Response to first protease inhibitor- and efavirenz-containing antiretroviral combination therapy The Swiss HIV Cohort Study

Friedl, Andrée; Ledergerber, Bruno; Flepp, Markus; Hirschel, Bernard; Telenti, Amalio; Furrer, Hansjakob; Bucher, Heiner C.; Bernasconi, Enos; Weber, Rainer

doi:10.1097/00002030-200109280-00008

Cited by 44 publications

(35 citation statements)

References 16 publications

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“…Our findings are consistent with those of other studies in demonstrating the importance of the initial HAART regimen in the probability and rate of achieving virological suppression [11,12,20]. As indicated here, individuals starting on ritonavir-boosted PI regimens or NNRTI regimens were more likely to achieve suppression than patients on unboosted PI regimens.…”

Section: Discussionsupporting

confidence: 92%

“…Additionally, choice of initial antiretroviral regimen plays an important role in the time it takes to achieve a viral load that is undetectable [11,12]. While the long-term clinical benefits of earlier suppression are unclear, achievement of suppression earlier reduces the length of time one carries detectable virus and may allow more immediate CD4 T-cell reconstitution [13].…”

Section: Introductionmentioning

confidence: 99%

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Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort

et al. 2010

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ObjectiveThe aim of the study was to evaluate time to virological suppression in a cohort of individuals who started highly active antiretroviral therapy (HAART), and to explore the factors associated with suppression. MethodsEligible participants were HIV-positive individuals from a multi-site Canadian cohort of antiretroviral-naïve patients initiating HAART on or after 1 January 2000. Viral load and CD4 measurements within 6 months prior to HAART initiation were assessed. Univariate and multivariate analyses were conducted using piecewise survival exponential models where time scale was divided into intervals (o10 months; 10 months). Virological suppression was defined as the time to the first of at least two consecutive viral load measurements o50 HIV-1 RNA copies/mL. ResultsA total of 3555 individuals were included in the study, of median age 40 years [interquartile range (IQR) 34-47 years]. Eighty per cent were male, 18% had a history of injecting drug use (IDU), and 13% presented with an AIDS-defining illness at baseline. The median time to suppression was 4.55 months . In multivariate analyses, older age, male sex, treatment in Ontario rather than British Columbia, non-IDU history, and having an AIDS diagnosis at baseline predicted increased likelihood of suppression. Patients with low baseline viral load were more likely to have suppression [4-5 log 10 copies/mL, hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.18-1.38; o4 log 10 copies/mL, HR 1.49, 95% CI 1.32-1.68] than patients with baseline viral load 5 log 10 copies/mL; however, this effect ceased after 18 months of follow-up. Suppression was more likely with nonnucleoside reverse transcriptase inhibitors and ritonavir-boosted HAART. ConclusionIdentification of patients at risk for diminished likelihood of virological suppression will allow focusing of efforts and the utilization of resources to maximize the benefits of HAART.Keywords: Canada, CANOC, highly active antiretroviral therapy, HIV, virological suppression Accepted 17 August 2010Correspondence: Dr Curtis Cooper, The Ottawa Hospital Division of Infectious Diseases, University of Ottawa, G12 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. Tel: 613 737 8924; fax: 613 737 8164; e-mail: ccooper@Ottawahospital.on.ca DOI: 10.1111/j.1468-1293.00890.x HIV Medicine (2011 r 2010 British HIV Association 352 IntroductionIt is well documented that highly active antiretroviral therapy (HAART) decreases morbidity and mortality amongst HIV-positive individuals [1][2][3][4]. In particular, one of the primary goals of HAART is the obtainment and maintenance of complete HIV RNA suppression [5]. Failure to achieve and maintain suppression can result in the development of drug resistance and also increases the risk of both horizontal and vertical viral transmission [6][7][8].When first initiating antiretroviral therapy, the obtainment of viral load suppression is an important objective that is associated with a variety of socio-demographic and baseline clinical factors [9,10]. Additionally, choice of initial...

