Antiviral activity of single-dose PRO 140, a CCR5 monoclonal antibody, in HIV-infected adults.

BACKGROUND: The current goal of human immunodeficiency virus type 1 (HIV-1) therapy is to maximally suppress viral replication. Securing this goal requires new drugs and treatment classes. The chemokine receptor CCR5 provides an entry portal for HIV-1, and PRO 140 is a humanized monoclonal antibody that binds to CCR5 and potently inhibits CCR5-tropic (R5) HIV-1 in vitro. METHODS: A randomized, double-blind, placebo-controlled, dose-escalating study was conducted in 39 individuals with HIV-1 RNA levels or =5000 copies/mL, CD4(+) cell counts > or =250 cells/microL, no antiretroviral therapy for 3 months, and only R5 HIV-1 detectable. Cohorts were randomized 3:10 to receive placebo or doses of PRO 140 of 0.5, 2, or 5 mg/kg. Subjects were monitored for 58 days for safety, antiviral effects, and serum concentrations of PRO 140. RESULTS: PRO 140 was generally well tolerated and demonstrated potent, rapid, prolonged, and dose-dependent antiviral activity. Mean reductions in HIV-1 RNA level of 0.58 log(10), 1.20 log(10) (P= .0002) and 1.83 log(10) (P= .0001) were observed for the 0.5-, 2-, and 5-mg/kg dose groups, respectively. Reductions in mean viral load of > or =10-fold were observed within 4 days and persisted for 2-3 weeks after treatment. CONCLUSIONS: This trial established clear proof of concept for PRO 140 as a potent antiretroviral agent with extended activity after a single dose. TRIAL REGISTRATION: ISRCTN Register: ISRCTN45537485 .

Effects of protease inhibitors on glucose tolerance, lipid metabolism, and body composition in children and adolescents infected with human immunodeficiency virus.

OBJECTIVE: To evaluate the effects of protease inhibitors (PIs) as antiretroviral therapy in comparison with other antiretroviral (non-PI) medications on glucose tolerance, lipid metabolism, and body fat distribution in human immunodeficiency virus (HIV)-infected young patients. METHODS: We conducted a cross-sectional clinical study in an outpatient HIV clinic. The study population consisted of 21 patients (15 female and 6 male) who had had at least 6 months of antiretroviral treatment. The mean age of the patients was 11.9 years (range, 6 to 16.5). RESULTS: Fifteen patients treated with PIs and 6 patients treated with non-PIs were enrolled in the study. We found no significant differences in the lipid panel and insulin resistance, as determined by using the Quantitative Insulin Sensitivity Check Index formula, in the PI group in comparison with the non-PI group. Lipodystrophy was observed in 47% (7 of 15) of the PI group and 33% (2 of 6) of the non-PI group (P = 0.66). In the presence of lipodystrophy, serum triglyceride levels were higher in the PI group than in the non-PI group (P = 0.046). No such difference was found between the treatment groups when no lipodystrophy was present. There was no significant difference in insulin resistance between the treatment groups in the presence or absence of lipodystrophy. CONCLUSION: Our study found the presence of lipodystrophy in HIV-infected young patients regardless of whether they were taking PIs or not. In the patients who had lipodystrophy, those treated with PIs had higher serum triglyceride levels than those not treated with PIs.

Caring for adolescents with HIV.

Adolescents comprise a growing proportion of people diagnosed with HIV or AIDS. Navigating adolescence while infected with HIV presents specific challenges not only to the youth but to their families and caregivers. As children enter their teen years, they have medical, physiologic, and psychosocial issues that differ greatly from both younger children and young adults. These issues include the limited number of medications available, mental illness (especially depression), and psychosocial issues such as distorted body image, sexual awareness, and problems with family and peer relations. Many of these issues are heightened in this population and can be important factors that can influence adherence. Awareness of these issues is important for health care providers, for if they understand not just the illness itself, but the psychosocial issues of the patient they are treating, the clinician can optimize treatments and adherence, and help these young persons successfully transition into adulthood.

The dark side of photomicrographs in pathology reports: liability and practical concerns hidden from view.

The rapid evolution of digital imaging has facilitated the ability to include photomicrographs in pathology reports. Although these pictures may seem to be an informative accompaniment to the written report, there are many problems raised by the images, which are not generally recognized. These include lack of quality standards, selection of representative images, and liability implications, which are addressed by well-established legal precedent. For dermatologists there is no such thing as a casual interest in a photomicrograph on a report, for it acts to distribute a share of liability by obligating the clinician to interpret the image properly. The risk management ramifications of these unintended consequences should be strongly considered by clinicians who favor the receipt of photomicrographic images in their pathology reports.

Diagnostic value of cytokines and C-reactive protein in the first 24 hours of neonatal sepsis.

The first objective of this article was to determine the diagnostic accuracy of tumor necrosis factor-alpha, interleukin-6 (IL-6), and interleukin-8 (IL-8) in differentiating infected from noninfected neonates during the first 24 hours of suspected sepsis and to compare them to the currently used laboratory parameters: C-reactive protein (CRP), immature-to-total neutrophil ratio, and leukocyte and platelet count. The secondary objective was to compare the cytokine levels in subpopulations of neonates. Seventy-five premature and 30 term infants were enrolled. Blood samples for the "currently used laboratory tests" and the cytokine levels were obtained at the first suspicion of sepsis ("0-hour") and 18 to 30 hours later ("24-hours"). Patients were classified as septic (48) or nonseptic (57). Thirty-two septic patients had positive blood cultures and 16 showed clinical signs of sepsis. Twenty septic patients had early-onset and 28 had late-onset sepsis. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated for each test. Receiver-operating characteristic curves were analyzed to determine the optimal thresholds. A combination of CRP > 10 pg/mL plus IL-6 > 18 pg/mL (sensitivity = 89%, specificity = 73%, PPV = 70%, NPV = 90%) was the best "0-hour" test, and CRP (sensitivity = 78%, specificity = 94%) was the best "24-hours" test. Lower IL-6 at 0-hour (p = 0.018) and IL-8 at 24 hours (p = 0.023) were detected among the patients infected with coagulase-negative staphylococci then with other bacteria. In conclusion, a combination of CRP + IL-6 provided additional diagnostic accuracy for differentiation between septic and nonseptic patients during the first 24 hours of suspected sepsis.