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PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. METHODS: Regional Asian data (2001–2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count

Objectives In multisite human immunodeficiency virus (HIV) observational cohorts, clustering of observations often occurs within sites. Ignoring clustering may lead to “Simpson's paradox” (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox regression models. Study Design and Setting Survival time from combination antiretroviral therapy (cART) initiation was analyzed using four Cox models: (1) no site adjustment; (2) site as a fixed effect; (3) stratification through site; and (4) shared frailty on site. Results A total of 6,454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (1) shows the hazard ratio (HR) for years 2010–2014 was higher than the HR for 2006–2009, compared to 2003–2005 (HR = 0.68 vs. 0.61). Models (2)–(4) consistently implied greater improvement in survival for those who initiated in 2010–2014 than 2006–2009 contrasting findings from model (1). The effects of other significant covariates on survival were similar across four models. Conclusions Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible.

Introduction Pelvic inflammatory disease (PID) and ectopic pregnancy (EP) among women are important sequelae of sexually transmissible infections (STIs). We assessed recent trends in these STI-related morbidities in three Australian states (Victoria, New South Wales, Queensland). Methods Hospital admission and emergency presentation PID and EP rates among women 15–44 years were extracted and analysed by residential postcode for 2009–2014 using population and live birth denominators where relevant. Final data were available in 2017. Zero Inflated Poisson (ZIP) models were used to assess variation in rates by year, age, socio-economic disadvantage and area of residence. A sub-analysis of acute and/or STI-confirmed PID admissions was undertaken. Results Admission and emergency presentation rates respectively per 1 00 000 women in 2014 were: i) 63.3 (95%CI: 60.8–65.9) and 97.0 (95%CI: 93.9–100.2) for PID; and ii) 107.8 (95%CI: 104.5–111.2) and 96.7 (95%CI: 93.6–99.9) for EP. Of all emergency cases, 68% of PID and 22% of EP were managed without admission. PID admission rates did not change by year, but acute/STI-confirmed PID admissions increased by 40% between 2009 and 2014 (Incidence rate ratio [IRR]: 1.4; 95% CI: 1.2–1.7). Emergency PID rates increased by 30% between 2009 and 2014 (IRR: 1.3; 95% CI: 1.2–1.5). PID admission and emergency rates were highest among women 15–24 years. Population based EP rates increased by 10% in emergency between 2009 and 2014 (IRR: 1.1; 95% CI: 1.1–1.2). EP rates per 1000 live births increased by 8% (IRR: 1.08; 95% CI: 1.06–1.11) for admissions and 27% (IRR: 1.27; 95% CI: 1.21–1.33) for emergency between 2009 and 2014. Increasing disadvantage and remoteness of area tended to be associated with higher PID and EP rates. Conclusion These data show that, for the first time in two decades, STI-related sequelae diagnoses at Australian hospitals are increasing.

OBJECTIVE: To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study. DESIGN: Prospective cohort collaboration. METHODS: Poisson regression was used to investigate the association between cumulative exposure to ATV and MI/stroke risk after adjusting for known demographic and clinical confounders, as well as cumulative and recent exposure to specific antiretroviral drugs. Follow-up started on enrolment in the study and ended at the earliest of: a new MI/stroke event, death, 6 months after last clinic visit, or 1 February 2011. RESULTS: The incidence of MI varied from 0.28 [95% confidence interval (CI) 0.26-0.30)]/100 person-years of follow-up (PYFU) in those with no exposure to ATV to 0.20 (0.12-0.32)/100 PYFU in those with more than 3 years exposure. There was no evidence of an association between cumulative exposure to ATV and MI risk, either in univariate [relative rate/year 0.96 (95% CI 0.88-1.04)] or multivariable [0.95 (0.87-1.05)] analyses. The incidence of stroke was 0.17 (0.16-0.19)/100 PYFU in those with no exposure to ATV and 0.17 (0.10-0.27)/100 PYFU in those with more than 3 years exposure. As with the MI endpoint, there was no evidence of an association with ATV exposure in either univariate [1.02 (0.98-1.05)] or multivariable [0.95 (0.87-1.05)] analyses. CONCLUSION: These results argue against a class-wide association between exposure to HIV protease inhibitors and the risk of cardio/cerebrovascular events. © 2013 Wolters Kluwer Health

A growth of the two-dimensional boundary layer over a smooth, horizontal, circular flat plate placed in a free stream with zero pressure gradient along the surface is described and quantified in the range 6.7 × 10 4 d 5 . The boundary layer thickness, velocity profile and transition region at varying transverse distances from the plate centre line are determined. It is shown that the growth of the laminar and turbulent boundary layers closely resembles that for flow over a flat plate with a straight leading edge, but the transitional Reynolds number is lower than for the straight edged flat plate and it decreases as the distance from the plate centre line increases.

