an important
therapeutical challenge. Incidence of DR transmission in newly infected
individuals may reflect the DR prevalence in chronically infected
population. As antiretroviral drug discontinuation is associated with
reversion to wild-type virus we should expect a decrease in DR among newly
infected individuals after 2001, where therapeutic recommendations have been
modified. The objectives of this study were: 1) to monitor the changes in DR
prevalence in the Montreal Primary HIV Infection Cohort; and 2) to assess if
decrease in DR prevalence may be explained by postponing or interruption of
antiretroviral therapy among chronically infected patients followed in HIV
clinics in Montreal.
METHODS:
From May 1996 to December 2002, 159 newly infected patients were studied for
DR using genotyping (Visible Genetics TRUGENE) and phenotyping analyses
(Virologic PhenoSense HIV assay). DR prevalence was compared before and
after 2001, when the therapeutic recommendations were introduced.
Assessments of antiretroviral usage were performed in chronically infected
patients followed in two downtown HIV clinics, together representing an
estimated 50% of the total followed Montreal HIV population
RESULTS:
Patient characteristics such as age, gender, risk factors and time
elapsed between infection and study enrolment remained similar over time.
Patients harbouring any mutation by genotypic analysis [either nucleoside
reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), protease
inhibitors (PIs)] before January 2001 represented 17% (n=20) of the
cohort as opposed to 8% (n=3) of such patients after 2001 (P=0.2).
Similarly, no significant decrease in DR prevalence for each drug class was
observed [NRTIs (4 vs 2.6%), NNRTIs (11.0 vs 2.6%), PI (8.7 vs 2.6%) and two
or three classes multi-DR (11 vs 3%)]. However, when risk factors were
analysed a significant decrease in DR prevalence was evidenced only among
men having sex with men (MSM) (16 vs 0%, P=0.05), injecting drug
users (IDU) (20 vs 9%, P=0.4) and heterosexuals (8 vs 40%, P=0.12).
Among patient characteristics only IDU predicts DR (OR=2.5 [95% CI=1.4–4.5],
P=0.002) and this higher ratio may be explained in part by low drug
compliance and by free drug assess in Canada. Likely, decrease in DR
prevalence observed after 2001 is not explained by an abrupt change in the
proportion of chronically infected patients (n=2560) who discontinued
therapy or were drug-naive for antiretroviral in the two Montreal clinics.
CONCLUSION:
Since 2001, DR prevalence significantly decreases only in MSM. Conversely,
IDU represents a predictive risk factor for DR. Behaviours and virological
determinants associated with current changes in DR prevalence among recently
infected individuals in Montreal have to be identified in source persons.