The demise of multidrug-resistant HIV-1: the national time trend in Portugal (original) (raw)
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Retrovirology, 2008
Despite improvements in HIV treatment, the prevalence of multidrug resistance and full class resistance is still reported to be increasing. However, to investigate whether current treatment strategies are still selecting for multidrug and full class resistance, the incidence, instead of the prevalence, is more informative. Temporal trends in multidrug resistance (MDR defined as at most 1 drug fully susceptible) and full class resistance (FCR defined as no drug in this class fully susceptible) in Portugal based on 3394 viral isolates genotyped from 2000 to 2006 were examined using the Rega 6.4.1 interpretation system. From July 2001 to July 2006 there was a significant decreasing trend of MDR with 5.7%, 5.2%, 3.8%, 3.4% and 2.7% for the consecutive years (P = 0.003). Multivariate analysis showed that for every consecutive year the odds of having a new MDR case decreased with 20% (P = 0.003). Furthermore, a decline was observed for NRTI-and PI-FCR (both P < 0.001), whereas for NNRTI-FCR a parabolic trend over time was seen (P < 0.001), with a maximum incidence in 2003-'04. Similar trends were obtained when scoring resistance for only one drug within a class or by using another interpretation system. In conclusion, the incidence of multidrug and full class resistance is decreasing over time in Portugal, with the exception of NNRTI full class resistance which showed an initial rise, but subsequently also a decline. This is most probably reflecting the changing drug prescription, the increasing efficiency of HAART and the improved management of HIV drug resistance. This work was presented in part at
Background: Treatment for all recommendations has allowed access to antiretroviral (ARV) treatment to an increasing number of patients. This minimizes transmission of infection but can potentiate the risk for development of transmitted drug resistance (TDR) and acquired drug resistance (ADR). Objective: To study the trends of TDR and ADR in patients followed in Portuguese hospitals between 2001 and 2017. Method: 11911 patients of the Portuguese REGA database were included. TDR was defined as the presence of one or more surveillance drug resistance mutations according to the WHO surveillance list. Phenotypic resistance to ARV was evaluated with Standford HIVdb v7.0. Patterns of TDR, ADR and prevalence of mutations over time were analysed with logistic regression. Results: The prevalence of TDR increased from 7.9% in 2003 to 13.1% in 2017 (pfor-trend<0.001). This was due to a significant increase of both resistance mutations to nucleotide reverse transcriptase inhibitors (NRTIs) an...
Enfermedades infecciosas y microbiología clínica, 2005
Genotypic resistance was tested to investigate changes in the rates of resistance to antiretroviral drugs in non-treated patients in Spain. A total of 209 HIV-infected patients from different autonomous communities in Spain without prior antiretroviral (AR) drug treatment were studied from 1997 to 2001. Regions of the HIV pol gene coding for protease (PR) and retrotranscriptase (RT) were sequenced in plasma samples by RT PCR amplification and automated PCR sequencing. At least one primary RT or PR mutation was detected in 14 patients (6.7%); 11 of them were associated with resistance to RT inhibitors (5.3%) and 3 to PR inhibitors (1.4%). The changes in the resistance rate between March 1997-February 1999 and March 1999-February 2001 were as follows: resistance mutations were detected in 3 of the 111 patients studied in the first period, and in 10 of 98 patients in the second period (2.7% versus 10.2%, P = 0.025). The infection time was less than three months in 1.5% of cases, less t...
