Preexisting Resistance to Nonnucleoside Reverse-Transcriptase Inhibitors Predicts Virologic Failure of an Efavirenz-Based Regimen in Treatment-Naive HIV-1–Infected Subjects
ABSTRACT A case-cohort study was used to determine the effect of baseline nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance, as assessed by viral genotyping, on the response to efavirenz-containing regimens in AIDS Clinical Trials Group A5095. The sample included a random cohort of efavirenz-treated subjects plus unselected subjects who experienced virologic failure. Of 220 subjects in the random cohort, 57 (26%) had virologic failure. The prevalence of baseline NNRTI resistance was 5%. The risk of virologic failure for subjects with baseline NNRTI resistance was higher than that for subjects without such resistance (hazard ratio 2.27 [95% confidence interval], 1.15-4.49; P = .018). These results support resistance testing before starting antiretroviral therapy.
- SourceAvailable from: Kim Thys[Show abstract] [Hide abstract]
ABSTRACT: There are conflicting data on the impact of low frequency HIV-1 drug-resistant mutants on the response of first-line highly active antiretroviral therapy (HAART), more specifically containing a NNRTI. As population sequencing does not detect resistant viruses representing less than 15-25% of the viral population, more sensitive techniques have been developed but still need clinical validation. We evaluated ultra-deep sequencing (UDPS), recently more available and affordable, as a tool for the detection of HIV-1 minority species carrying drug resistant mutation (DRM) in a clinical setting. A retrospective analysis of the reverse transcriptase (RT) gene of plasma HIV-1 from 70 patients starting a NNRTI based regimen was performed. Minority populations were defined as representing > 1% and < 20% of the total viral population. Using UDPS, we could not confirm an association between the presence of low minority variants harbouring RT mutations at the start of therapy and primary or secondary therapeutic failure.Virology 04/2012; 426(1):7-11. DOI:10.1016/j.virol.2012.01.002 · 3.28 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: In recent years relevant progress has been made in the treatment of HIV-1 with a consequent decrease in mortality. The availability of potent antiretroviral drugs and the ability of viral load assays that accurately evaluate the true level of viral replication, have led to a better understanding of pathogenesis of the disease and how to obtain improved therapeutic profiles. The highly active antiretroviral therapy (HAART), based on a combination of three or more antiretroviral drugs, has radically changed the clinical outcome of HIV. In particular, reverse transcriptase non-nucleoside inhibitors (NNRTIs) play an essential role in most protocols and are often used in first line treatment. The high specificity of these inhibitors towards HIV-1 has increased the number of structural and molecular modeling studies of enzyme complexes and that have led to chemical syntheses of more selective second and third-generation NNRTIs. However, a considerable percentage of new HIV-1 infections are caused by the emergence of drug-resistant mutant viruses that complicate treatment strategies. In this review we discuss relevant clinical and structural aspects for the management of antiretroviral drug resistance, with detailed explanations of mechanisms and mutation patterns useful to better understand the relation between drug resistance and therapy failure.Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy 02/2011; 14(3):141-9. DOI:10.1016/j.drup.2011.01.002 · 8.82 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Assays for drug resistance testing in human immunodeficiency virus type 1 (HIV-1) infection are now available and clinical studies suggest that viral drug resistance is correlated with poor virologic response to new therapy. The International AIDS Society-USA sought to update prior recommendations to provide guidance for clinicians regarding indications for HIV-1 resistance testing. An International AIDS Society-USA 13-member physician panel with expertise in basic science, clinical research, and patient care involving HIV resistance to antiretroviral drugs was reconvened to provide recommendations for the clinical use of drug resistance testing. EVIDENCE AND CONSENSUS PROCESS: The full panel met regularly between January and October 1999. Resistance and resistance testing data appearing in the last decade through April 2000 and presentations at national and international research conferences were reviewed. Recommendations and considerations were developed by 100% group consensus, acknowledging that definitive data to support final recommendations are not yet available. Emerging data indicate that despite limitations, resistance testing should be incorporated into patient management in some settings. Resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women. It should be considered in treatment-naive patients with established infection, but cannot be firmly recommended in this setting. Testing also should be considered prior to initiating therapy in patients with acute HIV infection, although therapy should not be delayed pending the results. Expert interpretation is recommended given the complexity of results and assay limitations.JAMA The Journal of the American Medical Association 06/2000; 283(18):2417-26. DOI:10.1001/jama.283.18.2417 · 30.39 Impact Factor