Prevalence of hepatitis C virus exposure and infection among Indigenous and tribal populations: a global systematic review and meta-analysis.

OBJECTIVES: The objective of this study was to estimate prevalence of hepatitis C virus (HCV) exposure and infection among Indigenous and tribal populations globally. STUDY DESIGN: Systematic review and meta-analysis. METHODS: We systematically searched bibliographic databases and grey literature (1/01/2000-16/06/2022). Prevalence estimates were synthesised overall, by World Health Organization region and HCV-risk group. For studies with comparator populations, prevalence ratios were estimated and pooled. RESULTS: Ninety-two studies were included. Globally, among general Indigenous and tribal populations, the median prevalence of HCV antibody (HCV Ab) was 1.3% (interquartile range [IQR]: 0.3-3.8%, I2 = 98.5%) and HCV RNA was 0.4% (IQR: 0-1.3%, I2 = 96.1%). The Western Pacific Region had the highest prevalence (HCV Ab: median: 3.0% [IQR: 0.4-11.9%], HCV RNA: median 5.6% [IQR: 2.0-8.8%]). Prevalence was highest in people who injected drugs (HCV Ab: median: 59.5%, IQR: 51.5-67.6%, I2 = 96.6%; and HCV RNA: median: 29.4%, IQR: 21.8-35.2%, I2 = 97.2%). There was no association between HCV Ab prevalence and Indigenous/tribal status for general populations (prevalence ratio = 0.91; 95% CI: 0.56, 1.49) or key risk groups. CONCLUSIONS: Indigenous and tribal peoples from the Western Pacific Region and recognised at-risk sub-populations had higher HCV prevalence. HCV prevalence showed no association with Indigenous/tribal status. However, this review was limited by heterogeneity and poor quality of constituent studies, varying definitions of Indigenous/tribal status, regional data gaps, and limited studies on chronic infection (HCV RNA). Comprehensive quality evidence on HCV epidemiology in Indigenous and tribal peoples is needed to tailor preventive and treatment interventions so these populations are not left behind in elimination efforts.

Population-level impact of beliefs and attitudes on vaccine decision-making in South Africa: results from the COVID-19 Vaccine Survey (2021/2022).

OBJECTIVES: In addition to being home to more than seven million HIV-infected individuals, South Africa also has a high burden of COVID-19 and related comorbidities worldwide. We aimed to identify the most influential "beliefs" and "attitudes" on vaccine decision-making behavior. STUDY DESIGN: This study used panel data from cross-sectional surveys. METHODS: We used the data from Black South Africans who participated in the "COVID-19 Vaccine Surveys" (November 2021 and February/March 2022) in South Africa. Besides standard risk factor analysis, such as multivariable logistic regression models, we also used the modified version of population attributable risk percent and estimated the population-level impacts of beliefs and attitudes on vaccine decision-making behavior using the methodology in multifactorial setting. RESULTS: A total of 1399 people (57% men and 43% women) who participated in both surveys were analyzed. Of these, 336 (24%) reported being vaccinated in survey 2. Overall low perceived risk, concerns around efficacy, and safety were identified as the most influential factors and associated with 52%-72% (<40 years) and 34%-55% (40+ years) of the unvaccinated individuals. CONCLUSION: Our findings highlighted the most influential beliefs and attitudes on vaccine decision-making and their population-level impacts, which are likely to have significant public health implications exclusively for this population.

Measuring school level attributable risk to support school-based HPV vaccination programs.

BACKGROUND: In Australia in 2017, 89% of 15-year-old females and 86% of 15-year-old males had received at least one dose of the HPV vaccine. However, considerable variation in HPV vaccination initiation (dose one) across schools remains. It is important to understand the school-level characteristics most strongly associated with low initiation and their contribution to the overall between-school variation. METHODS: A population-based ecological analysis was conducted using school-level data for 2016 on all adolescent students eligible for HPV vaccination in three Australian jurisdictions. We conducted logistic regression to determine school-level factors associated with lower HPV vaccination initiation (< 75% dose 1 uptake) and estimated the population attributable risk (PAR) and the proportion of schools with the factor (school-level prevalence). RESULTS: The factors most strongly associated with lower initiation, and their prevalence were; small schools (OR = 9.3, 95%CI = 6.1-14.1; 33% of schools), special education schools (OR = 5.6,95%CI = 3.7-8.5; 8% of schools), higher Indigenous enrolments (OR = 2.7,95% CI:1.9-3.7; 31% of schools), lower attendance rates (OR = 2.6,95%CI = 1.7-3.7; 35% of schools), remote location (OR = 2.6,95%CI = 1.6-4.3; 6% of schools,) and lower socioeconomic area (OR = 1.8,95% CI = 1.3-2.5; 33% of schools). The highest PARs were small schools (PAR = 79%, 95%CI:76-82), higher Indigenous enrolments (PAR = 38%, 95%CI: 31-44) and lower attendance rate (PAR = 37%, 95%CI: 29-46). CONCLUSION: This analysis suggests that initiatives to support schools that are smaller, with a higher proportion of Indigenous adolescents and lower attendance rates may contribute most to reducing the variation of HPV vaccination uptake observed at a school-level in these jurisdictions. Estimating population-level coverage at the school-level is useful to guide policy and prioritise resourcing to support school-based vaccination programs.

