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Transmission of Drug Resistant HIV-1: Conflicting Trends and Clinical Significance
Monday, 1:30 - 3:30 pm
Background: A significant decrease has been observed in the prevalence of drug resistance in recently infected (<6 months) individuals, from 13.4% in 1996 to 2000 to 3.6% in 2001 to 2003 (p = 0.04). A retrospective analysis of chronically infected patients who represent potential HIV-1 transmitters was performed in order to ascertain factors associated with this decrease.
Retrospective analysis of chronically infected
patients followed in a large clinic (n
= 2650), representing 30% of the potential transmitters in
Results: After 2001, the mean viral load in treated and untreated chronically infected populations decreased by 1.4 log both in men having sex with men (MSM) and in injection drug users (IDU). This viral drop coincided chronologically with the availability of genotypic resistance testing and the clinical introduction of nevirapine and boosted protease inhibitors (PI) such as nelfinavir, indinavir and lopinavir. The proportion of untreated chronically infected patients increased by 4% after 2001 (p <0.001) and was similar in both MSM and IDU groups. Since 1999, we have observed a 0.7 log decrease in mean viral load among chronically infected patients harboring any major mutation, in contrast to a significant increase in both number of mutations per patient and the proportion of patients harboring resistance mutations. The prevalence of V118I, M184V, and K103N increased (3% to 26%, 56% to 68%, and 14% to 33%, respectively) while most PI-associated mutations remain similar over time. The prevalence of M184V and D30N in chronically infected patients was >5 times more frequent than in recently infected patients. This diminution in transmission for these 2 mutations may be explained by a reduction in viral load of 0.7 and 0.8 log, respectively, when compared to wild type and to other reverse transcriptase and protease mutations.
Conclusions: The decrease in
viral load observed in chronically infected patients harboring major mutations
who represent potential transmitters, corresponds with a decrease in drug
resistance transmission. Other factors such as routine access to genotyping, availability of more potent drugs and delay of
introduction and/or discontinuation of antiretroviral therapy in patients with
elevated CD4, are associated temporally with the decrease in drug resistance
among recently infected patients
Keywords: HIV-1 transmission; Primary HIV-1 infection; M184V, D30N