CDC plans to persevere with prevention efforts

In this Q & A, AIDS Alert interviews Ronald Valdiserri, MD, MPH, deputy director of the National Center for HIV, STD, and TB Prevention at the CDC. Valdiserri discusses what has been achieved by the HIV Prevention Strategic Plan Through 2005, and what more needs to be accomplished.     

CDC consultation on methamphetamine use and sexual risk behavior for HIV/STD infection: summary and suggestions

In January 2005, the U.S. Centers for Disease Control and Prevention hosted a national consultation of scientists, public health officials, and community service providers to address growing concerns about the association of methamphetamine use and sexual risk behavior for HIV/STD infection, which is well documented among men who have sex with men. The purpose of the consultation was to review a representation of the current state of the science and practice on the topic in order to reduce the situational link of methamphetamine use and sexual risk. A set of suggestions for future research and programs were developed by the participants. This article provides a summary of content and recommendations from the consultation, and not an exhaustive review of the literature.     

Indirect immunofluorescence test performance and questionnaire results from the Centers for Disease Control Model Performance Evaluation Program for human immunodeficiency virus type 1 testing.

Results from laboratories performing indirect immunofluorescence (IIF) testing for human immunodeficiency virus type 1 antibody and participating in the Centers for Disease Control Model Performance Evaluation Program in 1988 are presented. Approximately 90% of all laboratories receiving specimen panels or questionnaires furnished results to the Centers for Disease Control. In September 1988, 111 reports were received from IIF laboratories from 34 states and nine countries; most of these laboratories did IIF testing in conjunction with other antibody tests. Hospital laboratories were the most common type of laboratory participating in the program. Laboratories that performed IIF employed fewer personnel and performed testing less frequently than did laboratories that performed enzyme immunoassays or Western blot (immunoblot) tests and were likely to use a commercial test kit. Most of the laboratories that referred specimens for IIF testing sent them to the state laboratory. The analytic specificity for the Model Performance Evaluation Program specimens was 98.5% when indeterminate results on a negative specimen were considered correct (negative) and 89.6% when indeterminate results on a negative specimen were considered incorrect; analytic sensitivity was 94.8% when indeterminate results on a positive specimen were correct (positive) and 91.4% when indeterminate results on a positive specimen were considered incorrect. When indeterminate results were considered correct, all types of laboratories (blood bank, state, hospital, independent, and other) had analytic specificities over 96%, and all manufacturers had analytic specificities above 95%. All types of laboratories had analytic sensitivities over 92%, and analytic sensitivities were above 94% for all manufacturers and reagent sources except Cellular Products. Comparison of percentages of correct responses between IIF and Western blot assays on those samples for which there was good agreement on the target interpretation revealed no significant differences. Both individual donor and diluted materials were included in the evaluations; the diluted donor material presented the greatest testing difficulty. Within-survey reproducibility was about 93% overall and by specimen type. Between-survey reproducibility was about 81% for negative and indeterminate specimens and 88.5% for positive specimens, for an overall between-survey reproducibility of 84.3%. Differences in performance were noted when results were compared by type of laboratory and test manufacturer.     

Intra-articular deformities of the knee in congenital hypoplasias of the lower limb: an arthroscopic study

A knowledge of the morphology of the cruciate ligaments in congenital hypoplasias of the lower limb, susceptible to treatment to even the length discrepancy, is of practical importance in the prevention of subdislocation and dislocation of the knee during the distraction phase of femoral and/or tibial lengthening. The authors report their experience with 20 arthroscopies diagnosed in 20 children affected with congenital hypoplasia of the lower limb (shoft congenital femur, longitudinal peroneal hemimelia) performed prior to assembling the Ilizarov external fixator for femoral and/or tibial lengthening. None of the patients had congenital dislocation of the knee or knee with recurvation. In the patients in our study, it is possible to demonstrate that the anatomical cause of instability of the knee in congenital hypoplasias of the lower limb may be constituted by aplasia of one or both cruciate ligaments.     

The Serostatus Approach to Fighting the HIV Epidemic: prevention strategies for infected individuals.

