STAT3 Gain-of-Function Mutations Underlie Deficiency in Human Nonclassical CD16+ Monocytes and CD141+ Dendritic Cells.

Genetic analysis of human inborn errors of immunity has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. The STAT family of transcription factors orchestrate hematopoietic cell differentiation. Patients with de novo activating mutations of STAT3 present with multiorgan autoimmunity, lymphoproliferation, and recurrent infections. We conducted a detailed characterization of the blood monocyte and dendritic cell (DC) subsets in patients with gain-of-function (GOF) mutations across the gene. We found a selective deficiency in circulating nonclassical CD16+ and intermediate CD16+CD14+ monocytes and a significant increase in the percentage of classical CD14+ monocytes. This suggests a role for STAT3 in the transition of classical CD14+ monocytes into the CD16+ nonclassical subset. Developmentally, ex vivo-isolated STAT3GOF CD14+ monocytes fail to differentiate into CD1a+ monocyte-derived DCs. Moreover, patients with STAT3GOF mutations display reduced circulating CD34+ hematopoietic progenitors and frequency of myeloid DCs. Specifically, we observed a reduction in the CD141+ DC population, with no difference in the frequencies of CD1c+ and plasmacytoid DCs. CD34+ hematopoietic progenitor cells from patients were found to differentiate into CD1c+ DCs, but failed to differentiate into CD141+ DCs indicating an intrinsic role for STAT3 in this process. STAT3GOF-differentiated DCs produced lower amounts of CCL22 than healthy DCs, which could further explain some of the patient pathological phenotypes. Thus, our findings provide evidence that, in humans, STAT3 serves to regulate development and differentiation of nonclassical CD16+ monocytes and a subset of myeloid DCs.

Toxocara species environmental contamination of public spaces in New York City.

Human toxocariasis has been identified as an under-diagnosed parasitic zoonosis and health disparity of significant public health importance in the United States due to its high seropositivity among socioeconomically disadvantaged groups, and possible links to cognitive and developmental delays. Through microscopy and quantitative PCR, we detected that Toxocara eggs are widespread in New York City public spaces, with evidence of significant levels of contamination in all five boroughs. The Bronx had the highest contamination rate (66.7%), while Manhattan had the lowest contamination rate (29.6%). Moreover, infective eggs were only found in the Bronx playgrounds, with over 70% of eggs recovered in embryonic form and the highest egg burden (p = 0.0365). All other boroughs had eggs in the pre-infectious, unembronyated form. Toxocara cati, the cat roundworm, was the predominant species. These results suggest that feral or untreated cats in New York City represent a significant source of environmental contamination. These findings indicate that human toxocariasis has emerged as an important health disparity in New York City, with ongoing risk of acquiring Toxocara infection in public spaces, especially in poorer neighborhoods. There is a need for reducing environmental Toxocara contamination. Additional rigorous public health interventions should explore further approaches to interrupt transmission to humans.

Hepatitis B Screening & Vaccination Behaviors in a Community-based Sample of Chinese & Korean Americans in New York City.

OBJECTIVES: As Asian Americans are dis- proportionately affected by the hepatitis B virus (HBV), we explored predictors of HBV screening and vaccination among Chinese and Korean Americans. METHODS: We used cross-sectional data from a com- munity-based sample of Chinese Americans (N = 502) and Korean Americans (N = 487) residing in the metropolitan New York City area during 2008-2009. Logistic regression models were stratified by Asian-American subgroup and sex to predict HBV screening (for the entire sam- ple) and HBV vaccination (among those not HBV positive). RESULTS: Overall, screening rates were high (71.3% among Chinese and 70.1% among Koreans). The majority of respondents were aware of HBV; however, knowledge about HBV transmission was low. In logistic regression, a physician recommendation was consistently associated with HBV screening and vaccination outcomes across all groups; having heard of HBV was significantly associated with screening and vaccination among Chinese males and screening among Korean males and females. Screening and vaccination barriers were reported among all groups, and included lack of knowledge and feeling well/having no health issues. CONCLUSIONS: Targeted efforts in these at-risk communities are necessary to improve HBV knowledge, address misinformation about HBV, and eliminate provider-, patient-, and resource-related barriers to HBV screening and vaccination.

Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.

Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles, paralleling responses to adjuvant-containing vaccines in vivo Age-specific in vitro modeling coupled with proteomics may provide fresh insight into the ontogeny of adjuvant action thereby informing targeted adjuvanted vaccine development for distinct age groups.

Sources of Health Information Among Select Asian American Immigrant Groups in New York City.

