Gay Men’s Use of Condoms With Casual Partners Depends on the Extent of Their Prior Acquaintance

Unprotected anal intercourse with casual partners (UAIC) is the strongest predictor of HIV incidence among gay men. Familiarity between sex partners has been associated with likelihood to engage in UAIC, but the decision to use condoms with partners who are previously acquainted is complex and multifaceted. Using data from the Pleasure and Sexual Health survey 2009, we investigated the association between aspects of familiarity with casual partners and disclosure of HIV serostatus. Compared with occasions when they engaged in protected anal intercourse (PAIC), when men engaged in UAIC they were more likely to report having previously met their partners (PAIC 45.9%; UAIC 54.9%), knowing them very well (PAIC 7.9%; UAIC 19.7%), and having previously had sex with them (PAIC 32.2%; UAIC 44.8%) (McNemar P < 0.001). Men were also more likely to disclose their HIV serostatus to their casual partners on occasions of UAIC, were more confident they knew their partner's HIV serostatus and trusted them more. Overall, UAIC was associated with both the broad concept of 'familiarity' (composed of elements of prior acquaintance and trust) and HIV disclosure. When men engage in UAIC without some prior familiarity, disclosure of HIV serostatus, or confidence and trust in their partners, they are probably at greater risk than on occasions when they engage in UAIC with partners with whom they do have these qualities. However, for some men, their trust in knowing specific details about their partners may not always be well-informed or reliable. These different circumstances are challenging for HIV prevention work.     

DNA Methylation in the Rectal Mucosa Is Associated with Crypt Proliferation and Fecal Short-Chain Fatty Acids

Background

DNA methylation varies throughout the normal colorectal mucosa and DNA methylation in normal appearing mucosa is associated with serrated and adenomatous neoplasia elsewhere within the colorectum.

Aims

The purpose of this study was to measure luminal chemistry, rectal proliferation and mucosal DNA methylation and thus determine whether regional and pathological patterns of DNA methylation could be explained by luminal and epithelial factors.

Methods

Twenty healthy subjects had normal rectal mucosal biopsies and a 24-h fecal collection. Rectal biopsies were analyzed for epithelial proliferation (Ki67 immunohistochemistry) and DNA methylation at 17 different markers, including ??type A?? markers (ESR1, GATA5, HIC1, HPP1, SFRP1), ??type C?? markers (MGMT, MLH1, CDKN2A, MINT1, MINT2, MINT31, IGF2, CACNA1G, NEUROG1, SOCS1, RUNX3), and LINE-1. Fecal analysis included short-chain fatty acids (SCFA), pH and ammonia. Mean ??type A?? and CIMP panel methylation Z-scores were calculated.

Results

Rectal proliferation was significantly correlated with methylation at ESR1 (?? = 0.81, P = 0.003) and GATA5 (?? = 0.78, P = 0.012). LINE-1 methylation was 71.7 vs. 74.1%, in patients with ??low?? and ??high?? fecal total SCFA concentration (defined by the median value), respectively (P = 0.0019). On multivariate linear regression ??type A?? methylation was independently associated with rectal proliferation (P = 0.001). LINE-1 methylation was directly associated with rectal proliferation (P = 0.038) and total fecal SCFA concentration (P = 0.002), and inversely associated with fecal NH₃ concentrations (P = 0.003).

Conclusions

DNA methylation in normal rectal mucosa is associated with crypt proliferation and fecal SCFA concentration. These associations may help to explain regional differences in DNA methylation as well as providing a possible link between the colorectal lumen and carcinogenesis.     

Tubular adenomas with minor villous changes show molecular features characteristic of tubulovillous adenomas