Differences in school factors associated with adolescent HPV vaccination initiation and completion coverage in three Australian states.

BACKGROUND: Schools are the primary setting for the delivery of adolescent HPV vaccination in Australia. Although this strategy has achieved generally high vaccination coverage, gaps persist for reasons that are mostly unknown. This study sought to identify school-level correlates of low vaccination course initiation and completion in New South Wales, Tasmania, and Western Australia to inform initiatives to increase uptake. METHODS: Initiation was defined as the number of first doses given in a school in 2016 divided by vaccine-eligible student enrolments. Completion was the number of third doses given in a school in 2015-2016 divided by the number of first doses. Low initiation and completion were defined as coverage ≤ 25thpercentile of all reporting schools. We investigated correlations between covariates using Spearman's rank correlation coefficients. Due to multicollinearity, we used univariable logistic regression to investigate associations between school characteristics and low coverage. RESULTS: Median initiation was 84.7% (IQR: 75.0%-90.4%) across 1,286 schools and median completion was 93.8% (IQR: 86.0%-97.3%) across 1,295 schools. There were strong correlations between a number of school characteristics, particularly higher Indigenous student enrolments and lower attendance, increasing remoteness, higher postcode socioeconomic disadvantage, and smaller school size. Characteristics most strongly associated with low initiation in univariate analyses were small school size, location in Tasmania, and schools catering for special educational needs. Low completion was most strongly associated with schools in Tasmania and Western Australia, remote location, small size, high proportion of Indigenous student enrolments, and low attendance rates. CONCLUSION: This study provides indicative evidence that characteristics of schools and school populations are associated with the likelihood of low initiation and completion of the HPV vaccination course. The findings will guide further research and help target initiatives to improve vaccination uptake in schools with profiles associated with lower coverage.

A reliable and easy to transport quality control method for chlamydia and gonorrhoea molecular point of care testing.

Quality control (QC) is an essential component of point-of-care testing programs. In the context of a randomised-controlled trial (TTANGO) using GeneXpert (Xpert) Chlamydia trachomatis and Neisseria gonorrhoeae (CT/NG) point-of-care testing in remote areas of Australia, we aimed to develop and utilise a stable positive control material. Bacterial cultures of CT and NG were resuspended together to provide cycle threshold (Ct) values of approximately 25 cycles for both CT and NG when tested on the Xpert CT/NG assay. These positive control suspensions were dried in aliquots, heat inactivated, and then provided to 12 participating health services as research-only QC samples in kit form. At each service, a QC sample was resuspended and tested each month on the Xpert. QC results, including Xpert Ct values, were analysed from each site over 30 months and we calculated costs per QC sample. Overall, at 12 health services there were 89 QC samples tested (average of 8 tests per site per year). Mean Ct values for the 89 controls samples were 25.25 cycles (SD = 1.15) for CT, 24.04 cycles (SD = 1.400) for one NG target and 23.35 cycles (SD = 1.55) for the other NG target. No significant differences in Ct value for CT or NG controls were observed over a trial period of 30 months. Positive QC samples for research use in a trial of a molecular point-of-care assay were inexpensive to produce and stable when stored at 2-8°C. For routine use, additional requirements such as meeting National Association of Testing Authority (NATA) regulations and Therapeutic Goods Administration (TGA) approval will need to be achieved.

Field Evaluation of Xpert HPV Point-of-Care Test for Detection of Human Papillomavirus Infection by Use of Self-Collected Vaginal and Clinician-Collected Cervical Specimens.

