Novel HIV Drug a 'Trade-Off'

Este artículo, salió publicado en http://www.medpagetoday.com/MeetingCoverage/ICAAC/22219?shield=0;  y habla de una nueva droga , pero también nos menciona que debemos ser cautos en su lectura e intrerpretación, hasta que sea publicado el artículo.  Espero que les sea útil. Dr. Carlos Erazo Action Points   Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal. Clinicians should note that when TMC278 was compared with efavirenz in naive patients, both taken with two nucleoside reverse transciptase agents, overall results were similar but adherence was especially critical to TMC278's efficacy in those with baseline HIV RNA over 100,000. Clinicians should note that TMC278 appeared to be better tolerated than efavirenz in these head-to-head studies. Note that mutational patterns developing on treatment were different in the two study groups. BOSTON -- In HIV patients starting therapy, an investigational non-nucleoside reverse transcriptase inhibitor had a higher rate of virologic failure than a standard medication, researchers said here. But treatment with TMC278 (rilpivirine) also caused fewer adverse events and led to fewer dropouts for such events than efavirenz (Sustiva), according to Joseph Eron, MD, of the University of North Carolina Chapel Hill. In both arms of two nearly identical phase III trials, virologic failure was more common in those with a higher baseline viral load and suboptimal adherence, Eron said during an oral presentation here at the Interscience Conference on Antimicrobial Agents and Chemotherapy. But the effect was more apparent among those taking the novel drug, he said. In the two trials -- dubbed THRIVE and ECHO -- a total of 1,368 treatment-naive patients were randomly assigned to get either TMC278 or efavirenz, combined with two other anti-HIV medications. In the ECHO trial, all patients also got the combination of tenofovir and emtricitabine (Truvada), but in THRIVE, physicians could choose any two nucleoside reverse transcriptase inhibitors. The main goal of the study was to see if the TMC278 regimens were noninferior to the efavirenz regimens, and researchers reported at the International AIDS Conference in Vienna that that was the case. (See IAC: New HIV Drug Matches Old Standard) At the AIDS meeting, Tibotec -- the developer of the drug and the sponsor of the two trials -- announced it was filing for approval of the drug. Here, Eron was filling in some of the gaps, including how and why some patients failed to respond to the drugs. In a pooled analysis of data from the two trials, the researchers found that 84.3% of TMC278 patients had a viral load of fewer than 50 copies of HIV RNA per milliliter of serum after 48 weeks of therapy, compared with 82.3% of efavirenz patients. The result met criteria for noninferiority, he said. When the patients were analyzed on the basis of baseline viral load, the two drugs were also noninferior among those starting with more than 100,000 copies, but TMC278 was actually better among those with a viral load below that cutoff with 90% responding, compared with 84%. The proportion of patients who suffered a grade 2,3, or 4 adverse event regarded as possibly related to treatment was 16% among TMC278 patients and 31% among efavirenz patients (P<0.0001), Eron said. Moreover, only 3% of TMC278 patients dropped out because of adverse events, compared with 8% of those taking efavirenz (P=0.0005). Neurological adverse events were also significantly more common (P<0.0001) among those taking efavirenz. The incidence of virologic failure -- defined as never having suppressed HIV or having rebounded after initial success -- was 10% among TMC278 patients and 6% among those taking efavirenz. Much of the difference was driven by patients with initial viral loads greater than 100,000 copies whose adherence to therapy was poor, Eron said. Among TMC278 patients, he said, there were 42 who met both criteria and 26 of them failed therapy. Among efavirenz patients, 38 met the criteria, but only 12 failed. Among those who failed therapy, Eron reported, 63% of TMC278 patients had developed at least one mutation that was associated with resistance to non-nucleoside reverse transcriptase inhibitors, compared with 54% of efavirenz patients. Each drug had a distinct pattern of resistance-associated mutations, he said, with only one seen in both groups. "The most important new information was that patients with both a high viral load at baseline and suboptimal adherence had a higher risk of failure on TMC278 than on efavirenz," said Paul Sax, MD, of Brigham and Women's Hospital in Boston, who co-moderated the session but was not involved in the research. On the other hand, he told MedPage Today, for patients who are easier to treat -- those with a low viral load when they start therapy -- "it did better." From the clinical point of view, he said, "it's a trade-off." His co-moderator, Jens Lundgren, MD, of the University of Copenhagen, commented that it's not surprising to see fewer TMC278 patients dropping out because of adverse effects, since efavirenz is known to have central nervous system impacts that many patients find difficult to tolerate "and TMC278 doesn't have that." But the bottom line, he said, may be that TMC278 is slightly less potent, but easier to take. The study was supported by Tibotec, which is developing the drug. Eron has disclosed financial relationships with GlaxoSmithKline, Bristol-Myers Squibb, Virologic, Boehringer Ingelheim, Virco, Abbott, and Merck. Some authors were employees of Tibotec. Sax reported financial links with a range of pharmaceutical companies. Lundgren said he had no disclosures.

Primary source: Interscience Conference on Antimicrobial Agents and Chemotherapy Source reference: Rimsky L, et al "Characterization of the resistance profile of TMC278: 48-week analysis of the phase III studies ECHO and THRIVE" ICAAC 2010.

