Time trends in drug resistant HIV-1 infections in the United Kingdom up to 2009: multicentre observational study (original) (raw)
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BMJ, 2005
Objective To examine whether the level of primary resistance to HIV drugs is increasing in the United Kingdom. Design Multicentre observational study. Setting All virology laboratories in the United Kingdom carrying out tests for HIV resistance as part of routine clinical care. Participants 2357 people infected with HIV who were tested for resistance before receiving antiretroviral therapy. Main outcome measure Prevalence of drug resistance on basis of the Stanford genotypic interpretation system. Results Over the study period (February 1996 to May 2003), 335 (14.2%, 95% confidence interval 12.8% to 15.7%) samples had mutations that conferred resistance to one or more antiretroviral drugs (9.3% high level resistance, 5.9% medium level resistance). The prevalence of primary resistance has increased markedly over time, although patterns are specific to drug class; the largest increase was for non-nucleoside reverse transcriptase inhibitors. In 2002-3, the prevalence of resistance to any antiretroviral drug to nucleoside or nucleotide reverse transcriptase inhibitors, to non-nucleoside reverse transcriptase inhibitors, or to protease inhibitors was 19.2% (15.7% to 23.2%), 12.4% (9.5% to 15.9%), 8.1% (5.8% to 11.1%), and 6.6% (4.4% to 9.3%), respectively. The risk of primary resistance was only weakly related to most demographic and clinical factors, including ethnicity and viral subtype. Conclusions The United Kingdom has one of the highest reported rates of primary resistance to HIV drugs worldwide. Prevalence seems still to be increasing and is high in all demographic subgroups.
Antiviral Therapy, 2009
Background: Newer antiretroviral treatment regimens for HIV carry a lower risk of inducing drug resistance mutations. We estimated changes in incidence rates (IRs) of new mutations in HIV-infected individuals receiving highly active antiretroviral therapy (HAART). Methods: Population-based data were obtained from the Danish HIV Cohort Study and the Danish HIV Sequence Database. We included treatment-naive patients initiating HAART after December 1997 and computed time to first drug resistance mutation, identified as new mutations detected within 1 year after a 60-day period of treatment failure (HIV RNA>1,000 copies/ml). We estimated annual IRs of new resistance mutations towards nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs) and protease inhibitors (PI), and of new specific resistance mutations. Results: A total of 1,829 individuals were observed for 7,294 person-years at risk (PYR). The IR of NRTI resistance decreased from 13.1 per 1,000 PYR (95% confidence interval [CI] 4.9-35.0) in 1999 to 3.7 (1.9-7.2) in 2004-2005 (test for trend P=0.024). The IR of NNRTI resistance decreased from 15.4 (2.2-109.6) in 1999 to 7.9 (4.6-13.6) in 2004-2005 (P=0.077). The IR of PI resistance decreased from 7.5 (1.4-21.8) in 1999 to 2.9 (0.7-11.4) in 2002-2003 (P=0.148). The IRs were low for specific resistance mutations, except for M184V (IR 5.6 [4.0-7.9]) and K103N (IR 8.2 [5.6-12.0]). Conclusions: The incidence of acquired drug resistance has decreased among HIV-infected patients treated with HAART in Denmark during 1999-2005.
Transmission of HIV‐1 Drug‐Resistant Variants: Prevalence and Effect on Treatment Outcome
Clinical Infectious Diseases, 2010
Background. Human immunodeficiency virus type 1 (HIV-1) drug resistance is an important threat to the overall success of antiretroviral therapy (ART). Because of the limited sensitivity of commercial assays, transmitted drug resistance (TDR) may be underestimated; thus, the effect that TDR has on treatment outcome needs to be investigated. The objective of this study was to investigate the prevalence of TDR in HIV-infected patients and to evaluate the significance of TDR with respect to treatment outcome by analyzing plasma viral RNA and peripheral blood mononuclear cell proviral DNA for the presence of drug resistance mutations. Methods. In a prospective study, we investigated the level of TDR in 61 patients by comparing the results of a sensitive multiplex-primer-extension approach (termed HIV-SNaPshot) that is capable of screening for 9 common nucleoside reverse-transcriptase inhibitor and nonnucleotide reverse-transcriptase inhibitor mutations with those of a commercial genotyping kit, ViroSeq (Abbott). Results. Twenty-two patients were found to carry mutations. More patients with TDR were identified by the HIV-SNaPshot assay than by ViroSeq analysis (33% vs 13%;). There was no significant difference in the P p .015 time from initiation of ART to virological suppression between susceptible patients and those carrying low-or high-level resistance mutations (mean ע standard deviation, 128 ע 59.1 vs 164.9 ע 120.4;). Furthermore, P p .147 analyses of CD4 cell counts showed no significant difference between these 2 groups 1 year after the initiation of ART (mean, 184 vs 219 cells/mL;). P p .267 Conclusion. We found the prevalence of TDR in recently infected ART-naive patients to be higher than that estimated by ViroSeq genotyping alone. Follow-up of patients after treatment initiation showed a trend toward there being more clinical complications for patients carrying TDR, although a significant effect on treatment outcome could not be demonstrated. Therefore, the clinical relevance of low-abundance resistant quasispecies in early infection is still in question. Although antiretroviral therapy (ART) has led to decreased mortality and morbidity among people with human immunodeficiency virus type 1 (HIV-1) infection, failure to suppress viremia still occurs as the result of the emergence of drug-resistant viral species [1-4]. In recent years, different estimates of the prevalence of transmitted drug resistance (TDR) in Europe and North America have been reported, ranging from as
Antiviral Therapy, 2010
Background There is an increasing prevalence of non-B subtype HIV type-1 (HIV-1) infections in Europe, refecting patterns of migration. We examined the characteristics of HIV-1 drug resistance in antiretroviral treatment (ART)-naive individuals migrating to the UK. Methods Resistance tests reported to the UK HIV Drug Resistance Database between 2001 and 2006 were included. Demographic data were obtained via linkage to national databases. Resistance was defined as ≥1 drug resistance mutation. Non-B HIV-1 subtype was used as a surrogate marker of infection acquired outside the UK. Logistic regression was used to examine the association between demographics and the prevalence of resistance. Results Overall, 196/4,291 (4.6%) samples with non-B subtype showed resistance compared with 745/6,435 (11.6%) samples for subtype B. Among non-B subtypes, the prevalence of resistance decreased over time (6.0% in 2001–2003 to 3.2% in 2006) and was independently associated with later calendar year o...
