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Background: Sexual behavior may influence the composition of the male urethral microbiota, but this hypothesis has not been tested in longitudinal studies of men who have sex with men (MSM)., Methods: From December 2014 to July 2018, we enrolled MSM with nongonococcal urethritis (NGU) attending a sexual health clinic. Men attended 5 in-clinic visits at 3-week intervals, collected weekly urine specimens at home, and reported daily antibiotics and sexual activity on weekly diaries. We applied broad-range 16S rRNA gene sequencing to urine. We used generalized estimating equations to estimate the association between urethral sexual exposures in the prior 7 days (insertive oral sex [IOS] only, condomless insertive anal intercourse [CIAI] only, IOS with CIAI [IOS + CIAI], or none) and Shannon index, number of species (observed, oral indicator, and rectal indicator), and specific taxa, adjusting for recent antibiotics, age, race/ethnicity, HIV, and preexposure prophylaxis., Results: Ninety-six of 108 MSM with NGU attended ≥1 follow-up visit. They contributed 1140 person-weeks of behavioral data and 1006 urine specimens. Compared with those with no urethral sexual exposures, those with IOS only had higher Shannon index ( P = 0.03 ) but similar number of species and presence of specific taxa considered, adjusting for confounders; the exception was an association with Haemophilus parainfluenzae . CIAI only was not associated with measured aspects of the urethral microbiota. IOS + CIAI was only associated with presence of H. parainfluenzae and Haemophilus ., Conclusions: Among MSM after NGU, IOS and CIAI did not seem to have a substantial influence on measured aspects of the composition of the urethral microbiota., Competing Interests: Conflict of Interest of Sources of Funding: This work was supported by the National Institutes of Health (grant number U19 AI113173). L.C.C. was supported by the National Institutes of Health (grant number TL1 TR002318 trainee support). K.A.T. was supported by the University of Washington/Fred Hutch Center for AIDS Research, a program funded by the National Institutes of Health (grant number P30 AI027757). Study data were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at the University of Washington Institute of Translational Health Sciences and supported by the National Institutes of Health (grant number UL1 TR002319). C.M.K. has received donations of test kits and reagents from Hologic, Inc. M.R.G. has conducted studies unrelated to this work supported by grants from Hologic, Inc. L.E.M. has received research support and honoraria from Hologic, Inc., and Nabriva Therapeutics. All other authors declare that they have no conflict of interest., (Copyright © 2024 American Sexually Transmitted Diseases Association. All rights reserved.)