Objective: To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-infected persons, and to investigate any association between such risk factors, stage of HIV disease, and use of antiretroviral therapies. Design: Baseline data from 17 852 subjects enrolled in DAD, a prospective multinational cohort study initiated in 1999. Methods: Cross-sectional analyses of CVD risk factors at baseline. The data collected includes data on demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidaemia, body mass index, stage of HIV infection, antiretroviral therapy. Results: Almost 25% of the study population were at an age where there is an,appreciable risk of CVD, with those receiving a protease inhibitor (PI) and/or non-nucleoside reverse transcriptase inhibitor (NNRTI) tending to be older. 1.4% had a previous history of CVD and 51.5% were cigarette smokers. Increased prevalence of elevated total cholesterol (greater than or equal to 6.2 mmol/l) was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 1.79; 95% confidence interval (Cl), 1.45-2.22], PI but no NNRTI (OR, 2.35; 95% Cl, 1.92-2.87), or NNRTI + PI (OR, 5.48; 95% Cl, 4.34-6.91) compared to the prevalence among antiretroviral therapy (ART)-naive subjects. Subjects who have discontinued ART as well as subjects receiving nucleoside reverse transcriptase inhibitors had similar cholesterol levels to treatment-naive subjects. Higher CD4 cell count, lower plasma HIV RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and Pl, and older age were all also associated with elevated total cholesterol level. Conclusion: HIV-infected persons exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the NNRTI and PI drug classes (alone and especially in combination), particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication, was associated with a lipid profile known to increase the risk of coronary heart disease. (C) 2003 Lippincott Williams Wilkins.

Self-collected samples have been shown to be an acceptable and sensitive method for the detection by polymerase chain reaction (PCR) of sexually transmitted infections (STIs) among women. GOAL The goal of the study was to compare self-collected sampling methods to conventional practitioner endocervical sampling for the PCR detection of Chlamydia trachomatis and Neisseria gonorrhoeae to compare two self-collected sampling methods for the detection of T vaginalis by PCR.Women (n = 318) from urban and remote areas of central Australia participated in the study when attending their health clinic for a check-up. They each provided a FVU sample, self-collected vaginal swab specimen, and tampon specimen. This was followed by a clinical examination by a practitioner, with collection of endocervical and high vaginal swabs for testing by conventional microscopy and culture for N gonorrhoeae and T vaginalis, respectively. The FVU, self-collected vaginal swab, tampon, and endocervical swab specimens were tested by Roche Cobas Amplicor for C trachomatis and N gonorrhoeae. The self-collected vaginal swab and tampon specimens were also tested by an in-house PCR method for the detection of T vaginalis.In toto, C trachomatis was detected by PCR in 11.5%, N gonorrhoeae in 11.8%, and T vaginalis in 24.6%. Molecular diagnostics for N gonorrhoeae and T vaginalis were significantly more sensitive than traditional assays with microscopy and culture. For the detection of C trachomatis by PCR, tampons were the most sensitive (100.0%) and urine the least sensitive (72.7%) specimens ( = 0.01). For the detection of by PCR, the self-collected tampon was the most sensitive specimen, followed by the endocervical swab, self-collected swab, and urine specimen, with sensitivities of 97.2%, 92.6%, 71.9%, and 31.2%, respectively. For detection of N gonorrhoeae, statistically significant differences were detected for urine versus tampon (0.0001), endocervical swab (0.001), and self-collected swab ( = 0.01) and for self-collected swab versus tampon ( = 0.01). Subsequent data collection showed that sensitivity of urine PCR for detection of N gonorrhoeae improved with freezing of urine specimens and shorter transport time. Tampons were also more sensitive than self-collected swabs for detection of T vaginalis (sensitivity of 100% versus 87.7%).Self-collected specimens offer women in remote communities an acceptable and sensitive alternative method of testing for STIs. The low sensitivity of N gonorrhoeae PCR of urine specimens may reflect poor transport and storage conditions, which we have shown can be improved by freezing urine specimens and reducing transport delays.

