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Biomedical subjects

Arthur E Brown

Publications and source records attributed to Arthur E Brown.

13 recordsLinked to original sources
PubMed2003

Safety and immunogenicity of combinations of recombinant subtype E and B human immunodeficiency virus type 1 envelope glycoprotein 120 vaccines in healthy Thai adults.

Safety and immunogenicity of 2 recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein (gp) 120 vaccines derived from SF2 (subtype B) and CM235 (CRF01_AE, Thai E) were evaluated in 370 Thai adults at low risk of HIV infection. Various doses of CM235 (25, 50, or 100 microg) and SF2 (0, 25, or 50 microg) gp120 were used. Eighty volunteers received placebo. There were no serious adverse events related to vaccination. Binding antibody developed in all vaccine recipients. There was no dose response to CM235 gp120, but a dose response to gp120 SF2 was present. Neutralizing antibodies to subtype E HIV-1 NPO3 and subtype B HIV-1 SF2 developed in 84% and 82% of vaccine recipients, respectively. Lymphoproliferative responses were detected in >95% of vaccine recipients. There was no evidence of antigenic interference in HIV-specific humoral or cellular responses. The gp120 Thai E and SF2 vaccines were safe and immunogenic in combination and could be advanced into phase 3 testing.

AIDS Vaccines↗
PubMed2003

The association between hepatitis C virus and HIV-1 in preparatory cohorts for HIV vaccine trials in Thailand.

OBJECTIVES: To study the association between hepatitis C virus (HCV) and HIV-1, and HCV seropositivity as an indicator of HIV-1 risk behavior for HIV vaccine preparatory cohorts in Thailand. DESIGN: Cross-sectional study of HIV-1-infected persons identified at screening for potential HIV vaccine trial cohort studies. METHODS: Sera from HIV-1-infected and uninfected volunteers was matched by age, sex, and community, and tested for HCV reactivity. Logistic regression methods were used to measure associations between HIV-1, HCV and other risk factors for HIV infection. RESULTS: The prevalence of HCV among HIV-negative controls was 8.3% (6/72) for men and 4.2% (5/118) for women. Co-infection with HIV and occurred in 50.7% (37/73) of men and 3.4% (4/118) of women. Among men who reported injection drug use (IDU), 96.4% (27/28) were HCV seropositive. No women reported IDU. HCV was associated with HIV infection [odds ratio (OR), 11.3; 95% confidence interval (CI), 4.4-29.3] and IDU (OR, 12.0; 95% CI, 3.4-41.9) among men, but not women (OR, 0.8; 95% CI, 0.2-3.0). After adjustment for potential confounding, HCV, but not IDU, remained strongly associated with HIV-1 infection among men (OR, 9.4; 95% CI, 2.7-32.6). CONCLUSIONS: The strong associations between HCV seropositivity, HIV-1 infection, and IDU history suggest that IDU was reported accurately in this study. The surprisingly high prevalence of HCV among HIV-1-infected young men may assist health policy makers in the choice of behavioral interventions for this important subgroup of the population.

AIDS Vaccines↗
PubMed2003

A new circulating recombinant form, CRF15_01B, reinforces the linkage between IDU and heterosexual epidemics in Thailand.

HIV-1 subtype B and CRF01_AE have been in circulation in Thailand and Southeast Asia for more than a decade. Initially separated by risk group, the two strains are increasingly intermixed, and two recombinant strains of essentially reciprocal structure have been recently reported. Here we identify additional CRF_01B recombinants and provide the evidence that HIV-1 strains now pass freely between the two high-risk populations. HIV isolates that showed discordance between CRF01_AE and subtype B in multi-region genotyping assays were selected for the study. They were drawn from 3 different cohorts in Thailand representing different risk behaviors and demographic characteristics: a drug user cohort in the north, a family planning clinic attendee cohort in the southeast, and a cohort study of the mucosal virology and immunology of HIV-1 infection in Thailand. The DNA from these isolates was PCR amplified to recover the full HIV-1 genome and subjected to sequencing and phylogenetic analysis. We establish that one particular CRF_01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01_AE, is circulating widely in Thailand. Termed CRF15_01B (also referred to as CRF15), the strain was primarily heterosexually transmitted, although injecting drug use (IDU) also played a role. In aggregate data from the studies, CRF15 constituted 1.7% of all HIV-1 infections (95% confidence interval 0.5-4.4%) and was dispersed widely in the country. The previously separate heterosexual and IDU epidemics have apparently been bridged by a new CRF. The entry of CRF15 into the mainstream of the epidemic signals new complexity in the long stable molecular picture in Thailand. These recombinants must be considered in ongoing or projected efficacy evaluations of HIV-1 vaccines and antiviral therapies.