In the United States, HIV prevention programs have historically tailored activities for specific groups primarily on the basis of behavioral risk factors and demographic characteristics. Through the Serostatus Approach to Fighting the Epidemic (SAFE), the Centers for Disease Control and Prevention is now expanding prevention programs, especially for individuals with HIV, to reduce the risk of transmission as a supplement to current programs that primarily focus on reducing the risk of acquisition of the virus. For individuals with HIV, SAFE comprises action steps that focus on diagnosing all HIV-infected persons, linking them to appropriate high-quality care and prevention services, helping them adhere to treatment regimens, and supporting them in adopting and sustaining HIV risk reduction behavior. SAFE couple a traditional infectious disease control focus on the infected person with behavioral interventions that have been standard for HIV prevention programs.     

A bicistronic therapeutic retroviral vector enables sorting of transduced CD34+ cells and corrects the enzyme deficiency in cells from Gaucher patients

Corrective gene transfer for therapeutic intervention in metabolic and hematopoietic disorders has been hampered by the relatively inefficient transduction of human hematopoietic stem cells. To overcome this, a bicistronic recombinant retrovirus has been generated that delivers both a therapeutic glucocerebrosidase (GC) cDNA for the treatment of Gaucher disease, and a small murine cell surface antigen (heat-stable antigen [HSA]) as a selectable marker. An amphotropic retroviral- producing cell clone was created, and filtered supernatant was used to transduce NIH 3T3 cells. Sorting of transduced cells by flow cytometry enabled separation into populations based on cell surface fluorescence intensity derived from the expressed HSA. Significant increases in GC enzyme activity were seen for the transduced and especially the transduced and sorted cells. Similarly, increases in GC specific activity were seen in transduced and sorted skin fibroblasts from a patient with Gaucher disease. To streamline future transfer and sorting protocols for hematopoietic cells, transformed B-cell lines from Gaucher patients were created. Type I B cells were transduced and sorted, and large increases in GC specific activity occurred with concomitant increases in integrated retroviral copy numbers. In addition, toward the goal of using this selectable approach for corrective gene transfer to bone marrow stem cells, CD34+ cells were isolated from normal BM donors, transduced, and sorted based on cell surface expression of HSA. Proviral DNA was detected in approximately 40% of clonogenic progenitor colonies derived from unsorted, transduced CD34+ cells, demonstrating the high titer of the vector. However, after sorting, 100% of the colonies had the corrective GC cDNA, demonstrating the efficiency of this selective system for human hematopoietic progenitors. It is expected that strategies based on this approach will allow sorting of transduced cells of many types before implantation of transduced cells to animals or patients. This vector system may also be used to simplify manipulations and studies on retroviral-mediated gene delivery in vitro and for in vivo models.     

Autopsy‐proven untreated previous pulmonary thromboembolism: frequency and distribution in the pulmonary artery and correlation with patients’ clinical characteristics

Summary. Background: This study aimed to evaluate untreated, previous pulmonary thromboembolism (PE) in patients with acute fatal PE. Patients and Methods: We studied 64 patients diagnosed as having died from acute PE by medico‐legal autopsy. Previous PE was histologically confirmed on the basis of organized thrombi (OT). The distributions of OT were analyzed in five different sizes of pulmonary artery branches in each of 18 pulmonary segmental arteries (90 in total). The frequency of OT in each patient was evaluated by determining the percentage of examined sections containing OT. Results: OT were confirmed in 59 of 64 (92%) patients. The mean frequency of OT per patient was 27% of the 90 branches. Among the segmental arteries, the right posterior basal lobe showed the highest frequency of OT; among the five artery branches examined, the subsegmental branch showed the highest frequency of OT. OT were not detected in arterioles. Patients with recent trauma or surgery and inpatients showed significantly lower frequencies of OT than those without these risk factors. The 26 patients with prolonged pre‐existing symptoms lasting more than a day showed a higher frequency of OT than the 12 patients who suffered for less than a day and the 26 without pre‐existing symptoms. Conclusions: Most patients with acute fatal PE have a subclinical history of recurrent PE. The frequency of their untreated PE is suspected to correlate with specific risk factors for venous thromboembolism and their clinical course.