673 
Increasing Prevalence of NNRTI-associated Drug-resistance Mutations in Patients with Acute, Early HIV in San Francisco
Vivek Jain*1, C Pilcher1, S Deeks1, T Liegler1, W Hartogensis1, T Schmidt1, L Loeb1, L Poole1, R Grant2, and F Hecht1
1San Francisco Gen Hosp, Univ of California, San Francisco, US and 2Gladstone Inst of Virology and Immunology, San Francisco, CA, US
Background: In prior data, the prevalence of
transmitted drug resistance in recently HIV-infected persons in the Options
Project cohort in San Francisco declined from an annual peak of 19 to 27% of
patients in 2000 to 2002 to 10 to 11% in 2003 to 2004. We sought to assess
changes in the prevalence of transmitted drug resistance in San Francisco since
2003.
Methods: All patients enrolled in the Options
Project, a longitudinal cohort study in San Francisco of acute/early HIV (<12
months), underwent genotype analysis at or soon after entry into the cohort.
Patients were assessed for the presence on an initial genotype of at least one
drug-resistance mutation, using published guidelines, which exclude common
polymorphisms. Genotypes were excluded if performed >10 days after
initiation of ART. The prevalence of transmitted drug-resistance mutations, as
well as the prevalence of these mutations by class (NRTI, NNRTI, PI) was
assessed in each year from 2003 to 2007. A c2
test for linear trend was used to assess whether prevalence changed
significantly over time.
Results: Of a total of 224 patients who entered the
cohort and underwent initial genotyping, 36 (16%) had evidence of transmitted
drug resistance mutations. There was a statistically significant increase in
the prevalence of transmitted drug resistance mutations over the study period (p
= 0.01). There was a statistically significant increase in the prevalence of
NNRTI mutations (p = 0.04). Changes over time in the prevalence in NRTI
mutations were not significant (p = 0.2), nor were changes in PI
mutations (p = 0.9).
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|
2003
|
2004
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2005
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2006
|
2007
|
|
Total patients
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58
|
54
|
43
|
29
|
40
|
|
Any resistance
|
10%
|
11%
|
19%
|
17%
|
28%
|
|
NRTI
|
7%
|
6%
|
12%
|
7%
|
15%
|
|
NNRTI
|
2%
|
6%
|
9%
|
10%
|
8%
|
|
PI
|
9%
|
4%
|
0%
|
7%
|
8%
|
Conclusions: We observed a fairly steady and
statistically significant increase in the prevalence of transmitted drug
resistance in San Francisco from a nadir in 2003. This was driven most strongly
by increases in NNRTI resistance, while PI resistance was steady or declined.
This increase may be related to the increasing use of NNRTI and subsequent
development of resistance in persons receiving treatment.
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