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The neurofibromatoses (neurofibromatosis type 1, neurofibromatosis type 2 and schwannomatosis) are rare disorders having clinical manifestations that vary greatly from patient to patient. The rarity and variability of these disorders has made it challenging for investigators to identify sufficient numbers of patients with particular clinical characteristics or specific germline mutations for participation in interventional studies. Similarly, because the natural history of all types of neurofibromatosis (NF) is variable and unique for each individual, it is difficult to identify meaningful clinical outcome measures for potential therapeutic interventions. In 2012, the Children’s Tumor Foundation created a web-based patient-entered database, the NF Registry, to inform patients of research opportunities for which they fit general eligibility criteria and enable patients to contact investigators who are seeking to enroll patients in approved trials. Registrants were recruited through CTF-affiliated NF clinics and conferences, through its website, and by word-of-mouth and social media. Following online consent, demographic information and details regarding manifestations of NF were solicited on the Registry website. Statistical analyses were performed on data from a cohort of 4680 registrants (the number of registrants as of October 9, 2015) who met diagnostic criteria for one of the 3 NF conditions. The analyses support our hypothesis that patient-reported symptom incidences in the NF Registry are congruent with published clinician-sourced data. Between April 26, 2013 and July 8, 2016, the registry has been useful to investigators in recruitment, particularly for observational trials, especially those for development of patient-reported outcomes.

OBJECTIVE: Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. DESIGN: Multiple logistic regression analysis of risks for HIV infection in female partners. METHODS: We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV-infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. RESULTS: In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P < 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P < 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P < 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. CONCLUSION: Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples.

Long-term follow-up of 44 patients with AIDS or AIDS-related complex (ARC) in a phase 1 trial of didanosine is reported. These patients were monitored for as long as 72 weeks (mean, 34 weeks) for toxicity and activity of didanosine. Pancreatitis and neuropathy, the major clinical toxicities, developed infrequently at the doses of didanosine (250-750 mg/d) employed during the latter part of the study. Consistent hematologic toxicity was not encountered; moreover, mean values for hematologic parameters such as hemoglobin concentration, white blood cell count, neutrophil count, lymphocyte count, and platelet count improved for up to 20-60 weeks. CD4 counts increased significantly through 10 weeks of therapy and in some patients remained at or above counts at enrollment for as long as 60 weeks. Serum concentrations of p24 antigen decreased significantly and remained at the decreased level for up to 48 weeks. An initial diagnosis of ARC (as opposed to AIDS), an initial CD4 count of > 100/mm3, and an increase in CD4 counts during the first 10 weeks of therapy were associated with a higher rate of survival and with lower rates of development of opportunistic infections and of other clinical manifestations of disease progression.

The relation between the average steady-state plasma concentration (Cpss) of didanosine and selected measures of efficacy, such as CD4 cell count, p24 antigenemia, and weight gain, was evaluated in patients participating in a phase 1 safety and pharmacokinetics study. All patients were diagnosed as having AIDS or severe AIDS-related complex. These individuals first received intravenous didanosine for 2 weeks at doses of 0.8-33 mg/(kg.d) and then took the drug orally at twice the intravenous dose. Cpss values were calculated on the basis of apparent oral clearance after 4 weeks of oral administration and average daily dose over the first 12 weeks of the study. These data were available for 61 patients enrolled at three clinical sites. High values for Cpss were strongly correlated with an increase in CD4 count (P = .006), a decrease in serum levels of p24 antigen (P = .006), and weight gain (P = .0001) at week 12. Logistic regression analysis was used to assess the influence of Cpss on response (as judged by the three criteria just mentioned) after adjustment for other potential factors related to infection with human immunodeficiency virus. The baseline CD4 cell count and the status with regard to prior zidovudine therapy were related to the CD4 response. However, the odds that a response would include all three parameters were nearly twice as high when the Cpss value increased by twofold.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect on immunologic and virological parameters of up to 24 weeks of therapy with didanosine at daily oral doses ofor = 12.5 mg/(kg.d) was studied retrospectively in 69 patients with advanced disease due to human immunodeficiency virus--i.e., AIDS or advanced AIDS-related complex--who had previously been treated with zidovudine. Patients entered the study with a low CD4 cell count (median, 39/microL) and with evidence of an ongoing depression of bone marrow function. Didanosine therapy was associated with a significant increase in CD4 counts and a prolonged decrease in serum levels of p24 antigen relative to baseline. These changes were more pronounced in the population with baseline CD4 counts ofor = 100/microL. A beneficial effect of didanosine therapy on hematologic parameters was observed in these patients, with increases during therapy of hemoglobin levels as well as white blood cell, granulocyte, and platelet counts. These responses were maximal at weeks 16-20. Further investigations are needed to establish the clinical correlates of these observations.

