National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. Mortality among the patients declined from 29.4 per 100 person-years in 1995 to 8.8 per 100 person-years in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.

MONITORING and controlling the spread of human immunodeficiency virus 1 (HIV-1) worldwide^1,2 would greatly benefit from a simple, practical method of identifying recently infected persons. Accurate and rapid diagnosis of recent infection also has clinical implications.

DNA methylation (DNAm) plays diverse roles in human biology, but this dynamic epigenetic mark remains far from fully characterized. Although earlier studies uncovered loci that undergo age-associated DNAm changes in adults, little is known about such changes during childhood. Despite profound DNAm plasticity during embryogenesis, monozygotic twins show indistinguishable childhood methylation, suggesting that DNAm is highly coordinated throughout early development. Here we examine the methylation of 27,578 CpG dinucleotides in peripheral blood DNA from a cross-sectional study of 398 boys, aged 3–17 yr, and find significant age-associated changes in DNAm at 2078 loci. These findings correspond well with pyrosequencing data and replicate in a second pediatric population (N = 78). Moreover, we report a deficit of age-related loci on the X chromosome, a preference for specific nucleotides immediately surrounding the interrogated CpG dinucleotide, and a primary association with developmental and immune ontological functions. Meta-analysis (N = 1158) with two adult populations reveals that despite a significant overlap of age-associated loci, most methylation changes do not follow a lifelong linear pattern due to a threefold to fourfold higher rate of change in children compared with adults; consequently, the vast majority of changes are more accurately modeled as a function of logarithmic age. We therefore conclude that age-related DNAm changes in peripheral blood occur more rapidly during childhood and are imperfectly accounted for by statistical corrections that are linear in age, further suggesting that future DNAm studies should be matched closely for age.

Objectives. We calculated the percentage of gestational diabetes mellitus (GDM) attributable to overweight and obesity. Methods. We analyzed 2004 through 2006 data from 7 states using the Pregnancy Risk Assessment Monitoring System linked to revised 2003 birth certificate information. We used logistic regression to estimate the magnitude of the association between prepregnancy body mass index (BMI) and GDM and calculated the percentage of GDM attributable to overweight and obesity. Results. GDM prevalence rates by BMI category were as follows: underweight (13–18.4 kg/m²), 0.7%; normal weight (18.5–24.9 kg/m²), 2.3%; overweight (25–29.9 kg/m²), 4.8%; obese (30–34.9 kg/m²), 5.5%; and extremely obese (35–64.9 kg/m²), 11.5%. Percentages of GDM attributable to overweight, obesity, and extreme obesity were 15.4% (95% confidence interval [CI] = 8.6, 22.2), 9.7% (95% CI = 5.2, 14.3), and 21.1% (CI = 15.2, 26.9), respectively. The overall population-attributable fraction was 46.2% (95% CI = 36.1, 56.3). Conclusions. If all overweight and obese women (BMI of 25 kg/m² or above) had a GDM risk equal to that of normal-weight women, nearly half of GDM cases could be prevented. Public health efforts to reduce prepregnancy BMI by promoting physical activity and healthy eating among women of reproductive age should be intensified.

In the United States, transmission of the human immunodeficiency virus (HIV) by blood transfusion occurs almost exclusively when a recently infected blood donor is infectious but before antibodies to HIV become detectable (during the “window period”). We estimated the risk of HIV transmission caused by transfusion on the basis of the window period associated with the use of current, sensitive enzyme immunosorbent assays and recent data on HIV incidence among blood donors.