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Objective A Swiss nonoccupational post-exposure prophylaxis ( NPEP) source-tracing study successfully reduced unnecessary NPEP prescriptions by recruiting and testing source partners of unknown HIV serostatus. The Victorian NPEP Service in Australia attempted to replicate this study with the addition of HIV rapid testing and a mobile service. Methods Patients presenting to two busy NPEP sites who reported a source partner of unknown HIV status were routinely asked if their source could be traced. If the exposed person indicated that their source partner was traceable they were asked to contact them and discuss the possibility of having an HIV test. Results No sources were enrolled and the study was terminated. Conclusion We hypothesize that there are a number of differences between Australia and Switzerland that make source tracing unfeasible in Australia. [ABSTRACT FROM AUTHOR]

Backgroud: Antiretroviral (ARV) side effects are a critical determinant of adherence among people living with HIV (PLWH). Integrase strand transfer inhibitors (INSTIs), a commonly used ARV, have been reported to cause weight gain. We determined the relative importance of weight gain compared with other side effects from the perspective of PLWH., Setting: Melbourne Sexual Health Centre and the Alfred Hospital in Victoria, Australia., Methods: We conducted a discrete choice experiment survey to explore PLWH's preferences for 8 short-term side effects (eg, weight gain and depression) and 4 long-term side effects (eg, long-term weight gain and risks of heart attack). We sent an anonymous survey link through short message service (SMS) and postcards to PLWH attending both centers between July and August 2021. The choice data were analyzed using random parameter logit (RPL) and latent class (LCM) models., Results: Three hundred thirty-five respondents were included: most were male (88.1%). In the RPL analyses, weight gain was the second most important attribute after depression for short-term side effects and the third most important attribute after risk of heart attack and kidney problem for long-term side effects. In the LCM analyses, 23.9% were most sensitive to short-term weight gain, whereas 16.0% were most sensitive to long-term weight gain., Conclusions: Weight gain was the second most important short-term side effect and the third most important long-term side effect in a cohort of Australian PLWH. However, weight gain was the most important side effect of ARV for a significant minority., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Ambitious World Health Organization targets for disease elimination require monitoring of epidemics using routine health data in settings of decreasing and low incidence. We evaluated 2 methods commonly applied to routine testing results to estimate incidence rates that assume a uniform probability of infection between consecutive negative and positive tests based on 1) the midpoint of this interval and 2) a randomly selected point in this interval. We compared these with an approximation of the Poisson binomial distribution, which assigns partial incidence to time periods based on the uniform probability of occurrence in these intervals. We assessed bias, variance, and convergence of estimates using simulations of Weibull-distributed failure times with systematically varied baseline incidence and varying trend. We considered results for quarterly, half-yearly, and yearly incidence estimation frequencies. We applied the methods to assess human immunodeficiency virus (HIV) incidence in HIV-negative patients from the Treatment With Antiretrovirals and Their Impact on Positive and Negative Men (TAIPAN) Study, an Australian study of HIV incidence in men who have sex with men, between 2012 and 2018. The Poisson binomial method had reduced bias and variance at low levels of incidence and for increased estimation frequency, with increased consistency of estimation. Application of methods to real-world assessment of HIV incidence found decreased variance in Poisson binomial model estimates, with observed incidence declining to levels where simulation results had indicated bias in midpoint and random-point methods., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease., Objective: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population., Design: A double-blind multicentre, randomised, placebo-controlled trial was performed., Methods: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357)., Results: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011]., Conclusion: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Emerging evidence suggests that risk of bacterial sexually transmitted infections (STIs) increases among gay and bisexual men following initiation of HIV preexposure prophylaxis (PrEP)., Objective: To describe STI incidence and behavioral risk factors among a cohort of predominantly gay and bisexual men who use PrEP, and to explore changes in STI incidence following PrEP commencement., Design, Setting, and Participants: The Pre-exposure Prophylaxis Expanded (PrEPX) Study, a multisite, open-label intervention study, was nested within the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) clinic network. A total of 4275 participants were enrolled (July 26, 2016-April 1, 2018) in Victoria, Australia. Of these, 2981 enrolled at 5 ACCESS clinics (3 primary care, 1 sexual health, and 1 community-based HIV rapid testing service), had at least 1 follow-up visit, and were monitored until April 30, 2018., Exposures: Upon enrollment, participants received daily oral tenofovir disoproxil fumurate and emtricitabine for HIV PrEP, quarterly HIV and STI testing, and clinical monitoring., Main Outcomes and Measures: The primary outcome was incidence of chlamydia, gonorrhea, or syphilis. Incidence rates and hazard ratios describing behavioral risk factors of STI diagnosis were calculated. Incidence rate ratios (IRRs), adjusted for change in testing frequency, described changes in STI incidence from 1-year preenrollment to study follow-up among participants with preenrollment testing data (n = 1378)., Results: Among the 2981 individuals (median age, 34 years [interquartile range, 28-42]), 98.5% identified as gay or bisexual males, 29% used PrEP prior to enrollment, 89 (3%) withdrew and were censored at date of withdrawal, leaving 2892 (97.0%) enrolled at final follow-up. During a mean follow-up of 1.1 years (3185.0 person-years), 2928 STIs were diagnosed among 1427 (48%) participants (1434 chlamydia, 1242 gonorrhea, 252 syphilis). STI incidence was 91.9 per 100 person-years, with 736 participants (25%) accounting for 2237 (76%) of all STIs. Among 2058 participants with complete data for multivariable analysis, younger age, greater partner number, and group sex were associated with greater STI risk, but condom use was not. Among 1378 participants with preenrollment testing data, STI incidence increased from 69.5 per 100 person-years prior to enrollment to 98.4 per 100 person-years during follow-up (IRR, 1.41 [95% CI, 1.29-1.56]). After adjusting for testing frequency, the increase in incidence from 1 year preenrollment to follow-up was significant for any STI (adjusted IRR, 1.12 [95% CI, 1.02-1.23]) and for chlamydia (adjusted IRR, 1.17 [95% CI, 1.04-1.33])., Conclusions and Relevance: Among gay and bisexual men using PrEP, STIs were highly concentrated among a subset, and receipt of PrEP after study enrollment was associated with an increased incidence of STIs compared with preenrollment. These findings highlight the importance of frequent STI testing among gay and bisexual men using PrEP.