The World Health Organization has recommended that testing for high-risk human papillomavirus (HPV) (hrHPV) infection be incorporated into cervical screening programs in all settings worldwide. In many high-burden, low-income countries, it will not be feasible to achieve high cervical screening coverage using hrHPV assays that require clinician-collected samples. We conducted the first evaluation of self-collected vaginal specimens compared with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. Women aged 30 to 54 years attending two well-woman clinics in Papua New Guinea were invited to participate and provided self-collected vaginal and clinician-collected cervical cytobrush specimens. Both specimen types were tested at the point of care by using the Xpert HPV test. Women were given their cervical test result the same day. Those with a positive hrHPV test and positive examination upon visual inspection of the cervix with acetic acid were offered same-day cervical cryotherapy. A total of 1,005 women were enrolled, with 124 (12.3%; 95% confidence interval [CI], 10.3%, 14.4%) being positive for any hrHPV infection. There was a 99.4% overall percent agreement (OPA) between vaginal and cervical tests for HPV-16 (95% CI, 98.9%, 99.9%), a 98.5% OPA for HPV-18/45 (95% CI, 97.7%, 99.3%), a 94.4% OPA for other hrHPV infections (95% CI, 92.9%, 95.9%), and a 93.4% OPA for all hrHPV types combined (95% CI, 91.8%, 95.0%). Self-collected vaginal specimens had excellent agreement with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. This approach provides for the first time an opportunity to incorporate point-of-care hrHPV testing into clinical cervical screening algorithms in high-burden, low-income settings.

The acceptability and cost of a home-based chlamydia retesting strategy: findings from the REACT randomised controlled trial.

BACKGROUND: Chlamydia retesting three months after treatment is recommended to detect reinfections, but retesting rates are typically low. The REACT (retest after Chlamydia trachomatis) randomised trial demonstrated that home-based retesting using postal home-collection kits and SMS reminders, resulted in substantial improvements in retesting rates in women, heterosexual men and men who have sex with men (MSM), with detection of more repeat positive tests compared with SMS reminder alone. In the context of this trial, the acceptability of the home-based strategy was evaluated and the costs of the two strategies were compared. METHODS: REACT participants (200 women, 200 heterosexual men, 200 MSM) were asked to complete an online survey that included home-testing acceptability and preferred methods of retesting. The demographics, sexual behaviour and acceptability of home collection were compared between those preferring home-testing versus clinic-based retesting or no preference, using a chi-square test. The costs to the health system of the clinic-based and home retesting strategies and the cost per infection for each were also compared. RESULTS: Overall 445/600 (74 %) participants completed the survey; 236/445 from the home-testing arm, and 141 of these (60 %) retested at home. The majority of home arm retesters were comfortable having the kit posted to their home (86 %); found it easy to follow the instructions and collect the specimens (96 %); were confident they had collected the specimens correctly (90 %); and reported no problems (70 %). Most (65 %) preferred home retesting, 21 % had no preference and 14 % preferred clinic retesting. Comparing those with a preference for home testing to those who didn't, there were significant differences in being comfortable having a kit sent to their home (p = 0.045); not having been diagnosed with chlamydia previously (p = 0.030); and living with friends (p = 0.034). The overall cost for the home retest pathway was $154 (AUD), compared to $169 for the clinic-based retesting pathway and the cost per repeat infection detected was $1409 vs $3133. CONCLUSIONS: Among individuals initially diagnosed with chlamydia in a sexual health clinic setting, home-based retesting was shown to be highly acceptable, preferred by most participants, and cost-efficient. However some clients preferred clinic-based testing, often due to confidentiality concerns in their home environment. Both options should be provided to maximise retesting rates. TRIAL REGISTRATION: The trial was registered with the Australia New Zealand Clinical Trials Registry on September 9, 2011: ACTRN12611000968976.

Spatial clustering of "measured" and "unmeasured" risk factors for HIV infections in hyper-endemic communities in KwaZulu-Natal, South Africa: results from geoadditive models.

