Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia

Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial.     

If You Are Not Counted,You Don’t Count: Estimating the Number of African-American Men Who Have Sex with Men in San Francisco Using a Novel Bayesian Approach

African-American men who have sex with men (AA MSM) have been disproportionately infected with and affected by HIV and other STIs in San Francisco and the USA. The true scope and scale of the HIV epidemic in this population has not been quantified, in part because the size of this population remains unknown. We used the successive sampling population size estimation (SS-PSE) method, a new Bayesian approach to population size estimation that incorporates network size data routinely collected in respondent-driven sampling (RDS) studies, to estimate the number of AA MSM in San Francisco. This method was applied to data from a 2009 RDS study of AA MSM. An estimate from a separate study of local AA MSM was used to model the prior distribution of the population size. Two-hundred and fifty-six AA MSM were included in the RDS survey. The estimated population size was 4917 (95 % CI 1267–28,771), using a flat prior estimated 1882 (95 % CI 919–2463) as a lower acceptable bound, and a large prior estimated 6762 (95 % CI 1994–13,863) as an acceptable upper bound. Point estimates from the SS-PSE were consistent with estimates from multiplier methods using external data. The SS-PSE method is easily integrated into RDS studies and therefore provides a simple and appealing tool to rapidly produce estimates of the size of key populations otherwise difficult to reach and enumerate.     

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.     

Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients

A prospective cohort study of 399 consecutive patients in a single ward over an 11-month period was conducted to identify risk factors for nosocomial C. difficile colonization and diarrhea. The incidence of asymptomatic carriage was 13.0/100 patient admissions and the incidence of C. difficile-associated diarrhea was 7.8/100 patient admissions. Increased age and more severe underlying illness were associated with increased risk of C. difficile carriage and diarrhea. Multivariate models adjusting for age and severity of underlying disease associated two risk factors with asymptomatic C. difficile carriage: stool softeners (relative risk [RR] = 2.04) and antacids (RR = 1.80). Five risk factors were associated with C. difficile-associated diarrhea: cephalosporin use (RR = 2.07), penicillin use (RR = 3.41), enemas (RR = 3.26), gastrointestinal stimulants (RR = 3.06), and stool softeners (RR = 1.74). C. difficile was a common nosocomial infection on this ward, resulting in asymptomatic carriage more often than diarrhea and accounting for one-fifth of all cases of nosocomial diarrhea.     

Effect of HIV on thymic function before and after antiretroviral therapy in children

Studies were undertaken to investigate the role of the thymus in T cell reconstitution in human immunodeficiency virus (HIV)-infected children treated with antiretroviral therapy. Nine pediatric patients who acquired HIV perinatally were treated with multidrug combinations of antiretroviral agents. Plasma virus load and CD4+ and CD8+ T cell subsets were measured, and thymus function was measured by quantifying T cell receptor rearrangement excision circles in peripheral blood. Patients with virus loads remaining >400 RNA copies/mL plasma were classified as virologic nonresponders. Thymus function was initially decreased in all subjects. After antiretrovirus therapy, peripheral CD4+ T cells increased in all subjects. Thymus function was restored in 4 of 5 virologic responders but in only 1 of 4 virologic nonresponders. This suggests that HIV has an adverse effect upon thymic function in pediatric HIV infection. Potent antiretroviral therapy restores thymic function but is affected by the degree to which virus suppression is achieved.     

Accessing Men Who have Sex with Men Through Long-Chain Referral Recruitment,Guangzhou, China

Men who have sex with men (MSM) may account for an increasing proportion of China’s HIV epidemic, but remain difficult to access for epidemiological studies due to high stigma. We compare the composition of two samples of MSM obtained in Guangzhou, China. The first survey, conducted in 2004, recruited MSM through convenience sampling. The second survey in 2006 used long-chain referral recruitment in the context of respondent-driven sampling. Compared to convenience sampling, the long-chain referral method included higher proportions of subgroups of MSM thought to be at elevated risk for HIV infection and more difficult to reach, including internal migrants and those engaging in commercial sex. Long-chain referral also recruited more MSM who were under 25 years, unemployed, and had lower education. We conclude that long-chain referral recruitment will be more effective in tracking the leading edge of the epidemic among MSM in China than convenience sampling.