| 1. |
- Edén, Arvid, 1975, et al.
(författare)
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Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.
- 2010
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Ingår i: AIDS research and human retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 26:5, s. 533-40
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Tidskriftsartikel (refereegranskat)abstract
- Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.
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| 2. |
- Eriksen, Jaran, et al.
(författare)
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Antiretroviral treatment for HIV infection: Swedish recommendations 2016.
- 2017
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Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 49:1, s. 1-34
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Medical Products Agency and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection on seven previous occasions (2002, 2003, 2005, 2007, 2009, 2011 and 2014). In February 2016, an expert group under the guidance of RAV once more revised the guidelines. The most important updates in the present guidelines are as follows: Tenofovir alafenamide (TAF) has recently been registered. TAF has several advantages over tenofovir disoproxilfumarate (TDF) and is recommended instead of TDF in most cases. First-line treatment for previously untreated individuals includes dolutegravir, boosted darunavir or efavirenz with either abacavir/lamivudine or tenofovir (TDF/TAF)/emtricitabine. Pre-exposure prophylaxis (PrEP) is recommended for high-risk individuals. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine ( http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ ) ( Table 1 ). This document does not cover treatment of opportunistic infections and tumours. [Table: see text].
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| 3. |
- Josephson, Filip, et al.
(författare)
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Antiretroviral treatment of HIV infection: Swedish recommendations 2007.
- 2007
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:6-7, s. 486-507
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Tidskriftsartikel (refereegranskat)abstract
- On 3 previous occasions, in 2002, 2003 and 2005, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. An expert group, under the guidance of RAV, has now revised the text again. Since the publication of the previous treatment recommendations, 1 new drug for the treatment of HIV has been approved - the protease inhibitor (PI) darunavir (Prezista). Furthermore, 3 new drugs have become available: the integrase inhibitor raltegravir (MK-0518), the CCR5-inhibitor maraviroc (Celsentri), both of which have novel mechanisms of action, and the non-nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (TMC-125). The new guidelines differ from the previous ones in several respects. The most important of these are that abacavir is now preferred to tenofovir and zidovudine, as a first line drug in treatment-naïve patients, and that initiation of antiretroviral treatment is now recommended before the CD4 cell count falls below 250/microl, rather than 200/microl. Furthermore, recommendations on the treatment of HIV infection in children have been added to the document. As in the case of the previous publication, recommendations are evidence-graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels).
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| 4. |
- Josephson, Filip
(författare)
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Studies on the clinical pharmacology of antiretroviral agents
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis begins with an account of the development of the antiretroviral treatment paradigm for HIV infection, focusing on the emergence of present day principles of antiretroviral therapy (e.g., how to rationally combine drugs, the monitoring of treatment effect, the definition of treatment failure, and the use of 'ritonavir-boosting' to augment drug exposure). The implications of the evolving treatment paradigm for drug development and the conduct of clinical trials are emphasized (e.g., the definition of study populations, the role of biomarkers and the definition of endpoints). Following this, the promises and limitations of therapeutic drug monitoring (TDM) of antiretrovirals is described, as well as the pharmacogenetics of HIV therapy, and the mechanisms of the substantial drug-drug interaction potential of some major antiretroviral agents. The introduction concludes with a discussion of the conduct, findings and implications of the four papers comprising the thesis, insofar as there is a need for justification or further comments beyond what is stated in the articles, or where important new data have appeared since the time of writing the papers. Paper 1 reports a study of the impact of pharmacogenetic variability at CYP3A on the metabolism of the HIV protease inhibitor (PI) saquinavir. This drug was shown to be a CYP3A5 substrate. Paper 