Edward R Cachay

University of California, San Diego, San Diego, California, United States

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Publications (28)113.5 Total impact

  • E Cachay, W Agmas, C Mathews
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    ABSTRACT: Objectives The aim of the study was to estimate the cumulative incidence of, and rates of progression to, invasive anal cancer (IAC) according to baseline anal cytology screening category in an unselected HIV clinical care cohort in the antiretroviral era.MethodsA retrospective cohort analysis of HIV-infected patients under care at the University of California at San Diego Owen Clinic was carried out. Patients were eligible for this analysis if they had at least two anal cytohistological results available for longitudinal analysis. Kaplan−Meier analysis was used to estimate the cumulative incidence of IAC over time according to baseline cytology category [less than high-grade intraepithelial lesion (HSIL) versus HSIL]. Cox regression analysis was used to adjust for the following covariates: antiretroviral use, level of HIV viraemia, smoking status and infrared photocoagulation (IRC) ablation therapy.ResultsBetween 2000 and 2012, we followed 2804 HIV-infected patients for a median of 4 years under a clinic protocol requiring baseline anal cytology screening. Incident IAC was diagnosed in 23 patients. Patients with a baseline HSIL anal cytology had an estimated 5-year probability of progression to IAC of 1.7% and an estimated annual progression risk of 1 in 263. None of the examined covariates was significantly associated with IAC incidence when examined in separate unadjusted Cox models.ConclusionsHIV-infected patients with a baseline HSIL anal cytology had a 5-year cumulative incidence of IAC of 1.65%, with an upper 95% confidence bound of 4.5%. This population-based study provides quantitative risk estimates that may be used for counselling patients regarding management options for abnormal cytology results.
    HIV Medicine 10/2014; · 3.16 Impact Factor
  • Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 09/2014;
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    ABSTRACT: Resistance to direct-acting antiviral (DAA) agents against hepatitis C virus (HCV) infection is driven by the selection of mutations at different positions in the NS3 protease, NS5B polymerase and NS5A proteins. With the exception of NS5B nucleos(t)ide inhibitors, most DAAs possess a low genetic barrier to resistance, with significant cross-resistance between compounds belonging to the same family. However, a specific mutation profile is associated with each agent or drug class and varies depending on the genotype/subtype (e.g., genotype 1b showed higher rates of sustained virological response (SVR) and a higher genetic barrier for resistance than genotype 1a). Moreover, some resistance mutations exist as natural polymorphisms in certain genotypes/subtypes at frequencies that require baseline drug resistance testing before recommending certain antivirals. For example, the polymorphism Q80K is frequently found among genotype 1a (19-48%) and is associated with resistance to simeprevir. Similarly, L31M and Y93H, key resistance mutations to NS5A inhibitors, are frequently found (6-12%) among NS5A genotype 1 sequences. In particular, the presence of these polymorphisms may be of relevance in poorly interferon-responsive patients (i.e. null responders and non-CC IL28B) under DAA-based therapies in combination with pegylated interferon-α plus ribavirin. The relevance of pre-existing resistance mutations for responses to interferon-free DAA therapies is unclear for most regimens and requires further study.
    Antiviral research. 06/2014;
  • Edward R Cachay, Wm Christopher Mathews
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    ABSTRACT: There are two commercially available vaccines licensed worldwide for the prevention of cervical cancer and other human papillomavirus-associated cancers such as anal cancer. However, only two countries have implemented healthcare programs that include human papillomavirus vaccination for boys and men. Although most of the human papillomavirus-related cancers in the world are attributable to cervical cancer, in developed countries anal cancer accounts for a larger proportion of human papillomavirus-related cancers. Most cases of anal cancer occur in HIV-infected men who have sex with men. In this review, we discuss the burden of human papillomavirus-related cancers in men, the most plausible immune mechanism associated with the high efficacy of the human papillomavirus vaccine, and address key issues of vaccination for HIV-infected men. Finally, we review cost-effectiveness considerations for the use of the vaccine in boys and recent guidelines for vaccination in boys, with attention to HIV-infected men.
    AIDS reviews 05/2014; 16(2). · 4.08 Impact Factor
  • Edward R Cachay
    Clinical Infectious Diseases 04/2014; · 9.37 Impact Factor
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    ABSTRACT: The aims were to investigate the hepatitis C (HCV) cascade of care among HIV-infected patients and to identify reasons for not referring for and not initiating HCV therapy after completion of HCV treatment staging.
