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This model links biological and epidemiological data related to heterosexual HIV-1 transmission. The model can be used to estimate transmission of HIV from men with high semen viral burden from inflammation, or reduced burden after antiretroviral therapy. The results offer a biological explanation for the magnitude of the HIV epidemic in places where earlier studies have shown men have high semen viral burden, such as in sub-Saharan Africa. The model can be used to develop and test HIV-1 prevention strategies.

In the phase I/II pediatric hydroxyurea safety trial (HUG-KIDS), school-aged children with sickle cell anemia receiving hydroxyurea at the maximally tolerated dose (MTD) had variable increases in the percentage of fetal hemoglobin (%HbF). To identify predictors of the HbF response to hydroxyurea therapy, baseline clinical and laboratory values (age, sex, hemoglobin concentration, %HbF, reticulocytes, white blood cell [WBC], platelets, and serum chemistries), as well as treatment variables (number of toxicities, noncompliance, MTD dose, and MTD blood counts) were analyzed in 53 HUG-KIDS children who achieved MTD. Baseline %HbF values (P ‫؍‬ .001), baseline hemoglobin concentration (P ‫؍‬ .01), MTD dose (P ‫؍‬ .02), and compliance (P ‫؍‬ .02) were significantly associated with a higher %HbF at MTD; in contrast, age, sex, number of toxicities, and other baseline hematologic parameters were not. After adjusting for variations in baseline %HbF, the baseline reticulocyte count (P ‫؍‬ .05) and baseline WBC count (P ‫؍‬ .05) were also significantly associated with a higher %HbF at MTD. Hydroxyurea-induced increases in the hemoglobin concentration and mean corpuscular volume (both higher absolute values at MTD and larger positive changes from baseline values), as well as hydroxyurea-induced decreases in reticulocytes and WBC count, were significantly associated with a higher %HbF at MTD. These data suggest that selected baseline laboratory parameters, a higher MTD dose with attention to compliance, and greater therapy-related changes in blood counts may predict the HbF response to hydroxyurea therapy for children with sickle cell anemia. The HbF response to hydroxyurea is variable and complex, however, and even children with IntroductionThe level of fetal hemoglobin (HbF) expression is one of the most important modifiers of disease expression for patients with sickle cell anemia. 1 The percentage of HbF (%HbF) influences both laboratory values and clinical features of children and adults with sickle cell anemia. For example, an elevated %HbF has been significantly associated with fewer painful vasoocclusive events, 2 fewer episodes of acute chest syndrome, 3 and reduced early mortality. 4,5 Pharmacologic enhancement of HbF expression has been accomplished by using myelosuppressive agents, cytokines, and short-chain fatty acids. [6][7][8] To date, however, the prototypic agent for increasing HbF expression is hydroxyurea, based on its ease of oral administration, modest toxicity profile, and rarity of serious side effects. A phase I/II trial of hydroxyurea for adults with sickle cell anemia demonstrated a significant increase in HbF expression, accompanied by a significant increase in hemoglobin concentration and significant decreases in reticulocytes, neutrophils, and platelets. 9 The Multicenter Study of Hydroxyurea (MSH), a doubleblinded, placebo-controlled phase III trial for adults with sickle cell anemia, demonstrated that hydroxyurea therapy significantly reduced the number of painful events, episodes of acute che...