Highly active antiretroviral treatment (HAART) reduces the risk of wasting in HIV infection and may alter the prognostic weight of wasting. The phase angle from bioelectrical impedance analysis (BIA) ...can be interpreted as a surrogate marker for the catabolic reaction to chronic HIV infection and opportunistic disease.
Our objective was to assess the prognostic ability of the phase angle in HIV-infected patients in the era of HAART.
Two cross-sectional observation studies were conducted in 1996 and 1997 at a German university outpatient HIV clinic. In the 1996 and 1997 cohorts, HAART was prescribed to 17 of 212 and 168 of 257 patients at baseline and to 179 of 212 and 234 of 257 patients during observation, respectively. Whole-body BIA was assessed at 50 KHz. Time to clinical progression and survival were calculated by using Cox proportional hazard models with time-dependent covariates. Median observation times were 1000 and 515 d for the 1996 and 1997 cohorts, respectively.
Higher phase angle was associated with a lower relative mortality risk, adjusted for viral load and CD4(+) cell count, of 0.49 (95% CI: 0.30, 0.81) per degree in 1996 and of 0.33 (95% CI: 0.18, 0.61) in 1997. The influence of phase angle on time to clinical progression, adjusted for viral load and CD4(+) cell count, was not significant in 1996 but the relative risk was 0.58 (0.36, 0.83) in 1997.
Despite the favorable effects of HAART on the nutritional status of HIV-infected persons, low phase angle remains an independent adverse prognostic marker of clinical progression and survival.
HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned. However, recently developed ...single-cell-based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies to HIV-1 (refs 4, 5). These antibodies can prevent infection and suppress viraemia in humanized mice and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favourable pharmacokinetics. A single 30 mg kg(-1) infusion of 3BNC117 reduced the viral load in HIV-1-infected individuals by 0.8-2.5 log10 and viraemia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that, as a single agent, 3BNC117 is safe and effective in reducing HIV-1 viraemia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy and cure.
Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a ...combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg
of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.
HIV-1 immunotherapy with a combination of first generation monoclonal antibodies was largely ineffective in pre-clinical and clinical settings and was therefore abandoned
1
–
3
. However, recently ...developed single cell based antibody cloning methods have uncovered a new generation of far more potent broadly neutralizing antibodies (bNAbs) to HIV-1
4
,
5
. These antibodies can prevent infection and suppress viremia in humanized mice (hu-mice) and nonhuman primates, but their potential for human HIV-1 immunotherapy has not been evaluated
6
–
10
. Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a potent human CD4 binding site antibody
11
, in uninfected and HIV-1-infected individuals. 3BNC117 infusion was well tolerated and demonstrated favorable pharmacokinetics. A single 30 mg/kg infusion of 3BNC117 reduced the viral load (VL) in HIV-1-infected individuals by 0.8 – 2.5 log
10
and viremia remained significantly reduced for 28 days. Emergence of resistant viral strains was variable, with some individuals remaining sensitive to 3BNC117 for a period of 28 days. We conclude that as a single agent 3BNC117 is safe and effective in reducing HIV-1 viremia, and that immunotherapy should be explored as a new modality for HIV-1 prevention, therapy, and cure.
Glutamine has stimulatory effects on lymphocytes and mucosa cells in vitro and, when given with parenteral nutrition, has been shown to improve the clinical course of patients after bone marrow ...transplantation and in the critically ill. This study investigated the clinical and immunologic effects of parenteral glycyl-glutamine supplementation in patients with acute leukemia receiving intensive conventional chemotherapy without bone marrow transplantation.
A randomized, double-blind, controlled study compared a standard glutamine-free parenteral nutrition with a glycyl-glutamine–supplemented parenteral nutrition (Glamin, Baxter, Erlangen, Germany) containing 20 g of glutamine in adult patients with acute myeloid leukemia undergoing myelosuppressive chemotherapy. Clinical end points included the duration of neutropenia and the incidence and duration of neutropenic fever. To analyze the effects of glutamine on immunocompetent cells, CD4
+ and CD8
+ T cells and HLA-DR expression on monocytes were assessed by flow cytometry throughout the treatment course.
Fifty-four adult patients entered the study and were randomized. In 45 of 127 chemotherapy cycles, parenteral nutrition was given, and 40 cycles (20 with and 20 without glutamine) were evaluated for comparison. The median durations of neutropenia were 18 d (range, 9–29 d) in the glutamine group and 22.5 d (range, 13–48 d) in the control group (
P = 0.052), whereas the median durations of neutropenic fever were 5.5 d (range, 0–13 d) and 5 d (range, 0–31 d), respectively (
P = 0.74). Using Kaplan-Meier analysis and controlling for the type of chemotherapy, we found a significantly faster neutrophil recovery in patients receiving glutamine than in the control group (
P = 0.040) in patients receiving a high-dose cytarabine regimen. There was no significant difference in the recovery of CD4
+ or CD8
+ lymphocytes or monocyte activation between groups.