Health information can potentially mitigate adverse health outcomes among ethnic minority populations, but little research has examined how minorities access health information. The aim of this study was to examine variations in the use of health information sources among Asian American (AA) subgroups and to identify differences in characteristics associated with the use of these sources. We analyzed data from a foreign-born community sample of 219 Asian Indians, 216 Bangladeshis, 484 Chinese, and 464 Koreans living in New York City. Results found that use of health information sources varied by AA subgroup. Print media source use, which included newspapers, magazines, and/or journals, was highest among Chinese (84%), Koreans (75%), and Bangladeshis (80%), while radio was most utilized by Chinese (48%) and Koreans (38%). Television utilization was highest among Bangladeshis (74%) and Koreans (64%). Koreans (52%) and Chinese (40%) were most likely to use the Internet to access health information. Radio use was best explained by older age and longer time lived in the United States, while print media were more utilized by older individuals. Results also highlighted differences in native-language versus non-native-language media sources for health information by subgroup. Media sources can be used as a vehicle to disseminate health information among AAs.

Chronic hepatitis B and liver cancer risks among Asian immigrants in New York City: Results from a large, community-based screening, evaluation, and treatment program.

BACKGROUND: Hepatitis B virus (HBV) infection, the predominant cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects Asian Americans. Limited data exist on the variability and characteristics of infection that determine disease progression risk within U.S. Asian ethnic subgroups. METHODS: Retrospective analyses were conducted on a large, community-based HBV screening and treatment program in New York City (NYC). From 2004 to 2008, the program enrolled 7,272 Asian-born individuals. Determinants of HBV seroprevalence were calculated and risk factors for HCC progression were compared across Asian subgroups. RESULTS: Among newly tested individuals, 13% were HBV positive. Seroprevalence varied significantly with age, gender, education, birthplace, and family history of infection. Chinese-born individuals, particularly from the Fujian province, had the highest seroprevalence (23.2% and 33.1%, respectively). Clinical and virologic characteristics placed HBV-infected individuals at significant risk for HCC. Significant differences in HCC risk existed among Asian subgroups in bivariate analysis, including age, gender, HBV viral load, and HBeAg status. Differences in HBV genotype and family history of HCC may further HCC risk among subgroups. CONCLUSIONS: Asian immigrants in NYC have a high prevalence of HBV infection and are at significant risk of disease progression and HCC. Although heterogeneity in HBV seroprevalence was found by Asian subgroups, HCC risk among infected individuals was primarily explained by age and gender differences. Country and province of birth, age, and gender may further explain seroprevalence differences. IMPACT: Findings provide estimates of HBV burden in Asian ethnic subgroups and identify high-risk groups to target for screening and treatment that can prevent HCC.

Hepatitis B testing and access to care among racial and ethnic minorities in selected communities across the United States, 2009-2010.

UNLABELLED: Hepatitis B virus (HBV) infection is widely prevalent among racial and ethnic minorities in the United States; however, few data have been available regarding HBV testing and referral to care for these populations. Using survey data collected in 2009-2010 from the Racial and Ethnic Approaches to Community Health (REACH) across the U.S., we assessed rates and determinants of hepatitis B testing and access to care in 28 minority communities in the U.S. Of 53,896 respondents, 21,129 (39.2%) reported having been tested for hepatitis B. Of the 1,235 who reported testing positive, 411 (33.3%) reported currently receiving specialty care. After controlling for demographic and socioeconomic characteristics, the likelihood of having been tested for hepatitis B and receiving care if infected was higher among males, non-English speaking persons, and those having health insurance compared to their counterparts. Compared to college graduates, respondents without a college education were less likely to get tested for hepatitis B. CONCLUSION: These data indicate that more than half of racial/ethnic minority persons in these communities had not been tested for hepatitis B, and only about one-half of those who tested positive had ever received treatment. More state and federal efforts are needed to screen racial/ethnic minorities, especially foreign-born persons, for HBV and link those with infection to care.

Efficacy and safety of long-term adefovir dipivoxil therapy in children with chronic hepatitis B infection.

