1,721,178 research outputs found
Dolutegravir: A new option for HIV treatment
No full textThe need for new strategies for treating HIV-1 infection has led to the development of a number of new drugs. The aim of this article is to review the latest results of clinical trials of dolutegravir, an integrase inhibitor whose efficacy, tolerability and safety have been confirmed in treatment-naive and treatment-experienced patients. The findings, together with its high genetic barrier and limited interactions with other drugs, indicate that dolutegravir will play an important role in the future treatment of HIV infection
Raltegravir in treatment nave patients
No full textAbstract. Raltegravir is the first integrase inhibitor approved for the treatment of HIV infection based on the superior efficacy it showed compared to optimized backbone therapy alone in patients harboring multidrug resistant viruses. Studies on nave patients showed comparable efficacy of raltegravir and efavirenz and just recently the US Food and Drug Administration (FDA) approved raltegravir for the use in nave patients based on the favorable results of the international double-blind phase III STARTMRK trial. Additional interesting findings were the faster, and not yet explained, decay of HIV-1 RNA and the higher CD4+ cells increase in the raltegravir group as compared to the efavirenz group. Raltegravir is generally well tolerated and adverse events were generally similar in raltegravir and comparator arms throughout all studies. When compared to efavirenz, patients on raltegravir showed less incidence of central nervous system-related adverse events. In studies on experienced patients higher incidence of cancers was found in the raltegravir arm: a relationship with the drug was, however not confirmed in a recent review considering all raltegravir studies. Raltegravir also showed a safe lipid profile expecially in nave patients, finding that renders the drug attractive for patients with other cardiovascular risk factors. All this characteristics in association with its specific mechanism of action, make raltegravir an interesting drug for nave patients and a large use in this type of patients is predictable. Only time and experience, however, will tell us whether raltegravir will maintain its promises in the long run. © 2009 I. Holzapfel Publishers
Bictegravir
No full textPurpose of review In this review, we will highlight and discuss the recent efficacy and safety data of bictegravir (BIC), a novel second-generation integrase strand transfer inhibitor (INSTI) that has been recently approved, in coformulation with emtricitabine and tenofovir alafenamide (B/F/TAF), for the treatment of HIV-1 infection in antiretroviral naïve subjects and in those with suppressed viremia. Recent findings Preclinical data showed that BIC has a genetic barrier that is higher than that of raltegravir and elvitegravir but is similar to that of dolutegravir (DTG), with retained activity in vitro against isolates containing substitutions associated with resistance against other INSTIs. Its pharmacokinetic interaction risks appear to be low. Results of the phase 3 GS-US-380-1489 and GS-US-380-1490 clinical trials showed that the coformulation B/F/TAF is not inferior to the recommended DTG-containing regimens in naïve subjects. Moreover, B/F/TAF exhibited excellent tolerability, and no treatment-emergent resistance to any component of the coformulation was observed. In addition, preliminary data support switching from DTG and emtricitabine/tenofovir alafenamide or boosted protease inhibitor-containing regimens to B/F/TAF in subjects with undetectable viremia. Summary The coformulation bictegravir/emtricitabine/tenofovir alafenamide is set to become a new option in the management of patients who are antiretroviral naïve and in those with suppressed viremia
Darunavir for the treatment of HIV infection
No full textIntroduction: Darunavir (DRV) was the last approved protease inhibitor (PI) and has been extensively used for the treatment of HIV in both naïve and experienced subjects due to its high genetic barrier and efficacy. The introduction in clinical practice of integrase strand transfer inhibitors limited its role in the management of naïve subjects and in antiretroviral treatment simplification strategies. However, recent data from trials that have investigated the new DRV/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) combination showed an excellent efficacy and tolerability of this coformulation both in naïve patients and in those with viral suppression, making D/C/F/TAF a new option for the treatment of HIV infection. Areas covered: The authors present and discuss the efficacy and safety data of DRV when used in antiretroviral-naïve, multiexperienced subjects and in the setting of treatment deintensification in subjects with viral suppression. Moreover, the authors evaluate the recent data from two different Phase III trials on D/C/F/TAF both in treatment-naïve and virologically suppressed subjects. Expert opinion: Although novel antiretroviral drugs may become available over time, DRV continues to represent a valuable option for multiexperienced subjects and has a role in simplification regimens. In addition, the convenience of D/C/F/TAF coformulation may be useful for the future management of HIV-infected subjects