Objectives To define the spectrum of HIV-1-related disease in New York City (NYC) and to determine how the clinical spectrum of illness differs in various populations. Design and methods The medical records of the 2983 HIV-infected individuals who had received care through 1989 at four hospital outpatient clinics and two private physicians' offices were reviewed retrospectively. Results Sixty-one per cent of the study patients and 48% of patients seen in 1989 had AIDS. HIV-infected women were significantly less likely to have AIDS and CD4 lymphocyte counts less than 200 x 10(6)/l than men. For every 100 AIDS patients seen in 1989, there were 88 non-AIDS patients with CD4 counts less than 500 x 10(6)/l, of whom 41 had CD4 counts less than 200 x 10(6)/l; thus, in addition to an estimated 16,425 individuals living with AIDS in NYC, we estimate that there are at least 14,454 HIV-infected individuals without AIDS with CD4 counts less than 500 x 10(6)/l, of whom 6734 have CD4 counts less than 200 x 10(6)/l. Men who have sex with men were significantly more likely to have Kaposi's sarcoma, cytomegalovirus disease and retinitis, cryptosporidiosis and lymphoma, and significantly less likely to have Pneumocystis carinii pneumonia, esophageal candidiasis, extrapulmonary tuberculosis (TB) and bacterial pneumonia than intravenous drug users. Whites were significantly less likely to have pulmonary TB than Hispanics, non-Haitian and Haitian blacks, toxoplasmosis than Hispanics and Haitian blacks, and salmonella septicemia than non-Haitian blacks. The frequencies of most diagnoses did not differ by sex; gynecologic diseases were recorded infrequently in the medical records of women in this study. Conclusions These data indicate that there are more than 30,000 HIV-infected adults living in NYC with significant immunosuppression, that an increasing proportion of AIDS cases in NYC will occur among women, and that the spectrum of HIV-related disease varies markedly in different populations.

To describe the incidence, clinical characteristics and dose relationship of dideoxyinosine (ddI)-associated pancreatitis.Patients enrolled in a Phase I dose escalation trial of ddI [AIDS Clinical Trials Group (ACTG) 064] were evaluated for signs and symptoms of pancreatic dysfunction.Two ACTG sites.Forty-four patients with AIDS or AIDS-related complex (ARC) and a CD4 cell count less than or equal to 400 x 10(6)/l.Seven patients developed pancreatitis that lasted from 1 to 7 weeks and varied in severity from mild to life-threatening. Seven other patients had evidence of hyperamylasemia or hypertriglyceridemia. Six patients who developed pancreatitis were able to tolerate rechallenge with lower doses of ddI.Development of pancreatitis correlated with cumulative dose of ddI but not with stage of disease or concomitant medications. Cumulative dose was not significantly associated with development of hyperamylasemia or hypertriglyceridemia in patients without clinical pancreatitis.The development of pancreatitis in AIDS or ARC patients receiving ddI varies in severity and time course and is associated with cumulative dose. Patients who develop pancreatitis may be able to tolerate therapy with a lower dose after resolution of their symptoms. Patients receiving ddI require careful monitoring for the development of this complication.

We performed a phase I study of escalating dosages of 2',3'-dideoxyinosine (didanosine; ddI) in 19 patients with AIDS or AIDS-related complex in order (1) to establish the maximal tolerated dosage, (2) to determine the nature of toxic adverse effects, (3) to measure changes in levels of circulating human immunodeficiency virus p24 antigen and in CD4+ cell counts, and (4) to evaluate the pharmacokinetics of ddI. Almost all patients had received zidovudine therapy previously. The maximal tolerated dosage of ddI was found to be approximately 12 mg/(kg.d) when it was administered orally for 28 weeks. The major dosage-limiting adverse effects encountered were neuropathy, pancreatitis, and hepatitis. These occurred at dosages higher than those associated with decreases in levels of p24 antigen. The major toxic effects of ddI are different from those associated with zidovudine. At the proper dosage, ddI may prove to be an effective agent for the chronic treatment of infection with human immunodeficiency virus and should be especially useful in the treatment of patients who cannot tolerate zidovudine.

