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Dive into the research topics where Stephen Follansbee is active.

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Featured researches published by Stephen Follansbee.


The Journal of Infectious Diseases | 2005

HIV-1 Protease and Reverse-Transcriptase Mutations: Correlations with Antiretroviral Therapy in Subtype B Isolates and Implications for Drug-Resistance Surveillance

Soo-Yon Rhee; W. Jeffrey Fessel; Andrew R. Zolopa; Leo B. Hurley; Tommy F. Liu; Jonathan Taylor; Dong Phuong Nguyen; Sally Slome; Daniel Klein; Michael A. Horberg; Jason Flamm; Stephen Follansbee; Jonathan M. Schapiro; Robert W. Shafer

Background. It is important, for drug-resistance surveillance, to identify human immunodeficiency virus type 1 (HIV-1) strains that have undergone antiretroviral drug selection.Methods. We compared the prevalence of protease and reverse-transcriptase (RT) mutations in HIV-1 sequences from persons with and without previous treatment with protease inhibitors (PIs), nucleoside RT inhibitors (NRTIs), and nonnucleoside RT inhibitors (NNRTIs). Treatment-associated mutations in protease isolates from 5867 persons and RT isolates from 6247 persons were categorized by whether they were polymorphic (prevalence, >0.5%) in untreated individuals and whether they were established drug-resistance mutations. New methods were introduced to minimize misclassification from transmitted resistance, population stratification, sequencing artifacts, and multiple hypothesis testing.Results. Some 36 established and 24 additional nonpolymorphic protease mutations at 34 positions were related to PI treatment, 21 established and 22 additional nonpolymorphic RT mutations at 24 positions with NRTI treatment, and 15 established and 11 additional nonpolymorphic RT mutations at 15 positions with NNRTI treatment. In addition, 11 PI-associated and 1 NRTI-associated established mutations were polymorphic in viruses from untreated persons.Conclusions. Established drug-resistance mutations encompass only a subset of treatment-associated mutations; some of these are polymorphic in untreated persons. In contrast, nonpolymorphic treatment-associated mutations may be more sensitive and specific markers of transmitted HIV-1 drug resistance.


The Journal of Infectious Diseases | 2013

Human Papillomavirus Genotype Attribution and Estimation of Preventable Fraction of Anal Intraepithelial Neoplasia Cases Among HIV-Infected Men Who Have Sex With Men

Vikrant V. Sahasrabuddhe; Philip E. Castle; Stephen Follansbee; Sylvia Borgonovo; Diane Tokugawa; Lauren M. Schwartz; Thomas Lorey; Brandon J. LaMere; Julia C. Gage; Barbara Fetterman; Sean Boyle; Mark Sadorra; Scott Dahai Tang; Teresa M. Darragh; Nicolas Wentzensen

BACKGROUND The prevention of human papillomavirus (HPV)-induced anal cancer in high-risk populations such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) remains an urgent priority, given rising incidence rates despite widespread antiretroviral therapy use. METHODS HPV genotypes and anal disease prevalence, by cytology and histopathologic findings, were evaluated among 363 HIV-infected MSM. We modeled fractions of high-grade anal intraepithelial neoplasia (HGAIN) attributable to individual carcinogenic HPV genotypes and estimated the range of the proportion of HGAIN cases potentially preventable by prophylactic HPV vaccines. RESULTS HPV16 was the most common genotype overall (26.4% of cases) and among HGAIN cases (55%). Prevalence of multiple (≥ 2) carcinogenic HPV genotypes increased from 30.9% in cases of AIN grade <1 to 76.3% in cases of AIN grade 3 (P(trend) < .001). The fractions of HGAIN cases attributable to carcinogenic HPV16/18 targeted by currently licensed bivalent and quadrivalent HPV vaccines ranged from 12% to 61.5%, and the fractions attributable to carcinogenic HPV16/18/31/33/45/52/58 targeted by an investigational nonavalent HPV vaccine ranged from 39% to 89.4%. CONCLUSIONS Our analytical framework allows estimation of HGAIN cases attributable to individual HPV genotypes in the context of multiple concurrent HPV infections, which are very common among HIV-infected MSM. Our results suggest that licensed and investigational HPV prophylactic vaccines have the potential to prevent a substantial proportion of HGAIN cases in this population.