Journal of Clinical Virology, 2005
Genotypic and phenotypic analysis of HIV-1 resistance mutations constitute one important point for providing guidelines in the choice of antiretroviral regimens and to design lines of rescue treatment for patients holding HIV-1 drug-resistant variants. However, some levels of discordance among them has been described.(i) To compare the genotypic analysis of resistance mutations to reverse transcriptase (RT) and protease (PR) inhibitors by Stanford HIVdb program (http:/hivdb.stanford.edu) (St-HIVdb), and genotype with quantitative phenotypic analysis (Virtual Phenotype™, VircoNET). (ii) To identify drug resistance mutations associated with discrepant results.Five hundred HIV-1 infected patients were included in this study. RNA was extracted from plasma. RT and PR regions were amplified and sequenced using ABI-Prism DNA sequencing system. Sequences were corrected and assembled with Seqman and Bioedit computer programs. The corrected sequences were submitted to the Stanford HIV-Seq program (http:/hivdb.stanford.edu) and to Virtual Phenotype™ (VircoNET).Discrepant cases were considered if results were high or intermediate resistant by Stanford HIV-Seq program and susceptible by Virtual Phenotype™, being detected as follows: (i) nucleoside RT inhibitors (NRT): 31.7% (ABC), 31% (d4T), 29.5% (ddC), 27.6% (ddI), 14.3% (TDF) and 11.3% (ZDV) and to PR inhibitors: 8.8% (SQV), 5% (APV), 3.8% (NFV) and 3.2% (IDV). These discrepant results were related to the presence of thymidine analogue mutations (TAMs) and also to key resistance mutations to NRT inhibitors: 65R, 69D/N, 74V/I, 184V/I and 215Y/F. (ii) PR inhibitors: 82A/F/T/S, 84I and 90M. Concordant results were considered when the interpretations by both programs were coincident, being higher than 96.7% for non-NRT inhibitors.The detection of discrepant results to NRT inhibitors and PR inhibitors, including the analysis of sequences with key resistant mutations to some drugs, means that further investigation is necessary in order to establish which is the best interpretation system as antiretroviral therapy guide.
Clinical Microbiology and Infection, 2011
We analysed trends of human immunodeficiency virus type 1 (HIV-1) drug resistance during 2007-2009 in the Italian national HIV drug resistance database 'ARCA'. Prevalence of resistance in each year was examined on the basis of the presence of major International AIDS Society-2009 mutations. Predictors of resistance were analysed by multivariable logistic regression. Nine hundred and sixty-six patients were selected. Resistance to nucleoside reverse transcriptase inhibitors and protease inhibitors showed a significant decline with respect to previous surveys. Resistance to any class of drug and three drug classes remained stable. Independent predictors of three-class resistance were the number of treatment regimens experienced, prior suboptimal nucleoside reverse transcriptase inhibitor therapy and the current use of ritonavir-boosted protease inhibitors.
PLoS ONE, 2014
Background: The aim was to analyse trends in clinically relevant resistance to first-line antiretroviral drugs in Spain, applying the Stanford algorithm, and to compare these results with reported Transmitted Drug Resistance (TDR) defined by the 2009 update of the WHO SDRM list. Methods: We analysed 2781 sequences from ARV naive patients of the CoRIS cohort (Spain) between 2007-2011. Using the Stanford algorithm ''Low-level resistance'', ''Intermediate resistance'' and ''High-level resistance'' categories were considered as ''Resistant''. Results: 70% of the TDR found using the WHO list were relevant for first-line treatment according to the Stanford algorithm. A total of 188 patients showed clinically relevant resistance to first-line ARVs [6.8% (95%Confidence Interval: 5.8-7.7)], and 221 harbored TDR using the WHO list [7.9% (6.9-9.0)]. Differences were due to a lower prevalence in clinically relevant resistance for NRTIs [2.3% (1.8-2.9) vs. 3.6% (2.9-4.3) by the WHO list] and PIs [0.8% (0.4-1.1) vs. 1.7% (1.2-2.2)], while it was higher for NNRTIs [4.6% (3.8-5.3) vs. 3.7% (3.0-4.7)]. While TDR remained stable throughout the study period, clinically relevant resistance to first line drugs showed a significant trend to a decline (p = 0.02). Conclusions: Prevalence of clinically relevant resistance to first line ARVs in Spain is decreasing, and lower than the one expected looking at TDR using the WHO list. Resistance to first-line PIs falls below 1%, so the recommendation of screening for TDR in the protease gene should be questioned in our setting. Cost-effectiveness studies need to be carried out to inform evidence-based recommendations.