    PLoS ONE 01/2014; 9(7):e102883. · 3.53 Impact Factor
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    ABSTRACT: (1) To model the natural history of anal neoplasia in HIV-infected patients using a 3-state Markov model of anal cancer pathogenesis, adjusting for cytology misclassification; and (2) to estimate the effects of selected time-varying covariates on transition probabilities.
    PLoS ONE 01/2014; 9(8):e104116. · 3.53 Impact Factor
  • Edward R Cachay, Wm C Mathews
    Clinical Infectious Diseases 12/2013; · 9.37 Impact Factor
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    ABSTRACT: To report the rates of grade IV adverse events and hepatitis C (HCV) treatment discontinuation associated with the use of telaprevir, pegylated interferon and ribavirin. Retrospective cohort analysis. The study included patients infected with human immunodeficiency virus (HIV) co-infected with HCV who underwent HCV treatment in a clinic-based setting with telaprevir, pegylated interferon and ribavirin. The United States of America National Institutes of Health Division of AIDS grading system was used to rate severity of adverse events. Of the 24 consecutive patients treated for HCV using telaprevir/pegylated interferon /ribavirin, 50% (12/24) developed serious adverse events and 29% (7/24) discontinued HCV treatment due to adverse events, despite an intensive multidisciplinary monitoring approach. In this HIV clinic-based experience a high rate of grade IV adverse events and treatment discontinuations were observed associated with HCV telaprevir-based treatment. Careful consideration of the risks and benefits of telaprevir-based therapy should be undertaken given prospects for interferon sparing therapy in the near future.
    AIDS (London, England) 07/2013; · 4.91 Impact Factor
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    ABSTRACT: Invasive anal cancer has become an important cause of non AIDS-related cancer among HIV-infected individuals. Human papillomavirus is the main etiological agent. This review explains the pathophysiologic role of human papillomavirus in the development of invasive anal cancer, summarizes recent epidemiological trends of invasive anal cancer, and reviews the evidence to address common clinical questions posed when screening for anal cancer in HIV-infected patients. The effect of highly active antiretroviral therapy on human papillomavirus oncogenesis is still unclear, but given the increased clinical burden of invasive anal cancer among HIV-infected patients, many clinics have implemented screening programs for anal cancer and its precursors. Despite the availability of several modalities for treatment of precursors of anal cancer, evidence that current treatment modalities favorably alter the natural history of human papillomavirus oncogenesis in the anal and perianal regions is still inconclusive. However, there is sufficient evidence to state that the accuracy of anal cancer screening procedures (cytology and high-resolution anoscopy directed biopsy) is comparable to the accuracy of those used in screening for cervical cancer precursors. Studies that systematically assess the efficacy of these anal cancer screening programs in reducing the incidence of and morbidity and mortality from invasive anal cancer among HIV-infected patients are needed.
    AIDS reviews 05/2013; 15(2):122-133. · 4.08 Impact Factor
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    ABSTRACT: BACKGROUND: Access to Hepatitis C (HCV) care is low among HIV-infected individuals, highlighting the need for new models to deliver care for this population. METHODS: Retrospective cohort analysis that compared the number of HIV patients who initiated HCV therapy: hepatology (2005--2008) vs. HIV primary care model (2008--2011). Logistic-regression modeling was used to ascertain factors associated with HCV therapy initiation and achievement of sustained viral response (SVR). RESULTS: Of 196 and 163 patients that were enrolled in the HIV primary care and hepatology models, 48 and 26 were treated for HCV, respectively (p = 0.043). The HIV/HCV-patient referral rate did not differ during the two study periods (0.10 vs. 0.12/patient-yr, p = 0.18). In unadjusted analysis, predictors (p < 0.05) of HCV treatment initiation included referral to the HIV primary care model (OR: 1.7), a CD4+ count >=400/mm3 (OR: 1.8) and alanine aminotranferase level >=63U/L (OR: 1.9). Prior psychiatric medication use correlated negatively with HCV treatment initiation (OR: 0.6, p = 0.045). In adjusted analysis the strongest predictor of HCV treatment initiation was CD4+ count (>=400/mm3, OR: 2.1, p = 0.01). There was no significant difference in either clinic model (primary care vs. hepatology) in the rates of treatment discontinuation due to adverse events (29% vs. 16%), loss to follow-up (8 vs. 8%), or HCV SVR (44 vs. 35%). CONCLUSIONS: Using a HIV primary care model increased the number of HIV patients who initiate HCV therapy with comparable outcomes to a hepatology model.
