Treatment with lamivudine, zidovudine, or both in hiv-positive patients with 200 to 500 cd4+ cells per cubic millimeter

Background. The reverse-transcriptase inhibitor lamivudine has in vitro synergy with zidovudine against the human immunodeficiency virus (HIV). We studied the activity and safety of lamivudine plus zidovudine as compared with either drug alone as treatment for patients with HIV infection, most of whom had not previously received zidovudine. Methods. Three hundred sixty-six patients with 200 to 500 CD4+ cells per cubic millimeter who had received zidovudine for four weeks or less were randomly assigned to treatment with one of four regimens: 300 mg of lamivudine every 12 hours; 200 mg of zidovudine every 8 hours; 150 mg of lamivudine every 12 hours plus zidovudine; or 300 mg of lamivudine every 12 hours plus zidovudine. The study was double-blind and lasted 24 weeks, with an extension phase for another 28 weeks. Results. Over the 24-week period, the low-dose and high-dose regimens combining lamivudine and zidovudine were associated with greater increases in the CD4+ cell count (P=0.002 and P=0.015, respectively) and the percentage of CD4+ cells (P<0.001 for both) and with greater decreases in plasma levels of HIV type 1 (HIV-1) RNA (P<0.001 for both) than was treatment with zidovudine alone. Combination therapy was also more effective than lamivudine alone in lowering plasma HIV-1 RNA levels and increasing the percentage of CD4+ cells (P<0.001 for all comparisons), and these advantages persisted through 52 weeks. Adverse events were no more frequent with combination therapy than with zidovudine alone. Conclusions. In HIV-infected patients with little or no prior antiretroviral therapy, treatment with a combination of lamivudine and zidovudine is well tolerated over a oneyear period and produces more improvement in immunologic and virologic measures than does treatment with either agent alone. (N Engl J Med 1995;333:1662-9.

Heat flow from the Southeast Indian Ridge flanks between 80°E and 140°E: Data review and analysis

International audienceWe analyze available heat flow data from the flanks of the Southeast Indian Ridge adjacent to or within the Australian-Antarctic Discordance (AAD), an area with patchy sediment cover and highly fractured seafloor as dissected by ridge- and fracture-parallel faults. The data set includes 23 new data points collected along a 14-Ma old isochron and 19 existing measurements from the 20- to 24-Ma old crust. Most sites of measurements exhibit low heat flux (from 2 to 50 mW m−2) with near-linear temperature-depth profiles except at a few sites, where recent bottom water temperature change may have caused nonlinearity toward the sediment surface. Because the igneous basement is expected to outcrop a short distance away from any measurement site, we hypothesize that horizontally channelized water circulation within the uppermost crust is the primary process for the widespread low heat flow values. The process may be further influenced by vertical fluid flow along numerous fault zones that crisscross the AAD seafloor. Systematic measurements along and across the fault zones of interest as well as seismic profiling for sediment distribution are required to confirm this possible, suspected effect

Depth-varying seismogenesis on an oceanic detachment fault at 13°20'N on the Mid-Atlantic Ridge

Extension at slow- and intermediate-spreading mid-ocean ridges is commonly accommodated through slip on long-lived faults called oceanic detachments. These curved, convex-upward faults consist of a steeply-dipping section thought to be rooted in the lower crust or upper mantle which rotates to progressively shallower dip-angles at shallower depths. The commonly-observed result is a domed, sub-horizontal oceanic core complex at the seabed. Although it is accepted that detachment faults can accumulate kilometre-scale offsets over millions of years, the mechanism of slip, and their capacity to sustain the shear stresses necessary to produce large earthquakes, remains subject to debate. Here we present a comprehensive seismological study of an active oceanic detachment fault system on the Mid-Atlantic Ridge near 13°20′N, combining the results from a local ocean-bottom seismograph deployment with waveform inversion of a series of larger teleseismically-observed earthquakes. The unique coincidence of these two datasets provides a comprehensive definition of rupture on the fault, from the uppermost mantle to the seabed. Our results demonstrate that although slip on the deep, steeply-dipping portion of detachment faults is accommodated by failure in numerous microearthquakes, the shallow, gently-dipping section of the fault within the upper few kilometres is relatively strong, and is capable of producing large-magnitude earthquakes. This result brings into question the current paradigm that the shallow sections of oceanic detachment faults are dominated by low-friction mineralogies and therefore slip aseismically, but is consistent with observations from continental detachment faults. Slip on the shallow portion of active detachment faults at relatively low angles may therefore account for many more large-magnitude earthquakes at mid-ocean ridges than previously thought, and suggests that the lithospheric strength at slow-spreading mid-ocean ridges may be concentrated at shallow depths