Sub-Saharan Africa contains more than 60% of all HIV infections worldwide. HIV prevalence was currently estimated to be at least 15% in KwaZulu-Natal and the epidemic is described as hyper-endemic. Knowledge of spatial clustering of risk factors which are linked to new HIV infections is important for prioritizing areas to change the trajectory of the epidemic. Geoadditive models were used to investigate spatial characteristics of the risk factors from two clinical trial units (Umkomaas and Botha's Hill) in the province of KwaZulu-Natal, South Africa. Study population was a cohort of women who screened and enrolled in an HIV prevention biomedical intervention trial. The results suggest high HIV incidence rates (5.8 and 8 per 100 person-year). Considerable spatial variations in behavioural factors within a relatively small geographical region, low level of education, early age at sexual debut, higher number of sexual partners, not being married/cohabitating with a sexual partner and sexual activity in exchange for money, gift and drugs were all determined to be clustered in certain regions; they were accounted for 25% (Umkomaas) and 65% (Botha's Hill) of the excess new HIV infections in two clinical trial units. Results from our study highlighted existence of significant spatial heterogeneity in "measured" and "unmeasured" risk factors in a relatively small region. As the HIV funding has been declining, identifying, targeting and reaching the most-at-risk individuals will likely play a significant role in developing the most efficient and cost-effective prevention programmes and subsequently will change the trajectory of the epidemic.

Uptake of hepatitis C treatment among people who inject drugs attending Needle and Syringe Programs in Australia, 1999-2011.

The majority of new and existing cases of hepatitis C virus (HCV) infection occur among people who inject drugs (PWID). Despite safe and efficacious HCV antiviral therapy, uptake remains low in this population. This study examined trends in HCV treatment uptake among a large national sample of PWID attending Australian Needle and Syringe Programs between 1999 and 2011. Annual cross-sectional sero-surveys conducted among PWID since 1995 involve completion of a self-administered questionnaire and provision of a dried blood spot for HCV antibody testing. Multivariate logistic regression identified variables independently associated with HCV treatment uptake among 9478 participants with both self-reported and serologically confirmed prior HCV infection. Between 1999 and 2011, the proportion currently receiving treatment increased from 1.1% to 2.1% (P < 0.001), while the proportion having ever received treatment increased from 3.4% to 8.6% (P < 0.001). Men were significantly more likely than women to have undertaken HCV treatment (P = 0.002). Among men, independent predictors of HCV treatment uptake were homosexual identity and older age; among women, independent predictors included homosexual identity and an incarceration history. Despite increases in HCV treatment among Australian PWID between 1999 and 2011, uptake remains low. Strategies are required to increase the proportion of PWID assessed and treated for HCV infection to address the increasing burden of disease. Specific approaches that target women may also be warranted. Continued surveillance of HCV treatment uptake among PWID will be important to monitor the roll-out of simple, safe and more effective HCV treatments expected to be available in the future.

Compliance with the current 12-month deferral for male-to-male sex in Australia.

BACKGROUND AND OBJECTIVES: In Australia since 2000, donors are deferred for 12 months since last male-to-male sexual contact. There is no estimate of the prevalence of non-compliance (i.e. failure to disclose a risk during the predonation interview which would lead to deferral) with the policy in Australia; however, published studies elsewhere indicate a range of 0·8-2.3% [corrected]. We investigated the rate of, timing and motivation for non-compliance. MATERIALS AND METHODS: A nationally representative sample of donors who had made a recent donation negative for transfusion-transmissible infection testing was surveyed using an anonymous, online instrument. Non-compliance was considered as a 'yes' response to the current screening question. Non-compliers were requested to define the timing of the last sexual contact relevant to their most recent donation. Univariate and multivariate regression analyses were used to define factors associated with non-compliance. RESULTS: Of 14 476 responses from male donors, 34 (0·23%, 95% CI: 0·16-0·33%) were non-compliant of whom 24 (0·17%, 95% CI: 0·11-0·25%) had contact within 6 months of donation. Factors significantly associated with non-compliance included: multiple sexual partners, history of injecting drug use, perception of a lack of privacy during interview and preference for a computer-based questionnaire. CONCLUSION: Our study confirms high compliance (>99·7%) to the 12-month deferral for male-to-male sex in Australia providing reassuring evidence for the efficacy of the screening question. Issues of 'privacy' and 'discomfort' associated with disclosure suggest the use of validated audio computer-assisted structured interview as a possible option for improving compliance with the donor questionnaire.

Is azithromycin adequate treatment for asymptomatic rectal chlamydia?