Journal of Infectious Diseases, 2013
HIV-1 drug resistance represents a major obstacle to infection and disease control. This retrospective study analyzes trends and determinants of resistance in antiretroviral treatment (ART)-exposed individuals across 7 countries in Europe. Of 20 323 cases, 80% carried at least one resistance mutation: these declined from 81% in 1997 to 71% in 2008. Predicted extensive 3-class resistance was rare (3.2% considering the cumulative genotype) and peaked at 4.5% in 2005, decreasing thereafter. The proportion of cases exhausting available drug options dropped from 32% in 2000 to 1% in 2008. Reduced risk of resistance over calendar years was confirmed by multivariable analysis.
The Journal of Infectious Diseases, 2005
Genotyping of human immunodeficiency virus type 1 (HIV-1) for antiretroviral drug resistance is routinely used both in clinical practice, to guide the selection of options for an individual's antiretroviral therapy, and in epidemiological studies, to estimate levels of antiretroviral drug resistance in a patient population. However, reliance on results of a single test can result in an underestimation of antiretroviral drug resistance. In the present study, we quantified the prevalence of resistance-associated mutations found in recent genotypic tests of 1734 HIV-1-infected, treatment-experienced subjects who had at least 3 genotypic tests (genotypic n p 11,404 tests total; median, 5 tests/subject) and compared it with that of resistance-associated mutations ever detected in these subjects between 1996 and 2004. Single-point analyses underestimated antiretroviral drug resistance, particularly for nucleoside analogues, in both individuals and patient populations. For example, the prevalence of resistance-associated mutation M184V/I was 25.5% in the most recent genotypes and 58.8% in available historical genotypes. Our results suggest that analysis of a combined historical genotype rather than of a crosssectional genotype may lead to more accurate estimates of antiretroviral drug resistance in individual patients and in patient populations. A major barrier to successful viral suppression in HIV type 1 (HIV-1)-infected individuals is the emergence of virus resistant to antiretroviral drugs [1-3]. Genotypic or phenotypic tests of HIV-1 for antiretroviral drug resistance can help predict responses to antiretroviral therapy and are now recommended for routine management of HIV-1 infections. However, because these tests detect only the most prominent HIV-1 genetic variant(s) circulating at the time, the number of resistance-associated mutations present may potentially be underestimated
Enhanced surveillance of HIV-1 drug resistance in recently infected MSM in the UK
Journal of Antimicrobial Chemotherapy, 2016
Objectives: To determine the prevalence of inferred low-frequency HIV-1 transmitted drug resistance (TDR) in MSM in the UK and its predicted effect on first-line therapy. Methods: The HIV-1 pol gene was amplified from 442 newly diagnosed MSM identified as likely recently infected by serological avidity testing in 2011-13. The PCR products were sequenced by next-generation sequencing with a mutation frequency threshold of .2% and TDR mutations defined according to the 2009 WHO surveillance drug resistance mutations list. Results: The majority (75.6%) were infected with subtype B and 6.6% with rare complex or unique recombinant forms. At a mutation frequency threshold of .20%, 7.2% (95% CI 5.0%-10.1%) of the sequences had TDR and this doubled to 15.8% (95% CI 12.6%-19.6%) at .2% mutation frequency (P, 0.0001). The majority (26/42, 62%) of low-frequency variants were against PIs. The most common mutations detected at .20% and 2%-20% mutation frequency differed for each drug class, these respectively being: L90M (n ¼ 7) and M46IL (n ¼ 10) for PIs; T215rev (n ¼ 9) and D67GN (n ¼ 4) for NRTIs; and K103N (n ¼ 5) and G190E (n ¼ 2) for NNRTIs. Combined TDR was more frequent in subtype B than non-B (OR ¼ 0.38; 95% CI ¼ 0.17-0.88; P ¼ 0.024) and had minimal predicted effect on recommended first-line therapies. Conclusions: The data suggest differences in the types of low-frequency compared with majority TDR variants that require a better understanding of the origins and clinical significance of low-frequency variants. This will better inform diagnostic and treatment strategies.