    AIDS Research and Therapy 03/2013; 10(1):9. · 2.54 Impact Factor
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    Edward R Cachay, Wollelaw Agmas, William C Mathews
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    ABSTRACT: We recently reported, using a receiver operating characteristic area metric, the first meta-analytic comparison of the relative accuracy of cervical and anal cytology in detecting moderate or severe histopathologic lesions by magnification directed punch biopsy. The aim of the present research was to meta-analytically examine cut-point specific operating characteristics (sensitivity, specificity) of cervical and anal cytology in detecting high grade squamous intraepithelial lesion (HSIL) histopathology by colposcope directed punch biopsy. The primary eligibility requirement was availability of tabulated cytology (normal, atypical cells of unclear significance [ASCUS], low grade squamous intraepithelial lesion, HSIL or atypical squamous cells cannot rule out high grade [ASC-H]) and biopsy (<HSIL, ≥ HSIL) counts. Meta-analysis and meta-regression of diagnostic accuracy was performed with examination of study quality criteria and heterogeneity. Thirty-three cervical and 11 anal publications were eligible between 1990 and 2010. Meta-analytically cut-point analysis showed that using a cut-point of ASCUS the sensitivity in both settings is similar while anal cytology is less specific than cervical cytology (specificity [95% confidence interval] 0.33 [0.20-0.49] vs. 0.53[0.40-0.66], p = 0.04) for the detection of HSIL histopathology by colposcope directed punch biopsy. Using a cytology cut-point of HSIL or ASC-H, anal cytology is less sensitive but comparably specific to cervical cytology. However, using a cut-point of ASCUS, differences in accuracy were of borderline significance.
    PLoS ONE 01/2012; 7(7):e38956. · 3.53 Impact Factor
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    ABSTRACT: We aimed to determine the reliability and validity of a hepatitis symptom inventory and to identify predictors of hepatitis C (HCV) treatment initiation in a cohort of HIV-infected patients. Prospective clinic based study that enrolled patients referred for HCV therapy consideration. A hepatitis symptom inventory and the Center for Epidemiologic Studies Depression Scale (CES-D) were administered to HIV/HCV individuals. The symptom inventory was factor analyzed and subscale reliability estimated with Cronbach's alpha. Predictive validity was evaluated using generalized estimating equations (GEE). Predictors of HCV treatment were identified using logistic regression. Between April 2008 to July 2010, 126 HIV/HCV co-infected patients were enrolled in the study. Factor analysis using data from 126 patients yielded a three-factor structure explaining 60% of the variance for the inventory. Factor 1 (neuropsychiatric symptoms) had 14 items, factor 2 (somatic symptoms) had eleven items, and factor 3 (sleep symptoms) had two items, explaining 28%, 22% and 11% of the variance, respectively. The three factor subscales demonstrated high intrinsic consistency reliability. GEE modeling of the 32 patients who initiated HCV therapy showed that patients developed worsening neuropsychiatric and somatic symptoms following HCV therapy with stable sleep symptoms. Bivariate analyses identified the following as predictors of HCV therapy initiation: lower HIV log10 RNA, lower scores for neuropsychiatric, somatic and sleep symptoms, lower CES-D scores and white ethnicity. In stepwise multiple logistic regression analysis, low neuropsychiatric symptom score was the strongest independent predictor of HCV therapy initiation and HIV log10 RNA was inversely associated with a decision to initiate HCV treatment. A 41-item hepatitis-related symptom inventory was found to have a clinically meaningful 3-factor structure with excellent internal consistency reliability and predictive validity. In adjusted analysis, low neuropsychiatric symptom scores and controlled HIV infection were independent predictors of HCV treatment initiation. The usefulness of the HCV symptom inventory in monitoring HCV treatment should be evaluated prospectively.
    AIDS Research and Therapy 08/2011; 8:29. · 2.54 Impact Factor
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    ABSTRACT: AIMS: To describe: 1) our cohort of patients diagnosed with NCPH in a HIV academic clinic in North America, and 2) longitudinal follow-up and outcomes of patients following NCPH diagnosis. STUDY DESIGN: Retrospective case series. PLACE AND DURATION OF STUDY: Owen clinic, University of California, San Diego, United States, between October 1990 and December 2010. METHODOLOGY: We describe a cohort of patients diagnosed with NCPH in a HIV academic clinic with emphasis on their follow-up and outcomes after NCPH diagnosis. RESULTS: During the study period, eight HIV-infected men were diagnosed with NCPH. All patients were exposed to Didanosine (ddI) for a median of 37 months. One patient died soon after NCPH diagnosis due to a condition unrelated to NCPH. The other seven patients have received B-blocker therapy and annual esophago-gastro-duodenectomy screenings with banding of esophageal varices when indicated and remain still alive. Three patients were on ddI at the time of NCPH diagnosis. In one patient ddI was discontinued shortly after NCPH diagnosis. The other two patients continued to use ddI after NCPH diagnosis and developed recurrent upper gastrointestinal bleeding in the subsequent 2 years, requiring revascularization interventions. The four patients that were already off ddI at the time of NCPH diagnosis have been followed for a median of 6 years. These four patients remained minimally symptomatic for up to 16 years of follow-up from NCPH diagnosis. CONCLUSION: When ddI was discontinued before portal hypertension was clinically apparent the progression of NCPH appeared to subside without major clinical complications.