Rectal chlamydia is a common sexually transmissible infection (STI) in men who have sex with men (MSM) that is predominantly asymptomatic. The recommended treatment of azithromycin 1 g as a single oral dose has not been subject to randomized trials and so its efficacy is unknown. We conducted a retrospective case-note review of all MSM diagnosed at the Sydney Sexual Health Centre with asymptomatic rectal chlamydia in 2009. We identified 116 MSM who received azithromycin; 85 (73%) attended for the recommended re-test at varying times (median 78 days, range 21-372 days). Of the men who returned, 11 (13%) had a persistently positive result; we reviewed behavioural data to classify these men as probable re-infections (6/11) or possible treatment failures (5/11), suggesting an efficacy of 94%. Until a randomized controlled trial (RCT) is conducted, patients with rectal chlamydia should be encouraged to attend for a re-test at 6-12 weeks.

Short message service reminder intervention doubles sexually transmitted infection/HIV re-testing rates among men who have sex with men.

OBJECTIVES: To evaluate the impact of a short message service (SMS) reminder system on HIV/sexually transmitted infection (STI) re-testing rates among men who have sex with men (MSM). METHODS: The SMS reminder programme started in late 2008 at a large Australian sexual health clinic. SMS reminders were recommended 3-6 monthly for MSM considered high-risk based on self-reported sexual behaviour. The evaluation compared HIV negative MSM who had a HIV/STI test between 1 January and 31 August 2010 and received a SMS reminder (SMS group) with those tested in the same time period (comparison group) and pre-SMS period (pre-SMS group, 1 January 2008 and 31 August 2008) who did not receive the SMS. HIV/STI re-testing rates were measured within 9 months for each group. Baseline characteristics were compared between study groups and multivariate logistic regression used to assess the association between SMS and re-testing and control for any imbalances in the study groups. RESULTS: There were 714 HIV negative MSM in the SMS group, 1084 in the comparison group and 1753 in the pre-SMS group. In the SMS group, 64% were re-tested within 9 months compared to 30% in the comparison group (p<0.001) and 31% in the pre-SMS group (p<0.001). After adjusting for baseline differences, re-testing was 4.4 times more likely (95% CI 3.5 to 5.5) in the SMS group than the comparison group and 3.1 times more likely (95% CI 2.5 to 3.8) than the pre-SMS group. CONCLUSION: SMS reminders increased HIV/STI re-testing among HIV negative MSM. SMS offers a cheap, efficient system to increase HIV/STI re-testing in a busy clinical setting.

No significant effect of uridine or pravastatin treatment for HIV lipoatrophy in men who have ceased thymidine analogue nucleoside reverse transcriptase inhibitor therapy: a randomized trial.

BACKGROUND: Lipoatrophy can complicate thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI)-based antiretroviral therapy (ART). Lipoatrophy may be less likely with ART including ritonavir-boosted lopinavir (LPV/r). Small, placebo-controlled studies found that uridine (in tNRTI recipients) and pravastatin improved HIV lipoatrophy over 12 weeks. Today, most patients with lipoatrophy receive non-tNRTI-based ART; the effect of uridine in such patients is unknown. METHODS: We performed a prospective, randomized trial in lipoatrophic adults with plasma HIV RNA<50 HIV-1 RNA copies/mL on tNRTI-sparing ART including LPV/r. Patients received uridine [36 g three times a day (tid) on 10 consecutive days per month; n=10], pravastatin [40 mg every night (nocte); n=12], uridine plus pravastatin (n=11) or neither (n=12) for 24 weeks. The primary endpoint was mean change in limb fat mass as assessed by dual-energy X-ray absorptiometry (DEXA). With 20 patients per intervention, the study had 80% power to detect a mean difference between a treatment and the control of 0.5 kg, assuming a standard deviation of 0.9 and an alpha threshold equal to 5% (two-sided). RESULTS: Of 45 participants (all men, with median age 49.5 years and median limb fat 2.6 kg), two discontinued pravastatin and one participant stopped both pravastatin and uridine. The difference between the mean changes in limb fat mass for uridine vs. no uridine was 0.03 kg [95% confidence interval (CI) -0.35, +0.28; P=0.79]. The respective difference for pravastatin was -0.03 kg (95% CI -0.29, +0.34; P=0.84). Pravastatin slightly decreased total cholesterol (0.44 mmol/L; P=0.099). Visceral adipose tissue measured by computed tomography did not change significantly. CONCLUSION: In this population and at the doses used, neither uridine nor pravastatin for 24 weeks significantly increased limb fat mass.

