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Todd Hulgan,
John P. Donahue,
Laura Smeaton, Minya Pu,
Hongying Wang,
Michael M. Lederman,
Kimberly Smith,
Hernan Valdez,
Christopher Pilcher,
David W. Haas,
The AIDS Clinical Trials Group Study Team
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ABSTRACT: PurposeP-glycoprotein limits the tissue penetration of many antiretroviral drugs. The aim of our study was to characterize the effects
of the P-glycoprotein substrate cyclosporin A on T cell P-glycoprotein activity in human immunodeficiency virus-infected participants
in the AIDS Clinical Trials Group study A5138.
MethodsWe studied P-glycoprotein activity on CD4 and CD8 T cells in 16 participants randomized to receive oral cyclosporin A (n = 9) or not (n = 7) during initiation antiretroviral therapy (ART) that did not include protease or non-nucleoside reverse transcriptase
inhibitors.
ResultsCD4 T cell P-glycoprotein activity decreased by a median of 8 percentage points with cyclosporin A/ART (difference between
cyclosporin A/ART vs. ART only, P = 0.001). Plasma trough cyclosporin A concentrations correlated with the change in P-glycoprotein activity in several T cell
subsets.
ConclusionsOral cyclosporin A can inhibit peripheral blood CD4 T cell P-glycoprotein activity. Targeted P-glycoprotein inhibition may
enhance the delivery of ART to T cells.
European Journal of Clinical Pharmacology 04/2012; 65(11):1081-1088. · 2.85 Impact Factor
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[show abstract]
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ABSTRACT: PURPOSE/OBJECTIVE(S): We report our experience using hypofractionated radiotherapy in older patients.
This analysis includes patients aged 60 years and older at our institution with inoperable Stage I (T1/T2 N0 M0) non--small-cell lung cancer that completed a curative course of radiotherapy alone using a hypofractionated schedule. Between 1991 and 2006, 75 such patients were identified with median age of 74 years (range, 60-86). Patient characteristics were as follows: male, 65/75 (86.7%); stage IA (T1N0), 47/75 (62.7%); stage IB (T2N0), 28/75 (37.3%). Patients received a median total dose of 6500 cGy using median daily dose fractions of 250 cGy. The following outcomes were analyzed: local failure free survival (time to local failure or death from any cause), time to distal failure as first event, and overall survival. Toxicities were evaluated using Common Terminology Criteria for Adverse Events v 3.0.
The median follow-up was 19.6 months (range: 4.0-128.8 months). Median local failure free survival was 19.6 months (95% confidence interval [CI]: 14.4-28.8 months); and median overall survival was 21.2 months (95% CI: 14.9-29.3 months). Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 22.1% (95% CI: 12.8%-32.9%); the probability of distal failure as the first detected event was 14.5% (95% CI: 7.3%-24.0%); and the probability of death without recording a failure was 48.6% (95% CI: 36.1%-60.1%). Radiation-related toxicity of grade 3 or greater was seen in 3 patients and there were no treatment-related deaths.
Hypofractionated radiotherapy is an effective, safe treatment for older patients with stage I non--small-cell lung cancer.
American journal of clinical oncology 06/2011; 34(3):254-8. · 2.21 Impact Factor
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Vered Padler-Karavani,
Nancy Hurtado-Ziola, Minya Pu,
Hai Yu,
Shengshu Huang,
Saddam Muthana,
Harshal A Chokhawala,
Hongzhi Cao,
Patrick Secrest,
Dinorah Friedmann-Morvinski,
Oded Singer,
Darius Ghaderi,
Inder M Verma,
Yu-Tsueng Liu,
Karen Messer,
Xi Chen,
Ajit Varki,
Richard Schwab
[show abstract]
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ABSTRACT: Human carcinomas can metabolically incorporate and present the dietary non-human sialic acid Neu5Gc, which differs from the human sialic acid N-acetylneuraminic acid (Neu5Ac) by 1 oxygen atom. Tumor-associated Neu5Gc can interact with low levels of circulating anti-Neu5Gc antibodies, thereby facilitating tumor progression via chronic inflammation in a human-like Neu5Gc-deficient mouse model. Here we show that human anti-Neu5Gc antibodies can be affinity-purified in substantial amounts from clinically approved intravenous IgG (IVIG) and used at higher concentrations to suppress growth of the same Neu5Gc-expressing tumors. Hypothesizing that this polyclonal spectrum of human anti-Neu5Gc antibodies also includes potential cancer biomarkers, we then characterize them in cancer and noncancer patients' sera, using a novel sialoglycan microarray presenting multiple Neu5Gc-glycans and control Neu5Ac-glycans. Antibodies against Neu5Gcα2-6GalNAcα1-O-Ser/Thr (GcSTn) were found to be more prominent in patients with carcinomas than with other diseases. This unusual epitope arises from dietary Neu5Gc incorporation into the carcinoma marker Sialyl-Tn, and is the first example of such a novel mechanism for biomarker generation. Finally, human serum or purified antibodies rich in anti-GcSTn-reactivity kill GcSTn-expressing human tumors via complement-dependent cytotoxicity or antibody-dependent cellular cytotoxicity. Such xeno-autoantibodies and xeno-autoantigens have potential for novel diagnostics, prognostics, and therapeutics in human carcinomas.