2 describes a pilot study of ritonavir-boosted atazanavir maintenance monotherapy, which was prematurely terminated due to an excess of protocol-defined treatment failure. Atazanavir plasma drug concentrations did not predict failure in this study, though on-treatment serum bilirubin (an increase of which is an exposure dependent side effect of atazanavir) did. Paper 3 describes the effects of three different antiretroviral drug regimens (based on efavirenz, ritonavir-boosted atazanavir and ritonavir-boosted lopinavir) on the plasma concentration of 4b-hydroxycholesterol, a suggested endogenous marker of CYP3A activity. This marker performed according to hypothesis in the efavirenz and ritonavir/boosted atazanavir arms (increase and decrease, respectively, due to CYP3A induction and inhibition), but failed to clearly reflect the profound CYP3A inhibition in the ritonavir-boosted lopinavir arm. Paper 4 reports the relation of the plasma concentrations of efavirenz, atazanavir and lopinavir, and treatment outcome in the NORTHIV clinical trial in treatment-naïve patients. No relation of drug concentration and effects was demonstrated thought there was a trend towards a relation of plasma bilirubin and outcome in patients treated with atazanavir. It is concluded that: (a) Genetic variability in CYP3A5 is unlikely to have any measurable clinical impact on present day boosted PI regimens. (b) Though boosted PI maintenance monotherapy may be an option in selected patients, there are important concerns about, e.g., CNS penetration. Increasing PI doses beyond those presently recommended is unlikely to alter the efficacy of boosted PI monotherapy. (c) Plasma bilirubin is a useful marker for adherence in atazanavir-treated patients. (d) Routine TDM of antiretrovirals is not mandated.
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| 5. |
- Josephson, Filip, et al.
(författare)
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The relation between treatment outcome and efavirenz, atazanavir or lopinavir exposure in the NORTHIV trial of treatment-na
- 2010
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Ingår i: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 1432-1041 .- 0031-6970. ; 66:4, s. 349-357
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Tidskriftsartikel (refereegranskat)abstract
- The relation between treatment outcome and trough plasma concentrations of efavirenz (EFV), atazanavir (ATV) and lopinavir (LPV) was studied in a pharmacokinetic/pharmacodynamic substudy of the NORTHIV trial-a randomised phase IV efficacy trial comparing antiretroviral-na < ve human immunodeficiency virus-1-infected patients treated with (1) EFV + 2 nucleoside reverse transcriptase inhibitors (2NRTI) once daily, (2) ritonavir-boosted ATV + 2NRTI once daily or (3) ritonavir-boosted LPV + 2NRTI twice daily. The findings were related to the generally cited minimum effective concentration levels for the respective drugs (EFV 1,000 ng/ml, ATV 150 ng/ml, LPV 1,000 ng/ml). The relation between atazanavir-induced hyperbilirubinemia and virological efficacy was also studied. Drug concentrations were sampled at weeks 4 and 48 and optionally at week 12 and analysed by high-performance liquid chromatography with UV detector. When necessary, trough values were imputed by assuming the reported average half-lives for the respective drugs. Outcomes up to week 48 are reported. No relation between plasma concentrations of EFV, ATV or LPV and virological failure, treatment withdrawal due to adverse effects or antiviral potency (viral load decline from baseline to week 4) was demonstrated. Very few samples were below the suggested minimum efficacy cut-offs, and their predictive value for treatment failure could not be validated. There was a trend toward an increased risk of virological failure in patients on ATV who had an average increase of serum bilirubin from baseline of < 25 mu mol/l. The great majority of treatment-na < ve and adherent patients on standard doses of EFV, ritonavir-boosted ATV and ritonavir-boosted LPV have drug concentrations above that considered to deliver the maximum effect for the respective drug. The results do not support the use of routine therapeutic drug monitoring (TDM) for efficacy optimisation in treatment-na < ve patients on these drugs, although TDM may still be of value in some cases of altered pharmacokinetics, adverse events or drug interactions. Serum bilirubin may be a useful marker of adherence to ATV therapy.
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| 6. |
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| 7. |
- Josephson, Filip, et al.
(författare)
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Treatment of HIV infection: Swedish recommendations 2009.
- 2009
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 41:11-12, s. 788-807
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Forskningsöversikt (refereegranskat)abstract
- On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/microl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.
