Resistance profile and cross‐resistance of HIV‐1 among patients failing a non‐nucleoside reverse transcriptase inhibitor‐containing regimen

Delaugerre, Constance; Rohban, R.; Simon, Anne; Mouroux, Mireille; Tricot, C.; Agher, Rachid; Huraux, J.M.; Katlama, C.; Cálvez, Vincent

doi:10.1002/jmv.2055.abs

Cited by 17 publications

(20 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Resistance to NNRTI was found in 6% of cases, consistently with extensive use and with high likelihood of resistance development to this class [Delaugerre et al, 2001]. A survey conducted over the period 1996-2002 among seroconverters in the Italian ICONA cohort reported a prevalence of mutations in the RT region of 15.2%, but only 1 out of 112 isolates carried mutations related to NNRTI resistance [Violin et al, 2004b].…”

Section: Discussionmentioning

confidence: 99%

Updated prevalence of genotypic resistance among HIV‐1 positive patients naïve to antiretroviral therapy: a single center analysis

Lapadula

Izzo

Gargiulo

et al. 2008

Journal of Medical Virology

View full text Add to dashboard Cite

Continuous surveillance of HIV primary resistance mutations is highly important due to their potential clinical impact. All patients naïve to antiretrovirals who had > or =1 genotypic resistance testing at the Institute of Infectious Diseases (Brescia, Northern Italy) between 2001 and 2006 were analyzed. Primary resistance mutations were defined using epidemiological and clinical criteria. Mutations were interpreted using the Stanford University Algorithm. Logistic regression analysis was used to assess possible predictors of primary resistance mutations. Among 569 patients, 11% presented > or =1 mutation. Prevalence of primary resistance mutations to nucleoside reverse-transcriptase inhibitors (NRTI), non-nucleoside reverse-transcriptase inhibitors (NNRTI), and protease inhibitors (PI) was 6.3%, 6%, and 1.6%, respectively. The most frequent mutations to NRTI were substitutions at position 215 (215Y in 3 patients, and 215 revertants in 16), 41L (13), 219Q (12), and 210W (10). Among mutations to NNRTI, 103N was found in 21 patients, while 181C, 188L, and 190A/S in 8, 3, and 4 patients, respectively. Fifty-one patients (9%) had high-to-intermediate resistance to > or =1 antiretroviral drug before starting the treatment. Regarding the new generation drugs, nine patients had intermediate resistance to etravirine, five patients had intermediate resistance to tipranavir, while five, one, and seven patients had low resistance to etravirine, tipranavir, and darunavir. Homosexuals were more likely to harbor a virus with primary resistance mutations (OR:2.68; 95% CI:1.44-5.00; P = 0.002) while non-Italian nationality was protective (OR:0.38; 95% CI:0.17-0.86; P = 0.020). Prevalence of primary resistance mutations suggests that genotypic resistance testing should be performed before starting treatment in naïve patients in Italy, particularly when NNRTI are prescribed.

show abstract

Section: Discussionmentioning

confidence: 99%

Updated prevalence of genotypic resistance among HIV‐1 positive patients naïve to antiretroviral therapy: a single center analysis

Lapadula

Izzo

Gargiulo

et al. 2008

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…Tel: 1 41 44 255 34 50; fax: 1 41 44 255 32 91; e-mail: huldrych.guenthard@usz.ch [1,2]. Because of the overlapping resistance profiles of currently approved NNRTI drugs, cross-resistance can emerge rapidly, which excludes future use of this drug class [3][4][5]. Recently, the situation has changed with the introduction of the diarylpyrimidine derivative etravirine (ETV), a novel, next-generation NNRTI [6].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS)

et al. 2009

View full text Add to dashboard Cite

Objectives Etravirine (ETV) is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs, which has been primarily studied in randomized clinical trials and not in routine clinical settings. Methods ETV resistance-associated mutations (RAMs) were investigated by analysing 6072 genotypic tests. The antiviral activity of ETV was predicted using different interpretation systems: International AIDS Society-USA (IAS-USA), Stanford, Rega and Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS). Results The prevalence of ETV RAMs was higher in NNRTI-exposed patients [44.9%, 95% confidence interval (CI) 41.0-48.9%] than in treatment-naı¨venaı¨ve patients (9.6%, 95% CI 8.5-10.7%). ETV RAMs in treatment-naı¨venaı¨ve patients mainly represent polymorphism, as prevalence estimates in genotypic tests for treatment-naı¨venaı¨ve patients with documented recent (o1 year) infection, who had acquired HIV before the introduction of NNRTIs, were almost identical (9.8%, 95% CI 3.3-21.4). Discontinuation of NNRTI treatment led to a marked drop in the detection of ETV RAMs, from 51.7% (95% CI 40.8-62.6%) to 34.5% (95% CI 24.6-45.4%, P50.032). Differences in prevalence among subtypes were found for V90I and V179T (Po0.001). Estimates of restricted virological response to ETV varied among algorithms in patients with exposure to efavirenz (EFV)/nevirapine (NVP), ranging from 3.8% (95% CI 2.5-5.6%) for ANRS to 56.2% (95% CI 52.2-60.1%) for Stanford. The predicted activity of ETV decreased as the sensitivity of potential optimized background regimens decreased. The presence of major IAS-USA mutations (L100I, K101E/H/P and Y181C/I/V) reduced the treatment response at week 24. Conclusions Most ETV RAMs in drug-naı¨venaı¨ve patients are polymorphisms rather than transmitted RAMs. Uncertainty regarding predictions of antiviral activity for ETV in NNRTI-treated patients remains high. The lowest activity was predicted for patients harbouring extensive multidrug-resistant viruses, thus limiting ETV use in those who are most in need.

show abstract

“…78 Oteromycin exhibited much reduced inhibition compared to the other three structural homologs. 80 Integrasone [63], 81 a dihydroxy bicyclic epoxy lactone polyketide fungal metabolite, isolated by same group from an unidentified mycelium, which moderately inhibited the strand transfer reaction of HIV-1 integrase with an IC 50 value of 41 mM. The aliphatic chain may play a significant role in the activity, as was observed in the case of integric acid.…”

Section: Inhibitors Of Hivmentioning

confidence: 92%

“…Both clinical and in vitro studies have shown that E138K is a resistant mutation to ETR and RPV, which were approved by the FDA in 2008 and 2012, respectively. 63,64 Therefore, there remains a strong demand for the development of new NNRTIs that can effectively inhibit NNRTI-resistant viruses.…”

Section: Inhibitors Of Hivmentioning

confidence: 99%

Potential of small-molecule fungal metabolites in antiviral chemotherapy

Roy

2017

Antivir Chem Chemother

View full text Add to dashboard Cite

Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5–10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure–activity relationship of some common and important classes of fungal metabolites.

show abstract

Resistance profile and cross‐resistance of HIV‐1 among patients failing a non‐nucleoside reverse transcriptase inhibitor‐containing regimen

Cited by 17 publications

References 12 publications

Updated prevalence of genotypic resistance among HIV‐1 positive patients naïve to antiretroviral therapy: a single center analysis

Updated prevalence of genotypic resistance among HIV‐1 positive patients naïve to antiretroviral therapy: a single center analysis

Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS)

Potential of small-molecule fungal metabolites in antiviral chemotherapy

Contact Info

Product

Resources

About