Background: Nongonococcal urethritis (NGU) is a common syndrome with no known etiology in ≤50% of cases. We estimated associations between urethral bacteria and NGU in men who have sex with men (MSM) and men who have sex with women (MSW)., Methods: Urine was collected from NGU cases (129 MSM, 121 MSW) and controls (70 MSM, 114 MSW) attending a Seattle STD clinic. Cases had ≥5 polymorphonuclear leukocytes on Gram stain plus symptoms or discharge; controls had <5 PMNs, no symptoms, no discharge. NGU was considered idiopathic when Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, adenovirus, and herpes simplex virus were absent. The urethral microbiota was characterized using 16S rRNA gene sequencing. Compositional lasso analysis was conducted to identify associations between bacterial taxa and NGU and to select bacteria for targeted qPCR., Results: Among NGU cases, 45.2% were idiopathic. Based on compositional lasso analysis, we selected Haemophilus influenzae (HI) and Mycoplasma penetrans (MP) for targeted qPCR. Compared with 182 men without NGU, the 249 men with NGU were more likely to have HI (14% vs 2%) and MP (21% vs 1%) (both P ≤ .001). In stratified analyses, detection of HI was associated with NGU among MSM (12% vs 3%, P = .036) and MSW (17% vs 1%, P < .001), but MP was associated with NGU only among MSM (13% vs 1%, P = .004). Associations were stronger in men with idiopathic NGU., Conclusions: HI and MP are potential causes of male urethritis. MP was more often detected among MSM than MSW with urethritis., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: To examine whether radiologists' mammogram reading performance varies according to how long they have been awake ("hours awake") and the number of hours they slept ("hours slept") the night before a reading session., Methods: Retrospective data were retrieved from the BreastScreen Reader Assessment Strategy database. Malignancy-enriched mammographic readings were performed by 133 radiologists. Information on their hours awake and hours slept was collected. Analysis of covariance was performed to determine whether these two variables influenced radiologists' sensitivity, specificity, lesion sensitivity, receiver operating characteristic (ROC) curve, and jackknife alternative free-response ROC. Radiologists were divided into a more experienced and a less experienced groups (based on reading ≥2,000 and <2,000 mammogram readings per year, respectively)., Results: The hours awake significantly influenced less experienced radiologists' lesion sensitivity (F 6,63  = 2.51; P = .03). Those awake for <2 hours had significantly lower lesion sensitivity than those awake for 8 to 10 hours (P = .01), and those awake for 4 to 6 hours had significantly lower lesion sensitivity than those awake for 8 to 10 hours (P = .002) and 10 to 12 hours (P = .02). The hours slept also influenced the ROC values of less experienced radiologists (F 1,68  = 4.96; P = .02). Radiologists with up to 6 hours of sleep had a significantly lower value (0.72) than those who had slept more than 6 hours (0.77). No statistically significant findings were noted for more experienced radiologists., Conclusion: Inexperienced radiologists' performance may be influenced by the hours awake and hours slept before reading sessions., (Copyright © 2020 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the effect that a test set from 1 region of the world has on the performance of expert breast radiologists from that region and from a distant region., Methods: Forty-seven Australian and 15 Singaporean breast radiologists interpreted the same test set (ie, 60 mammograms of Australian women consisting of 40 typical and 20 atypical cases) in their respective locations. The radiologists assigned each case a confidence score of 1 to 5, where 1 was typical, 2 was benign, and 3 to 5 indicated identifiable cancer. Localization-response operating characteristic area under the curve (AUC), receiver operating characteristic AUC, location sensitivity, case sensitivity, and specificity were calculated for each radiologist and compared between Australian and Singaporean readers using nonparametric 2-tailed Mann-Whitney U tests., Results: Australian readers performed better than did their Singaporean counterparts with respect to localization-response operating characteristic AUC (.738 vs .642, P = .0395) and location sensitivity (.775 vs .660, P = .0185)., Discussion: Technological advancement has made possible telereporting, in which radiologists report on mammograms originating from other countries. However, those readers' levels of performance might be affected by interpreting images from populations that are different from those with which they are familiar., Conclusion: Radiologist performance differed between the groups when localization of lesions was taken into account. This difference might be because of the Australians' reading mammograms from populations with which they were familiar, in contrast to the Singaporeans., (© 2021 American Society of Radiologic Technologists.)

Objectives: This study aims to explore the reading performances of radiologists in detecting cancers on mammograms using Tabar Breast Imaging Reporting and Data System (BIRADS) classification and identify factors related to breast imaging reporting scores., Methods: 117 readings of five different mammogram test sets with each set containing 20 cancer and 40 normal cases were performed by Australian radiologists. Each radiologist evaluated the mammograms using the BIRADS lexicon with category 1 - negative, category 2 - benign findings, category 3 - equivocal findings (Recall), category 4 - suspicious findings (Recall), and category 5 - highly suggestive of malignant findings (Recall). Performance metrics (true positive, false positive, true negative, and false negative) were calculated for each radiologist and the distribution of reporting categories was analyzed in reader-based and case-based groups. The association of reader characteristics and case features among categories was examined using Mann-Whitney U and Kruskal-Wallis tests., Results: 38% of cancer-containing mammograms were reported with category 3 which decreased to 32.3% with category 4 and 16.2% with category 5 while 16.6 and 10.3% of cancer cases were marked with categories 1 and 2. Female readers had less false-negative rates when using categories 1 and 2 for cancer cases than male readers ( p < 0.01). A similar pattern as gender category was also found in Breast Screen readers and readers completed breast reading fellowships compared with non-Breast Screen and non-fellowship readers ( p < 0.05). Radiologists with low number of cases read per week were more likely to record the cancer cases with category 4 while the ones with high number of cases were with category 3 ( p < 0.01). Discrete mass and asymmetric density were the two types of abnormalities reported mostly as equivocal findings with category 3 (47-50%; p = 0.005) while spiculated mass or stellate lesions were mostly selected as highly suggestive of malignancy with category 5 (26%, p = 0.001)., Conclusions: Most radiologists used category 3 when reporting cancer mammograms. Gender, working for BreastScreen, fellowship completion, and number of cases read per week were factors associated with scoring selection. Radiologists reported higher Tabar BIRADS category for specific types of abnormalities on mammograms than others., Advances in Knowledge: The study identified factors associated with the decision of radiologists in assigning a BIRADS Tabar score for mammograms with abnormality. These findings will be useful for individual training programs to improve the confidence of radiologists in recognizing abnormal lesions on screening mammograms.

