Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team.

BACKGROUND: Efavirenz is a nonnucleoside reverse-transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). We compared two regimens containing efavirenz, one with a protease inhibitor and the other with two nucleoside reverse-transcriptase inhibitors, with a standard three-drug regimen. METHODS: The study subjects were 450 patients who had not previously been treated with lamivudine or any nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. In this open-label study, patients were randomly assigned to one of three regimens: efavirenz (600 mg daily) plus zidovudine (300 mg twice daily) and lamivudine (150 mg twice daily); the protease inhibitor indinavir (800 mg every eight hours) plus zidovudine and lamivudine; or efavirenz plus indinavir (1000 mg every eight hours). RESULTS: Suppression of plasma HIV-1 RNA to undetectable levels was achieved in more patients in the group given efavirenz plus nucleoside reverse-transcriptase inhibitors than in the group given indinavir plus nucleoside reverse-transcriptase inhibitors (70 percent vs. 48 percent, P<0.001). The efficacy of the regimen of efavirenz plus indinavir was similar (53 percent) to that of the regimen of indinavir, zidovudine, and lamivudine. CD4 cell counts increased significantly with all combinations (range of increases, 180 to 201 cells per cubic millimeter). More patients discontinued treatment because of adverse events in the group given indinavir and two nucleoside reverse-transcriptase inhibitors than in the group given efavirenz and two nucleoside reverse-transcriptase inhibitors (43 percent vs. 27 percent, P=0.005). CONCLUSIONS: As antiretroviral therapy in HIV-1-infected adults, the combination of efavirenz, zidovudine, and lamivudine has greater antiviral activity and is better tolerated than the combination of indinavir, zidovudine, and lamivudine.

A phase I study of HGP-30, a 30 amino acid subunit of the human immunodeficiency virus (HIV) p17 synthetic peptide analogue sub-unit vaccine in seronegative subjects.

HGP-30-KLH vaccine in alum at doses of 10, 25, 50, and 100 micrograms/kg administered intramuscularly at weeks 0, 4, and 10 appear well-tolerated clinically. Local pain at the injection site, appears to be the main clinical toxicity. Laboratory parameters are not affected by administration of the vaccine candidate except for perhaps mild urinalysis abnormalities at the highest dose. This vaccine candidate has no apparent immunotoxicity and does not appear to affect lymphocyte populations or T-cell functional studies. Low levels and transient antibodies develop in a minority of subjects early after immunization with the vaccine candidate. These responses were observed in the lowest dose range. Higher doses, and longer follow-up will be needed to confirm this observation. T-cell proliferative responses to KLH and KLH-HGP-30 are consistent and may not be dose dependent, but the proliferative responses are variable and more data need to be accumulated. Preliminary, there appears to be an HGP-30-induced CTL response of HGP-30-coated EBV-transformed autologous B cell lines. This study was approved under an IND for the California Department of Health Services' Food and Drug Branch. They have provided excellent support and regulatory guidelines for this project. Future work will extend and confirm these initial observations.

Overwhelming postsplenectomy infection.

A characteristic case of overwhelming postsplenectomy infection in a previously healthy, 25-year-old man is presented. The patient progressed from influenza-like symptoms to irreversible septic shock and death within 24 hours. His spleen had been removed nine years earlier because of abdominal trauma. Aggressive therapy, including IV fluids, antibiotics, vasopressers, steroids, heparin, packed red blood cells, platelets, cryoprecipitates, and fresh frozen plasma, failed to alter the course of this fulminant septic syndrome. The cause, treatment, and certain prevention options are presented.

The effect of managerial interventions on high personnel turnover in nursing homes.

This study indicates that administrator attention and intervention can reduce high turnover in nursing homes. It also indicates a need to investigate the contributing factors in a specific organization, to select interventions based on this knowledge and for multiple but related actions that will support one another. Increased supervision of new employees, increased recruitment efforts, supervisory training, revised personnel policies, and avoidance of personnel pools seem to have particularly high impact on the reduction of turnover in nursing homes and are recommended as a place to begin.

How to develop a therapeutic community.

Long-term care in nursing homes needs a therapeutic, not a custodial, focus. Given that many such institutions are custodial, how can the orientation be changed? Transforming the environment of a nursing home is not merely a pipe dream--it has been successfully accomplished. The founders of one such project have written a book that charts their program's development, providing ten principles as guidelines. Jona's special consultant in Extended and Long-Term Care Administration presents these principles, along with a commentary on each, in the hope that nursing administrators in long-term care will find the book an invaluable guide for improving care of the aged.