Cancer Research 05/2011; 71(9):3352-63. · 7.86 Impact Factor
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Jiehua Zhou,
Asad Bashey,
Ruikun Zhong,
Sue Corringham,
Karen Messer, Minya Pu,
Wenxue Ma,
Theresa Chut,
Robert Soiffer,
Rachel C Mitrovich,
Israel Lowy,
Edward D Ball
[show abstract]
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ABSTRACT: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a key negative regulator of T cell activation and proliferation. Ipilimumab is a human monoclonal antibody that specifically blocks the binding of CTLA-4 to its ligand. To test the hypothesis that blockade of CTLA-4 by ipilimumab could augment graft-versus-malignancy (GVM) effects without a significant impact on graft-versus-host disease (GVHD), we conducted a phase I clinical trial of ipilimumab infusion in patients with relapsed malignancy following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we report the analysis of peripheral blood T lymphocyte reconstitution, T regulatory cell (Treg) expression, and T cell activation markers after a single dose of ipilimumab in 29 patients. Peripheral blood samples were collected from all patients before and after ipilimumab infusion. Lymphocyte immunophenotyes, including levels of CD4(+)CD25(high) cells and T cell activation markers, were analyzed in all cases. Levels of CD4(+)CD25(high)Foxp3(+) cells and intracellular CTLA-4 in CD4(+) T cells also were evaluated in the last 11 cases. We found lower baseline levels of CD4(+) and CD45RO(+) T cells in patients compared with normal controls. More than 50% of the patients had abnormally low lymphocyte counts (CD4 or/and CD8 T cells), and some had no circulating B lymphocytes. The percentages of both CD4(+)CD25(high) and CD4(+)CD25(high)Foxp3(+) T cells were significantly higher in patients before ipilimumab infusion than in healthy donors. Twenty of 29 patients exhibited an elevated level of CD4(+)CD25(low) activated T cells at baseline, compared with only 3 of 26 healthy donors. Both CD4(+) and CD8(+) T lymphocyte counts were significantly increased after ipilimumab infusion. There was no consistent change in absolute lymphocyte count or in the number of T cells expressing the activation marker CD69. However, increases in CD4(+)CD25(low) T cells were seen in 20 of 29 patients and increases in CD4(+)HLA-DR(+) T cells were seen in the last 10 patients in the first 60 days after ipilimumab infusion. Although the percentages of both CD4(+)CD25(high) and CD4(+)CD25(high)Foxp3(+) T cells decreased significantly during the observation period, the absolute cell counts did not change. Intracellular CTLA-4 expression in CD4(+)CD25(lo/-) T cells increased significantly after ipilimumab infusion. We conclude that CTLA-4 blockade by a single infusion of ipilimumab increased CD4(+) and CD4(+)HLA-DR(+) T lymphocyte counts and intracellular CTLA-4 expression at the highest dose level. There was no significant change in Treg cell numbers after ipilimumab infusion. These data demonstrate that significant changes in T cell populations occur on exposure to a single dose of ipilimumab. Further studies with multiple doses are needed to explore this phenomenon further and to correlate changes in lymphocyte subpopulations with clinical events.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2011; 17(5):682-92. · 3.15 Impact Factor
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ABSTRACT: Purpose: We report our single-institution experience using hypofractionated radiotherapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) Non-Small Cell Lung Carcinoma. Materials and methods: This is a single-institution, retrospective analysis examining disease free and overall survival and toxicity after hy-pofractionated radiation therapy in a patient population 75 years and older diagnosed with stage IA or IB (T1/T2 N0) NSCLC. Between 1991 and 2005, a total of 33 such patients were identified with a median age of 79 years. Patients were treated with a median total dose of 7000 cGy using median daily dose fractions of 250 cGy. Analysis of competing risks (local failure, distal failure or death as the first event) was performed and cumulative incidence functions (CIF) were estimated. Results: The median length of follow-up was 19.8 months (range: 4.3 -103.8 months). Of the 33 pa-tients treated, 21 (63.6% of total) had no evidence of disease recurrence on follow-up imaging over the course of the study. Of the 12 patients with disease recurrence, 6 (18.2% of total) had local failure as the first event and 6 (18.2% of total) had distant metastasis as the first event. Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 19.5% (95%CI: 7.6%, 35.6%); the probability of distal failure as the first detected event was 21.5% (95%CI: 7.9%,39.4%); and the probability of death without recording a failure was 44.1% (95%CI: 26.1%, 60.7%). There were no treatment related deaths reported. Conclusions: Elderly patients diagnosed with stage I non-small cell lung cancer may safely be offered hypofractionated radiotherapy as an effective option with curative intent.
Journal of Cancer Therapy. 01/2011; 2:167-171.
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ABSTRACT: A cost- and time-efficient means to define the prognosis of patients with chronic lymphocytic leukemia (CLL) is desirable but does not yet exist. On the basis of the evidence that CLL cells have enhanced expression of the cyclic nucleotide phosphodiesterase isoform 7B (PDE7B), we hypothesized that PDE7B expression might provide such information. We assessed PDE7B mRNA expression using quantitative real-time PCR in peripheral blood mononuclear cells isolated from 85 patients and 30 normal subjects. We compared PDE7B mRNA expression with that of other disease features to determine if its expression correlates with the prognosis of patients with CLL. We found that CLL patients with PDE7B mRNA levels in the top quartile (greater than ninefold elevation relative to normal controls) have a several-year shorter median time-to-treatment (TTT, 36 months) compared to that of patients whose CLL cells express lower levels of PDE7B mRNA (TTT, 77 months, p=0.001). High PDE7B mRNA expression correlates with expression of zeta-chain-associated protein kinase 70 (ZAP-70), unmutated immunoglobulin heavy chain variable (IGHV) region genes and β2 microglobulin (β2M), but use of a multivariate Cox model revealed that high PDE7B mRNA expression independently predicts a short TTT, even after adjusting for several other disease characteristics (ZAP-70 or CD38 expression, IGHV mutation status and Rai status). High expression of PDE7B is an unfavorable characteristic in CLL. Assessment of PDE7B mRNA expression thus appears to be a clinically useful biomarker to define the prognosis of patients with CLL.
International Journal of Cancer 11/2010; 129(5):1162-9. · 5.44 Impact Factor
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ABSTRACT: Surgical resection for stage I non-small-cell lung cancer (NSCLC) is not always feasible because of the high likelihood of medical comorbidity in this patient population. We report our experience using conventional and hypofractionated radiation therapy schedules with a conformal approach.
Between 1991 and 2006, 102 patients with medically or otherwise inoperable stage T1/T2 N0 NSCLC were treated with curative radiation therapy alone at our institution. Patients received a median total dose of 6600 cGy, with median daily dose fractions of 250 cGy. The following outcomes were analyzed: local failure-free survival (LFFS; time to local failure or death from any cause), time to local or distal failure or death as first event, and overall survival (OS). Local failure was defined as an increase in size on imaging studies. Toxicities were evaluated using Common Terminology Criteria for Adverse Events, version 3.0.
Median follow-up was 20.9 months (range, 4.0-138.9 months). Median LFFS was 21.2 months (95% CI, 17.3-27.2 months), and median OS was 21.3 months (95% CI, 17.9-28.8 months). Analysis of competing risks showed that at 5 years, the probability of local failure as the first detected event was 15.1% (95% CI, 8.5%-23.4%), the probability of distal failure as the first detected event was 18% (95% CI, 10.9%-26.5%), and the probability of death without recording a failure was 51.6% (95% CI, 40.6%-61.5%). No patients experienced grade >or= 4 toxicity, and only 4 patients experienced grade 3 toxicity.
