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Transmitted Resistance in Rural US (north Carolina) Matches That in Cities
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XVI International HIV Drug Resistance Workshop
June 12-16, 2007
Barbados
Mark Mascolini
A survey of transmitted drug-resistance mutations in 126 recently infected residents of largely rural North Carolina reflected rates in US cities, which are the best-studied US sites [1]. Women had a 3 to 4 times higher risk of getting infected with mutant virus than men.
Christopher Hurt and colleagues at the University of North Carolina and other centers searched for cases of transmitted resistance in North Carolina because several states in the region have new HIV infection rates exceeding the national average and because HIV epidemiology in the South differs from overall national trends in several ways: more heterosexual transmissions, more infections among women, and more infections among non-Hispanic blacks.
The researchers analyzed viral samples collected since 1998 from 117 people with a negative antibody test and positive HIV RNA and 9 people with evidence of enzyme immunoassay seroconversion within 45 days of a negative HIV test. They used standard genotyping to search for resistance mutations listed by the IAS-USA or in the Stanford database. As other studies presented at this workshop show, more sensitive assays routinely detect more transmitted resistance mutations [2,3]. No one had taken antiretrovirals before resistance testing.
The study group was largely male (81.0%). While 46.0% were black, 43.7% were white and 5.6% Hispanic. Only slightly more than one third (38.1%) identified themselves as men who have sex with men, and only 3 (2.4%) injected drugs.
Twenty-one people (16.7%) had one or more major IAS-USA mutations and 20 (15.9%) had any Stanford mutation. These rates compare with a 10% prevalence in a 2006 US population of clinical trial participants and a 10.4% rate in a 2005 pan-European study. Looking only at Stanford mutations, Hurt saw a nonsignificant trend toward increasing transmitted resistance, from 2 cases in 1998-2000 to 11 in 2005-2006 (P = 0.37); nonnucleoside-related mutations drove that trend (P = 0.21).
Mutations evoked by nonnucleosides proved the most frequent in this cohort (9.5% IAS-USA, 7.9% Stanford), and the nonnucleoside-killing K103N was the most frequent single mutation, detected in 8 people (6.6%). The L90M protease change was the next most common individual mutation, spotted in 3 people (2.5%), while only 4 people (3.2%) had thymidine nucleoside analog mutations. Only 2 people (1.7%) had mutations conferring resistance to two antiretroviral classes, and none had triple-class resistance.
Univariate analysis determined that women had a 3.46 times higher risk of getting infected with a Stanford mutation (95% confidence interval [CI] 1.15 to 10.2) and a 4.26 times higher risk of picking up an IAS-USA mutation (95% CI 1.48 to 12.24). Compared with asymptomatic individuals, people diagnosed when they had the acute retroviral syndrome were 3.60 times more likely to have a Stanford mutation (95% CI 0.45 to 28.93) and 3.85 times more likely to have an IAS-USA mutation (95% CI 0.48 to 32.85). Age, race, or being a man who has sex with men did not substantially affect the risk of infection with resistant virus.
These findings are provocative because they show that transmission of drug-resistant HIV is at least as common in this largely rural Southern state as it is in US cities--and more common than in many US and European cities. If the US epidemic continues its currently rapid spread in nonurban areas, these trends could have a telling impact on first-line antiretroviral response, especially among people who cannot access care at top-line HIV centers like the University of North Carolina. Although the study group included only 21 women, the correlation of gender with a higher resistance risk is troubling because of the disadvantages endured by many women at risk of HIV infection.
References
1. Hurt C, McCoy S, Kerkau M, et al. Frequency of transmitted drug resistance among
acute and recently HIV-infected patients in North Carolina is similar to reports from more urbanized areas. Antiviral Therapy. 2007;12:S55. Abstract 48.
2. Johnson JA, Lipscomb J, J-F Li, et al. Real-time PCR testing allows for sensitive drug
resistance screening and mutation linking in HIV-1. Antiviral Therapy. 2007;12:S153. Abstract 39.
3. Metzner KJ, Rauch P, von Wyl V, et al. Prevalence of minority quasispecies of drug-resistant HIV-1 in patients with primary HIV-1 infection in Zurich in the years 2002-2006. Antiviral Therapy. 2007;12:S47. Abstract 40.
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