AIDS | 2012

Human papillomavirus genotyping, human papillomavirus mRNA expression, and p16/Ki-67 cytology to detect anal cancer precursors in HIV-infected MSM

Nicolas Wentzensen; Stephen Follansbee; Sylvia Borgonovo; Diane Tokugawa; Lauren M. Schwartz; Thomas Lorey; Vikrant V. Sahasrabuddhe; Brandon J. LaMere; Julia C. Gage; Barbara Fetterman; Teresa M. Darragh; Philip E. Castle

Objective:Anal cancer incidence is high in HIV-infected MSM. Screening for anal intraepithelial lesions and cancers is performed at specialized clinics and relies on high-resolution anoscopy (HRA) and anal cytology. Both approaches have limited reproducibility and sensitivity for detecting anal cancer precursors. We evaluated biomarkers for human papillomavirus (HPV)-related disease in a population of HIV-infected MSM. Methods:A cross-sectional screening study with passive follow-up included 363 MSM followed at a HIV/AIDS clinic. All men had anal cytology samples taken and were evaluated using HRA and anal biopsies. Using a composite endpoint of biopsy results and cytology, we compared the performance of HPV16/18 genotyping, HPVE6/E7 mRNA expression, and p16/Ki-67 cytology to detect high-grade anal intraepithelial neoplasias (AINs). Results:For all biomarkers analyzed, there was a significant trend of increasing percentage of men testing positive with increasing severity of disease (P < 0.001). HPV DNA testing had the highest sensitivity for anal intraepithelial neoplasia grade 2 and anal intraepithelial neoplasia grade 3 (AIN3), followed by p16/Ki-67, HPVE6/E7 mRNA testing, and HPV16/18 genotyping. The highest Youdens index was observed for HPVE6/E7 mRNA testing, followed by HPV16/18 genotyping, p16/Ki-67 cytology, and HPV DNA testing. Increasing the threshold for positivity of p16/Ki-67 to five or more positive cells led to significantly higher specificity, but unchanged sensitivity for detecting AIN3. Conclusion:Molecular features of anal disease categories are similar to those of corresponding cervical lesions. Biomarkers evaluated for cervical cancer screening may be used for primary anal cancer screening or to decide who should require immediate treatment vs. expectant management.


The Journal of Infectious Diseases | 2013

Risk factors for anal HPV infection and anal precancer in HIV-infected men who have sex with men.

Lauren M. Schwartz; Philip E. Castle; Stephen Follansbee; Sylvia Borgonovo; Barbara Fetterman; Diane Tokugawa; Thomas Lorey; Vikrant V. Sahasrabuddhe; Patricia Luhn; Julia C. Gage; Teresa M. Darragh; Nicolas Wentzensen

BACKGROUND Carcinogenic human papillomaviruses (HPVs) cause a large proportion of anal cancers. Human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) are at increased risk of HPV infection and anal cancer compared with HIV-negative men. We evaluated risk factors for HPV infection and anal precancer in a population of HIV-infected MSM. METHODS Our study included 305 MSM at an HIV/AIDS clinic in the Kaiser Permanente Northern California Health Maintenance Organization. Logistic regression was used to estimate associations of risk factors comparing men without anal HPV infection; men with anal HPV infection, but no precancer; and men with anal precancer. RESULTS Low CD4 count (<350 cells/mm(3)) and previous chlamydia infection were associated with an increased risk of carcinogenic HPV infection (odds ratio [OR], 3.65; 95% confidence interval [CI], 1.28-10.40 and OR, 4.24; 95% CI, 1.16-15.51, respectively). History of smoking (OR, 2.71 95% CI, 1.43-5.14), duration, recency, and dose of smoking increased the risk of anal precancer among carcinogenic HPV-positive men but had no association with HPV infection. CONCLUSIONS We found distinct risk factors for anal HPV infection and anal precancer. Risk factors for HPV infection and anal precancer are similar to established risk factors for cervical cancer progression.


Journal of Acquired Immune Deficiency Syndromes | 2009

Virologic outcomes of changing enfuvirtide to raltegravir in HIV-1 patients well controlled on an enfuvirtide based regimen: 24-week results of the CHEER study.