Aim: To examine the impact of the time of day on radiologists' mammography reading performance., Materials and Methods: Retrospective mammographic reading assessment data were collected from the BreastScreen Reader Assessment Strategy database and included timestamps of the readings and reader-specific demographic data of 197 radiologists. The radiologists performed the readings in a workshop setting with test case sets enriched with malignancies (one-third of cases were malignant). The collected data were evaluated with an analysis of covariance to determine whether time of day influenced radiologists' specificity, lesion sensitivity or the jackknife alternative free-response receiver operating characteristic (JAFROC)., Results: After adjusting for radiologist experience and fellowship, specificity varied significantly by time of day (p=0.027), but there was no evidence of any significant impact on lesion sensitivity (p=0.441) or JAFROC (p=0.120). The collected data demonstrated that specificity during the late morning (10.00-12.00) was 71.7%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively. Specificity during the late afternoon (16.00-18.00) was 73.95%; this was significantly lower than in the early morning (08.00-10.00) and mid-afternoon (14.00-16.00), which were 82.74% (p=0.003) and 81.39% (p=0.031), respectively., Conclusion: The results indicated that the time of day may influence radiologists' performance, specifically their ability to identify normal images correctly., (Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Birth weight (BW) is an important indicator for newborn health. Both high and low BW is associated with increased risks for adult metabolic diseases. AMPK (AMP-activated protein kinase), mTOR (mechanistic target of rapamycin), and insulin/IGF1 (insulin-like growth factor 1) pathways may function as placental sensors of maternal hormonal and nutritional status. However, the physiological role of these pathways in placenta has not been completely elucidated. To evaluate expression and activation of AMPK, mTOR, and insulin/IGF1 pathways and its association with placental weight (PW), BW, and maternal hormonal and metabolic status, we performed a cross-sectional study in placentas from non-obese mothers with SGA (n = 17), AGA (n = 19) and LGA (n = 10) newborns. We analyzed placental expression of total and phosphorylated key proteins from the AMPK, mTOR and insulin/IGF1 pathways. Maternal and cord blood hormones were determined by ELISA. AMPK and LKB1 activation correlated negatively with PW and BW, cord leptin, and pregestational BMI. Placental SIRT1 inversely correlated with BW, cord leptin, neonatal HOMA-IR, and maternal IGF1. PGC1α correlated negatively with PW and BW. Phosphorylated mTOR positively correlated with maternal glucose, PW and BW. IGF1R was lower in SGA. No changes in p-IGF1R, INSRb, total AKT or p-AKT were found, and pPDK1 was lower in SGA and LGA. These results suggest that placental AMPK, insulin/IGF1, and mTOR pathways may influence fetal growth, perhaps regulating placental physiology, even in metabolically healthy pregnancies. Our study highlights these nutrient sensing pathways as potential molecular mechanisms modulating placental adaptations and, thus, long-term metabolic health.

