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Background:  From 1995–1998 to 1999–2001, the transmission of drug-resistant HIV-1 increased from 13.2 to 19.7%, then decreased slightly during 2001–2002 to 17%. Here we report data for the years 2003 to 2004.

Methods:  We identified 95 newly infected individuals on the basis of the presence of viremia with a negative HIV serology, a negative detuned ELISA, or a documented negative serology within 1 year of presentation. Pretreatment plasma virus was sequenced for PR and RT using TruGene (Bayer). A subset of 27 isolates, 21 with drug resistance and 6 with wild type virus, were examined for changes in Env consistent with resistance to enfurvitide. Statistical analyses were done using the Mantel Haenszel c² test and Fisher’s exact test to compare changes in percentage of strains that were resistant. Independent t test and 1-way ANOVA were used to compare differences between the CD4 T cells and HIV-1 RNA.

Results:  The cohort is predominantly men who have sex with men (MSM) (98%). The median duration of infection was 58 days. Initial mean plasma HIV-1 RNA was 2,016,451 copies/mL. Drug resistant HIV-1 was found in 28 (26.7%):  11 patients (11.2%) were multi-drug resistant, a significant increase since 2000 (p =0.03). Genotypic resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) increased from 2.6% in 1995–1998 to 16.3% in 2003–2004 (p = 0.002). The prevalence of resistance to protease inhibitors (PI) showed a modest increase, from 1.3% in 1995–1998 to 8.2% in 2003-04. NRTI-associated mutations appeared not to increase in frequency since 2000. Genotypic resistance to any 2 classes of antiretroviral drugs increased from 2.6% in 2000 to 9.4% in 2004 (p = 0.001). Of 95 newly infected patients from 2003 to 2004, 3 (3.1%) showed genotypic resistance to all 3 classes of antiretroviral drugs. NNRTI resistance associated with multi-drug resistance transmission was seen in 10 of the 11 subjects, compared with 2 of 2 in 2001 and 2002. We did not find evidence of transmitted resistance to enfurvitide (amino acids 36 to 45 in the HR-1 region of gp41) in 6 subjects with wild type HIV-1, 10 subjects with multi-drug resistance, and 11 subjects with resistance to 1 class.

Conclusions:  Transmission of drug resistant HIV, particularly those variants resistant to NNRTI and multiple classes of ARV rose significantly in 2003 to 2004. We did not detect transmitted resistance to enfurvitide in a subset of individuals, including 10 subjects with multi-drug resistant HIV-1. These data support continued effort to monitor for transmitted drug-resistant variants and underscore the need for better prevention efforts amongst the treated infected population.

Keywords: Resistance; Transmission; acute HIV-1