BACKGROUND: Cervical cancer screening might contribute to the prevention of anal cancer in women. We aimed to investigate if routine cervical cancer screening results-namely high-risk human papillomavirus (HPV) infection and cytohistopathology-predict anal HPV16 infection, anal high-grade squamous intraepithelial lesions (HSIL) and, hence, anal cancer. METHODS: We did a systematic review of MEDLINE, Embase, and the Cochrane library for studies of cervical determinants of anal HPV and HSIL published up to Aug 31, 2018. We centrally reanalysed individual-level data from 13 427 women with paired cervical and anal samples from 36 studies. We compared anal high-risk HPV prevalence by HIV status, cervical high-risk HPV, cervical cytohistopathology, age, and their combinations, using prevalence ratios (PR) and 95% CIs. Among 3255 women with anal cytohistopathology results, PRs were similarly calculated for all anal HSIL and HPV16-positive anal HSIL. FINDINGS: Cervical and anal HPV infections were highly correlated. In HIV-negative women, anal HPV16 prevalence was 41% (447/1097) in cervical HPV16-positive versus 2% (214/8663) in cervical HPV16-negative women (PR 16.5, 95% CI 14.2-19.2, p<0.0001); these values were 46% (125/273) versus 11% (272/2588) in HIV-positive women (4.4, 3.7-5.3, p<0.0001). Anal HPV16 was also associated with cervical cytohistopathology, with a prevalence of 44% [101/228] for cervical cancer in HIV-negative women (PR vs normal cytology 14.1, 11.1-17.9, p<0.0001). Anal HSIL was associated with cervical high-risk HPV, both in HIV-negative women (from 2% [11/527] in cervical high-risk HPV-negative women up to 24% [33/138] in cervical HPV16-positive women; PR 12.9, 95% CI 6.7-24.8, p<0.0001) and HIV-positive women (from 8% [84/1094] to 17% [31/186]; 2.3, 1.6-3.4, p<0.0001). Anal HSIL was also associated with cervical cytohistopathology, both in HIV-negative women (from 1% [5/498] in normal cytology up to 22% [59/273] in cervical HSIL; PR 23.1, 9.4-57.0, p<0.0001) and HIV-positive women (from 7% [105/1421] to 25% [25/101]; 3.6, 2.5-5.3, p<0.0001). Prevalence of HPV16-positive anal HSIL was 23-25% in cervical HPV16-positive women older than 45 years (5/20 in HIV-negative women, 12/52 in HIV-positive women). INTERPRETATION: HPV-based cervical cancer screening programmes might help to stratify anal cancer risk, irrespective of HIV status. For targeted secondary anal cancer prevention in high-risk groups, HIV-negative women with cervical HPV16, especially those older than 45 years, have a similar anal cancer risk profile to that of HIV-positive women. FUNDING: International Agency for Research on Cancer.

OBJECTIVES: Among virally suppressed HIV-infected persons, we examined the relationship between obesity and alterations in key clinical markers of immune activation and inflammation. These markers have also been associated with excess HIV-related cardiovascular disease and mortality. METHODS: We evaluated data from virally suppressed participants in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy, including inflammatory biomarkers (interleukin-6 and highly sensitive C-reactive protein), monocyte biomarkers [soluble CD163 (sCD163), sCD14], and monocyte immunophenotypes. We assessed associations with these immunologic measures and obesity, via logistic regression preadjustment and postadjustment for demographic and clinical factors, homeostatic model assessment of insulin resistance, and leptin levels. RESULTS: Among 452 evaluable participants, median (interquartile range) age was 41 (36-48) years, CD4 cell count was 475 (308-697) cells/mul, and 21% were obese (BMI ≥ 30 kg/m). In univariable models, obesity, smoking, and lower CD4 cell count were associated with higher measures of inflammation and monocyte activation. After adjustment, obesity remained independently associated with elevated levels (highest vs. lower two tertiles) of interleukin-6 [odds ratio (OR) 1.96; P = 0.02], highly sensitive C-reactive protein (OR 2.79; P < 0.001) and sCD163 (OR 1.94; P = 0.02), and elevated frequency of CD14CD16 (OR 1.77; P = 0.03) and CD14dimCD16 (OR 1.97; P = 0.01). Adjusting for homeostatic model assessment of insulin resistance and leptin modestly affected associations for obesity with inflammation and monocyte activation. CONCLUSION: Obesity was prevalent and independently associated with greater monocyte activation and systemic inflammation. Research is needed to determine how adipose tissue excess is functionally related to persistent immunologic abnormalities among HIV-infected persons with viral suppression.

