Collaboration of the NIH and PHS Commissioned Corps in the International Ebola Clinical Research Response.

The U.S. response to the Ebola epidemic resulted in many federal agencies assessing their ability to respond to global threats and improve the efficiency of humanitarian efforts.

Safety and immunogenicity of a Gag-Pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1-seronegative subjects.

OBJECTIVE: To evaluate the safety and immunogenicity of a candidate HIV DNA vaccine administered using a needle-free device. DESIGN: In this phase 1, dose escalation, double-blind, placebo-controlled clinical trial, 21 healthy adults were randomized to receive placebo or 0.5, 1.5, or 4 mg of a single plasmid expressing a Gag/Pol fusion protein. Each participant received repeat immunizations at days 28 and 56 after the first inoculation. Safety and immunogenicity data were collected. RESULTS: The vaccine was well tolerated, with most adverse events being mild injection site reactions, including pain, tenderness, and erythema. No dose-limiting toxicities occurred. HIV-specific antibody response was not detected in any vaccinee by enzyme-linked immunosorbent assay. HIV-specific T-cell responses to Gag or Pol as measured by enzyme-linked immunospot assay and intracellular cytokine staining were of low frequency and magnitude. CONCLUSIONS: This candidate HIV DNA vaccine was safe and well tolerated. No HIV-specific antibody responses were detected, and only low-magnitude HIV-specific T-cell responses were detected in 8 (53%) of 15 vaccinees. This initial product led to the development of a 4-plasmid multiclade HIV DNA Vaccine Research Center vaccine candidate in which envelope genes expressing Env from clades A, B, and C and a Nef gene from clade B have been added.

High prevalence of osteonecrosis of the femoral head in HIV-infected adults.

BACKGROUND: Osteonecrosis has been reported to occur occasionally among HIV-infected patients. The diagnosis of symptomatic osteonecrosis of the hip in two of the authors' patients, together with reports from community physicians, raised a concern that the prevalence of osteonecrosis is increasing. OBJECTIVE: To determine the prevalence of osteonecrosis of the hip in asymptomatic HIV-infected patients and to identify potential risk factors associated with osteonecrosis. DESIGN: Survey and comparison study. SETTING: The Clinical Center of the U.S. National Institutes of Health. PARTICIPANTS: 339 asymptomatic HIV-infected adults (of 364 asked to participate) and 118 age- and sex-matched HIV-negative volunteers enrolled between 1 June and 15 December 1999. MEASUREMENTS: Osteonecrosis of the hip, as documented by magnetic resonance imaging. Data from clinic records and a patient questionnaire administered before magnetic resonance imaging were used in an analysis of risk factors. A subset of patients was evaluated for hypercoagulable state. RESULTS: Fifteen (4.4% [95% CI, 2.5% to 7.2%]) of 339 HIV-infected participants had osteonecrosis lesions on magnetic resonance imaging, and no HIV-negative participants had similar lesions. Among HIV-infected participants, osteonecrosis occurred more frequently in those who used systemic corticosteroids, lipid-lowering agents, or testosterone; those who exercised routinely by bodybuilding; and those who had detectable levels of anticardiolipin antibodies. CONCLUSIONS: Patients infected with HIV have an unexpectedly high occurrence of osteonecrosis of the hip. Although screening asymptomatic patients is not warranted, HIV-infected patients with persistent groin or hip pain should be evaluated for this debilitating complication.

Diagnosis of avascular necrosis of the hip in asymptomatic HIV-infected patients: Clinical correlation of physical examination with magnetic resonance imaging.

OBJECTIVE: To determine if physical examination can identify avascular necrosis of the hip (AVN) in asymptomatic HIV-infected patients. DESIGN: Prospective, blinded population studyResults: Ten of the 176 patients were positive for AVN by MRI. Four subjects had unilateral disease and six had bilateral disease. Five hips (1.4%) in four patients were indeterminate. We evaluated physical examination maneuvers both singly and in combination. Tests done singly generally provided a higher degree of specificity (67-92%) but sensitivities were lower (0-50%) with all p-values ≥0.08. Positive predictive values based on physical exam, were <17% and negative predictive values were >90% for any single test. Combining all tests gave a high sensitivity (88%) and negative predictive value (98%), but low specificity (34%) and positive predictive value (6%) with p = 0.10. Only two of 16 hips with positive MRI findings showed no abnormalities when all tests were combinedConclusions: This study establishes the limited usefulness of a detailed physical examination of the hip early in the course of AVN. Patients who test negative on physical exam are unlikely to have AVN positive by MRI. Positive findings on physical examination of the hip may help identify patients who need further evaluation by MRI based on overall clinical suspicion.