William Towner; Daniel Klein; Hai Linh Kerrigan; Stephen Follansbee; Kalvin Yu; Michael A. Horberg

Objectives:To determine the safety and efficacy of changing enfuvirtide to raltegravir in HIV-1-infected patients with HIV-1 RNA below the level of quantification for at least 6 months on an enfuvirtide-containing antiretroviral regimen. Design:Prospective, nonrandomized, historical control study. Methods:Patients were recruited from 11 Kaiser Permanente HIV clinics in California. Those patients eligible for inclusion (≥18 years old, well controlled on antiretroviral medications) had enfuvirtide changed to raltegravir 400 mg, given twice daily orally; all other background antiretrovirals remained unchanged. The primary end point was percentage of patients with HIV-1 RNA below the limit of quantification after 24 weeks of raltegravir therapy. Analyses were by intention to treat. Results:Fifty-two patients were enrolled in the trial. After 24 weeks of therapy with raltegravir, 49 (94.2%, confidence interval: 1.2% to 15.9%) patients had HIV-1 RNA levels below the limit of quantification. Patients had a median CD4 cell increase of 32 cells per cubic millimeter after 24 weeks of raltegravir therapy. Treatment satisfaction as measured by patient questionnaires improved with the raltegravir-containing regimen. Adverse events were infrequent and generally mild in nature. Conclusions:In treatment-experienced patients on a stable virologically suppressive enfuvirtide-containing regimen, raltegravir can safely be substituted for enfuvirtide.


Cancer Cytopathology | 2013

Interrater agreement of anal cytology

Teresa M. Darragh; Diane Tokugawa; Philip E. Castle; Stephen Follansbee; Sylvia Borgonovo; Brandon J. LaMere; Lauren M. Schwartz; Julia C. Gage; Barbara Fetterman; Thomas Lorey; Nicolas Wentzensen

The majority of anal cancers are caused by persistent infections with carcinogenic human papillomaviruses (HPV). Similar to cervical carcinogenesis, the progression from HPV infection to anal cancer occurs through precancerous lesions that can be treated to prevent invasion. In analogy to cervical cytology, anal cytology has been proposed as a screening tool for anal cancer precursors in high‐risk populations.


AIDS | 2002

High-density lipoprotein cholesterol is low in HIV-infected patients with lipodystrophic fat expansions: implications for pathogenesis of fat redistribution.

W. Jeffrey Fessel; Stephen Follansbee; John Rego

ObjectiveTo demonstrate relationships between plasma high-density lipoprotein (HDL) cholesterol and fat expansions in the fat redistribution syndrome. DesignPatients who had significant buffalo humps or intra-abdominal fat (IAF) expansions were identified and their HDL levels were measured. Control patients were all those undergoing a single trial of antiretroviral treatment. Some patients answered a self-administered questionnaire concerning self-perceived fat expansions, and their responses were related to their HDL levels. In other patients, relationships were studied between IAF measured by cross-section computerized tomography scans and HDL levels. Finally, patients who had IAF > 70 cm2, were administered niacin, 3000 mg/day for ⩾ 6 months, in order to test whether raising HDL induced a decrease in IAF. ResultsTwenty-three patients with buffalo humps had mean HDL of 30.4 mg/dl; 47 HIV-positive controls had mean HDL of 41.9 mg/dl (P = 0.001). In 27 patients, IAF area and HDL were negatively correlated (r, 0.40;P = 0.04). Among these 27, the 17 patients with IAF area > 100 cm2 had mean HDL of 35.3 mg/dl; the 10 patients with IAF area < 100 cm2 had mean HDL of 51 mg/dl (P < 0.05). The 24 patients who indicated in a questionnaire that they had self-perceived IAF expansion had a median HDL of 36.0 mg/dl; the 20 who indicated that they did not have IAF expansion had a median HDL of 44.5mg/dl (P = 0.06). IAF decreased by 26.9% in 13 (81%) of the 16 patients who took niacin for 1 year; and the decrease in IAF was associated with a significant (P = 0.002) increase in HDL.


Journal of Clinical Microbiology | 2014

Analytic and Clinical Performance of cobas HPV Testing in Anal Specimens from HIV-Positive Men Who Have Sex with Men

Nicolas Wentzensen; Stephen Follansbee; Sylvia Borgonovo; Diane Tokugawa; Vikrant V. Sahasrabuddhe; Jie Chen; Thomas Lorey; Julia C. Gage; Barbara Fetterman; Sean Boyle; Mark Sadorra; Scott Dahai Tang; Teresa M. Darragh; Philip E. Castle