    British journal of medicine and medical research. 01/2011; 1(4):346-355.
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    ABSTRACT: The accuracy of screening for anal cancer precursors relative to screening for cervical cancer precursors has not been systematically examined. The aim of the current meta-analysis was to compare the relative accuracy of anal cytology to cervical cytology in discriminating between histopathologic high grade and lesser grades of dysplasia when the reference standard biopsy is obtained using colposcope magnification. The outcome metric of discrimination was the receiver operating characteristic (ROC) curve area. Random effects meta-analysis of eligible studies was performed with examination of sources of heterogeneity that included QUADAS criteria and selected covariates, in meta-regression models. Thirty three cervical and eleven anal screening studies were found to be eligible. The primary meta-analytic comparison suggested that anal cytologic screening is somewhat less discriminating than cervical cytologic screening (ROC area [95% confidence interval (C.I.)]: 0.834 [0.809-0.859] vs. 0.700 [0.664-0.735] for cervical and anal screening, respectively). This finding was robust when examined in meta-regression models of covariates differentially distributed by screening setting (anal, cervical). Anal cytologic screening is somewhat less discriminating than cervical cytologic screening. Heterogeneity of estimates within each screening setting suggests that other factors influence estimates of screening accuracy. Among these are sampling and interpretation errors involving both cytology and biopsy as well as operator skill and experience.
    PLoS ONE 01/2011; 6(9):e24946. · 3.53 Impact Factor
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    ABSTRACT: The study aim is to estimate sensitivity and specificity of anal cytology for histologic HSIL in analyses adjusted for the imperfect biopsy reference standard. Retrospective cohort study of an anal dysplasia screening program for HIV infected adults. We estimated the prevalence of histologic HSIL by concurrent cytology category and the associated cytology ROC area. Cytology operating characteristics for HSIL were estimated and adjusted for the imperfect reference standard by 3 methodologies. The study cohort included 261 patients with 3 available measures: (1) referral cytology; (2) HRA cytology; and (3) HRA directed biopsy. The prevalence of biopsy HSIL varied according to the concurrent HRA cytology result: 64.5% for HSIL or ASC-H, 12.6% for LSIL, 10.9% for ASCUS, and 6.3% for no abnormality. The cytology ROC area was 0.78. The observed prevalence of HSIL was 37% (referral cytology), 24% (HRA cytology), and 24% (HRA biopsy). Unadjusted estimates of sensitivity and specificity of cytology were 0.66 and 0.90, respectively. Adjusted estimates varied from 0.47-0.89 (sensitivity) and 0.89-1.0 (specificity). Analysis of a single dataset yields widely different estimates of anal cytology operating characteristics that depend on difficult to verify assumptions regarding the accuracy of the imperfect reference standard.
    PLoS ONE 01/2010; 5(8):e12284. · 3.53 Impact Factor
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    ABSTRACT: This study aimed to evaluate the prevalence and predictors of AIDS-related complicated cryptococcal meningitis. The outcome was complicated cryptococcal meningitis: prolonged (>/= 14 days) altered mental status, persistent (>/= 14 days) focal neurologic findings, cerebrospinal fluid (CSF) shunt placement or death. Predictor variable operating characteristics were estimated using receiver operating characteristic curve (ROC) analysis. Multivariate analysis identified independent predictors of the outcome. From 1990-2009, 82 patients with first episode of cryptococcal meningitis were identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal meningitis (prolonged altered mental status 6, persistent focal neurologic findings 7, CSF surgical shunt placement 8, and death 5). Patients with complicated cryptococcal meningitis had higher frequency of baseline focal neurological findings, head computed tomography (CT) abnormalities, mean CSF opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC area of log2 serum and CSF CRAG titers to predict complicated forms of cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95% CI: 0.67 to 0.89), respectively (chi2, p = 0.95). The ROC areas to predict the outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple logistic regression model, the following were significant predictors of the outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF CRAG titer. During initial clinical evaluation, a focal neurologic exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are associated with the outcome of complicated cryptococcal meningitis following 2 weeks from antifungal therapy initiation.