Advanced colorectal polyps are identified based on size ≥10 mm, high-grade dysplasia, and/or villous histology. A diagnosis of tubular adenoma (TA) is recommended if villous change occupies <20% of the lesion, or tubulovillous adenoma (TVA) is recommended if there is 20% to 80% villosity. We hypothesized that even subtle villous changes (1% to 20%) would correlate with advanced molecular features. Two hundred sixty-nine colorectal adenomas were examined for KRAS and BRAF mutation and immunohistochemical staining of β-catenin, O6-Methyl Guanine DNA Methyltransferase (MGMT), and p53. Adenomas were classified as TA1 (0% villosity, n=70), TA2 (1% to 20% villosity, n=81), or TVA (21% to 80% villosity, n=118). Clinical and molecular features were analyzed by univariate χ2 and multivariate logistic regression. There was an incremental increase in KRAS mutation frequency with increasing villous compartment (17.9% TA1, 59.0% TA2, 78.4% TVA; P<0.001). MGMT was more frequently lost in TA2 (37.0%) than in TA1 (8.6%) (P<0.001) but did not differ from TVA (39.8%). p53 overexpression was more common in TA2 (38.3%) than in TA1 (10.0%) (P<0.001) but did not differ from TVA (32.2%). On multivariate analysis, TA2 adenomas were more likely to have a KRAS mutation [odds ratio (OR) 6.6, 95% confidence interval (CI), 3.0-14.2], MGMT loss (OR 6.2, 95% CI, 2.4-16.0), or p53 overexpression (OR 5.6, 95% CI, 2.3-13.7) than TA1. We have identified a subgroup of TAs based on subtle villous changes. These adenomas are more likely to show molecular features that are characteristic of TVAs than TAs. These data support the concept that any villous change may indicate increased malignant potential and may be useful to consider when assigning surveillance guidelines.     

p53 mutation is common in microsatellite stable, BRAF mutant colorectal cancers

The majority of "serrated pathway" colorectal cancers have mutation of the BRAF oncogene and display the CpG island methylator phenotype (CIMP). Half these cancers have microsatellite instability (MSI) and an excellent prognosis. In the absence of MSI (microsatellite stable, MSS), BRAF mutation has been associated with a particularly poor prognosis. "Traditional pathway" cancers are BRAF wild type. Mutation of p53 is common and this correlates with advanced stage. We therefore hypothesized that p53 mutation would be common in MSS/BRAF mutant colorectal cancer. One thousand and eighty-one colorectal cancers were screened for BRAF mutation to identify two BRAF mutant study groups (MSI: n = 77; MSS: n = 69) and a BRAF wild type control group (n = 101). These were screened for p53 mutation by high resolution melt analysis and classified for CIMP and MGMT methylation by quantitative methylation specific PCR. Molecular data were compared to patient age, gender, tumor location and stage. p53 was mutated significantly more frequently in MSS/BRAF mutant (28/69, 40.6%) compared to MSI/BRAF mutant cancers (13/77, 16.9%), but this mutation rate did not differ from MSS/BRAF wild type cancers (47/101, 46.5%)(p < 0.0001). CIMP was less common in MSS/BRAF mutant (26/47, 55.3%) compared to MSI/BRAF mutant cancers (41/54, 75.9%), but was more common than in MSS/BRAF wild type cancers (3/85, 3.5%) (p < 0.0001). MSS/BRAF mutant cancers were more commonly proximal (38/54, 70.3%), but were similar to MSS/BRAF wild type cancers in terms of patient age, gender distribution and stage at presentation. MSS/BRAF mutant cancers share molecular and clinical features of both the serrated and traditional pathways of colorectal tumorigenesis.     

Access to antiretroviral therapy and survival in eastern Europe and central Asia: a case study in Armenia

Introduction

Antiretroviral therapy (ART) substantially improves the health of people living with HIV and contributes to preventing new infections. While HIV incidence is decreasing in most regions, the epidemic in eastern Europe continues to rise, as new infections currently outnumber the rate of ART initiation. In this study, we assess ART use in Armenia and its impact on the number of AIDS diagnoses and mortality.

Methods

National surveillance data were obtained from the National Centre for AIDS Prevention, Armenia. Cox-proportional hazard models were used to determine the effect of demographic and clinical risk factors, including access to ART, on AIDS and mortality.

Results

Among people diagnosed with HIV since 2005, approximately 40% per year were diagnosed with CD4<200 cells per mL. Overall, 232 people (57.1%) with AIDS or a low CD4 count had not received ART by the end of 2010. Mortality was 34.1% among people living with HIV who did not initiate ART, and 0.3% among people who received ART. Among people diagnosed with HIV from 1996 to 2010, age at diagnosis, no use of ART, likely mode of transmission, likely place of transmission, low baseline CD4 count and no STI diagnosis at last contact are significantly associated with death.

Discussion

In Armenia, HIV is frequently diagnosed at a late stage of disease, indicating low testing rates. Of people diagnosed with HIV and in need of ART, a large proportion (approximately 60%) either do not provide consent for treatment, or are who migrants who cannot be located.

Conclusions

Globally, the scale-up of ART has resulted in substantial reductions in mortality among individuals initiating therapy. However, in an era of momentum for treatment as prevention, treatment levels are not at adequate levels for preventing morbidities and mortality in some settings. Particular focus should be placed on key at-risk subgroups.