Wm. Christopher Mathews

Incidence of and risk factors for clinically significant methicillin-resistant Staphylococcus aureus infection in a cohort of HIV-infected adults.

Objectives:Outbreaks of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) have been noted in multiple sites in the United States. This studys purpose was to estimate trends in the incidence of and risk factors for clinically significant MRSA (CS-MRSA) infection in a cohort of HIV-infected adults. Design:A retrospective clinic-based cohort (January 1, 2000-December 31, 2003) study. Methods:We ascertained all initial episodes of CS-MRSA and categorized them by primary site. Incidence rates were estimated by half year. Risk factors for CA-MRSA infection were identified using Cox modeling. Results:Of 126 potential events, 94 were CS. Their primary sources were 83% skin or soft tissue, 10% blood, 6% respiratory, and 1.0% other sites. Among these, 60% were CA and 40% were nosocomial. Of antibiotics tested, only cotrimoxazole resistance was associated with nosocomial acquisition. The 3455 patients contributed 7003 person-years at risk. The incidence of CS-MRSA infection increased 6.2-fold from the first to the last half year. In multivariate analysis, independent predictors of CA-MRSA infection included HIV transmission by men who have sex with men or by injection drug use, CD4 count <50 cells/μL, log10 HIV plasma viral load, and absence of cotrimoxazole prophylaxis. Conclusions:The incidence of initial CS-MRSA events increased more than 6-fold in a 4-year period. The associations between CA-MRSA infection and HIV severity indicators merit examination in other cohorts.

National estimates of HIV-related symptom prevalence from the HIV Cost and Services Utilization Study.

OBJECTIVES The objectives of this study were (1) to estimate the prevalence, bothersomeness, and variation of HIV-related symptoms in a nationally representative sample of HIV-infected adults receiving medical care and (2) to evaluate new aggregate measures of symptom frequency and bothersomeness. METHODS Beginning in January 1996, 76% of a multistage national probability sample of 4,042 HIV-infected adults receiving medical care were interviewed. Participants endorsed the presence and degree of bothersomeness of 14 HIV-related symptoms during the preceding 6 months. Sex-standardized symptom number and bothersomeness indices were constructed. After sampling weights were incorporated, symptom distributions were compared according to selected characteristics by analysis of variance and multiple linear regression modeling. RESULTS Prevalence of specific symptoms in the reference population was as follows: fever/night sweats, 51.1%; diarrhea, 51%; nausea/anorexia, 49.8%; dysesthesias, 48.9%; severe headache, 39.3%; weight loss, 37.1%; vaginal symptoms, 35.6% of women; sinus symptoms, 34.8%; eye trouble, 32.4%; cough/dyspnea, 30.4%; thrush, 27.3%; rash, 24.3%; oral pain, 24.1%; and Kaposis sarcoma, 4%. Aggregate measures were reliable (Cronbachs alpha > or =0.75) and demonstrated construct validity when compared with other measures of disease severity. After adjustment for CD4 count, both symptom number and bothersomeness varied significantly (P <0.05) by teaching status of care setting, exposure/risk group, educational achievement, sex, annual income, employment, and insurance category. However, the magnitude of variation was small. Symptoms were greatest in women and injection drug users, as well as in persons with lower educational levels, lower income, and Medicare enrollment or those who were followed up at teaching hospitals. CONCLUSIONS The prevalence and bothersomeness of HIV-related symptoms are substantial and vary by setting of care and patient characteristics.

Measurement characteristics of anal cytology, histopathology, and high-resolution anoscopic visual impression in an anal dysplasia screening program.

