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Wide US Study Finds 16% With Newly Diagnosed HIV Carry Resistant Virus
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20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
Just over 16% of US residents newly diagnosed with HIV infection in 10 metropolitan areas or states carried antiretroviral-resistant virus, according to a CDC study spanning the years 2007 to 2010 [1]. The survey confirmed a continuing climb in prevalence of transmitted nonnucleoside-related mutations.
Transmitted antiretroviral resistance that goes undetected can jeopardize response to first-line therapy if that regimen includes drugs compromised by resistant virus. The World Health Organization believes prevalence of transmitted drug resistance (TDR) stands between 10% and 17% in the United States, Europe, Australia, and Japan [2]. A 2006 report by the Adolescent Medicine Trials Network for HIV/AIDS Interventions found a TDR prevalence of 18% in 55 US youngsters [3].
But the CDC study is the first systematic effort to measure TDR prevalence in newly diagnosed US residents. The CDC cautions, though, that findings come from a convenience sample of 10 states or metropolitan regions that have data for the study period, so the results may not reflect resistance transmission across the United States.
The survey included people with HIV infection diagnosed from 2007 through 2010 who had no evidence of taking antiretrovirals. Health workers collected all specimens within 3 months of HIV diagnosis. The investigators used the CDC HIV-1 mutation surveillance list to identify transmitted resistance mutations associated with nucleosides, nonnucleosides, and protease inhibitors--but not with more recent antiretroviral classes. The CDC team calculated the prevalence of TDR and estimated annual percentage changes of TDR. They also compared prevalence of TDR by duration of infection, estimated by BED HIV-1 results or report by the newly infected person.
Of the 18,144 viral samples analyzed, 2932 (16.2%) carried 4788 mutations conferring resistance to one of more drugs in the first three antiretroviral classes. Rates of virus conferring resistance to one, two, and three antiretroviral classes were 13.6%, 2.1%, and 0.5%. Nonnucleoside mutations were most prevalent (8.1%), followed by nucleoside mutations (6.7%) and protease inhibitor mutations (4.5%).
The CDC team classified 3904 people as recently infected and 11,953 as having long-standing infection. TDR prevalence was significantly higher in recently infected people than in people with long-standing infection for any antiretroviral class (prevalence ratio [PR] 1.15, P < 0.01), for a single class (PR 1.11, P = 0.02), for 2 classes (PR 1.58, P < 0.01), and for nonnucleoside mutations (PR 1.43, P < 0.01), but not for 3 classes, nucleoside mutations, or protease inhibitor mutations. Because most people in the survey had long-standing infection, some resistance mutations they acquired when infected probably faded to undetectable levels by the time of sampling.
Prevalence of mutations conferring resistance to any class rose from 15.0% in 2007 to 16.7% in 2010, but the resulting 1.0% estimated annual percentage change stopped short of statistical significance (P = 0.06). Prevalence of mutations to a single class rose from 12.6% in 2007 to 14.3% in 2010, and the resulting 4.3% estimated annual percentage change was statistically significant (P = 0.01).
Prevalence of nonnucleoside-related mutations jumped from 7.1% in 2007 to 8.6% in 2010 to yield a 5.2% estimated annual percentage change (P = 0.03). Over the same period, prevalence of nucleoside-related mutations and protease inhibitor mutations remained largely unchanged (6.3% to 6.1% for nucleosides and 4.7% to 4.8% for protease inhibitors).
The most prevalent mutations were K103N for nonnucleosides (71.8%), M41L for nucleosides (24.8%), and L90M for protease inhibitors (29.5%). That last findings struck resistance expert Daniel Kuritzkes (Harvard) as curious because the protease inhibitors associated with this mutation--nelfinavir and saquinavir--were seeing little use by 2007.
Prevalence of the tenofovir-related K65R mutation measured only 0.5% in this analysis. The CDC's David Kim, who presented the findings, raised the prospect that transmission of this mutation could swell if people use tenofovir/emtricitabine preexposure prophylaxis incorrectly.
The US Department of Health and Human Services recommends resistance testing when a person enters HIV care and before antiretroviral therapy begins [4].
References
1. Kim D, Ziebell R, Saduvala N, et al. Trend in transmitted HIV-1 ARV drug resistance-associated mutations: 10 HIV surveillance areas, US, 2007-2010. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 149.
2. World Health Organization. HIV resistance report, 2012. http://apps.who.int/iris/bitstream/10665/75183/1/9789241503938_eng.pdf.
3. Viani RM, Peralta L, Aldrovandi G, et al. Adolescent Medicine Trials Network for HIV/AIDS Interventions. Prevalence of primary HIV-1 drug resistance among recently infected adolescents: a multicenter adolescent medicine trials network for HIV/AIDS interventions study. J Infect Dis. 2006;194:1505-1509.
4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. February 12, 2013.
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