ABSTRACT Anal human papillomavirus (HPV) infections are common, and the incidence of anal cancer is high in HIV-infected men who have sex with men (MSM). To evaluate the performance of HPV assays in anal samples, we compared the cobas HPV test (cobas) to the Roche Linear Array HPV genotyping assay (LA) and cytology in HIV-infected MSM. Cytology and cobas and LA HPV testing were conducted for 342 subjects. We calculated agreement between the HPV assays and the clinical performance of HPV testing and HPV genotyping alone and in combination with anal cytology. We observed high agreement between cobas and LA, with cobas more likely than LA to show positive results for HPV16, HPV18, and other carcinogenic types. Specimens testing positive in cobas but not in LA were more likely to be positive for other markers of HPV-related disease compared to those testing negative in both assays, suggesting that at least some of these were true positives for HPV. cobas and LA showed high sensitivities but low specificities for the detection of anal intraepithelial neoplasia grade 2/3 (AIN2/3) in this population (100% sensitivity and 26% specificity for cobas versus 98.4% sensitivity and 28.9% specificity for LA). A combination of anal cytology and HPV genotyping provided the highest accuracy for detecting anal precancer. A higher HPV load was associated with a higher risk of AIN2/3 with HPV16 (P trend < 0.001), HPV18 (P trend = 0.07), and other carcinogenic types (P trend < 0.001). We demonstrate that cobas can be used for HPV detection in anal cytology specimens. Additional tests are necessary to identify men at the highest risk of anal cancer among those infected with high-risk HPV.


Antiviral Research | 2011

The efficacy of an anti-CD4 monoclonal antibody for HIV-1 treatment

W. Jeffrey Fessel; Brooke Anderson; Stephen Follansbee; Mark A. Winters; Stanley Lewis; Steven P. Weinheimer; Christos J. Petropoulos; Robert W. Shafer

The availability of 24 antiretroviral (ARV) drugs within six distinct drug classes has transformed HIV-1 infection (AIDS) into a treatable chronic disease. However, the ability of HIV-1 to develop resistance to multiple classes continues to present challenges to the treatment of many ARV treatment-experienced patients. In this case report, we describe the response to ibalizumab, an investigational CD4-binding monoclonal antibody (mAb), in a patient with advanced immunodeficiency and high-level five-class antiretroviral resistance. After starting an ibalizumab-based salvage regimen, the patient had an approximately 4.0 log(10) reduction in viral load. An inadvertently missed infusion at week 32 led to the rapid loss of virologic response and decreased susceptibility to the remainder of the patients salvage therapy regimen. Following the reinstitution of ibalizumab, phenotypic and genotypic resistance to ibalizumab was detected. Nonetheless, plasma HIV-1 RNA levels stabilized at ∼2.0 log(10) copies/ml below pre-ibalizumab levels. Continued ARV drug development may yield additional clinical and public health benefits. This report illustrates the promise of mAbs for HIV-1 therapy in highly treatment-experienced patients. Therapeutic mAbs may also have a role in pre-exposure prophylaxis in high-risk uninfected populations and may facilitate directly observed therapy (DOT) if two or more synergistic long acting agents become available.


Acta Cytologica | 2011

A comparison of dacron versus Flocked nylon swabs for anal cytology specimen collection.

Julia C. Gage; Arpita Ghosh; Sylvia Borgonovo; Stephen Follansbee; Nicolas Wentzensen; Patti E. Gravitt; Niels Grabe; Bernd Lahrmann; Philip E. Castle

Objectives: We compared the performance of commonly used Dacron versus flocked nylon swabs for anal cytology. Study Design: From 23 HIV-positive men screened at Kaiser Permanente San Francisco (San Francisco, Calif., USA), 2 anal specimens were collected, 1 with each swab in random order, and placed into liquid cytology medium. Specimens were tested for cellularity by quantifying a genomic DNA (erv-3). The number of cells was assessed from prepared slides by automated image analysis. Performance was compared between swabs using 2-sample t tests and standard crossover trial analysis methods accounting for period effect. Results: Flocked swabs collected slightly more erv-3 cells than Dacron for the first sample although not significantly (p = 0.18) and a similar number of erv-3 cells for the second sample (p = 0.85). Flocked swabs collected slightly more cells per slide than the Dacron swabs at both time periods although this was only significant in the second time period (p = 0.42 and 0.03 for first and second periods, respectively). In crossover trial analysis, flocked swabs outperformed Dacron for cell count per slide based on slide imaging (p = 0.03), but Dacron and flocked swabs performed similarly based on erv-3 quantification (p = 0.14). Conclusions: Further studies should determine whether flocked swabs increase the representation of diagnostically important cells compared to Dacron.

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Philip E. Castle

Albert Einstein College of Medicine

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Julia C. Gage

National Institutes of Health

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Lauren M. Schwartz

National Institutes of Health

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