The aim of the study was to estimate the levels of transmitted drug resistance (TDR) in HIV-1 using very sensitive assays to detect minority drug-resistant populations.
MethodsWe tested unlinked anonymous serum specimens from sexual health clinic attendees, who had not received an HIV diagnosis at the time of sampling, by both standard genotyping and using minority detection assays.
ResultsBy standard genotyping, 21 of 165 specimens (12.7%) showed evidence of drug resistance, while, using a combination of standard genotyping and minority mutation assays targeting three commonly observed drug resistance mutations which cause high-level resistance to commonly prescribed first-line antiretroviral therapy (ART), this rose to 32 of 165 (19.4%). This increase of 45% in drug resistance levels [95% confidence interval (CI) 15.2-83.7%; P 5 0.002] was statistically significant. Almost all of this increase was accounted for by additional detections of the M184V mutation.
ConclusionsFuture surveillance studies of TDR in the United Kingdom should consider combining standard genotyping and minority-specific assays to provide more accurate estimates, particularly when using specimens collected from chronic HIV infections in which TDR variants may have declined to low levels.Keywords: drug resistance, HIV-1, minority-specific polymerase chain reaction, surveillance
IntroductionThe use of genotypic resistance testing to detect drugresistant HIV type 1 variants has helped to guide decision making about appropriate antiretroviral therapy (ART) choices. Following evidence of transmission of drug resistance [2], which may compromise response to firstline therapy [3], routine screening for transmitted drug resistance (TDR) at the time of new diagnosis has been implemented [4]. This allows optimized first-line treatment, as well as surveillance of transmitted resistance.The levels of HIV-transmitted resistance in the United Kingdom peaked in 2002 at about 12% but subsequently fell to around 7-8% by 2006 [5]. It has been previously noted that there is discordance in the spectrum of resistance-associated mutations observed at transmission, compared with those emerging during ART in treated individuals [6,7]. The key lamivudine mutation, M184V, which is the most commonly observed mutation in treated patients, is seldom seen in viruses from untreated patients, DOI: 10.1111/j.1468-1293.2010.00882.x HIV Medicine (2011 r 2010 British HIV Association
250including those who have other drug resistance-associated mutations. This has been thought to be attributable either to it causing reduced transmissibility of the virus or to the rapid loss of this mutation in the absence of treatment as a result of its impact on viral fitness [6]. Standard resistance testing on plasma is limited to detecting viruses present as majority populations (420%) within the viral quasispecies. By contrast, some variants may only be present in low proportions, and thus avoid detection. A number of studies in ART-naïve patients have identified drug-resistant variants...
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