Accurate interpretation of radiological images involves a complex visual search that relies on several cognitive processes, including selective attention, working memory, and decision-making. Patient outcomes often depend on the accuracy of image interpretations, and yet research has revealed that conclusions vary significantly from one radiologist to another. A myriad of factors has been shown to contribute to the likelihood of interpretative errors and discrepancies, including the radiologist's level of experience and fatigue, and these factors are well reported elsewhere; however, a potentially important factor that has been given little previous consideration is how radiologists' interpretations might be impacted by the time of day at which the reading takes place, a factor that other disciplines have shown to be a determinant of competency. The available literature shows that while the time of day is known to significantly impact some cognitive functions that likely relate to reading competence, including selective visual attention and visual working memory, little is known about the impact of the time of day on radiology interpretation performance. This review explores the evidence regarding the relationship between time of day and performance, with a particular emphasis on radiological activities., (Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objectives: To compare the mammographic densities and other characteristics of Aboriginal and non-Aboriginal women screened in Australia., Methods: Population screening programme data of Aboriginal (n = 857) and non-Aboriginal women (n = 3236) were used. Mann-Whitney U test compared ages at screening and Chi-square tests compared personal and clinical information. Logistic regression analysis was used for density groupings. OR and 95% CI were calculated for multivariate association for density., Results: Mammographic density was lower amongst Aboriginal women (P < 0.001). For non-Aboriginal women, higher density was associated with younger age (OR 2.4, 95% CI 2.1-2.8), recall to assessment (OR 2.2, 95% CI 1.6-3.0), family history of breast cancer (OR 1.4, 95% CI 1.2-1.6), English-speaking background (OR 1.4, 95% CI 1.2-1.6), and residence in remote areas (OR 1.2, 95% CI 1.1-1.4). For Aboriginal women, density was associated with younger age (OR 2.7, 95% CI 2.0-3.5; P < 0.001), and recall to assessment (OR 2.3, 95% CI 1.4-3.9; P < 0.05)., Conclusions: Significant differences between Aboriginal and non-Aboriginal women were found. There were more significant associations for dense breasts for non-Aboriginal women than for Aboriginal women.

Objective: To compare breast screening attendances of Indigenous and non-Indigenous women., Methods: A total of 4,093 BreastScreen cases were used including 857 self-identified Indigenous women. Chi-squared analysis compared data between Indigenous and non-Indigenous women. Logistic regression was used for groupings based on visits-to-screening frequency. Odds ratios and 95% confidence intervals were calculated for associations with low attendance., Results: Indigenous women were younger and had fewer visits to screening compared with non-Indigenous women. Non-English speaking was mainly associated with fewer visits for Indigenous women only (OR 1.9, 95%CI 1.3-2.9). Living remotely was associated with fewer visits for non-Indigenous women only (OR 1.3, 95%CI 1.1-1.5). Shared predictors were younger age (OR 12.3, 95%CI 8.1-18.8; and OR 11.5, 95%CI 9.6-13.7, respectively) and having no family history of breast cancer (OR 2.1, 95%CI 1.3-3.3; and OR 1.8, 95%CI 1.5-2.1, respectively)., Conclusions: Factors associated with fewer visits to screening were similar for both groups of women, except for language which was significant only for Indigenous women, and remoteness which was significant only for non-Indigenous women. Implications for public health: Health communication in Indigenous languages may be key in encouraging participation and retaining Indigenous women in BreastScreen; improving access for remote-living non-Indigenous women should also be addressed., (© 2019 The Authors.)

Background: Breast cancer, is increasing in prevalence amongst South East (SE) Asian women, highlighting the need for high quality, early diagnoses. This study investigated radiologists’ detection efficacy in a developing (DC) and developed (DDC) SE Asian country, as compared to Australian radiologists. Methods: Using a test-set of 60 mammographic cases, 20 containing cancer, JAFROC figures of merit (FOM) and ROC area under the curves (AUC) were calculated as well as location sensitivity, sensitivity and specificity. The test set was examined by 35, 15, and 53 radiologists from DC, a DDC and Australia, respectively. Results: DC radiologists, compared to both groups of counterparts, demonstrated significantly lower JAFROC FOM, ROC AUC and specificity scores. DC radiologists had a significantly lower location sensitivity than Australian radiologists. DC radiologists also demonstrated significantly lower values for age, hours of reading per week, and years of mammography experience when compared with other radiologists. Conclusion: Significant differences in breast cancer detection parameters can be attributed to the experience of DC radiologists. The development of inexpensive, innovative, interactive training programs are discussed. This nonuniform level of breast cancer detection between countries must be addressed to achieve the World Health Organisation goal of health equity., (Creative Commons Attribution License)