In patients with acute myeloid leukemia requiring parenteral nutrition, glycyl-glutamine supplementation could hasten neutrophil recovery after intensive myelosuppressive chemotherapy. However, no impact of glutamine on neutropenic fever or other criteria of immunologic recovery was detected.
Triple antiretroviral treatment including protease inhibitors (PIs) delays the clinical progression of HIV infection and may thus reduce the risk of malnutrition. However, fat redistribution ...(lipodystrophy) was recognized recently as a metabolic side effect of PIs.
The study aimed to assess the effect of triple antiretroviral treatment on body composition and on the prevalence of malnutrition.
Two cross-sectional studies, 1 in 1996 (t96; n = 247) and 1 in 1997 (t97; n = 266), were conducted in HIV-infected outpatients. Among patients who participated in both studies, 111 patients started a new antiretroviral treatment including a PI between t96 and t97 and were studied longitudinally. Total body water (TBW), intracellular water (ICW), extracellular water (ECW), and fat mass were estimated by monofrequency bioelectrical impedance analysis (BIA).
Prevalence of malnutrition was reduced by 30–50% from t96 to t97, depending on the definition used. In the longitudinal study, TBW and the ratio between ICW and ECW increased and fat mass decreased (P < 0.001). BIA indicated a greater increase in ICW in 23 (21%) patients with clinically apparent fat redistribution than in patients without this syndrome, but estimates of fat mass changes were not significantly different.
Triple antiretroviral treatment may protect HIV-infected patients against the development of malnutrition. Whole-body BIA data suggest an increase in appendicular body cell mass associated with improved antiretroviral treatment. However, the method is unreliable in detecting fat redistribution, and current prediction equations will need to be recalibrated for HIV-infected patients receiving highly active antiretroviral treatment.
Effective reduction of HIV replication by protease inhibitor (PI) treatment was expected to reverse some of the weight loss associated with HIV infection. Body weight changes in undernourished ...HIV-infected patients starting PI treatment were compared to its virologic and immunologic effects. This was designed as a retrospective study using prospectively collected weight data; the setting was the HIV outpatient department of a university hospital. Among 223 consecutive HIV-positive patients starting treatment with PI February 1996 to September 1997, 63 undernourished patients were evaluable. The main outcome measures were weight trend, calculated by linear regression of a patient’s weight versus time, and its change from a 4–14-wk baseline period to the first 14 wk, and 28 wk, after treatment. In our results, weight trend remained unchanged (baseline, + 0.4 ± 4.0 kg/100 d; 14 wk, + 0.7 ± 4.1 kg/100 d, and 28 wk, + 1.0 ± 3.4 kg/100 d, n.s.). Reduction of viremia and increase in CD4 cell count were unrelated to weight trends. Treatment with PI did not result in an improved weight trend. Altered body composition with PI treatment, as observed in other studies, does not seem to result in body weight changes. Drug side effects may have counteracted any positive effects. The metabolic and nutritional impact of effective antiviral treatment merits further study.
Highly active antiretroviral treatment (HAART) reduces the risk of wasting in HIV infection and may alter the prognostic weight of wasting. The phase angle from bioelectrical impedance analysis (BIA) ...can be interpreted as a surrogate marker for the catabolic reaction to chronic HIV infection and opportunistic disease.
Our objective was to assess the prognostic ability of the phase angle in HIV-infected patients in the era of HAART.
Two cross-sectional observation studies were conducted in 1996 and 1997 at a German university outpatient HIV clinic. In the 1996 and 1997 cohorts, HAART was prescribed to 17 of 212 and 168 of 257 patients at baseline and to 179 of 212 and 234 of 257 patients during observation, respectively. Whole-body BIA was assessed at 50 KHz. Time to clinical progression and survival were calculated by using Cox proportional hazard models with time-dependent covariates. Median observation times were 1000 and 515 d for the 1996 and 1997 cohorts, respectively.
Higher phase angle was associated with a lower relative mortality risk, adjusted for viral load and CD4+ cell count, of 0.49 (95% CI: 0.30, 0.81) per degree in 1996 and of 0.33 (95% CI: 0.18, 0.61) in 1997. The influence of phase angle on time to clinical progression, adjusted for viral load and CD4+ cell count, was not significant in 1996 but the relative risk was 0.58 (0.36, 0.83) in 1997.
Despite the favorable effects of HAART on the nutritional status of HIV-infected persons, low phase angle remains an independent adverse prognostic marker of clinical progression and survival.
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