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort

et al. 2010

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“…In long-term controlled clinical trials, the combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate has demonstrated durable efficacy and safety (Friedl et al, 2001;Gallant et al, 2006;Squires et al, 2003). Recently published data from Gallant et al, (2006) have demonstrated that the combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate provides superior outcomes in terms of virologic suppression, CD4 cell response and adverse events in treatment-naive patients compared with the previous gold-standard regimen of fixed dose zidovudinelamivudine plus efavirenz.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous quantification of a non‐nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometry

Nirogi

Bhyrapuneni

Kandikere

et al. 2008

Biomedical Chromatography

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A high-performance liquid chromatography/positive ion electrospray tandem mass spectrometry method for the simultaneous quantification of efavirenz, emtricitabine and tenofovir was developed and validated with 100 microL human plasma. Following solid-phase extraction, the analytes were separated using a gradient mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H]+ ions, m/z 316 to 168 for efavirenz, m/z 248-130 for emtricitabine and m/z 288-176 for tenofovir, m/z 482-258 for rosuvastatin (IS), m/z 260-116 for propranolol (IS). The method exhibited a 100-fold linear dynamic range for all the three analytes in human plasma (20-2000, 2-200 and 20-2000 ng/mL for efavirenz, emtricitabine and tenofovir respectively). The lower limit of quantification was 2 ng/mL for emtricitabine and 20 ng/mL for both efavirenz and tenofovir with a relative standard deviation of less than 11%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The total chromatographic run time of 4 min for each sample made it possible to analyze more than 250 human plasma samples per day. The method is precise and sensitive enough for its intended purpose. The method is also successfully applied to quantify efavirenz, emtricitabine and tenofovir concentrations in a rodent pharmacokinetic study.

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“…Opportunistic Infect.). Finally, recent data comparing the virologic effect of NNRTI-and PI-based antiretroviral combinations suggest that the use of NNRTI is associated with a faster and more frequent initial virologic response (14,23).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Human Immunodeficiency Virus (HIV)-Specific Immune Response by Using Efavirenz, Nelfinavir, and Stavudine in a Rescue Therapy Regimen for HIV-Infected, Drug-Experienced Patients

Trabattoni

Caputo

Biasin

et al. 2002

Clin Vaccine Immunol

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Analysis of the virologic and immunomodulatory effects of an association of efavirenz (EFV), nelfinavir (NFV), and stavudine (d4T) was performed in 18 human immunodeficiency virus (HIV)-infected and highly active antiretroviral therapy (HAART)-experienced patients who failed multiple therapeutic protocols. Patients (<500 CD4 ؉ cells/l; >10,000 HIV copies/ml) were nonnucleoside reverse transcriptase inhibitor (NNRTI)-naive and were treated for 10 months with EFV (600 mg/day) in association with NFV (750 mg three times daily) and d4T (30 or 40 mg twice daily). Measurement of HIV peptide-and mitogen-stimulated production of interleukin-2 (IL-2), gamma interferon (IFN-␥), IL-4, and IL-10 as well as quantitation of mRNA for the same cytokines in unstimulated peripheral blood mononuclear cells were performed at baseline and 2 weeks (t1), 2 months (t2), and 10 months (t3) into therapy. The results showed that HIV-specific (but not mitogen-stimulated) IL-2 and IFN-␥ production was augmented and IL-10 production was reduced in patients who received EFV, NFV, and d4T. Therapy was also associated with a reduction in HIV RNA in plasma and an increase in CD4 ؉ cell count. These changes occurred in the first year of therapy (t2 and t3) and were confirmed by quantitation of cytokine-specific mRNA. Therapy with EFV, NFV, and d4T increases HIV-specific type 1 cytokine production as well as CD4 counts and reduces plasma viremia. This therapeutic regimen may be considered for use in cases of advanced HIV infection.

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Response to first protease inhibitor- and efavirenz-containing antiretroviral combination therapy The Swiss HIV Cohort Study

Abstract: Treatment with efavirenz-, compared with PI-based regimens, appeared to result in a superior virological response but no difference in immunological or clinical efficacy. The relevance of these observations remains to be determined in studies with longer follow-up.

Cited by 44 publications

References 16 publications

Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort

Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort

Simultaneous quantification of a non‐nucleoside reverse transcriptase inhibitor efavirenz, a nucleoside reverse transcriptase inhibitor emtricitabine and a nucleotide reverse transcriptase inhibitor tenofovir in plasma by liquid chromatography positive ion electrospray tandem mass spectrometry

Modulation of Human Immunodeficiency Virus (HIV)-Specific Immune Response by Using Efavirenz, Nelfinavir, and Stavudine in a Rescue Therapy Regimen for HIV-Infected, Drug-Experienced Patients

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