High Degree of Interlaboratory Reproducibility of Human Immunodeficiency Virus Type 1 Protease and Reverse Transcriptase Sequencing of Plasma Samples from Heavily Treated Patients

We assessed the reproducibility of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease sequencing using cryopreserved plasma aliquots obtained from 46 heavily treated HIV-1-infected individuals in two laboratories using dideoxynucleotide sequencing. The rates of complete sequence concordance between the two laboratories were 99.1% for the protease sequence and 99.0% for the RT sequence. Approximately 90% of the discordances were partial, defined as one laboratory detecting a mixture and the second laboratory detecting only one of the mixture's components. Only 0.1% of the nucleotides were completely discordant between the two laboratories, and these were significantly more likely to occur in plasma samples with lower plasma HIV-1 RNA levels. Nucleotide mixtures were detected at approximately 1% of the nucleotide positions, and in every case in which one laboratory detected a mixture, the second laboratory either detected the same mixture or detected one of the mixture's components. The high rate of concordance in detecting mixtures and the fact that most discordances between the two laboratories were partial suggest that most discordances were caused by variation in sampling of the HIV-1 quasispecies by PCR rather than by technical errors in the sequencing process itself

Zidovudine in Asymptomatic Human Immunodeficiency Virus Infection A Controlled Trial in Persons with Fewer Than 500 CD4-Positive Cells per Cubic Millimeter

Zidovudine (AZT) is a potent inhibitor of the replication of the human immunodeficiency virus (HIV), and it has been shown to improve survival in advanced HIV disease. We conducted a randomized, double-blind trial in adults with asymptomatic HIV infection who had CD4+ cell counts of fewer than 500 per cubic millimeter on entry into the study. The subjects (92 percent male) were randomly assigned to one of three treatment groups: placebo (428 subjects); zidovudine, 500 mg per day (453); or zidovudine, 1500 mg per day (457). After a mean follow-up of 55 weeks (range, 19 to 107), 33 of the subjects assigned to placebo had the acquired immunodeficiency syndrome (AIDS), as compared with 11 of those assigned to receive 500 mg of zidovudine (P = 0.002; relative risk, 2.8; 95 percent confidence interval, 1.4 to 5.6) and 14 of those assigned to receive 1500 mg of zidovudine (P = 0.05; relative risk, 1.9; 95 percent confidence interval, 1.0 to 3.5). In the three treatment groups, the rates of progression (per 100 person-years) to either AIDS or advanced AIDS-related complex were 7.6, 3.6, and 4.3, respectively. As compared with those assigned to placebo, the subjects in the zidovudine groups had significant increases in the number of CD4+ cells and significant declines in p24 antigen levels. In the 1500-mg zidovudine group, severe hematologic toxicity (anemia or neutropenia) was more frequent than in the other groups (P<0.0001). In the 500-mg zidovudine group, nausea was the only toxicity that was significantly more frequent (in 3.3 percent) than in the placebo group (P = 0.001). We conclude that zidovudine is safe and effective in persons with asymptomatic HIV infection and fewer than 500 CD4+ cells per cubic millimeter. Additional study will be required to determine whether such treatment will ultimately improve survival for persons infected with HIV. (N Engl J Med 1990; 322:941–9.) INFECTION with the human immunodeficiency virus (HIV) causes chronic, progressive depletion of CD4+ helper/inducer T lymphocytes (CD4+ cells). 1 2 3 4 Together with the infection of macrophages and other cells, this depletion creates an immune deficiency that leads to the cancers and opportunistic infections characteristic of the acquired immunodeficiency syndrome (AIDS). Although HIV does not usually cause clinically apparent illness for many years, 5 this progression may be inevitable in untreated persons. From the time of diagnosis of AIDS, the three-year mortality rate is higher than 90 percent. 6 , 7 Because of the long period of latency from the primary infection to the development of clinical . . 

Systemic Crisis Intervention as a Response to Adolescent Crises: An Outcome Study

The present study demonstrates the safety and effectiveness of an outpatient program designed to respond to adolescent‐precipitated crises by mobilizing and restructuring the family\u27s kinship system. Families of 75 adolescents at risk for hospitalization were followed up to 24 months after treatment with Systemic Crisis Intervention. Measures of offspring and family functioning, suicidal behavior, institutional use, and treatment costs are presented. Results clearly demonstrate the safety, effectiveness, and economic viability of Systemic Crisis Intervention. Copyright © 1988, Wiley Blackwell. All rights reserve