BACKGROUND: Anal cancer rates are higher for HIV-infected than uninfected adults. Limited published data exist characterizing precursor abnormal anal cytology incidence. METHODS: The Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy was a prospective cohort of 700 HIV-infected participants in four U.S. cities. At baseline and annually thereafter, each completed a behavioral questionnaire, and providers collected anorectal swabs for cytologic examination and human papillomavirus (HPV) detection and genotyping. RESULTS: Among 243 participants with negative baseline anal cytology, 37% developed abnormal cytology (incidence rate 13.9/100 person-years [p-y], 95% confidence interval [CI] 11.3 - 16.9) over a median 2.1 years of follow-up. Rates among men having sex with men, women, and men having sex with women, were 17.9 p-y (CI: 13.9 - 22.7), 9.4 p-y (CI: 5.6 - 14.9), 8.9 p-y (CI: 4.8 - 15.6), respectively. In multivariable analysis, number of persistent high-risk HPV (HR) types (adjusted hazards ratio [adjHR] 1.17, CI: 1.01 - 1.36), persistent HR-HPV types except 16 or 18 ([adjHR] 2.46, CI 1.31 - 4.60), and persistent types 16 or 18 (adjHR 3.90, CI: 1.78 - 8.54) remained associated with incident abnormalities. CONCLUSIONS: Abnormal anal cytology incidence was high and more likely to develop among persons with persistent HR-HPV.

BACKGROUND: Persons with human immunodeficiency virus (HIV) infection are at risk for premature cardiovascular disease (CVD). Predictors of atherosclerotic disease progression in contemporary patients have not been well described. METHODS: Using data from a prospective observational cohort of adults infected with HIV (Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy), we assessed common carotid artery intima-media thickness (CIMT) at baseline and year 2 by ultrasound. We examined HIV-associated predictors of CIMT progression after adjusting for age, sex, race/ethnicity, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol level, and baseline CIMT using linear regression. RESULTS: Among 389 participants (median age at baseline, 42 years; male sex, 77%; median CD4+ cell count at baseline, 485 cells/mm(3); 78% receiving antiretroviral therapy), the median 2-year CIMT change was 0.016 mm (interquartile range, -0.003 to 0.033 mm; P < .001). Lesser CIMT progression was associated with a suppressed viral load at baseline (-0.009 mm change; P = .015) and remaining virologically suppressed throughout follow-up (-0.011 mm change; P < .001). After adjusting for additional risk factors and a suppressed viral load during follow-up, nonnucleoside reverse transcriptase inhibitor versus protease inhibitor exposure was associated with lesser CIMT progression (-0.011 mm change; P = .02). CONCLUSIONS: Suppressing HIV replication below clinical thresholds was associated with less progression of atherosclerosis. The proatherogenic mechanisms of HIV replication and the net CVD benefit of different antiretroviral drugs should be a focus of future research.

BACKGROUND: Adherence of 95% or greater to highly active combination antiretroviral therapy is generally considered necessary to achieve optimal virologic suppression in HIV-infected patients. Understanding factors associated with poor adherence is essential to improve patient compliance, maximize virologic suppression, and reduce morbidity and mortality. METHODS: We evaluated baseline data from 528 patients taking antiretrovirals, enrolled from March 2004 to June 2006, in a multicenter, longitudinal, prospective cohort study (the SUN study). Using multiple logistic regression, we examined independent risk factors for non-adherence, defined as reporting having missed one or more antiretroviral doses in the past three days on the baseline questionnaire. RESULTS: Of 528 participants (22% female, 28% black, median age 41 years, and median CD4 cell count 486 cells/mm(3)), 85 (16%) were non-adherent. In the final parsimonious multivariate model, factors independently associated with non-adherence included black race (adjusted odds ratio (aOR): 2.08, 95% confidence interval (CI): 1.20-3.60 vs. white race), being unemployed and looking for work (aOR: 2.03, 95% CI: 1.14-3.61 vs. all other employment categories), having been diagnosed with HIV ≥5 years ago (aOR: 1.95, 95% CI: 1.18-3.24 vs. being HIV-diagnosed <5 years ago), drinking three or more drinks per day (aOR: 1.73, 95% CI: 1.02-2.91 vs. drinking <3 drinks per day), and having not engaged in any aerobic exercise in the last 30 days (aOR: 2.13, 95% CI: 1.25-3.57). CONCLUSION: Although the above factors may not be causally related to non-adherence, they might serve as proxies for identifying HIV-infected patients at greatest risk for non-adherence who may benefit from additional adherence support.