Introduction : There is a lack of data on potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) in HIV-positive individuals. We investigated whether such differences exist in the D:A:D study. Material and Methods : Follow-up was from 01/02/99 until the earliest of death, 6 months after last visit or 01/02/13. Rates of initiation of lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives and receipt of invasive cardiovascular procedures (ICPs; bypass, angioplasty, endarterectomy) were calculated in those without a myocardial infarction (MI) or stroke at baseline, overall and in groups known to be at higher CVD risk: (i) age >50, (ii) total cholesterol >6.2 mmol/l, (iii) triglyceride >2.3 mmol/l, (iv) hypertension, (v) previous MI, (vi) diabetes, or (vii) predicted 10-year CVD risk >10%. Poisson regression was used to assess whether rates of initiation were higher in men than women, after adjustment for these factors. Results : At enrolment, women ( n =13,039; median (interquartile range) 34 (29–40) years) were younger than men ( n =36,664, 39 (33–46) years, p =0.001), and were less likely to be current smokers (29% vs. 39%, p =0.0001), to have diabetes (2% vs. 3%, p =0.0001) or to have hypertension (7% vs. 11%, p =0.0001). Of 49,071 individuals without a MI/stroke at enrolment, 0.6% women vs. 2.1% men experienced a MI while 0.8% vs. 1.3% experienced a stroke. Overall, women received ICPs at a rate of 0.07/100 person-years (PYRS) compared to 0.29/100 PYRS in men. Similarly, the rates of initiation of LLDs (1.28 vs. 2.46), anti-hypertensives (1.11 vs. 1.38) and ACEIs (0.82 vs. 1.37) were all significantly lower in women than men (Table 1). As expected, initiation rates of each intervention were higher in the groups determined to be at moderate/high CVD risk; however, within each high-risk group, initiation rates of most interventions (with the exception of anti-hypertensives) were generally lower in women than men. These gender differences persisted after adjustment for potential confounders (Table 1). Conclusion : Use of most CVD interventions was lower among women than men in the D:A:D study. Our findings suggest that actions should be taken to ensure that both men and women are monitored for CVD and, if eligible, receive appropriate CVD interventions. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Hatleberg CI et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19516 http://www.jiasociety.org/index.php/jias/article/view/19516 | http://dx.doi.org/10.7448/IAS.17.4.19516

BACKGROUND: With the aging of the population living with HIV, the absolute risk of cardiovascular disease (CVD) is increasing. There is a need to further facilitate the identification of persons at elevated risk in routine practice.METHODS AND RESULTS: Prospective information was collected on 32,663 HIV-positive persons from 20 countries in Europe and Australia, who were free of CVD at entry into the Data-collection on Adverse Effects of Anti-HIV Drugs (D:A:D) study. Cox regression models (full and reduced) were developed that predict the risk of a global CVD endpoint. The predictive performance of the D:A:D models were compared with a recent CVD prediction model from the Framingham study, which was assessed recalibrated to the D:A:D dataset. A total of 1010 CVD events occurred during 186,364.5 person-years. The full D:A:D CVD prediction model included age, gender, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, high-density lipoprotein, CD4 lymphocyte count, cumulative exposure to protease- and nucleoside reverse transcriptase-inhibitors, and current use of abacavir. A reduced model omitted antiretroviral therapies. The D:A:D models statistically significantly predicted risk more accurately than the recalibrated Framingham model (Harrell's c-statistic of 0.791, 0.783 and 0.766 for the D:A:D full, D:A:D reduced, and Framingham models respectively; p CONCLUSIONS: An updated, easily recalibrated, global CVD-risk equation tailored to HIV-positive persons was developed using routinely collected CVD risk parameters and incorporating markers on immune function (CD4 lymphocyte count), and exposure to antiretroviral therapies. The estimated CVD risk can be used to quantify risk and to guide preventive care.