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Biomedical subjects

Keith Henry

Publications and source records attributed to Keith Henry.

28 records · Page 2Linked to original sources
PubMed2003

Enfuvirtide, an HIV-1 fusion inhibitor, for drug-resistant HIV infection in North and South America.

BACKGROUND: The T-20 vs. Optimized Regimen Only Study 1 (TORO 1) was a randomized, open-label, phase 3 study of enfuvirtide (T-20), a human immunodeficiency virus type 1 (HIV-1) fusion inhibitor. METHODS: Patients from 48 sites in the United States, Canada, Mexico, and Brazil with at least six months of previous treatment with agents in three classes of antiretroviral drugs, resistance to drugs in these classes, or both, and with at least 5000 copies of HIV-1 RNA per milliliter of plasma were randomly assigned in a 2:1 ratio to receive enfuvirtide plus an optimized background regimen of three to five antiretroviral drugs or such a regimen alone (control group). The primary efficacy end point was the change in the plasma HIV-1 RNA level from base line to week 24. RESULTS: A total of 501 patients underwent randomization, and 491 received at least one dose of study drug and had at least one measurement of plasma HIV-1 RNA after treatment began. The two groups were balanced in terms of the median base-line HIV-1 RNA level (5.2 log10 copies per milliliter in both groups), median CD4+ cell count (75.5 cells per cubic millimeter in the enfuvirtide group, and 87.0 cells per cubic millimeter in the control group), demographic characteristics, and previous antiretroviral therapy. At 24 weeks, the least-squares mean change from base line in the viral load (intention-to-treat, last observation carried forward) was a decrease of 1.696 log10 copies per milliliter in the enfuvirtide group, and a decrease of 0.764 log10 copies per milliliter in the control group (P<0.001). The mean increases in CD4+ cell count were 76 cells per cubic millimeter and 32 cells per cubic millimeter, respectively (P<0.001). Reactions at the site of the injections were reported by 98 percent of patients receiving enfuvirtide. There were more cases of pneumonia in the enfuvirtide group than in the control group. CONCLUSIONS: The addition of enfuvirtide to an optimized antiretroviral regimen provided significant antiretroviral and immunologic benefit through 24 weeks in patients who had previously received multiple antiretroviral drugs and had multidrug-resistant HIV-1 infection.

Adult↗
PubMed2003

A comprehensive approach to percutaneous injury prevention during phlebotomy: results of a multicenter study, 1993-1995.

OBJECTIVE: To examine a comprehensive approach for preventing percutaneous injuries associated with phlebotomy procedures. DESIGN AND SETTING: From 1993 through 1995, personnel at 10 university-affiliated hospitals enhanced surveillance and assessed underreporting of percutaneous injuries; selected, implemented, and evaluated the efficacy of phlebotomy devices with safety features (ie, engineered sharps injury prevention devices [ESIPDs]); and assessed healthcare worker satisfaction with ESIPDs. Investigators also evaluated the preventability of a subset of percutaneous injuries and conducted an audit of sharps disposal containers to quantify activation rates for devices with safety features. RESULTS: The three selected phlebotomy devices with safety features reduced percutaneous injury rates compared with conventional devices. Activation rates varied according to ease of use, healthcare worker preference for ESIPDs, perceived "patient adverse events," and device-specific training. CONCLUSIONS: Device-specific features and healthcare worker training and involvement in the selection of ESIPDs affect the activation rates for ESIPDs and therefore their efficacy. The implementation of ESIPDs is a useful measure in a comprehensive program to reduce percutaneous injuries associated with phlebotomy procedures.

Attitude of Health Personnel↗
PubMed2003

Current trends in the treatment of HIV infection, 2003.

The HIV/AIDS epidemic appears to have stabilized in the world's developed countries while it is still worsening in many areas of the resource-poor world. HIV/AIDS patients in countries such as the United States are living longer primarily due to the availability of potent antiretroviral drug combinations and tests to monitor the risk of progression of disease. Management of HIV is very complicated. General guidelines for treatment are available. Published guidelines, however, are often too simplistic and do not reflect new or controversial information. Most patients will develop resistant virus during their treatment. Several antiretroviral medications are on the horizon that will afford better options for treatment, and studies are underway to evaluate treatment strategies that would be potent, less toxic, and convenient for patients. Because the field of HIV care continues to evolve rapidly and there is increasing diversity among infected patients, treatment and prevention are optimized when provided by a dedicated care team supervised by an HIV specialist.