BACKGROUND: The safety and efficacy of adefovir dipivoxil (ADV) for chronic hepatitis B infection in children was demonstrated in a randomized, placebo-controlled trial. Those children were followed for 4 more years, and many continued to receive ADV for all or part of this time. OBJECTIVES: To examine the therapeutic effects and safety of prolonged ADV therapy in children with chronic hepatitis B infection. METHODS: After 48 weeks of double-blind treatment, all placebo-treated subjects who did not exhibit HBeAg seroconversion at week 44, and all ADV-treated subjects, were offered open-label ADV for up to 192 additional weeks. Treatment was discontinued if there was no virologic effect, except for adolescents with previous lamivudine exposure, in whom lamivudine was added to ADV. Durability of HBeAg seroconversion was assessed. Annual resistance surveillance was conducted in subjects who had detectable hepatitis B virus DNA. RESULTS: Of the 170 subjects who completed the 48-week study, 162 participated in the open-label study. ADV was discontinued in 61 subjects due to virologic failure. In subjects who continued treatment, either as monotherapy or with lamivudine, continued viral suppression and alanine aminotransferase normalization were noted. HBeAg seroconversions were observed in 55 subjects, and hepatitis B surface antigen seroconversion in 5. Mean duration of HBeAg seroconversion at last observation was 762 ± 371.2 days in the ADV-ADV group and 643 ± 291.5 days in the PLB-ADV group. ADV was safe and well-tolerated. Resistance to ADV was observed in 1 child on ADV monotherapy. Nine treatment-experienced subjects entered the study with mutations associated with lamivudine resistance. All responded to ADV therapy. CONCLUSIONS: Prolonged ADV treatment is safe in children. If reserved only for those with virologic response within 6 months, viral resistance was minimal.

The Asian American hepatitis B program: building a coalition to address hepatitis B health disparities.

BACKGROUND: Community coalitions are increasingly recognized as important strategies for addressing health disparities. By providing the opportunity to pool resources, they provide a means to develop and sustain innovative approaches to affect community health. OBJECTIVES: This article describes the challenges and lessons learned in building the Asian American Hepatitis B Program (AAHBP) coalition to conduct a community-based participatory research (CBPR) initiative to address hepatitis B (HBV) among New York City Asian-American communities. METHODS: Using the stages of coalition development as a framework, a comprehensive assessment of the process of developing and implementing the AAHBP coalition is presented. LESSONS LEARNED: Findings highlight the importance of developing a sound infrastructure and set of processes to foster a greater sense of ownership, shared vision, and investment in the program. CONCLUSION: Grassroots community organizing and campus-community partnerships can be successfully leveraged to address and prevent a significant health disparity in an underserved and diverse community.

A comprehensive screening and treatment model for reducing disparities in hepatitis B.

Chronic hepatitis B affects Asian Americans at a much higher rate than the general US population. Appropriate care can limit morbidity and mortality from hepatitis B. However, access to care for many Asian Americans and other immigrant groups is limited by their lack of knowledge about the disease, as well as cultural, linguistic, and financial challenges. This article describes the results of BfreeNYC, a New York City pilot program that, from 2004 to 2008, provided hepatitis B community education and awareness, free screening and vaccinations, and free or low-cost treatment primarily to immigrants from Asia, but also to residents from other racial and ethnic minority groups. The program was the largest citywide screening program in the United States, reaching nearly 9,000 people, and the only one providing comprehensive care to those who were infected. During the program, new hepatitis B cases reported annually from predominantly Asian neighborhoods in the city increased 34 percent. More than two thousand people were vaccinated, and 1,162 of the 1,632 people who tested positive for hepatitis B received care from the program's clinical services. Our analysis found that the program was effective in reaching the target population and providing care. Although follow-up care data will be needed to demonstrate long-term cost-effectiveness, the program may serve as a useful prototype for addressing hepatitis B disparities in communities across the United States.

A simulation shows that early treatment of chronic hepatitis B infection can cut deaths and be cost-effective.

Chronic hepatitis B affects between 800,000 and two million people in the United States and causes 4,000 deaths each year. Yet the costs and benefits of treatment have not been fully evaluated. Using a model that simulates disease progression, we compare treatment programs for hepatitis B that start at an early stage of the disease to treatment that begins at a late stage. Our analysis concludes that early hepatitis B care can improve health, reduce premature deaths, and prevent expensive complications, making it highly cost-effective in the long term. Our results demonstrate the importance of screening for hepatitis B among at-risk groups and then linking screening to treatment. They also illustrate how predictive models can be used to evaluate strategies for improving access to care.

High sustained virologic response rates in children with chronic hepatitis C receiving peginterferon alfa-2b plus ribavirin.