Background: The study aims were (1) to estimate agreement between consecutive anal cytologic examinations, between concurrent cytologic examination and histopathology, and between high-resolution anoscopy (HRA) visual impression and histopathology and (2) to estimate the prevalence of severe dysplasia by concurrent cytologic category. Methods: Prospective study of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa-statistics. Results: Between July 2000 and September 2003, 1864 patients underwent 2947 anal cytology tests. Excluding unsatisfactory tests (6%), 642 patients had repeat cytologic evaluation and 154 had concurrent cytology tests and biopsy. Using 4-category cytology grading, kappa-agreement between the first 2 cytologic measurements was 0.36. Comparing concurrent cytology tests and biopsy, kappa-agreement was 0.36. Comparing the most severe HRA visual impression and biopsy, kappa-agreement was 0.32. The prevalence of anal intraepithelial neoplasia 3 at biopsy by concurrent cytology category was 0 (cytology normal), 21% (atypical squamous cells of uncertain significance), 27% (low-grade squamous intraepithelial lesion), and 54% (high-grade squamous intraepithelial lesion). Conclusions: These data suggest that the reproducibility of key screening measures is moderate at best but of similar magnitude to that of other studies of anal and cervical dysplasia screening. As candidate interventions to treat or prevent precursor lesions enter clinical development, standardization and improvement of measurement methods are essential.

Comparative accuracy of anal and cervical cytology in screening for moderate to severe dysplasia by magnification guided punch biopsy: a meta-analysis.

Background 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. Methods and Findings 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). Conclusions 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.

Active methamphetamine use is associated with transmitted drug resistance to non-nucleoside reverse transcriptase inhibitors in individuals with HIV infection of unknown duration.

Background: Frequent methamphetamine use among recently HIV infected individuals is associated with transmitted drug resistance (TDR) to non-nucleoside reverse transcriptase inhibitors (NNRTI); however, the reversion time of TDR to drug susceptible HIV may exceed 3 years. We assessed whether recreational substance use is associated with detectable TDR among individuals newly diagnosed with HIV infection of unknown duration. Design: Cross-sectional analysis. Methods: Subjects were enrolled at the University California, San Diego Early Intervention Program. Demographic, clinical and substance use data were collected using structured interviews. Genotypic resistance testing was performed using GeneSeq™, Monogram Biosciences. We analyzed the association between substance use and TDR using bivariate analyses and the corresponding transmission networks using phylogenetic models. Results: Between April 2004 and July 2006, 115 individuals with genotype data were enrolled. The prevalence of alcohol, marijuana and methamphetamine use were 98%, 71% and 64% respectively. Only active methamphetamine use in the 30 days prior to HIV diagnosis was independently associated with TDR to NNRTI (OR: 6.6; p=0.002). Conclusion: Despite not knowing the duration of their HIV infection, individuals reporting active methamphetamine use in the 30 days prior to HIV diagnosis are at an increased risk of having HIV strains that are resistant to NNRTI.

Latent class profiles of internalizing and externalizing psychosocial health indicators are differentially associated with sexual transmission risk: Findings from the CFAR Network of Integrated Clinical Systems (CNICS) cohort study of HIV-infected men engaged in primary care in the United States

OBJECTIVE To examine whether latent class indicators of negative affect and substance use emerged as distinct psychosocial risk profiles among HIV-infected men, and if these latent classes were associated with high-risk sexual behaviors that may transmit HIV. METHODS Data were from HIV-infected men who reported having anal intercourse in the past 6 months and received routine clinical care at 4 U.S. sites in the Centers for AIDS Research Network of Integrated Clinical Systems cohort (n = 1,210). Latent class membership was estimated using binary indicators for anxiety, depression, alcohol and/or drug use during sex, and polydrug use. Generalized estimating equations modeled whether latent class membership was associated with HIV sexual transmission risk in the past 6 months. RESULTS Three latent classes of psychosocial indicators emerged: (a) internalizing (15.3%; high probability of anxiety and major depression); (b) externalizing (17.8%; high probability of alcohol and/or drug use during sex and polydrug use); (c) low psychosocial distress (67.0%; low probability of all psychosocial factors examined). Internalizing and externalizing latent class membership were associated with HIV sexual transmission risk, compared to low psychosocial class membership; externalizing class membership was also associated with higher sexual transmission risk compared to internalizing class membership. CONCLUSIONS Distinct patterns of psychosocial health characterize this sexually active HIV-infected male patient population and are strongly associated with HIV sexual transmission risk. Public Health intervention efforts targeting HIV sexual risk transmission may benefit from considering symptom clusters that share internalizing or externalizing properties.