Adult↗
PubMed2003

Longitudinal study of humoral immune responses in HIV type 1 subtype CRF01_AE (E)-infected Thai patients with different rates of disease progression.

Identification of immune correlates associated with disease progression will provide information for HIV-1 vaccine design in countries such as Thailand, where the prevalent subtypes (B and CRF01_AE [E]) are characterized. In this study, plasma viral load and humoral immune responses were measured in 20 HIV-1 subtype E-infected Thai patients with different rates of disease progression, based on CD4(+) T cell decline and clinical symptoms. Nine progressors (PRs) and 11 slower progressors (SPs) were evaluated. CD4(+) T cell counts were inversely correlated with viral load (p = 0.004) and positively correlated with p24 Ab (p = 0.022). In progressors, p24 Ab showed a significant decrease (p < 0.001) over time. V3 and gp41 Ab did not change significantly in either group. Both CD4-binding site (CD4/gp120BS) and gp120 titers correlated positively with neutralizing antibody (NAb) against both a subtype E cell line-adapted virus (NP03) and a primary isolate (TH023). However, V3 Ab correlated only with NAb against NP03 (p < 0.001). Increased NAb over time was observed more frequently in SPs as compared with PRs, against both the TH023 (p = 0.004) and NPO3 (p = 0.004) viruses. Cross-clade antibody-dependent cellular cytotoxicity was demonstrated in both groups. These data suggest that in HIV-1 subtype E infection, declining p24 Ab titer is a predictive marker of disease progression, as described for subtype B. Furthermore, in subtype E-infected patients, slower progressors retain the immune competence to develop new antibody responses to Env over time; these evolving responses may contribute to prolonged survival during HIV-1 disease progression.

Antibody-Dependent Cell Cytotoxicity↗
PubMed2003

Human immunodeficiency virus type 1 primary isolate neutralization resistance is associated with the syncytium-inducing phenotype and lower CD4 cell counts in subtype CRF01_AE-infected patients.

A number of human immunodeficiency virus type 1 (HIV-1) non-B-subtype products have been developed for present or future vaccine trials; in Thailand, several studies using subtype B and/or CRF01_AE vaccines have been conducted. To better characterize the biologic properties of these subtypes, 70 HIV-1 subtype B and E isolates were phenotyped as syncytium-inducing (SI) or non-syncytium-inducing (NSI) isolates and assessed for sensitivity to neutralizing antibody (NAb). A significantly higher number of NSI subtype E viruses were neutralization sensitive than SI subtype E viruses (P = 0.009), while no association between viral phenotype and sensitivity to NAb was observed for subtype B (P = 0.856), suggesting a difference in the neutralization patterns of subtypes B and E. Strikingly, concurrent CD4 T-cell numbers were significantly lower for subtype E-infected patients whose isolates were more resistant to NAb, both for the overall study group (P < 0.001) as well as for the 22 patients with NSI isolates (P = 0.013). Characterization of the evolution of biologic properties of both B and non-B HIV-1 subtypes will provide a clearer understanding of the repertoire of antibodies that must be elicited for a vaccine to be effective against all phenotypes and subtypes.

Antibodies, Viral↗
PubMed2003

HIV epidemic among young Thai Men, 1991-2000.

Characterization of the HIV epidemic in Thailand has benefited from the systematic testing of young men upon entry into the military. These data, which have shown that public health measures can reverse an HIV epidemic, have been reanalyzed with current geographic information systems methods. The resulting maps are, thus far, the best means of visualizing the geography of the dynamic HIV epidemic in Thailand.

Adult↗
PubMed2003

A joint clinical research center in Thailand: role in HIV vaccine development.

In 1992 the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand, collaborated with the Phramongkutklao Army Medical Center to set up the Joint Clinical Research Center (JCRC). The purpose of the Center is to conduct clinical research in support of HIV vaccine development and testing. To date, eight HIV vaccine-related research protocols have been conducted at the JCRC, involving 1,668 volunteers. The JCRC has been, and continues to be, a key site for the transfer of clinical trial expertise to new sites at universities, government clinics and hospitals in Thailand and other countries. Overall rates of follow-up have been excellent, while protocol violations and data clarification errors have been minimal.