BACKGROUND & AIMS: Pegylated interferon (PEG-IFN) alfa-2b plus ribavirin (RBV) is the standard of care for adults with chronic hepatitis C but was not approved for the treatment of children at the time of this study. The aim of this study was to evaluate the efficacy and safety of PEG-IFN alfa-2b plus RBV in children. METHODS: Children and adolescents ages 3-17 years were treated with PEG-IFN alfa-2b (60microg/m(2)/week) plus RBV (15mg/kg/day). The duration of therapy was 24 weeks for genotype (G) 2 and G3 patients with low viral load (<600,000IU/ml) and 48 weeks for G1, G4, and G3 with high viral load (>or=600,000IU/ml). The primary end point was sustained virologic response (SVR), defined as undetectable hepatitis C virus (HCV) RNA 24 weeks after completion of therapy. RESULTS: SVR was attained by 70 (65%) children. Genotype was the main predictor of response: G1, 53%; G2/3, 93%; G4, 80%. SVRs were similar in younger and older children. Baseline viral load was the main predictor of response in the G1 cohort. No new safety signals were identified, and adverse events (AEs) were generally mild or moderate in severity. Dose was modified because of AEs in 25% of children; 1 child discontinued because of an AE (thrombocytopenia). No serious AEs related to study drugs were reported. CONCLUSION: Therapy with PEG-IFN alfa-2b plus RBV in children and adolescents with chronic hepatitis C offers favorable efficacy, reduced injection frequency, and an acceptable safety profile.

Latent tuberculosis diagnosis in children by using the QuantiFERON-TB Gold In-Tube test.

BACKGROUND: The QuantiFERON-TB Gold test was the first blood test to be approved for the diagnosis of latent tuberculosis infection. Although it has been shown to be sensitive and specific in adults, limited data on its performance in children are available. METHODS: This was a prospective study of children receiving health care in New York, New York. Each child was assessed for risk factors for Mycobacterium tuberculosis infection, underwent tuberculin skin testing, and had a QuantiFERON-TB Gold In-Tube test performed. The concordance between tuberculin skin test and QuantiFERON-TB Gold In-Tube test results was calculated, and the results were analyzed according to the likelihood of exposure to M tuberculosis. RESULTS: Data for 207 children with valid tuberculin skin test and QuantiFERON-TB Gold In-Tube test results were analyzed. There was excellent correlation between negative tuberculin skin test results and negative QuantiFERON-TB Gold In-Tube test results; however, only 23% of children with positive tuberculin skin test results had positive QuantiFERON-TB Gold In-Tube test results. Positive QuantiFERON-TB Gold In-Tube test results were associated with increased likelihood of M tuberculosis exposure, and interferon gamma levels were higher in children with known recent exposure to M tuberculosis, compared with children with older exposure histories. Younger children produced lower interferon gamma levels in response to the mitogen (phytohemagglutinin) control used in the QuantiFERON-TB Gold In-Tube test, but indeterminant results were low for children of all ages. Performance characteristics were similar across all age groups. CONCLUSION: The QuantiFERON-TB Gold In-Tube test is a specific test for M tuberculosis exposure in children, with performance characteristics similar to those for adults residing in regions with low levels of endemic disease. Concerns about test sensitivity, especially for children <2 years of age, will require additional prospective long-term evaluation.

Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B.

UNLABELLED: This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment-naive and treatment-experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to <18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA <1,000 copies/mL and normal alanine aminotransferase) compared to placebo-treated subjects (23% versus 0%; P = 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P = 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA <1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P = 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to <18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg+ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups. CONCLUSION: ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB, but was not different from placebo in subjects aged 2 to 11 years.

Role of imiquimod and parenteral meglumine antimoniate in the initial treatment of cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis is a serious public health problem in the developing world. The main therapeutic agent--pentavalent antimony, developed >50 years ago--is expensive, often accompanied by severe adverse effects, and complicated by the emergence of drug resistance. Better therapies are urgently needed. In the present pilot study, we compared the use of imiquimod, an immunomodulatory molecule, to the use of meglumine antimoniate alone and in combination for the initial treatment of cutaneous leishmaniasis. MATERIALS AND METHODS: Patients with newly diagnosed cutaneous leishmaniasis were enrolled from a single referral center in Lima, Peru, from August 2005 through October 2005. Patients were randomly assigned to 1 of 3 treatment groups and received either imiquimod 7.5% cream administered topically every other day for 20 days, intravenous meglumine antimoniate administered at a dosage of 20 mg/kg per day every day for 20 days, or combination therapy with both intravenous meglumine antimoniate and imiquimod 7.5% cream. Patients were evaluated weekly and at 1 and 3 months after treatment. Patients who had healed lesions at 3 months were considered to be clinically cured. RESULTS: Although several patients showed initial resolution of symptoms with imiquimod treatment alone, all of these patients experienced relapse after treatment discontinuation. Four (57%) of 7 patients treated with meglumine antimoniate alone and 7 (100%) of 7 patients treated with combination therapy were cured. Combination therapy was not only more effective than the other 2 treatments (P<.05) but also led to faster healing and better cosmetic results. CONCLUSION: Combination therapy with imiquimod and meglumine antimoniate is a promising regimen for the initial treatment of cutaneous leishmaniasis that warrants additional larger studies.