Etravirine for the treatment of HIV infection
No full textEtravirine (TMC 125) is a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) that is being developed for the treatment of HIV-1 infections. The drug was recently approved by the US FDA to be used in combination with other anti-HIV medications. Etravirine is a highly flexible diarylpyrimidine compound, with favorable binding interactions toward mutant HIV strains as well as wild-type virus. This conformation confers an increased genetic barrier to resistance compared with other NNRTIs: multiple mutations are required before there is a decrease in susceptibility to etravirine; whereas, only one mutation (K103N) is typically needed to confer high-level resistance to the first-generation NNRTIs. In vitro, etravirine is predominantly metabolized by cytochrome P450 (CYP)3A4 and CYP2C (2C9, 2C 18 and 2C 19). In vivo, the most important metabolic pathway for etravirine is methyl hydroxylation, with subsequent glucuronidation of the metabolites. Etravirine is an inducer of CYP3A4 and a weak inhibitor of CYP2C9, CYP2C19 and P-glycoprotein. In Phase II and III trials in treatment-experienced patients, treatment with etravirine led to better virological suppression than placebo. In the DUET I and II trials (Phase 111), approximately 60% of the etravirine group achieved a confirmed viral load of less than 50 copies/ml at week 24, compared with approximately 40% in the placebo arm. The mean change in viral load at week 24 was -2.34 (standard deviation: 1.31) and -1.68 (1.40) log10 copies/ml in the etravirine and placebo groups, respectively. The presence of three or more NNRTI-associated mutations at baseline negatively influenced the outcome. There were no safety concerns and no major differences in frequency or severity of side effects between etravirine and placebo groups, with the exception of rash. Furthermore, the overall rate of discontinuation due to any adverse event was similar between the etravirine and placebo groups. The most common adverse events reported were rash and nausea. © 2008 Expert Reviews Ltd
Ability of different lopinavir genotypic inhibitory quotients to predict 48-week virological response in highly treatment-experienced HIV-infected patients receiving lopinavir/ritonavir
No full textThe genotypic inhibitory quotient (GIQ) is the ratio between drug concentration and the number of resistance mutations. However, as different resistance scores can be calculated for the same protease inhibitor, the ability of a GIQ to predict the virological outcome may vary depending on the resistance score used as the denominator. Forty-four highly treatment-experienced HIV-infected patients failing on their current regimen were treated with a lopinavir/ritonavir-containing combination for at least 48 weeks.-Three GIQs were calculated for each patient: the denominator of the first (GIQ-A) was the lopinavir/ritonavir score calculated using the mutations listed by IAS-USA as being related to lopinavir/ritonavir resistance; the denominator of the second (GIQ-B) was the total number of mutations related to resistance to any protease inhibitor as reported by IAS-USA; and the denominator of the third (GIQ-C) was the lopinavir/ritonavir score proposed by Parkin et al. The median (IQR) of the GIQ-A, B, and C was 4.69 (3.83-9.76), 0.97 (0.74-1.62), and 1.02 (0.68-2.52), respectively. At week 48, the median decrease in HIV-RNA was 1.09 (0.32-2.34) log(10) copies/ml (P < 0.0001), with 13 subjects (29.5%) attaining undetectable levels. All of the GIQs independently predicted the change in viral load from baseline and undetectable HIV-RNA at week 48. The partial R-2 of GIQ-C was greater than that of GIQ-B, which was greater than that of GIQ-A. All of the GIQs were independent predictors of the 48-week virological response. The predictive value of the GIQ for lopinavir/ritonavir may vary depending on the algorithm used to score drug resistance
Increased hyperglycaemia during cotreatment with pentamidine and corticosteroids in AIDS patients
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Rate of cirrhosis progression reduced in HIV/HCV co-infected non-responders to anti-HCV therapy
No full textThis is a retrospective longitudinal follow-up study of 25 HIV/HCV positive cirrhotic patients not responding to peg-IFN plus ribavirin, and 25 untreated controls matched for age ( 5 years), gender and Child-Pugh score. The primary endpoint of the study was the incidence of cirrhosis progression (CP) defined as the occurrence of at least one of the following events: death, ascites, jaundice, encephalopathy, gastrointestinal bleeding and hepatocellular carcinoma (HCC). During the median follow-up of 54 months (34-89), four treated (16%) and 13 untreated patients (52%) experienced CP (p=0.02). Poisson's regression model showed that the independent predictors of CP were Peg-IFN therapy (p=0.016), positive HIV-RNA (p=0.024), and altered ALP values (p=0.012). Peg-IFN therapy seems to slow down the rate of cirrhosis progression also in HIV/HCV co-infected patients nonresponders to anti-HCV therapy, in comparison with untreated patients
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