The Indigenous people of Australia face significant health gaps compared with the general population, with lower life expectancies, higher rates of death, and chronic illness occurring more often than in non-indigenous Australians. Cancer is the second largest contributor to the burden of disease with breast cancer being the most common invasive cancer diagnosed for females. Despite a lower breast cancer incidence compared with non-indigenous women, fatalities occur at an elevated rate and breast cancers have an earlier age of onset. For indigenous women there are also more advanced and distant tumours at diagnosis, fewer hospitalisations for breast cancer, and lower participation in breast screening. Concomitantly there are demographic, socio-economic and lifestyle factors associated with breast cancer risks that are heavily represented within Indigenous communities. The aim of this two-part narrative review is to examine the available evidence on breast cancer and its risk factors in Australian Indigenous women. Part One presents a summary of the latest incidence, survival and mortality data. Part Two presents the risk factors most strongly associated with breast cancer including age, place of residence, family risk, genetics, reproductive history, tobacco use, alcohol intake, physical activity, participation in screening and breast density. With increasing emphasis on personalized health care, a clear understanding of breast cancer incidence, survival, mortality, and causal agents within the Indigenous population is required if breast cancer prevention and management is to be optimized for Indigenous Australians., (Creative Commons Attribution License)

Background: US guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. To date, testing for integrase strand transfer inhibitor (INSTI) mutations has not been routinely recommended. We aimed to evaluate the prevalence of transmitted INSTI mutations among persons with primary HIV-1 infection in Seattle, WA, USA., Methods: Persons with primary HIV-1 infection have enrolled in an observational cohort at the University of Washington Primary Infection Clinic since 1992. We performed a retrospective analysis of plasma specimens collected prospectively from the 82 antiretroviral-naive subjects who were enrolled from 2007-2013, after FDA-approval of the first INSTI. Resistance testing was performed by consensus sequencing., Results: Specimens for analysis had been obtained a median of 24 (IQR 18-41, range 8-108) days after the estimated date of HIV-1 infection. All subjects were infected with HIV-1 subtype B except for one subject infected with subtype C. Consensus sequencing identified no subjects with major INSTI mutations (T66I, E92Q, G140S, Y143C/H/R, S147G, Q148H/K/R, N155H). Using exact binomial CIs, the upper bound of the 95% CI was 4.4%., Conclusions: Although our sample size was small, this study does not support the need at this time to evaluate integrase mutations as part of routine consensus sequencing among persons newly diagnosed with HIV-1 infection. However, it is likely that the prevalence of transmitted INSTI mutations may increase with the recent commercial introduction of additional INSTIs and presumably greater INSTI use among persons living with HIV-1.

Background: Resumption of sex before complete wound healing after male circumcision may increase risk of postoperative surgical complications, and HIV acquisition and transmission. We aimed to determine the effect of text messaging to deter resumption of sex before 42 days postcircumcision., Methods: We conducted a randomized trial where men older than18 years who owned mobile phones and had just undergone circumcision were randomized to receive a series of text messages (n = 600) or usual care (n = 600). The primary outcome was self-reported resumption of sex before 42 days., Results: Sex before 42 days was reported by 139 of 491 (28.3%) men in the intervention group and 124 of 493 (25.2%) men in the control group [relative risk = 1.13, 95% confidence interval (CI): 0.91 to 1.38, P = 0.3]. Men were more likely to resume early if they were married or had a live-in sexual partner [adjusted relative risk (aRR) 1.57, 95% CI: 1.18 to 2.08, P < 0.01]; in the month before circumcision had 1 (aRR: 1.50, 95% CI: 1.07 to 2.12, P = 0.02) or more than 1 (aRR: 1.81, 95% CI: 1.24 to 2.66, P < 0.01) sexual partner(s); had primary school or lower education (aRR: 1.62, 95% CI: 1.33 to 1.97, P< 0.001); were employed (aRR: 1.35, 95% CI: 1.05 to 1.72, P = 0.02); or were 21-30 years old (aRR: 1.58, 95% CI: 1.01 to 2.47, P = 0.05), 31-40 years old (aRR: 1.91, 95% CI: 1.18 to 3.09, P < 0.01), or older than 40 years (aRR: 1.76, 95% CI: 1.04 to 2.97, P = 0.03) compared with younger than 21 years., Conclusions: Text messaging as used in this trial did not reduce early resumption of sex after circumcision. We identified key risk factors for early resumption that need to be considered in circumcision programs.

