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Recent Trends in Transmitted Drug Resistance in a New York City Cohort
Andrea Low*1,2, Andrea Low*1,2, H Mohri1, M Markowitz1,2, and M Markowitz1,2
1Aaron Diamond AIDS Res Ctr, The Rockefeller Univ, New York, NY, US and 2The Rockefeller Univ, New York, NY, US
Background: We have tracked the prevalence of transmitted HIV-1
variants resistant to antiretroviral drugs since 1996. During 2003-2004 we observed increasing rates
of non-nucleoside reverse transcriptase inhibitor (NNRTI) -resistant
transmissions, as well as an increasing trend in multi-drug-resistant
transmissions. Here we present resistance data generated during 2005-2006 in
our cohort of acute and early HIV-1 infected individuals.
Methods: We identified 92 patients as having acute or
recent HIV-1 infection based on laboratory data documenting infection within 1
year between January 2005 and September 2006. Plasma viral RNA was used for
nucleotide sequence analysis of the protease and reverse transcriptase using
the TRUGENE HIV-1 genotyping kit. Drug-resistance
mutations were characterized using the August 2006 International AIDS Society-USA
consensus guidelines. Changes in drug-resistant-conferring
mutation frequencies were analyzed using the Fisher’s exact test.
Results: We identified and studied 90 male patients
and 2 female patients, all of whom reported a history of having sex with men.
The prevalence of transmitted resistance during the 2005-2006 period was 14 of 92,
(15.2%), a decrease from 27 of 112 (24.1%) during the period 2003-2004 (p = 0.20). NNRTI resistance also decreased to 9 of 92
(9.8%) in 2005-2006 from 15 of 112 (13.4%) in 2003-2004 (p = 0.5). However, of the NNRTI-resistant viruses, 6 of 9 harbored
the K103N mutation—6.5% of all patients versus 3 of 112 (2.7%) during the prior
period (p = 0.18). Unlike the
previous interval, transmission of variants harboring the M184V mutation was
observed in 2 patients, both with multi-drug-resistant HIV-1. The total number
of thymidine analog-associated mutations (TAM) decreased from 15 of 112 (13.4%)
in 2003-2004 to 7 of 92 (7.6%) (p = 0.26),
and the number of patients harboring major protease mutations also dropped from
8 of 112 (7.1%) to 2 of 92 (2.1%) (p =
0.12). Transmission of multi-drug-resistant HIV-1 decreased from 9.8% in
2003-2004 to 4.3% in 2005-2006 (p = 0.18).
No K65R mutations were seen during this period, despite the increasing use of
tenofovir-containing regimens.
Conclusions: The transmission of drug resistant virus in
this homogenous cohort is trending downward, possibly due to better adherence
to current regimens in the local HIV-1-infected population. However,
transmitted NNRTI-resistance continues at comparable rates, and the most common
mutation identified is K103N. Initial treatment options for these individuals
are affected, mainly depriving them of the now available 1-pill-once-daily
option.
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