Conformal radiation therapy is an effective and safe alternative to surgery for selected patients with stage I NSCLC.
Clinical Lung Cancer 11/2009; 10(6):433-7. · 2.94 Impact Factor
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Andre S Jung,
Peter R Holman,
Januario E Castro,
Ewa K Carrier,
Asad Bashey,
Thomas A Lane,
Connie L Nelson, Minya Pu,
Karen Messer,
Sue M Corringham,
Edward D Ball
[show abstract]
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ABSTRACT: Autologous peripheral blood stem/progenitor cell transplantation (APBSCT) has been investigated as a potential therapeutic option to improve outcome in patients with acute myelogenous leukemia (AML). However, its optimal role in treatment for adults in remission has not been clearly established. We performed a retrospective analysis on 45 patients aged 21 to 73 years (median 51 years) with de novo AML who underwent APBSCT stratified by age, complete remission status, and cytogenetic risk. The 5-year disease-free survival (DFS) for all patients was 33.9% (95% confidence interval [CI], 20.1%-53.7%) and overall survival (OS) was 43.6% (CI, 29.2%-62.8%). For patients under the age of 60 years, the 5-year DFS for intermediate and high cytogenetic risk was 53.3% (CI, 23.5%-85.6%) and 50.0% (CI, 16.1%-100.0%); the 5-year OS for patients under the age of 60 years with low, intermediate, and high cytogenetic risk was 80.0% (CI, 40.0%-100.0%), 60.0% (CI, 31.2%-90.7%), and 75.0% (CI, 39.0%-100.0%), respectively. For patients over the age of 60 years, the 5-year DFS and OS for intermediate cytogenetic risk was 21.4% (CI, 7.9%-58.4%) and 21.4% (CI, 7.9%-58.4%). The DFS and OS of these patients are comparable to the historic survival of those who underwent allogeneic stem cell transplantation when adjusted by age. In addition, there was no treatment-related mortality (TRM). We conclude that APBSCT is a reasonable and safe intensive consolidation for patients with AML who do not have a suitable HLA-matched donor.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2009; 15(10):1306-13. · 3.15 Impact Factor
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ABSTRACT: Current intraperitoneal (IP) regimens for the treatment of ovarian cancer rely on cisplatin (DDP) whereas intravenous regimens rely on carboplatin (CBDCA). A major question in the field is whether CBDCA can replace DDP for IP treatment. We compared the uptake of IP administered DDP and CBDCA into human ovarian carcinoma nodules of various sizes growing on the peritoneal surface of nu/nu mice.
Human 2008 cells expressing GFP were inoculated IP in nu/nu mice. When small tumor nodules became visible by external imaging, a maximum tolerated dose of DDP, or either an equimolar or equitoxic dose of CBDCA, was injected IP. Platinum (Pt) concentration in tumor nodules was measured by inductively coupled plasma mass spectrometry.
A total of 749 tumors harvested from 33 mice were analyzed for Pt concentration. DDP produced a 3.4-fold higher level of Pt in tumor nodules when compared to an equimolar dose of CBDCA (p=0.02). However, when DDP and CBDCA were injected at doses that were equitoxic to the mice, tumor Pt levels were equivalent (p=0.63). Although Pt concentrations of equal-sized nodules were highly variable, tumor Pt content (ng Pt/mg tumor) decreased with increasing nodule size following IP DDP, an effect not seen with IP administration of equitoxic doses of CBDCA (p<0.001).
These results suggest that IP CBDCA has comparable or better drug penetration when compared to DDP given at equitoxic doses, and thus provide support for replacing DDP with CBDCA in the IP treatment of patients with ovarian cancer.
Gynecologic Oncology 09/2009; 115(3):362-6. · 3.89 Impact Factor
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ABSTRACT: The aim of this study was to examine the effect of a case management intervention on retention in opiate agonist therapy among injection drug users (IDUs) referred from a needle exchange program (NEP). DESIGN, INTERVENTION, PARTICIPANTS, AND SETTING: A randomized trial of a strengths-based case management intervention versus passive referral (control) was conducted among NEP attendees requesting and receiving referrals to subsidized, publicly funded opiate agonist treatment programs in Baltimore, MD.