In-situ measurement of thermal conductivity using the continuous-heating line source method and WHOI outrigged probe

The outrigged thermal probes of a "pogo" marine geothermal probe have been adapted to measure thermal conductivity in-situ by the continuous-heating line source technique. The instrumental uncertainty in applying the analytical theory to a single-probe and double-probe configuration is found to be 3 and 6 percent, respectively. The in-situ outrigged single probe <.32 cm dia.) is essentially a scaled-up version of the needle probe (.08 cm dia.). The main advantage of the outrigged probe over a larger radius probe <e.g., violin-bow probe) is that for short-time temperatures (<2 min.), simple approximations to the exact solution for a perfectly conducting cylindrical probe are achieved. The continuous-heating compares favorably with the pulse-heating technique, the latter being more energy efficient. The continuous-heating method applied to the thin outrigged probe allows for accurate equilibrium in-situ temperature and thermal conductivity estimates in less than 15 minutes of recording time. The technique has been applied to several hundred marine heat flow stations. Comparison of in-situ measurements to needle probe measurements made on nearby piston cores indicate agreement to within 5%. The conductivity profiles of the in-situ data and core data show that the piston coring process frequently does not retrieve the upper meter of surficial sediment.Support was provided by the U. S. National Science Foundation under grant Nos. OCE-8025181, OCE-8117886, and OCE-8409170

A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: Selection of thymidine analog regimen therapy (Start II)

Objective: Comparison of stavudine (d4T), didanosine (ddl) and indinavir (IDV) with zidovudine (ZDV), lamivudine (3TC) and IDV in HIV-1 infected patients. Design: Randomized, open-label. Setting: Fourteen HIV Clinical Research Centers. Patients: Two-hundred and five patients with less than 4 weeks antiretroviral treatment, naive to 3TC and protease inhibitors and with CD4 cell counts ≥ 200 x 10 6/l and plasma HIV-1 RNA levels ≥ 10 000 copies/ml. Interventions: Stavudine 40 mg and ddl 200 mg twice daily plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h or 300 mg twice daily, 3TC 150 mg twice daily plus IDV. Main outcome measures: The proportion of patients with plasma HIV-1 RNA levels \u3c 500 copies/ml and ≤ 50 copies/ml and changes in CD4 cell counts were compared. Results: In an analysis of the primary endpoint, 61% of patients on d4T + ddl + IDV and 45% of patients on ZDV+ 3TC + IDV had all HIV-1 RNA values obtained between weeks 40 and 48 \u3c 500 copies/ml [95% confidence interval (Cl) for the difference between proportions, 1.7-30.3%; P = 0.038]. In an intent-to-treat analysis, the percentage of all patients randomized with all HIV-1 RNA levels \u3c 500 copies/ml between 40 and 48 weeks were 53% for the d4T + ddl + IDV arm and 41% for the ZDV + 3TC + IDV arm (95% Cl, -1.4% to 25.7%; P = 0.068). At 48 weeks 41% and 35% were ≤ 50 copies/ml for the stavudine- and ZDV-containing arms respectively (P \u3e 0.2). The median time-weighted average increases in CD4 cells count over 48 weeks were 150 x 10 6/l cells for the d4T arm and 106 x 10 6/l cells for the ZDV arm (P = 0.001). The occurrence of serious adverse events was not significantly different between arms. Conclusion: The combination of stavudine, ddl and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddl and a protease inhibitor as an initial antiretroviral treatment. (C) 2000 Lippincott Williams and Wilkins