Background: HIV-1-related inflammation is associated with increased levels of biomarkers of vascular adhesion and endothelial activation, and may increase production of the inflammatory protein angiopoietin-2 (ANG-2), an adverse prognostic biomarker in severe systemic infection. We hypothesized that antiretroviral therapy (ART) initiation would decrease endothelial activation, reducing plasma levels of ANG-2., Methods: Antiretroviral-naïve Kenyan women with advanced HIV infection were followed prospectively. Endothelial activation biomarkers including soluble intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin, and plasma ANG-2 and angiopoietin-1 (ANG-1) were tested in stored plasma samples from 0, 6, and 12 months after ART initiation. We used Wilcoxon matched-pairs signed rank tests to compare endothelial activation biomarkers across time-points, generalized estimating equations to analyze associations with change in log10-transformed biomarkers after ART initiation, and Cox proportional-hazards regression to analyze associations with mortality., Results: The 102 HIV-1-seropositive women studied had advanced infection (median CD4 count, 124 cells/μL). Soluble ICAM-1 and plasma ANG-2 levels decreased at both time-points after ART initiation, with concomitant increases in the beneficial protein ANG-1. Higher ANG-2 levels after ART initiation were associated with higher plasma HIV-1 RNA, oral contraceptive pill use, pregnancy, severe malnutrition, and tuberculosis. Baseline ANG-2 levels were higher among five women who died after ART initiation than among women who did not (median 2.85 ng/mL [inter-quartile range (IQR) 2.47-5.74 ng/mL] versus median 1.32 ng/mL [IQR 0.35-2.18 ng/mL], p = 0.01). Both soluble ICAM-1 and plasma ANG-2 levels predicted mortality after ART initiation., Conclusions: Biomarkers of endothelial activation decreased after ART initiation in women with advanced HIV-1 infection. Changes in plasma ANG-2 were associated with HIV-1 RNA levels over 12 months of follow-up. Soluble ICAM-1 and plasma ANG-2 levels represent potential biomarkers for adverse outcomes in advanced HIV-1 infection.

Background: Whether unique human immunodeficiency type 1 (HIV) genotypes occur in the genital tract is important for vaccine development and management of drug resistant viruses. Multiple cross-sectional studies suggest HIV is compartmentalized within the female genital tract. We hypothesize that bursts of HIV replication and/or proliferation of infected cells captured in cross-sectional analyses drive compartmentalization but over time genital-specific viral lineages do not form; rather viruses mix between genital tract and blood., Methods: Eight women with ongoing HIV replication were studied during a period of 1.5 to 4.5 years. Multiple viral sequences were derived by single-genome amplification of the HIV C2-V5 region of env from genital secretions and blood plasma. Maximum likelihood phylogenies were evaluated for compartmentalization using 4 statistical tests., Results: In cross-sectional analyses compartmentalization of genital from blood viruses was detected in three of eight women by all tests; this was associated with tissue specific clades containing multiple monotypic sequences. In longitudinal analysis, the tissues-specific clades did not persist to form viral lineages. Rather, across women, HIV lineages were comprised of both genital tract and blood sequences., Conclusions: The observation of genital-specific HIV clades only in cross-sectional analysis and an absence of genital-specific lineages in longitudinal analyses suggest a dynamic interchange of HIV variants between the female genital tract and blood.