Multivariable Cox regression models were used to identify predictors of treatment retention using an ecological model approach, taking into account factors at the individual, social, and environmental level.
Of 245 IDUs, 127 (51.8%) entered opiate agonist treatment, for whom median retention was 7.9 months. The intervention was not associated with longer retention (p = .91). Individual-level factors predictive of shorter retention included being employed and greater levels of psychiatric distress. Participants who had prior treatment experience and multiple treatment requests were retained significantly longer. Social factors adversely affecting treatment retention included unstable housing and buying drugs for others. Living further away from the treatment site was an environmental barrier that negatively affected treatment retention.
Multilevel interventions that address individual, social, and environmental factors are necessary to improve substance abuse treatment retention and treatment outcomes among IDUs referred from NEP.
Journal of substance abuse treatment 11/2008; 36(3):306-12. · 2.90 Impact Factor
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MSW Jacqueline J. Lloyd PhD,
Steffanie A. Strathdee PhD,
Minya Pu MS,
MPH Jennifer R. Havens PhD,
MA Llewellyn J. Cornelius PhD,
Steven Huettner BS,
Carl A. Latkin PhD,
Jacqueline J. Lloyd,
Steffanie A. Strathdee, Minya Pu,
Jennifer R. Havens,
Llewellyn J. Cornelius,
Steven Huettner,
Carl A. Latkin
[show abstract]
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ABSTRACT: This study examined whether participation in opiate drug treatment is associated with changes in drug use and injecting drug use within the social networks of injecting drug users. Participants were 245 injecting drug users who attended the Baltimore Needle Exchange Program during 2002–2004 and requested treatment and received a referral for opiate agonist treatment as part of an intervention to improve treatment outcomes. Data included interviews at baseline, 3, 6, 12, and 18 months and drug treatment program agency records. The mean age of participants was 42.2 years; 77% were African American, 69% were male, and 48% entered treatment. Final generalized estimating equations (GEE) models indicated that participants that entered opiate drug treatment exhibited approximately a 20% decrease in the proportional odds of having friends that used drugs (p = 0.04). Additionally, participants that entered opiate drug treatment exhibited a 26% decrease in the proportional odds of having friends that injected drugs (p = 0.01). These findings contribute evidence to further understand the dynamics between opiate drug treatment, changes in social network risk, and treatment outcomes, as well as suggest an important role for peer-based interventions to support entry and retention in opiate drug treatment.
American Journal on Addictions 09/2008; 17(5):414 - 421. · 1.74 Impact Factor
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Mary H Latka,
Holly Hagan,
Farzana Kapadia,
Elizabeth T Golub,
Sebastian Bonner,
Jennifer V Campbell,
Micaela H Coady,
Richard S Garfein, Minya Pu,
Dave L Thomas,
Thelma K Thiel,
Steffanie A Strathdee
[show abstract]
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ABSTRACT: We evaluated the efficacy of a peer-mentoring behavioral intervention designed to reduce risky distributive injection practices (e.g., syringe lending, unsafe drug preparation) among injection drug users with hepatitis C virus (HCV) infection.
A randomized trial with a time-equivalent attention-control group was conducted among 418 HCV-positive injection drug users aged 18 to 35 years in 3 US cities. Participants reported their injection-related behaviors at baseline and at 3- and 6-month follow-ups.
Compared with the control group, intervention-group participants were less likely to report distributive risk behaviors at 3 months (odds ratio [OR]=0.46; 95% confidence interval [CI]=0.27, 0.79) and 6 months (OR=0.51; 95% CI=0.31, 0.83), a 26% relative risk reduction, but were no more likely to cite their HCV-positive status as a reason for refraining from syringe lending. Effects were strongest among intervention-group participants who had known their HCV-positive status for at least 6 months. Peer mentoring and self-efficacy were significantly increased among intervention-group participants, and intervention effects were mediated through improved self-efficacy.
This behavioral intervention reduced unsafe injection practices that may propagate HCV among injection drug users.
American Journal of Public Health 06/2008; 98(5):853-61. · 3.93 Impact Factor
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Thomas L Patterson,
Shirley J Semple,
Hugo Staines,
Remedios Lozada,
Prisci Orozovich,
Jesus Bucardo,
Morgan M Philbin, Minya Pu,
Miguel Fraga,
Hortensia Amaro,
Adela de la Torre,
Gustavo Martinez,
Carlos Magis-Rodríguez,
Steffanie A Strathdee
[show abstract]
[hide abstract]
ABSTRACT: We examined human immunodeficiency virus (HIV) prevalence and correlates among female sex workers (FSWs) in Tijuana and Ciudad Juarez, 2 large cities on the Mexico-US border.