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| 8. |
- Lagging, Martin, 1965, et al.
(författare)
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Treatment of hepatitis C virus infection for adults and children: Updated Swedish consensus recommendations.
- 2016
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Ingår i: Infectious diseases (London, England). - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 48:4, s. 251-261
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In a recent expert meeting, Swedish recommendations for the treatment of HCV infection were updated. An interferon-free combination of direct-acting antiviral agents was recommended as the first line standard-of-care treatment for chronic HCV infection. Interferon-based therapy should be considered as a second line option after an individual benefit-risk assessment. Treatment is strongly recommended for HCV infected patients with bridging fibrosis or cirrhosis (Metavir stages F3-4), before and after liver transplantation, and in the presence of extra-hepatic manifestations. Additionally, patients with moderate liver fibrosis (stage F2) as well as women in need of in vitro fertilisation should be prioritised for therapeutic intervention. Treatment indications for people who inject drugs, children, chronic kidney disease and HIV co-infection are also discussed.
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| 9. |
- Lagging, Martin, 1965, et al.
(författare)
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Treatment of hepatitis C virus infection: updated Swedish Consensus recommendations.
- 2009
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 41:6-7, s. 389-402
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Tidskriftsartikel (refereegranskat)abstract
- In a recent expert meeting, Swedish recommendations for the treatment of HCV infection were upgraded. The panel recommends vaccination against both hepatitis A and B in patients with HCV. Therapy for symptomatic acute HCV infection should be initiated if spontaneous resolution has not occurred within 12 weeks, whereas asymptomatic acute HCV should be treated upon detection. Patients with genotype 2/3 infection should generally be treated for 24 weeks. In patients with a very rapid viral response (vRVR), i.e. HCV RNA below 1000 IU/ml on d 7, treatment can be shortened to 12-16 weeks, provided that no dose reduction has been made. For genotype 1 patients with rapid viral response (RVR), 24 weeks treatment is recommended. For patients with a complete early viral response (cEVR), 48 weeks treatment is recommended, whereas 72 weeks treatment should be considered for patients with partial early viral response (pEVR). For patients with difficult-to-treat disease and with pronounced anaemia, erythropoietin can be used to maintain the ribavirin dose. In HCV-HIV coinfected patients, combination therapy for HCV should, if possible, be initiated before anti-retroviral therapy (ART) is indicated. For liver transplant patients pre-emptive therapy is not recommended; hence, treatment should be deferred until histological recurrence.
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| 10. |
- Naver, Lars, et al.
(författare)
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Prophylaxis and treatment of HIV-1 infection in pregnancy: Swedish recommendations 2007
- 2008
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 1651-1980 .- 0036-5548. ; 40:6-7, s. 451-461
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Forskningsöversikt (refereegranskat)abstract
- Prophylaxis and treatment with antiretroviral drugs, a consequent low viral load, and the use of elective Caesarean section, are factors that radically decrease the risk of HIV transmission from mother to child during pregnancy and delivery. The availability of new antiretroviral drugs, updated general treatment guidelines and increasing knowledge of the importance of drug resistance, have necessitated recurrent revisions of the recommendations for 'Prophylaxis and treatment of HIV-1 infection in pregnancy'. For these reasons, The Swedish Reference Group for Antiviral Therapy (RAV) has, at an expert meeting on May 4, 2007, once more updated the treatment recommendations of 1999, 2002 and 2005, which were defined in cooperation with the Swedish Medical Products Agency (Lakemedelsverket). This new text takes the recently updated general HIV treatment recommendations into account. Furthermore, the very low risk of HIV transmission when the mother is treated with combination antiretroviral therapy, has undetectable levels of viraemia and no obstetric risk factors, has been considered in the recommendations concerning the mode of delivery. Finally, the recommendations for monitoring of infants born to HIV-infected mothers have been modified. The recommendations are evidence graded in accordance with the Oxford Centre for Evidence Based Medicine, 2001 (see http://www.cebm.net/levels_of_evidence.asp#levels).
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