Understanding how HIV-1 persists during effective antiretroviral therapy (ART) should inform strategies to cure HIV-1 infection. We hypothesize that proliferation of HIV-1-infected cells contributes to persistence of HIV-1 infection during suppressive ART. This predicts that identical or monotypic HIV-1 DNA sequences will increase over time during ART. We analyzed 1,656 env and pol sequences generated following single-genome amplification from the blood and sputum of six individuals during long-term suppressive ART. The median proportion of monotypic sequences increased from 25.0% prior to ART to 43.2% after a median of 9.8 years of suppressive ART. The proportion of monotypic sequences was estimated to increase 3.3% per year (95% confidence interval, 2.3 to 4.4%; P < 0.001). Drug resistance mutations were not more common in the monotypic sequences, arguing against viral replication during times with lower antiretroviral concentrations. Bioinformatic analysis found equivalent genetic distances of monotypic and nonmonotypic sequences from the predicted founder virus sequence, suggesting that the relative increase in monotypic variants over time is not due to selective survival of cells with viruses from the time of acute infection or from just prior to ART initiation. Furthermore, while the total HIV-1 DNA load decreased during ART, the calculated concentration of monotypic sequences was stable in children, despite growth over nearly a decade of observation, consistent with proliferation of infected CD4(+) T cells and slower decay of monotypic sequences. Our findings suggest that proliferation of cells with proviruses is a likely mechanism of HIV-1 DNA persistence, which should be considered when designing strategies to eradicate HIV-1 infection.

Objectives: Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, integrated management of childhood illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants., Methods: From 1999 to 2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis., Results: Overall IMCI sensitivity, specificity, PPV, and NPV value were 58, 87, 52, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV infections already had occurred. Sensitivity increased with age (P < 0.0001), but remained low throughout infancy (range 1.4-35%). Specificity (range 97-100%) was high at each time point and was not associated with age. Fifty-eight percent of HIV-1-infected infants (50 of 86) were eventually diagnosed by IMCI, and use of IMCI was estimated to delay diagnosis in HIV-infected infants by a median of 5.9 months (P < 0.0001)., Conclusion: IMCI had low sensitivity during the first month of life, when the majority of HIV-1 infections had already occurred and initiation of treatment is most critical. Although sensitivity increased with age, the substantial delay in HIV-1 diagnosis using IMCI limits its utility in early infant HIV-1 diagnosis.

Background: Following male circumcision for HIV prevention, a high proportion of men fail to return for their scheduled seven-day post-operative visit. We evaluated the effect of short message service (SMS) text messages on attendance at this important visit., Methodology: We enrolled 1200 participants >18 years old in a two-arm, parallel, randomized controlled trial at 12 sites in Nyanza province, Kenya. Participants received daily SMS text messages for seven days (n = 600) or usual care (n = 600). The primary outcome was attendance at the scheduled seven-day post-operative visit. The primary analysis was by intention-to-treat., Principal Findings: Of participants receiving SMS, 387/592 (65.4%) returned, compared to 356/596 (59.7%) in the control group (relative risk [RR] = 1.09, 95% confidence interval [CI] 1.00-1.20; p = 0.04). Men who paid more than US$1.25 to travel to clinic were at higher risk for failure to return compared to those who spent ≤ US$1.25 (adjusted relative risk [aRR] 1.35, 95% CI 1.15-1.58; p<0.001). Men with secondary or higher education had a lower risk of failure to return compared to those with primary or less education (aRR 0.87, 95% CI 0.74-1.01; p = 0.07)., Conclusions: Text messaging resulted in a modest improvement in attendance at the 7-day post-operative clinic visit following adult male circumcision. Factors associated with failure to return were mainly structural, and included transportation costs and low educational level., Trial Registration: ClinicalTrials.govNCT01186575.