FSWs aged > or =18 years underwent interviews and testing for HIV, syphilis, gonorrhea, and chlamydia. Logistic regression identified factors associated with HIV infection.
In 924 FSWs, the prevalence of HIV, gonorrhea, chlamydia, and syphilis titers > or =1:8 was 6%, 6.4%, 13%, and 14.2%, respectively. Factors independently associated with HIV were the injection of cocaine (odds ratio [OR], 2.96); the smoking, snorting, or inhalation of methamphetamine (OR, 3.32); and syphilis titers > or =1:8 (OR, 4.16).
Culturally appropriate interventions are needed to identify and treat ulcerative sexually transmitted infections and reduce HIV risks associated with stimulants among FSWs in the Mexico-US border region.
The Journal of Infectious Diseases 03/2008; 197(5):728-32. · 6.41 Impact Factor
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Steffanie A Strathdee,
Remedios Lozada,
Shirley J Semple,
Prisci Orozovich, Minya Pu,
Hugo Staines-Orozco,
Miguel Fraga-Vallejo,
Hortensia Amaro,
Adela Delatorre,
Carlos Magis-Rodríguez,
Thomas L Patterson
[show abstract]
[hide abstract]
ABSTRACT: HIV prevalence is increasing among female sex workers (FSWs) in Tijuana and Ciudad Juarez, 2 Mexican cities on the US border. Quasilegal prostitution in both cities attracts large numbers of sex tourists. We compared FSWs with and without US clients in both cities.
FSWs aged > or =18 years reporting unprotected sex with > or =1 client within the last 2 months, who were not knowingly HIV-infected, were enrolled in a behavioral intervention study. At baseline, participants underwent interviews, antibody testing for HIV and syphilis, and vaginal swabs for detecting gonorrhea and Chlamydia. Logistic regression identified factors associated with reporting >1 US client.
Of 924 FSWs, 69% had US clients. Median age and duration in sex work were 32 and 4 years. Prevalence of HIV, infectious syphilis (titer > or =1:8), gonorrhea, Chlamydia, and any STI was 6%, 14%, 6%, 13%, and 27%, respectively. Compared with other FSWs, FSWs with US clients were more likely to have syphilis titers > or =1:8 (16% vs. 10%, P = 0.01), gonorrhea (8% vs. 2%, P <0.001) or any STI, including HIV (30% vs. 20%, P = 0.002). Factors independently associated with having US clients were: living in Tijuana, being younger, speaking English, being paid more for having sex without a condom, having >250 clients in the last 6 months, having syphilis titers > or =1:8, and injecting drugs.
In these border cities, FSWs reporting US clients were more likely to have current STIs and to engage in higher-risk behaviors. Intensified binational prevention efforts involving both FSWs and their clients are urgently needed.
Sex Transm Dis 03/2008; 35(3):263-8. · 2.87 Impact Factor
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Steffanie A Strathdee,
Morgan M Philbin,
Shirley J Semple, Minya Pu,
Prisci Orozovich,
Gustavo Martinez,
Remedios Lozada,
Miguel Fraga,
Adela de la Torre,
Hugo Staines,
Carlos Magis-Rodríguez,
Thomas L Patterson
[show abstract]
[hide abstract]
ABSTRACT: To characterize the overlap between injection drug use and sex work by women in Tijuana and Cd. Juarez, situated on the Mexico-U.S. border.
FSWs aged > or =18 years who were not knowingly HIV-positive and reported having unprotected sex with > or =1 client in the prior 2 months underwent interviews and testing for HIV, syphilis, gonorrhea and Chlamydia. Logistic regression identified factors associated with injecting drugs within the last month.
Of 924 FSWs, 18.0% had ever injected drugs. Among FSW-IDUs (N=114), prevalence of HIV, syphilis titers > or =1:8, gonorrhea and Chlamydia was significantly higher at 12.3%, 22.7%, 15.2% and 21.2% compared to 4.8%, 13.1%, 5.2% and 11.9% among other FSWs (N=810). FSW-IDUs also had more clients in the past 6 months (median: 300 versus 240, p=0.02). Factors independently associated with injecting drugs in the past month included living in Tijuana, being younger, being married/common-law, longer duration in the sex trade, speaking English, earning less for sex without condoms, often using drugs before sex, and knowing other FSWs who injected drugs.