    AIDS Research and Therapy 01/2010; 7:29. · 2.54 Impact Factor
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    ABSTRACT: Cryptococcomas have been described in AIDS patients in the setting of immune reconstitution inflammatory syndrome. We report the first case of human immunodeficiency virus-related inflammatory cerebral cryptococcoma to be treated with a recombinant human monoclonal tumor necrosis factor antagonist.
    Clinical Infectious Diseases 11/2009; 50(2):e7-10. · 9.37 Impact Factor
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    ABSTRACT: The Centers for Disease Control recommend screening for asymptomatic sexually transmitted infection (STI) among HIV-infected men when there is self-report of unprotected anal-receptive exposure. The study goals were: (1) to estimate the validity and usefulness for screening policies of self-reported unprotected anal-receptive exposure as a risk indicator for asymptomatic anorectal infection with Neisseria gonorrhoeae (GC) and/or Chlamydia trachomatis (CT). (2) to estimate the number of infections that would be missed if anal diagnostic assays were not performed among patients who denied unprotected anorectal exposure in the preceding month. Retrospective analysis in HIV primary care and high resolution anoscopy (HRA) clinics. HIV-infected adult men were screened for self-reported exposure during the previous month at all primary care and HRA appointments. Four sub-cohorts were defined based on microbiology methodology (GC culture and CT direct fluorescent antibody vs. GC/CT nucleic acid amplification test) and clinical setting (primary care vs. HRA). Screening question operating characteristics were estimated using contingency table methods and then pooled across subcohorts. Among 803 patients, the prevalence of anorectal GC/CT varied from 3.5-20.1% in the 4 sub-cohorts. The sensitivity of the screening question for self-reported exposure to predict anorectal STI was higher in the primary care than in the HRA clinic, 86-100% vs. 12-35%, respectively. The negative predictive value of the screening question to predict asymptomatic anorectal STI was > or = 90% in all sub-cohorts. In sensitivity analyses, the probability of being an unidentified case among those denying exposure increased from 0.4-8.1% in the primary care setting, and from 0.9-18.8% in the HRA setting as the prevalence varied from 1-20%. As STI prevalence increases, denial of unprotected anal-receptive exposure leads to an increasingly unacceptable proportion of unidentified asymptomatic anorectal STI if used as a criterion not to obtain microbiologic assays.
    PLoS ONE 01/2009; 4(12):e8504. · 3.53 Impact Factor
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    ABSTRACT: Human immunodeficiency virus type 1 blood plasma viral load is correlated with the sexual transmission of HIV, although transmission from men involves virus from semen instead of blood. We quantified HIV-1 RNA in the blood and semen of men who did or did not transmit HIV to their sex partners. We compared the relationships of HIV-1 transmission risk with blood plasma viral load, seminal plasma viral load, herpes simplex virus 2 serostatus and other factors. A case-control study. Participants were men evaluated for primary HIV infection and their recent male sex partners. They were interviewed, and clinical specimens were collected. Epidemiologic and phylogenetic linkages were determined by history and molecular techniques. Couples were grouped on the basis of transmission after exposure. Fisher's exact test and Wilcoxon tests were used for comparisons between groups. Multivariable logistic regressions were fit to identify independent predictors of transmission. HIV-transmitting partners (n = 15) had a higher median seminal plasma viral load (P < 0.015) and median blood plasma viral load (P < 0.001) than nontransmitting partners (n = 32). Herpes simplex virus 2 serostatus was associated with transmission only when the HIV-infected source partner was herpes simplex virus 2 seropositive and the HIV-exposed partner was not (odds ratio 16, P < 0.03). Adjusting for other factors, HIV transmission was significantly associated with blood plasma viral load (odds ratio 13.4, P < 0.02) but not seminal plasma viral load (odds ratio 0.69, P = not significant). Blood and seminal plasma viral load were both associated with human immunodeficiency virus type 1 transmission, but blood plasma viral load was the stronger predictor in this cohort. Herpes simplex virus 2 coinfection was associated with the risk of transmission but not acquisition of human immunodeficiency virus type 1.
    AIDS (London, England) 08/2008; 22(13):1667-71. · 4.91 Impact Factor