Trends in drug resistance prevalence in HIVchildren in Madrid 93 to 10 analysis PIDJ 2012
Background: Drug resistance mutations compromise antiretroviral treatment (ART) effectiveness in HIV-1-infected children. Trends in drug resistance prevalence have not been previously evaluated in HIV-infected children in Spain. Methods: HIV-1 variants, drug resistance prevalence dynamics and drug susceptibility were analyzed from 1993 to 2010 in HIV-infected children with available pol sequence, sample or drug resistance profile. HIV-1 variants were characterized by phylogenetic analysis. Resistance mutations in pretreated and naive patients were identified according to International AIDS Society-2010 and the World Health Organization list, respectively. Results: In 232 patients, genotypic resistance profiles (n = 11) or pol sequences (n = 128) were recovered or newly generated from infected samples (n = 93). Patients were mainly in care at pediatric units (63%), were mostly Europeans (84%), with moderate AIDS symptoms (65%), on ART (91%) and infected by HIV-1 subtype B (89%). Transmitted major drug resistance mutations were selected in 6 (13.6%) of the 44 ART-naive children: 4.8%, 9.3% and 11.6%, for protease inhibitors, nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. Overall resistance prevalence was higher (71.8%) among ARTexposed children: 39.9%, 66.5% and 35.3% for protease inhibitors, nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors, respectively. Resistance prevalence among ART-exposed children was higher in 2009 to 2010 relative to 1993 to1999 for nonnucleoside reverse transcriptase inhibitors (42% versus 6%; P = 0.006), protease inhibitors (39% versus 13%; P = 0.004) and nucleoside reverse transcriptase inhibitors (63% versus 44%; P = NS). Susceptibility to each drug in resistant viruses was predicted. The rate of non-B infections increased in the last years, mainly caused by recombinant viruses. Conclusions: The increasing resistance prevalence among the HIV-infected pediatric population in Spain highlights the importance of specific drug resistance and drug susceptibility surveillance in long-term pretreated children to optimize treatment regimens. FIGURE 3. Predicted susceptibility to each of the drugs used as ART in pretreated patients. Top represents patients from 1993 to 1999 period (n = 18), second panel from the top shows patients from period 2000 to 2004 (n = 68), third panel from the top, patients from 2005 to 2008 (n = 55) and bottom panel represents patients from the 2009 to 2010 period (n = 47). Susceptibility was estimated according to the HIVdb Interpretation Algorithm (Stanford University, Palo Alto, CA)
Acta dermatovenerologica Alpina, Pannonica, et Adriatica, 2010
Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy. The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries. Genotypic resistance was interpreted using the ANRS algorithm. Phenotypic resistance was predicted using the Virco geno- to phenotype system. 80.7% of the sequences included at least one drug-resistance mutation. Mutations were found for NRTIs (73.5%), NNRTIs (48.5%), and protease inhibitors (35.8%). Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. Among NRTIs, resistance was most frequently predicted for lamivudine. About half of all sequences had reduced susceptibility for NNRTIs. Resistance to most boosted protease inhibitors was found in < 25%. No seque...
2002
The knowledge of which drug-resistant human immunodeficiency virus (HIV) genotypes are the most prevalent in a community may be helpful for designing the best salvage regimens. A total of 540 individuals on antiretroviral therapy attending 18 different outclinics in Spain were examined in a cross-sectional study conducted during June 2000. The overall rate of virologic failure (>50 HIV RNA copies/ml) was 54%. Among the subjects showing treatment failure, 79% harbored resistant HIV genotypes, 77% showed resistance to nucleoside analogues, 53% showed resistance to protease inhibitors, and 42% showed resistance to nonnucleoside reverse transcriptase inhibitors. Overall, 78.5% of individuals harbored HIV strains which showed resistance to two or more drug classes. Moreover, nucleotide substitutions causing broad cross-resistance among compounds within each drug family were quite common. These findings suggest that drug resistance mutations are very prevalent among subjects who have experienced several treatment failures. Therefore, facilitating the arrival of compounds belonging to new drug classes should be considered a priority.