FSW-IDUs had higher STI levels, engaged in riskier behaviors and were more vulnerable to having unsafe sex with clients compared to other FSWs, indicating that this subgroup is an important bridge population requiring focused prevention.
Drug and Alcohol Dependence 02/2008; 92(1-3):132-40. · 3.38 Impact Factor
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Robin A Pollini,
Kimberly C Brouwer,
Remedios M Lozada,
Rebeca Ramos,
Michelle F Cruz,
Carlos Magis-Rodriguez,
Patricia Case,
Scott Burris, Minya Pu,
Simon D W Frost,
Lawrence A Palinkas,
Cari Miller,
Steffanie A Strathdee
[show abstract]
[hide abstract]
ABSTRACT: To identify factors associated with receptive syringe sharing among injection drug users (IDUs) and elucidate the association between syringe possession arrests and syringe sharing.
Cross-sectional study.
Mexican border cities of Tijuana, Baja California and Ciudad Juarez, Chihuahua.
IDUs in Tijuana (n = 222) and Ciudad Juarez (n = 206) were recruited using respondent-driven sampling (RDS). IDUs were > or = 18 years and had injected illicit drugs in the past month.
An interviewer-administered survey was used to collect quantitative data on socio-demographic, behavioral and contextual characteristics, including self-reported syringe sharing and arrests for syringe possession. Associations with receptive syringe sharing were investigated using logistic regression with RDS adjustment.
Overall, 48% of participants reported ever being arrested for carrying an unused/sterile syringe, even though syringe purchase and possession is legal in Mexico. Arrest for possessing unused/sterile syringes was associated independently with receptive syringe sharing [adjusted odds ratio (AOR) = 2.05; 95% confidence interval (CI): 1.26, 3.35], as was injecting in a shooting gallery (AOR = 3.60; 95% CI: 2.21, 5.87), injecting in the street (AOR = 2.05; 95% CI: 1.18, 3.54) and injecting methamphetamine (AOR = 2.77; 95% CI: 1.41, 5.47) or cocaine (AOR = 1.96; 95% CI: 1.15, 3.36). More than half of participants (57%) had been arrested for possessing a used syringe; in a second model, arrest for used syringe possession was also associated independently with receptive sharing (AOR = 2.87; 95% CI: 1.76, 4.69).
We documented high levels of syringe-related arrests in two Mexican-US border cities and an independent association between these arrests and risky injection practices. Public health collaborations with law enforcement to modify the risk environment in which drug use occurs are essential to facilitate safer injection practices.
Addiction 01/2008; 103(1):101-8. · 4.31 Impact Factor
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Michael M Lederman,
Laura Smeaton,
Kim Y Smith,
Benigno Rodriguez, Minya Pu,
Hongying Wang,
Anne Sevin,
Pablo Tebas,
Scott F Sieg,
Kathy Medvik,
David M Margolis,
Richard Pollard,
Hildegund C J Ertl,
Hernan Valdez
[show abstract]
[hide abstract]
ABSTRACT: Although the determinants of immune deficiency and immune restoration in chronic human immunodeficiency virus (HIV)-1 infection are not well understood, immune activation has been proposed as being central to the pathogenesis of HIV.
A randomized, controlled trial of cyclosporin A treatment for 2 weeks was performed in persons with chronic HIV-1 infection who were beginning a standardized antiretroviral therapy (ART) regimen.
Treatment with cyclosporin A provided only a marginal and transient enhancement in circulating T cell restoration that was largely restricted to cells expressing the CCR7 chemokine receptor and that did not persist beyond 2 weeks.
Cyclosporin A coadministered for 2 weeks with ART provided no sustained immunologic benefit to persons with chronic HIV-1 infection. If immune activation drives progressive immune deficiency in chronic HIV-1 infection, these activation pathways may not be sensitive to cyclosporin.
