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Methods We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non–AIDS-related event, or death from any cause. Results A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P.

Figure 1 Antiretroviral Therapy, HIV RNA Suppression, and CD4+ Count. Shown are the percentages of patients who were receiving antiretroviral therapy (ART) and the percentages of patients who had an HIV RNA level of less than 200 copies per milliliter (Panel A) and the mean CD4+ count (Panel B) in the immediate-initiation group and the deferred-initiation group over a 5-year period. The vertical lines around the data points in Panel B indicate 95% confidence intervals. Once ART was initiated, appropriate changes in regimens were mandated in cases of treatment-limiting adverse drug reactions or if the existing regimen did not fully suppress viral replication.

Additional details regarding study-specified initial regimens of antiretroviral therapy and the frequency of specific antiretroviral drugs that were used in the initial regimens are provided in Section 3 and Table S2 in the. Bernadette Brady Predictive Astrology Pdf Files on this page. Figure 2 Primary and Secondary End Points. Shown are Kaplan–Meier estimates of the cumulative percentages of patients with the composite primary end point (a serious AIDS-related or serious non–AIDS-related event, including death) in the two study groups (Panel A). Secondary end points included serious AIDS-related events (Panel B), serious non–AIDS-related events (Panel C), death from any cause (Panel D), and grade 4 events (Panel E).

Grade 4 events were defined as potentially life-threatening symptomatic events that were not attributable to AIDS and that required medical intervention. The immune compromise caused by the human immunodeficiency virus (HIV) is characterized by a loss of CD4+ T cells. Rates of HIV-associated complications and death increase as the number of these cells in peripheral blood (CD4+ count) declines. It has been general practice to defer the initiation of antiretroviral therapy in asymptomatic patients with a CD4+ count above a certain threshold level. The applicable threshold has changed over time, and recommendations remain inconsistent across various guidelines. Randomized studies that have assessed the benefits and risks of treating patients with HIV infection sooner rather than later have largely enrolled patients with a CD4+ count of less than 500 cells per cubic millimeter.

In such studies, “later” has been defined as a CD4+ count of 200 or 250 cells per cubic millimeter. These data, along with observational studies, provide strong evidence for the initiation of antiretroviral therapy in patients with a CD4+ count of 350 cells per cubic millimeter. Evidence for initiating antiretroviral therapy in patients with a CD4+ count of more than 350 cells per cubic millimeter comes mainly from the results of observational studies. However, the findings of these studies are inconsistent and are subject to residual confounding.

Furthermore, most studies have focused only on the risks of the acquired immunodeficiency syndrome (AIDS) and death and have not fully addressed the risks and benefits of initiating antiretroviral therapy in patients with a high CD4+ count, in whom complications and death are largely attributed to non–AIDS-related events. Some studies have raised concern about the adverse effects of antiretroviral therapy on cardiovascular and renal disease, particularly in an aging HIV-positive population. However, in an earlier large, randomized study, the continuous use of antiretroviral therapy, as compared with intermittent therapy, reduced these risks. Given the small absolute risk of AIDS among patients with a high CD4+ count, it is important to establish whether it is safe and beneficial to initiate antiretroviral therapy in asymptomatic patients who have a CD4+ count that is much higher than 350 cells per cubic millimeter. This information is particularly important given the known benefits of antiretroviral therapy in reducing infectivity.