LINK:  http://www.medpagetoday.com/MeetingCoverage/ICAAC/22219?shield=0

The Pattern of Indeterminate Human Immunodeficiency Virus Test and Follow-Up Evaluation in Pregnant Women.

Este arículo es interesante, el link esta al final de esta entrada para que ustedes puedan obtener más información. 

Dr. Carlos Erazo

Am J Perinatol. 2010 Dec 6. [Epub ahead of print]

Jain S, Basraon S, Loeffelholz MJ, Patel JA.

Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas.

Abstract

We studied the pattern of indeterminate HIV serological tests among pregnant women with follow-up testing in the postpartum period. Medical records of pregnant women were reviewed over a 2-year period. Of 16,596 pregnant women, 127 (0.8%) had positive HIV enzyme-linked immunoassay (ELISA) result. With Western blot (WB) test, 54 (0.33%) were positive, 43 (0.26%) were negative, and 30 (0.18%) were indeterminate. One of the 30 women (3.3%) with indeterminate WB converted to positive WB during pregnancy. White and black women were more likely to have an unconfirmed positive ELISA (indeterminate or negative WB) than Hispanics ( P = 0.021). The positive WB rate for black women was significantly higher ( P < 0.001) than other racial/ethnic groups. The postpartum follow-up testing of 14 women with indeterminate WB varied between 4 to 20 weeks; 16 did not have any postpartum follow-up test. The common bands in indeterminate WB were P24, P18, and nonviral proteins. The pattern of indeterminate WB result and its follow-up was variable during pregnancy and postpartum period. There is a need for development of national standards of care for indeterminate WB mothers and their infants in the postpartum period. Additional studies are needed to determine the cause of indeterminate tests, reducing their occurrence in the testing process, and the optimum time for testing in the postpartum period.

LINK :  http://www.ncbi.nlm.nih.gov/pubmed/21136348

Approach to Dyslipidemia, Lipodystrophy, and Cardiovascular Risk in Patients with HIV Infection.

Pensando en la Atención Integral de los pacientes con VIH /SIDA , me parece interesante este tipo de artículos.

Les dejo aqui el abstract y el link en la parte inferior para que puedan acceder a más información.

Saludos

Dr. Carlos Erazo

Curr Atheroscler Rep. 2010 Dec 23. [Epub ahead of print]

Troll JG.

Touro University College of Osteopathic Medicine, 1310 Club Drive, Vallejo, CA, 94592, USA, greg.troll@tu.edu.

Abstract

There is a significant prevalence (20%-80% depending on the population and the study) of lipid disorders and other cardiovascular risk factors in people living with HIV infection. This review focuses on HIV and HIV treatment-associated metabolic and cardiovascular concerns, including dyslipidemias, lipodystrophy syndromes, endothelial dysfunctions, and associated metabolic events such as insulin resistance. Emerging hypotheses of the underlying pathophysiology of these issues, with impact on selection of specific antiretroviral treatment (ART) strategies, therapy, and preventive approaches to decreasing cardiovascular risk and other problems associated with these syndromes are discussed. Screening for cardiovascular risk as part of the decision of starting antiretroviral therapy, and during care of patients with HIV regardless of ART therapy status, is suggested with particular areas of focus. Statins, other hyperlipidemic therapies, treatment for specific problems arising due to lipodystrophy, and implications on ART selection to avoid drug interactions and adverse effects are also discussed.

LINK:     http://www.ncbi.nlm.nih.gov/pubmed/21181310

TB and HIV in children - advances in prevention and management.

Interesante artículo, debemos pensar un poco más en la Co- infección. Aqui les mando el abstract y el link, este no esta disponible sin subscripción. Pero pueden pedirlo y comprarlo a quien esté interesado.

Paediatr Respir Rev. 2011 Mar;12(1):39-45. Epub 2010 Oct 18.

Marais BJ, Rabie H, Cotton MF.

Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, South Africa. bjmarais@sun.ac.za

Abstract

The human immunodeficiency virus (HIV) epidemic has had a major impact on the age and gender profile of adult tuberculosis (TB) patients, resulting in increased exposure of HIV-infected and uninfected children at a very young age. Young and/or HIV-infected children are extremely vulnerable to develop severe forms of TB following recent exposure and infection. There is an urgent need to implement safe and pragmatic strategies to prevent TB in children, especially in TB endemic areas where they suffer the greatest burden of disease. The management of TB in HIV-infected children poses multiple challenges, but recent advances in the implementation of prevention of mother to child transmission (PMTCT) strategies and HIV care of infants offer hope. These include HIV testing and access to PMTCT for all pregnant women, routine testing of all HIV exposed infants and rapid initiation of antiretroviral treatment irrespective of clinical or immunological disease staging. In addition, careful scrutiny for TB exposure should occur at every health care visit, with provision of isoniazid preventive therapy (IPT) following each documented exposure event. Knowing the HIV infection status of child TB suspects is essential to optimize case management. Although multiple difficulties remain, recent advances demonstrate that the management of children with TB and/or HIV can be vastly improved by well focused interventions using readily available resources.
2010 Elsevier Ltd. All rights reserved.

 

Link: http://www.ncbi.nlm.nih.gov/pubmed/21172674