Drug and Alcohol Rehabilitation: HIV-1 Amino Acid Changes Among Participants With Virologic Failure: Associations With First-Line Efavirenz or Atazanavir Plus Ritonavir and Disease Status.
HIV-1 Amino Acid Changes Among Participants With Virologic Failure: Associations With First-line Efavirenz or Atazanavir Plus Ritonavir and Disease Status.
Filed under: Drug and Alcohol Rehabilitation
J Infect Dis. 2012 Nov 12;
Mollan K, Daar ES, Sax PE, Balamane M, Collier AC, Fischl MA, Lalama CM, Bosch RJ, Tierney C, Katzenstein D,
Background.?Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes.Methods.?In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences.Results.?Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ? .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes.Conclusions.?Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non-drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count.Clinical Trials Registration.?NCT00118898. HubMed – drug
Development of proteasome inhibitors as research tools and cancer drugs.
Filed under: Drug and Alcohol Rehabilitation
J Cell Biol. 2012 Nov 12; 199(4): 583-8
Goldberg AL
The proteasome is the primary site for protein degradation in mammalian cells, and proteasome inhibitors have been invaluable tools in clarifying its cellular functions. The anticancer agent bortezomib inhibits the major peptidase sites in the proteasome’s 20S core particle. It is a “blockbuster drug” that has led to dramatic improvements in the treatment of multiple myeloma, a cancer of plasma cells. The development of proteasome inhibitors illustrates the unpredictability, frustrations, and potential rewards of drug development but also emphasizes the dependence of medical advances on basic biological research.
HubMed – drug
Cell biology: A key driver of therapeutic innovation.
Filed under: Drug and Alcohol Rehabilitation
J Cell Biol. 2012 Nov 12; 199(4): 571-5
Hantschel O, Superti-Furga G
All processes associated with cellular function are likely to contribute to disease. Particularly in the cancer field, most major therapeutic innovations have originated from the elucidation of basic molecular mechanisms by academic researchers. Recent breakthroughs in molecularly targeted drug discovery have made it clear that it is the depth with which a biological process is understood that empowers its translation. We propose that early, more strategic, support of cutting-edge academic research by industry may be more effective for translational purposes than the current model of a late selection of community-evolved projects.
HubMed – drug
Interview with Ken Spencer, Case Manager – Alcohol and Drug Services – Bozeman, Montana – PART 1 – drivingequality.com Driving Equality is a 100-day, 16000-mile, 48-state trek across America to collect stories from LGBTQ people in an effort to raise awareness of the various forms of discrimination faced by our community in each state of the nation. Highlighting the differences in rights, laws, and amendments between the states will shed light on the current social standing of queer individuals today. I hope to create a dialogue about the disparities across the nation, and what can be done to end discrimination for all. During the 100-day trip, I am meeting with LGBTQ community organizers, activists, and any citizens willing to talk, as well as our opposition. Through these interviews, I will gain an understanding of the current political climates, and explore ways of combating discrimination. Throughout my journey, I will make frequent posts on the website, including photos and video clips.
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