9The Women's Interagency HIV Study (WIHS) is an ongoing long-term observational study of 3,772 women who are either infected with human immunodeficiency virus (HIV) or considered to be at risk for acquiring HIV. Since 1994, the WIHS (pronounced like "wise") has developed a large database and specimen repository that serve as resources for WIHS investigators as well as for nonaffiliated researchers working on HIVrelated or HIV coinfection issues. The purpose of this report is to update researchers on the progress of the WIHS and to provide information on WIHS resources, the methods by which they were obtained, and background for any new potential researchers interested in conducting collaborative research through shared use of these resources. BACKGROUND

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Introduction Human papillomavirus (HPV) is an important risk factor for oropharyngeal cancer. Individuals with human immunodeficiency virus (HIV) have higher oral HPV prevalence but the risk factors for oral HPV infection are not well understood for either HIV-positive or HIV-negative individuals. Methods This study was nested within the MACS (men) and WIHS (women) cohorts. Exfoliated oral epithelial cells were collected from 379 HIV-positive and 266 at-risk HIV-negative individuals using a rinse and gargle with Scope™ mouthwash. Samples were tested for 36 types of HPV DNA using PGMY09/11 consensus primers and reverse line blot hybridization. Risk factors for oral HPV infection were explored using logistic regression with generalized estimating equations (GEE) in this cross-sectional analysis. Results Prevalent oral HPV infection was common (34%), including HPV16 infection in 5.7% of participants. HIV-positive individuals had increased odds of prevalent oral HPV infection compared to HIV-negative individuals (aOR=2.1, 95%CI=1.6–2.8). Risk factors for prevalent oral HPV differed in HIV-positive and HIV-negative participants. Among HIV-negative individuals, higher number of recent oral sex or rimming partners were strong risk factors for prevalent oral HPV infection (each p-trend<0.01). In contrast, among HIV-positive individuals lower CD4 T-cell count (p-trend<0.001) and higher number of lifetime sexual partners (p-trend=0.03) were strong risk factors. Conclusions Oral HPV prevalence was elevated in HIV-positive individuals after controlling for differences in cigarette smoking and sexual behavior, supporting the possibility that HIV may affect the natural history of oral HPV. Impact Immunosuppression may contribute to increased persistence or progression of oral HPV infection.

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Human papillomavirus (HPV) causes the majority of oropharyngeal cancers in the United States, yet the risk factors for and natural history of oral HPV infection are largely unknown. In 2010-2011, a US-based longitudinal cohort study of 761 human immunodeficiency virus (HIV)-infected and 469 at-risk HIV-uninfected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study was initiated. Semiannually collected oral rinses were evaluated for 37 HPV genotypes using the Roche LINEAR ARRAY HPV Genotyping Test (Roche Molecular Systems, Pleasanton, California), and factors associated with oral HPV incidence and clearance were explored using adjusted Wei-Lin-Weissfeld modeling. Through 2013, the 2-year cumulative incidence of any type of oral HPV infection was 34% in HIV-infected persons and 19% in HIV-uninfected persons. However, many of these infections cleared. Seven percent of incident infections and 35% of prevalent infections persisted for at least 2 years. After adjustment for other risk factors, HIV infection (adjusted hazard ratio = 2.3, 95% confidence interval: 1.7, 3.2), reduced current CD4 cell count, and increased numbers of oral sex and "rimming" partners increased the risk of incident oral HPV infection, whereas male sex, older age, and current smoking increased the risk of oral HPV persistence (each P < 0.05). This helps explain the consistent associations observed between these factors and prevalent oral HPV infection in previous cross-sectional studies.

Objective Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH.MethodsFree glycogen in lavage samples was quantified. Pyrosequencing of the 16S rRNA gene was used to identify microbiota from 21 African American women collected over 8–11 years.ResultsFree glycogen levels varied greatly between women and even in the same woman. Samples with the highest free glycogen had a corresponding median genital pH that was significantly lower (pH 4.4) than those with low glycogen (pH 5.8; p<0.001). The fraction of the microbiota consisting of Lactobacillus was highest in samples with high glycogen versus those with low glycogen (median = 0.97 vs. 0.05, p<0.001). In multivariable analysis, having 1 vs. 0 male sexual partner in the past 6 months was negatively associated, while BMI ≥30 was positively associated with glycogen. High concentrations of glycogen corresponded to higher levels of L. crispatus and L. jensenii, but not L. iners.ConclusionThese findings show that free glycogen in genital fluid is associated with a genital microbiota dominated by Lactobacillus, suggesting glycogen is important for maintaining genital health. Treatments aimed at increasing genital free glycogen might impact Lactobacillus colonization.

Human papillomavirus (HPV) infection is etiologically associated with a subset of oral cancers, and yet, the natural history of oral HPV infection remains unexplored. The feasibility of studying oral HPV natural history was evaluated by collecting oral rinse samples on 2 occasions at a 6-month interval from 136 HIV-positive and 63 HIV-negative participants. Cervical vaginal lavage samples were concurrently collected for comparison. HPV genomic DNA was detected in oral and cervical samples by consensus primer PCR and type-specified for 37 HPV types. The sixmonth cumulative prevalence of oral HPV infection was significantly less than for cervical infection (p < 0.0001). HIV-positive women were more likely than HIV-negative women to have an oral (33 vs. 15%, p 5 0.016) or cervical (78 vs. 51%, p < 0.001) infection detected. Oral HPV infections detected at baseline were as likely as cervical infections to persist to 6 months among HIVnegative (60% vs. 51%, p 5 0.70) and HIV-positive (55% vs. 63%, p 5 0.27) women. Factors that independently elevated odds for oral HPV persistence differed from cervical infection and included current smoking (OR 5 8, 95% CI 5 1.3-53), age above 44 years (OR 5 20, 95% CI 5 4.1-83), CD4 < 500 (OR 5 6, 95% CI 5 1.1-26), use of HAART therapy (OR 5 12, 95% CI 5 1.0-156), and time on HAART therapy (trend p 5 0.04). The rate of oral HPV infections newly detected at follow-up was significantly lower than cervical infection among HIV-positive (p < 0.001) and HIV-negative women (p < 0.001). Our study not only demonstrates that it is feasible to study the natural history of oral HPV infection with oral rinse sampling, but also indicates that oral and cervical HPV natural history may differ. ' 2007 Wiley-Liss, Inc.Key words: oral; HPV; natural history; comparison; cervical; human papillomavirus; infectionThe majority of oral cancers are attributable to alcohol and tobacco use, however a subset are etiologically associated with human papillomavirus (HPV) infection.1 Case-control studies have shown that oral HPV infection elevates risk of oral cancer, 2,3 and therefore is likely a prerequisite for cancer development. Although natural history studies of oral infection are yet to be performed, seropositivity to HPV16 increases risk for incident oral cancer, supporting a temporal association between infection and cancer risk. While the natural history of cervical HPV infection is well studied, it is unclear whether it is appropriate to extrapolate data from the cervical literature to oral HPV infection. Unfortunately, 2 studies with consecutive measures of oral HPV infection provide limited insight into its natural history. One study evaluated persistence of oral HPV infection at baseline and a subsequent two and a half year time-point among only 4 subjects. 5 In a study of husband-wife pairs, only overall HPV infection status was considered.6 Because analysis of type-specific HPV infection was not performed, meaningful estimates of incidence and clearance could not be obtained. Our study was designed ...

PI use was associated with a threefold increase in the risk of reporting incident DM. Routine screening for diabetes, particularly among older and heavier patients using PI therapy, is advisable.