The behaviour and sexual health of young international travellers (backpackers) in Australia.

OBJECTIVES: To study the demographics, risk behaviours and morbidity of young long-term international travellers (backpackers) attending a sexual health service in Sydney, Australia. METHODS: Data on new patients were extracted from the Sydney Sexual Health Centre database for the period 1998 to 2006. The sexual risk behaviours and morbidity of the backpackers were compared with other patients of a similar age. RESULTS: The 5698 backpackers who attended the centre reported higher numbers of sexual partners (three or more partners in the past 3 months, 18% vs 12%, p<0.001) and a greater proportion drank alcohol at hazardous levels (22%) than the comparison group (9%, p<0.001). Rates of consistent (100%) condom use in the past 3 months were low in both backpackers (22%) and the comparison population (19%). Backpackers had higher rates of genital chlamydia infection (7% vs 5%, p<0.001) and reported higher rates of previous sexually transmitted infections (15% vs 10%, p<0.001). CONCLUSIONS: Backpackers should be a priority population for sexual health promotion and access to services.

Increasing HIV transmission through male homosexual and heterosexual contact in Australia: results from an extended back-projection approach.

OBJECTIVES: The aim of the study was to reconstruct the HIV epidemic in Australia for selected populations categorized by exposure route; namely, transmission among men who have sex with men (MSM), transmission among injecting drug users (IDUs), and transmission among heterosexual men and women in Australia. DESIGN: Statistical back-projection techniques were extended to reconstruct the historical HIV infection curve using surveillance data. Methods We developed and used a novel modified back-projection modelling technique that makes maximal use of all available surveillance data sources in Australia, namely, (1) newly diagnosed HIV infections, (2) newly acquired HIV infections and (3) AIDS diagnoses. RESULTS: The analyses suggest a peak HIV incidence in Australian MSM of approximately 2000 new infections per year in the late 1980s, followed by a rapid decline to a low of <500 in the early 1990s. We estimate that, by 2007, cumulatively approximately 20 000 MSM were infected with HIV, of whom 13% were not diagnosed with HIV infection. Similarly, a total of approximately 1050 and approximately 2600 individuals were infected through sharing needles and heterosexual contact, respectively, and in 12% and 23% of these individuals, respectively, the infection remained undetected. DISCUSSION: Male homosexual contact accounts for the majority of new HIV infections in Australia. However, the transmission route distribution of new HIV infections has changed over time. The number of HIV infections is increasing substantially among MSM, increasing moderately in those infected via heterosexual exposure, and decreasing in IDUs.

Long-term clinical and surrogate marker effects of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients.

OBJECTIVES: Subcutaneous administration of interleukin-2 (IL-2) has been shown to increase CD4 counts in HIV-infected patients. It remains unclear whether this effect is associated with a clinical benefit. PATIENTS AND METHODS: We conducted a long-term follow-up in the cohort of the UK-Vanguard study in which three groups of 12 antiretroviral-naive subjects with CD4 cell counts >350 cells/mm(3) received no treatment or IL-2 at either 4.5 or 7.5 MIU twice daily in 5 day cycles, respectively. RESULTS: Mean follow-up was 376 weeks. IL-2 therapy was associated with a higher area under the curve of CD4 cell count change from baseline at week 48 but not thereafter. HIV-RNA levels were unaffected. Highly active antiretroviral therapy (HAART) was initiated after a mean of 172, 175 and 152 weeks in the control group, low-dose and high-dose IL-2 treatment group, respectively, a statistically non-significant difference. There was a tendency to start HAART soon after discontinuation of IL-2 therapy which may have been triggered by the steep decay of CD4 counts. There were two serious adverse events in the control group, seven in the low-dose IL-2 group and eight in the high-dose IL-2 group. No pattern of disease was detected, making an association with IL-2 therapy unlikely. CONCLUSIONS: We could detect neither a benefit of IL-2 therapy after week 48 nor delayed initiation of HAART. This is currently the longest follow-up data comparing IL-2 therapy with no therapy in antiretroviral-naive HIV-infected patients and does not show a persistent benefit of the intervention.

Early changes in adipokine levels and baseline limb fat may predict HIV lipoatrophy over 2 years following initiation of antiretroviral therapy.