2',3'-Dideoxyinosine (ddI) is a purine analogue that after intracellular metabolic conversion suppresses the replication of the human immunodeficiency virus (HIV). We conducted a Phase I dose-escalation study of ddI in 17 patients with the acquired immunodeficiency syndrome (AIDS) and 20 patients with AIDS-related complex. The drug was administered twice daily over a dose range of 0.4 to 66 mg per kilogram of body weight per day for 2 to 44 weeks. The maximal tolerated oral dose of ddI was estimated to be 12 mg per kilogram per day. The major dose-limiting toxic effects were a painful peripheral neuropathy (in eight patients) and pancreatitis (in five). Asymptomatic elevations of the serum aminotransferase levels (in 13 patients) and the serum urate level (in 10) were also noted, but there was no dose-related hematologic toxicity. At the maximal tolerated dose, the peak plasma levels of ddI were 6.3 to 9.6 mumol per liter 0.6 to 1 hour after oral administration; the mean plasma half-life was 1.5 hours. The administration of ddI was associated with statistically significant decreases in serum level of p24 antigen and increases in the numbers of CD4 cells at 2, 6, 10, and 20 weeks. These changes were seen at all dose levels studied. Either a clinical improvement or a weight gain of greater than or equal to 2 kg was observed in 25 of 34 patients at six weeks. We conclude that ddI is a promising therapeutic agent in patients with AIDS or AIDS-related complex. Its efficacy is currently being evaluated in large-scale, controlled clinical trials.

Eight patients being treated for tuberculosis prior to starting azidothymidine therapy (study group) were compared with 56 patients who were treated with azidothymidine but not with antimycobacterial agents (control group). Toxicity was assessed 12 wk after the initiation of treatment with azidothymidine. Study group patients were more likely than control subjects to be either black or Hispanic (75% versus 30%, p = 0.02). There were no other statistically significant demographic differences. Seven study patients, and 20 control subjects experienced a fall in leukocyte count greater than 10% (88% versus 36%, p = 0.01). Within each group, patients with acquired immune deficiency syndrome (AIDS) were more likely to experience this degree of hematologic toxicity than were patients with AIDS-related complex (p = 0.03). However, analysis of covariance showed no significant differences between the groups after 12 wk of azidothymidine with regard to mean leukocyte or platelet counts, hemoglobin levels, or values for tests of liver function. The groups were similar in transfusion requirements and frequency of changes in azidothymidine dosage. Although this study was limited in power by the number of patients and the nonrandomized, retrospective design, the data suggest that patients can tolerate concurrent therapy with azidothymidine and antimycobacterial agents without unacceptable toxicity.

We studied 35 otherwise healthy adults with frequently recurring genital herpes (greater than or equal to 1 episode per month), in a double-blind trial comparing oral acyclovir with placebo capsules for suppression of recurrent infection. The patients were treated for 125 days unless herpes recurred. Among 32 evaluable patients, there were significantly fewer recurrences during acyclovir treatment (4 of 16) than during placebo treatment (16 of 16, P less than 0.001). The mean duration of therapy was significantly longer for patients receiving acyclovir than for those receiving placebo (114.9 vs. 24.8 days, P less than 0.001). Of 19 patients who had recurrences in the blind trial, only 2 had recurrences when given acyclovir in a second, open-study phase. All patients had recurrences after completing acyclovir treatment. The therapy was well tolerated, with minimal gastrointestinal upset and one hypersensitivity reaction. Studies of the viral isolates demonstrated that lesions developing in patients receiving acyclovir contained drug-resistant virus. Later recurrences in these patients were associated with drug-sensitive virus. We conclude that oral acyclovir suppresses genital herpes in patients with frequent recurrences, but the potential for problems with drug resistance and the long-term safety need to be more fully explored.