The Journal of Infectious Diseases 01/2007; 194(12):1677-85. · 6.41 Impact Factor
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Robert C Kalayjian,
John Spritzler, Minya Pu,
Alan Landay,
Richard B Pollard,
Vicki Stocker,
Lena-Al Harthi,
Barry H Gross,
Isaac R Francis,
Susan A Fiscus,
Pablo Tebas,
Ronald J Bosch,
Victor Valcour,
Michael M Lederman
[show abstract]
[hide abstract]
ABSTRACT: We have attempted to identify factors associated with T cell reconstitution in response to highly active antiretroviral therapy.
In a prospective, multicenter cohort study, we compared clinical, immune, and viral responses to an initial antiretroviral regimen in older (>or=45 years old) versus younger (18-30 years old) human immunodeficiency virus type 1-infected subjects. Multivariable linear-regression models identified independent factors associated with changes in T cell counts.
Older subjects had smaller increases in naive T cells but greater T cell receptor-excision circle DNA content after 48 weeks, despite similar virologic responses and comparable reductions in immune activation. Changes in T cell counts were associated with plasma interleukin (IL)-7 levels in subjects with low thymic scores, whereas first-phase T cell increases (perhaps mediated by redistribution to the circulation of tissue-associated lymphocytes) were associated with reductions in immune activation in subjects with high thymic scores. Reductions in immune activation were associated with reductions in spontaneous lymphocyte apoptosis.
Distinct processes may underlie T cell restoration, according to estimated thymic volumes. IL-7-mediated peripheral expansion may drive T cell restoration in persons with low thymic volume, whereas therapy-associated reversal of immune reactivation may drive T cell losses and their restoration in persons with larger thymic volume.
The Journal of Infectious Diseases 11/2005; 192(9):1577-87. · 6.41 Impact Factor
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ABSTRACT: We compared immune restoration in patients who suppressed human immunodeficiency virus type 1 replication after treatment with a protease inhibitor (PI) plus nevirapine or with 3 nucleoside reverse-transcriptase inhibitors (NRTIs) plus nevirapine. Changes in total and memory CD4 and CD8 cells were similar in the groups, as were decreases in immune activation (e.g., CD38 and HLA-DR) and increases in CD28 expression. Increases in naive CD4 and CD8 cells tended to be greater in the NRTI-treated group, with differences in naive CD4 cells significant at weeks 8 and 12 (P<.05) but not at week 48. Lymphocyte apoptosis decreased in both groups, but the week-1 decrease was greater in the PI-treated group (P<.02). Lymphocyte proliferation and skin-test responses were comparable. We find little evidence for differences in the major direct immunologic effect of PI versus NRTI regimens and propose that effects observed elsewhere were indirect, mediated through antiviral activity or adaptation of the virus to selection pressure.
The Journal of Infectious Diseases 12/2003; 188(10):1444-54. · 6.41 Impact Factor
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Robert C Kalayjian,
Alan Landay,
Richard B Pollard,
Dennis D Taub,
Barry H Gross,
Isaac R Francis,
Anne Sevin, Minya Pu,
John Spritzler,
Miriam Chernoff,
Ann Namkung,
Lawrence Fox,
Ana Martinez,
Karen Waterman,
Susan A Fiscus,
Beverly Sha,
Debra Johnson,
Stanley Slater,
Frank Rousseau,
Michael M Lederman
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ABSTRACT: Older age is a strong predictor of accelerated human immunodeficiency virus (HIV) disease progression. We investigated the possible immunologic basis of this interaction by comparing older (>/=45 years) and younger (</=30 years) HIV-infected adults with simultaneously enrolled, aged-matched, healthy volunteers. Cross-sectional comparisons suggested age-associated reductions in naive CD8(+) cells and in the expression of CD28(+) on CD8(+) cells among both HIV-infected subjects and control subjects. Opposite patterns of CD4(+) and CD8(+) cell differences were apparent between these subject groups. HIV infection, but not age, was associated with impairments in delayed-type hypersensitivity responses, lymphoproliferation, and spontaneous apoptosis and with alterations in expression of chemokine receptors CCR5 and CXCR4. Reduced thymic volumes were associated with age and with HIV infection among younger, but not older, subjects. Because of their common association with age and HIV disease, naive CD8(+) cell depletion, diminished CD28 expression on CD8(+) cells, and reduced thymic volumes are possible correlates of the interaction of age with HIV disease.
The Journal of Infectious Diseases 06/2003; 187(12):1924-33. · 6.41 Impact Factor