Background: The role of sexual activity in hepatitis C virus (HCV) transmission remains controversial. Studies to date have not explored the relationship between HCV shedding in cervicovaginal fluids and the presence of menstrual or other blood., Objectives: Since cross-sectional studies may underestimate the prevalence of viral shedding, we performed a 56-day longitudinal study of cervical HCV shedding., Study Design: Women self-collected cervicovaginal swabs for 56 consecutive days, while keeping a diary of menses and genital symptoms. Swabs were tested for HCV RNA and cellular DNA by quantitative PCR, and hemoglobin by spectrophotometry., Results: Sixteen women contributed a total of 701 cervicovaginal swabs (mean collection period 48 days, range 18-56). Detection of HCV RNA was associated with detection of hemoglobin. Premenopausal women were more likely than post-menopausal women to have HCV RNA detected in cervicovaginal fluids. For premenopausal women, detection of HCV RNA was more likely during menstruation (OR=56.4) or when hemoglobin was detected in cervicovaginal fluids, even if menstruation was not occurring (OR=35.4). No woman post-hysterectomy had HCV RNA detected in cervicovaginal fluids on any day, regardless of whether hemoglobin was detected., Conclusions: Our findings are consistent with a low likelihood of sexual transmission of HCV. The results suggest that shedding of HCV RNA in the female genital tract is associated with the presence of blood, and requires the presence of a cervix. Clinicians should consider advising premenopausal women who are concerned about transmitting infection that infectivity may increase during menstruation., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Information regarding the prevalence of mental illness and substance use among HIV-infected patients and the effect of these problems on HIV treatment is needed. We conducted an observational study of patients in the University of Washington (UW) HIV Cohort to determine prevalence rates for mental illness and substance use. Cox regression analyses were used to examine the relationship between mental illness and substance use, pharmacologic treatment for depression/anxiety, and initiation of highly active antiretroviral therapy (HAART) within 9 months of becoming eligible for HAART. Among 1774 patients in the UW HIV cohort during 2004, 63% had a mental illness (including mood, anxiety, psychotic, or personality disorders), 45% had a substance use disorder, and 38% had both. There were 278 patients who met criteria for HAART eligibility. After controlling for other factors, patients with depression and/or anxiety were significantly less likely to initiate HAART compared with patients without a mental illness (hazard ratio [HR] 0.4, p = 0.02). However, patients with depression/anxiety who received antidepressant/antianxiety medications were equally likely to initiate HAART as patients without a mental illness (HR 0.9, p = 0.5). We found that patients with mental illness or substance use disorders receive HAART at lower CD4+ cell counts and higher HIV-1 RNA levels than patients without these disorders. However, HAART initiation among patients who receive treatment for depression/anxiety is associated with no delay. Screening for these disorders in primary care settings and access to appropriate treatment are increasingly important components of providing care to HIV-infected patients.

In El Salvador, Guatemala, Honduras, Nicaragua, and Panama, we recruited 2466 female sex workers (FSWs) by probabilistic or comprehensive sampling and 1418 men who have sex with men (MSM) by convenience sampling to measure sociobehavioral risk and sexually transmitted infections. For MSM, HIV seroprevalence ranged from 7.6% in Nicaragua to 15.3% in El Salvador, and estimated HIV seroincidence per 100 person-years ranged from 2.7 in Panama to 14.4 in Nicaragua; 61% reported using condoms consistently with casual male partners, 29% reported exposure to behavioral interventions, and 22% reported recent sex with male and female partners. For FSWs, HIV seroprevalence ranged from 0.2% in Nicaragua and Panama to 9.6% in Honduras, where estimated HIV seroincidence was also highest (3.2 per 100 person-years); 77% and 72% of FSWs reported using condoms consistently with new and regular clients. Herpes simplex virus (HSV)-2 seroprevalence averaged 85.3% in FSWs and 48.2% in MSM, and syphilis seropositivity averaged 9.6% in FSWs and 8.3% in MSM. Chlamydia trachomatis and Neisseria gonorrhoeae prevalences in FSWs averaged 20.1% and 8.1%, and Trichomonas vaginalis and bacterial vaginosis prevalences averaged 11.0% and 54.8%. An ongoing HIV epidemic involves Central American MSM with potential bridging to women. In FSWs, HSV-2 infection was associated with HIV infection (odds ratio = 11.0, 95% confidence interval: 2.9 to 7.9). For these vulnerable populations, prevention must incorporate acceptable and effective sexual health services, including improved condom access and promotion.