BACKGROUND: No biological marker has been identified that predicts the development of lipodystrophy (LD). We investigated whether metabolic and body composition parameters could predict the development of LD over 2 years in adults initiating antiretroviral therapy (ART). METHODS: We used stored plasma collected at baseline and weeks 12, 24 and 48 from adults initiating combination ART. Adipocytokine, inflammatory cytokine, lipid and glycaemic parameters were measured and related to subsequent lipoatrophy (loss of limb fat mass of at least 2 kg from weeks 24 to 96 by dual-energy X-ray absorptiometry) and an increase in visceral adipose tissue (VAT; an increase of at least 18 cm(2) from baseline to week 48 by abdominal computed tomography). Risk factors associated with limb fat loss and VAT gain were analysed by logistic regression. RESULTS: Fifty-four HIV-infected, treatment-naïve adults were included in the study: 53 (98%) of them were men, and they had a median age of 39 years [interquartile range (IQR) 34-48 years] and a median body mass index of 22.6 kg/m(2) (IQR 20-24.8 kg/m(2)). In multivariate analysis, a higher baseline limb fat percentage, and a 1 mmol/L increase in plasma leptin levels during the first 6 months of ART, independently predicted a peripheral fat loss of > or = 2 kg [odds ratio (OR) 2.58, 95% confidence interval (CI) 1.04-6.41; OR 3.15, 95% CI 1.34-7.35, respectively). VAT changes showed a borderline association with high baseline tumour necrosis factor-alpha levels and hip circumference (OR 1.04, 95% CI 1.00-1.07; OR 1.44, 95% CI 1.07-1.95, respectively). CONCLUSIONS: In ART-naïve men, higher baseline limb fat and an early increase in leptin concentrations may predict the subsequent development of lipoatrophy. We did not find the same risk factors in the two different groups of patients with peripheral fat loss and central fat gain, suggesting a partially independent pathogenesis.

Point and interval estimates of partial population attributable risks in cohort studies: examples and software.

The concept of the population attributable risk (PAR) percent has found widespread application in public health research. This quantity describes the proportion of a disease which could be prevented if a specific exposure were to be eliminated from a target population. We present methods for obtaining point and interval estimates of partial PARs, where the impact on disease burden for some presumably modifiable determinants is estimated in, and applied to, a cohort study. When the disease is multifactorial, the partial PAR must, in general, be used to quantify the proportion of disease which can be prevented if a specific exposure or group of exposures is eliminated from a target population, while the distribution of other modifiable and non-modifiable risk factors is unchanged. The methods are illustrated in a study of risk factors for bladder cancer incidence (Michaud DS et al., New England J Med 340 (1999) 1390). A user-friendly SAS macro implementing the methods described in this paper is available via the worldwide web.

Removal of bacteria by filtration in planted and non-planted sand columns.

In order to diminish hygienic hazards from pathogens, the elimination of pathogenic bacteria in a pre-treatment step is important for the use of domestic wastewater for irrigation purposes. Therefore, we analysed the removal of bacteria in laboratory-scale model sand filters simulating vertical flow systems of constructed wetlands (CW). Sand-filled glass columns were planted with Juncus effusus or Phragmites australis and non-planted columns were used as controls. Processes of bacteria removal such as adsorption, lysis, and the biotic effects caused by plants, protozoa, and Bdellovibrio were studied with E. coli as a model bacterium. E. coli suspensions (10(8) cellsml(-1)) were trickled on the columns by intermittent loading under non-water-saturated operation conditions. In non-planted and sterilized sand columns, an initial removal of cells was observed in the range as expected by the adsorption capacity of the sand columns. After loading of the sand with cells, an increasing reduction of the cell concentrations by 3-4 orders of magnitude in the effluent was registered up to volumetric loads of more than 548mll(-1) day(-1) (230mm day(-1)). In planted columns, no higher levels of removal were observed. Predation by protozoa, which were found in concentrations up to 10(4)ml(-1) in the effluent, is considered to be the main reason for the elimination. However, Bdellovibrio bacteriovorus was also found in plaque-forming units of about 10(4)g(-1) sand, suggesting that this bacteriovorous bacterium plays an additional role in the removal process. In a second series of experiments, domestic wastewater was applied and removal efficiencies up to four orders of magnitude of the cfu's of coliform bacteria, faecal streptococci, and salmonellae were observed. Considering the transpiration of the plants, higher removal efficiencies were found in the planted variants. Protozoa and Bdellovibrio were detected in the domestic wastewater in varying concentrations, suggesting that predation and lysis were the major removal mechanisms.