Community HIV-1 drug resistance is associated with transmitted drug resistance.

As community viral load (CVL) measurements are associated with the incidence of new HIV‐1 infections in a population, we hypothesized that similarly measured community drug resistance (CDR) could predict the prevalence of transmitted drug resistance (TDR).

Estimation of the effect of neutropenia on rates of clinical bacteraemia in HIV-infected patients

A retrospective cohort study was conducted to quantitate the relationship between neutropenia and rates of clinical bacteraemia among adults with HIV infection receiving medical care at one institution between 1991-5. The primary exposure, absolute neutrophil count (ANC), was summarized as mean ANC within a given week, using a five-level stratification (reference > 1000/microl). ANC stratum-specific rates of bacteraemia were calculated, by organism type. Linear trend tests were performed to assess dose-response relationship between neutropenia and rates of bacteraemia. The cohort included 1645 patients contributing 26,785 patients-weeks and 191 episodes of bacteraemia. The unadjusted effect of neutropenia was most evident for bacteraemia due to E. coli (RR 3.4), Klebsiella pneumoniae (RR 16.7), and P. aeruginosa (RR 10.4). For bacteraemia due to any of these three organisms (47 episodes), with reference ANC > 1000/microl, relative rates were: 751-1000/microl, 1.12; 501-750/microl, 2.11; 251-500/microl, 13.58; 0-250/microl, 21.89.

The impact of HIV-associated lipodystrophy on healthcare utilization and costs

BackgroundHIV disease itself is associated with increased healthcare utilization and healthcare expenditures. HIV-infected persons with lipodystrophy have been shown to have poor self-perceptions of health. We evaluated whether lipodystrophy in the HIV-infected population was associated with increased utilization of healthcare services and increased healthcare costs.ObjectiveTo examine utilization of healthcare services and associated costs with respect to presence of lipodystrophy among HIV-infected patients.MethodsHealthcare utilization and cost of healthcare services were collected from computerized accounting records for participants in a body image study among HIV-infected patients treated at a tertiary care medical center. Lipodystrophy was assessed by physical examination, and effects of lipodystrophy were assessed via body image surveys. Demographic and clinical characteristics were also ascertained. Analysis of healthcare utilization and cost outcomes was performed via between-group analyses. Multivariate modeling was used to determine predictors of healthcare utilization and associated costs.ResultsOf the 181 HIV-infected participants evaluated in the study, 92 (51%) had clinical evidence of HIV-associated lipodystrophy according to physician examination. Total healthcare utilization, as measured by the number of medical center visits over the study period, was notably increased among HIV-infected subjects with lipodystrophy as compared to HIV-infected subjects without lipodystrophy. Similarly, total healthcare expenditures over the study period were

Provider perceptions of the value of same-day, electronic patient-reported measures for use in clinical HIV care

1,718 more for HIV-infected subjects with lipodystrophy than for HIV-infected subjects without lipodystrophy. Multivariate modeling demonstrated strong associations between healthcare utilization and associated costs, and lipodystrophy score as assessed by a clinician. Healthcare utilization and associated costs were not related to body image survey scores among HIV-infected patients with lipodystrophy.ConclusionPatients with HIV-associated lipodystrophy demonstrate an increased utilization of healthcare services with associated increased healthcare costs as compared to HIV-infected patients without lipodystrophy. The economic and healthcare service burdens of HIV-associated lipodystrophy are significant and yet remain inadequately addressed by the medical community.