Adolescent↗
PubMed2002

Effect of prolonged discontinuation of successful antiretroviral therapy on CD4+ T cell decline in human immunodeficiency virus-infected patients: implications for intermittent therapeutic strategies.

This study evaluates the change in CD4(+) T cell counts among patients who achieved complete viral suppression and subsequently discontinued highly active antiretroviral therapy (HAART). We included 72 human immunodeficiency virus (HIV)-1-infected patients with plasma HIV RNA loads of <500 copies/mL for at least 3 months who then discontinued therapy for at least 12 weeks. The median CD4(+) T decay while off HAART was 16 cells/mm(3)/month (interquartile range, -6 to -34 cells/month). The mean follow-up after therapy ended was 45 weeks. The slope of the CD4(+) T cell decay was inversely correlated with the increase of CD4(+) T cells while receiving HAART, baseline virus load, CD4(+) T cell count at the time therapy was discontinued, age, and duration HIV RNA levels were undetectable. In a multiple regression analysis model, the increase of CD4(+) T cells while receiving therapy and age were independently associated with the rate of CD4(+) T cell loss.

Adult↗
PubMed2002

Concentration-controlled compared with conventional antiretroviral therapy for HIV infection.

OBJECTIVES: To demonstrate the feasibility of a concentration-controlled approach to combination antiretroviral therapy, and to compare the virological responses and safety of this strategy versus conventional fixed-dose therapy. DESIGN: A prospective, randomized, 52 week, open-label trial of concentration-controlled compared with conventional dose zidovudine, lamivudine, and indinavir therapy conduced in a university-based general clinical research center in the United States. PATIENTS: Forty antiretroviral-naive individuals with plasma HIV-RNA levels > 5000 copies/ml. INTERVENTIONS: Zidovudine, lamivudine, and indinavir plasma concentrations were measured in all participants. Doses were adjusted in those assigned to concentration-controlled therapy to achieve levels equal to or greater than target values. MAIN OUTCOME MEASURES: The proportion of patients who achieved the desired drug concentrations, the proportion of patients with HIV-RNA levels < 50 copies/ml at week 52, and safety and tolerance in the concentration-controlled versus conventional therapy arms. RESULTS: Significantly more concentration-controlled recipients achieved the desired concentration targets for all three drugs: 15 of 16 concentration-controlled recipients compared with nine of 17 conventional recipients (P = 0.017) had HIV-RNA levels < 50 copies/ml at week 52. No difference was observed in the occurrence of drug-related clinical events or laboratory abnormalities between the two treatment arms. CONCLUSION: Concentration-controlled therapy implemented simultaneously for three antiretroviral agents was feasible, as well tolerated as conventional therapy, and resulted in a greater proportion of recipients with HIV-RNA levels < 50 copies/ml after 52 weeks. These findings provide a scientific basis to challenge the accepted practice of administering the same dose of antiretroviral agents to all adults, ignoring the concentrations actually achieved.

Adult↗
PubMedDate not supplied

Blockade of HERG channels by HIV protease inhibitors.

The HIV protease inhibitor class of antiretroviral drug causes unpredicted adverse effects by changing elements of normal cellular metabolism. A case of QT prolongation in a patient receiving protease inhibitors made us question whether these drugs might be responsible. We identified 24 patients with QT prolongation or torsade de pointes, or both, associated with protease inhibitors, using the Food and Drug Administration's voluntary adverse event reporting system. Attending physicians thought that protease inhibitors were the most probable cause of these symptoms in 14 of the patients. Drug-induced QT prolongation is usually caused by block of human ether-a-go-go-related gene (HERG) potassium channels, and we showed that lopinavir, nelfinavir, ritonavir, and saquinavir caused dose-dependent block of HERG channels heterologously expressed in HEK293 cells in vitro. We also recorded block by lopinavir of repolarising potassium current (I(Kr)) channels in neonatal mouse cardiac myocytes. Our data show that four protease inhibitors block HERG channels, suggesting that protease inhibitors could predispose individuals to QT prolongation and torsade de pointes.

Action Potentials↗