Development of a molecular-beacon assay to detect the G1896A precore mutation in hepatitis B virus-infected individuals.

The 1896 precore (PC) mutation is the most frequent cause of hepatitis B virus e-antigen (HBeAg)-negative chronic hepatitis B virus (HBV) infection. Detection of the 1896 PC mutation has application in studies monitoring antiviral therapy and the natural history of the disease. Identification of this mutation is usually performed by direct sequencing, which is both costly and laborious. The aim of this study was to develop a rapid, high-throughput assay to detect the 1896 PC mutation using real-time PCR and molecular-beacon technology. The assay was initially standardized on oligonucleotide targets and plasmids containing the wild-type (WT) and PC mutation and then tested on plasma samples from children with HBV DNA of >10(6) copies/ml. Nine individuals were HBeAg negative and suspected to harbor HBeAg mutations, while 12 children were HBeAg positive and selected as controls. Ninety percent (19 of 21) of plasma samples tested with molecular beacons were in complete agreement with sequencing results. The remaining 10% (2 of 21) of samples were identified as heterogeneous mixtures of WT and mutant virus by molecular beacons, though sequencing found only a homogeneous mutant in both cases. Overall, the 1896 PC mutation was detected by this assay in 55.5% of the children with HBeAg-negative infection. In summary, this assay is a rapid, sensitive, and specific technique that effectively discriminates WT from 1896 PC mutant HBV and may be useful in clinical and epidemiological studies.

Perinatal transmission and viral evolution of hepatitis C virus quasispecies in infants coinfected with HIV.

OBJECTIVES: Three HIV/hepatitis C virus (HCV)-coinfected children and the mothers of 2 were studied to examine the nature of perinatal HCV infection in HIV-coinfected infants and to assess the evolution of viral quasispecies thereafter. Sequences of the hypervariable region in the N terminus of the E2/NS1 region (HVR-1) of the children and their mothers were compared. HCV quasispecies changes in the infants were tracked over several years. METHODS: Sequence similarity comparisons and phylogenetic trees were derived from cDNA of plasma isolates. Quantitation of plasma HCV and HIV was performed in the children, as well as CD4 T-cell percentage and liver transaminases. RESULTS: Phylogenetic analysis of the mother-child pairs suggested that transmission of multiple dominant and nondominant variants identified in the mother were seen. HCV diversification in the children was seen as early as 2 months of life. The child with the best immune status and HIV control demonstrated the most diversification throughout. CONCLUSION: Multiples HCV variants transmitted from mother to child and their early changes in the child may be related to maternal antibody. Variation after the 1st year of life may reflect immunologic pressure from the child. There was no trend suggesting that the presence or absence of selective immunologic pressure affected HCV load or liver transaminase values.

Response to lamivudine treatment in children with chronic hepatitis B virus infection.

Despite the recent approval of lamivudine for the treatment of children with chronic hepatitis B virus (HBV) infection, there is insufficient information on the kinetics of HBV clearance and the factors that predict a favorable treatment response to lamivudine in this population. In a small retrospective study of 16 HBV-infected children treated with lamivudine, we examined changes in virus load and other factors associated with hepatitis B e antigen (HBeAg) clearance. High pretherapy alanine aminotransferase level, low serum HBV DNA load, and age at the start of treatment were independently associated with HBeAg clearance. HBeAg clearance was also associated with the achievement of specific levels of virus suppression, and failure to achieve those levels was associated with the development of lamivudine resistance. Additional studies are necessary to provide better indications and guidelines for the treatment of children with chronic HBV infection.

Recombinant glycoprotein vaccines for human immunodeficiency virus-infected children and their effects on viral quasispecies.

In individuals infected with human immunodeficiency virus type 1 (HIV-1), specific immunity is associated with a more diverse viral repertoire and slower disease progression. Attempts to enhance antiviral immunity with therapeutic vaccination have shown that recombinant glycoprotein (RGP) vaccines are safe, well tolerated, and immunogenic, but the effect of RGP vaccines on the viral repertoire is unknown. We evaluated diversification of the viral envelope in 12 HIV-infected children who received placebo or RGP vaccines. At baseline, 11 of 12 patients had multiple viral variants. On follow-up 6 months later, children who had a strong vaccine-associated lymphoproliferative immune response showed less viral diversification than those in whom the immune response was weak or absent. These results suggest that the immune response elicited by RGP vaccines does not exert a significant selection pressure on the viral quasispecies and therefore may not be helpful in changing the course of the disease.