AIDS Vaccines↗
PubMed2002

Heterosexually acquired CRF01_AE/B recombinant HIV type 1 found in Thailand.

CRF01_AE and subtype B are circulating in Thailand and the strains have become intermixed in some high-risk groups, establishing the possibility of intersubtype recombination. The first such recombinant, mostly B with gp120 from CRF01_AE, was recently identified. Here we report a heterosexually acquired recombinant of different structure, with most of the genome from CRF01_AE but almost the entire envelope from subtype B. Surveillance by V3 serotype and genotype in multiple regions, followed by full-genome sequencing, was used to identify this strain. Pending vaccine trials in Thailand require knowledge of the presence of such strains in the population, and these recombinants provide valuable reagents for the laboratory evaluation of cross-subtype immunity. Studies are underway to determine whether either recombinant is circulating widely.

HIV Infections↗
PubMed2002

Pythium insidiosum pleuropericarditis complicating pneumonia in a child with leukemia.

We describe a 12-year-old boy with acute myeloid leukemia who developed pleuropericarditis while he was neutropenic and was receiving intravenously administered antibiotic and antifungal therapy for pneumonia. A KOH preparation of the purulent material from an extensive diagnostic and therapeutic pleuropericardial drainage procedure revealed multiple irregularly septate hyphae, and cultures yielded the organism Pythium insidiosum. After completing a 12-month course of intravenously administered liposomal amphotericin B (AmBisome; Fujisawa Healthcare) and itraconazole, the patient remained alive, in clinical remission, and symptom free.

Amphotericin B↗
PubMed2002

Recruiting volunteers for a multisite phase I/II HIV preventive vaccine trial in Thailand.

Factors believed to be predictive of retention through the recruitment and screening processes for preventive HIV trials were investigated in a large multisite phase I/II HIV vaccine trial in Thailand. Retention through recruitment was equal to or greater than in previous smaller trials with similar populations. The data suggested that recruitment proceeded in a stepwise manner with different influences at each step. Demographic and motivational variables were most important in predicting retention in making and keeping screening appointments. Altruistic or mixed altruistic and nonaltruistic motives were associated with greater retention. Laboratory/medical variables appeared to be the main influence on retention during screening, although some volunteers withdrew for different reasons. The frequent presence of mixed (altruistic and nonaltruistic) motives at initial contact suggests that motivation for trials is more complex than has been previously acknowledged.

AIDS Vaccines↗
PubMed2002

Rhodococcus equi: an emerging pathogen.

More than 100 cases of Rhodococcus equi infection have been reported since the first description of human disease caused by this organism. The vast majority of patients infected with R. equi are immunocompromised, and two-thirds have human immunodeficiency virus infection. The clinical manifestations of R. equi infection are diverse, although 80% of patients have some pulmonary involvement. The organism is easily cultured from specimens of infected tissue or body fluid, but it may be misdiagnosed as a contaminant. Treatment is often prolonged, and relapses at distant sites are common. This article summarizes the history, diagnosis, clinical features, and treatment of infection with this emerging pathogen.

Actinomycetales Infections↗
PubMed2002

Anthrax of the gastrointestinal tract.

When swallowed, anthrax spores may cause lesions from the oral cavity to the cecum. Gastrointestinal anthrax is greatly underreported in rural disease-endemic areas of the world. The apparent paucity of this form of anthrax reflects the lack of facilities able to make the diagnosis in these areas. The spectrum of disease, ranging from subclinical infection to death, has not been fully recognized. In some community-based studies, cases of gastrointestinal anthrax outnumbered those of cutaneous anthrax. The oropharyngeal variant, in particular, is unfamiliar to most physicians. The clinical features of oropharyngeal anthrax include fever and toxemia, inflammatory lesion(s) in the oral cavity or oropharynx, enlargement of cervical lymph nodes associated with edema of the soft tissue of the cervical area, and a high case-fatality rate. Awareness of gastrointestinal anthrax in a differential diagnosis remains important in anthrax-endemic areas but now also in settings of possible bioterrorism.

Anthrax↗