Objective: To compare the effects of switching tenofovir disoproxil fumarate (TDF) or treatment with an intravenous bisphosphonate on bone mineral density (BMD) in HIV-positive adults with low bone mass., Design: Two-year, randomized, open-label study at 10 sites in Australia and Spain., Participants: Of 112 adults on TDF-based antiretroviral therapy (ART) screened, 87 with low BMD (T-score < -1.0 at hip or spine by dual-energy X-ray absorptiometry) and undetectable plasma HIV viral load were randomized to either switch TDF to another active antiretroviral drug or to continue TDF-based ART and receive intravenous zoledronic acid (ZOL) 5 mg annually for 2 years., Primary Outcome Measure: Change in lumbar spine BMD at 24 months by intention-to-treat analysis. Secondary outcomes included changes in femoral neck and total hip BMD, fractures, safety, and virological failure., Results: Forty-four participants were randomized to TDF switch and 43 to ZOL, mean age 50 years (SD 11), 96% men, mean TDF duration 5.9 years (SD 3.1), and mean spine and hip T-scores -1.6 and -1.3, respectively. At 24 months, mean spine BMD increased by 7.4% (SD 4.3%) with ZOL vs. 2.9% (SD 4.5%) with TDF-switch (mean difference 4.4%, 95% CI 2.6-6.3; P < 0.001). Mean total hip BMD increased by 4.6 (SD 2.6%) and 2.6% (SD 4%), respectively (mean difference 1.9%, 95% CI 0.5-3.4; P = 0.009). There was one fracture in the ZOL group vs. seven fractures in four TDF-switch participants. Virological failure occurred in one TDF-switch participant. Other safety endpoints were similar., Conclusion: ZOL is more effective than switching TDF at increasing BMD in HIV-positive adults with low bone mass.

Objective: The current study aimed to validate existing risk prediction scores and identify predictors of chronic kidney disease (CKD) in the setting of HIV., Design and Methods: A retrospective cohort study of HIV-positive individuals (n = 748) with baseline estimated glomerular filtration rate (eGFR) more than 60 ml/min was conducted at the Alfred Hospital, Melbourne, Australia. Multivariable regression analysis was performed to determine factors associated with development of CKD, defined as two consecutive measurements of eGFR less than 60 ml/min. The performance of CKD risk scores proposed by the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group and Scherzer and colleagues were estimated by the area under the receiver operator curve (AUROC)., Results: CKD developed in 37 individuals (5.0%), at a median of 4.7 (interquartile range 2.2, 6.2) years. Older age [odds ratio (OR) 3.03, 95% confidence interval (CI): 1.20, 7.65, P = 0.02] and lower baseline eGFR (OR 10.39, 95% CI: 4.73, 22.83, P < 0.001) were associated with the development of CKD. Neither current, nor cumulative tenofovir disoproxil fumarate (TDF) use was associated with progression to CKD [current TDF hazard ratio (HR) 1.05, 95% CI: 0.54, 2.07, P = 0.88; cumulative TDF HR 1.03, 95% CI: 0.86, 1.24, P = 0.75]. The short D:A:D and Scherzer scores were well calibrated, with the short D:A:D score demonstrating superior discrimination (short D:A:D AUROC 0.85, Scherzer AUROC 0.78, P = 0.02)., Conclusion: Older individuals and those with a lower baseline eGFR are at higher risk for CKD. Risk prediction tools may be useful in identifying those at greatest risk, who may benefit from aggressive management of risk factors.

Background The aim of this study is to estimate the reduction in new HIV infections and resultant cost outcomes of providing antiretroviral treatment (ART) through Australia's 'universal access' health scheme to all temporary residents with HIV infection living legally in Australia, but currently deemed ineligible to access subsidised ART via this scheme., Methods: A mathematical model to estimate the number of new HIV infections averted and the associated lifetime costs over 5 years if all HIV-positive temporary residents in Australia had access to ART and subsidised medical care was developed. Input data came from a cohort of 180 HIV-positive temporary residents living in Australia who are receiving free ART donated by pharmaceutical companies for up to 4 years., Results: Expanding ART access to an estimated total 450 HIV+ temporary residents in Australia for 5 years could avert 80 new infections. The model estimated the total median discounted (5%) cost for ART and associated care to be A$36million, while the total savings in lifetime-discounted costs for the new infections averted was A$22million., Conclusions: It is estimated that expanded access to ART for all HIV-positive temporary residents in Australia will substantially reduce HIV transmission to their sexual partners at little additional cost. In the context of Australia's National HIV strategy and Australia's endorsement of global goals to provide universal access to ART for all people with HIV, this is an important measure to remove inequities in the provision of HIV-related treatment and care.

Background and Objective: Periodontal disease has been associated with cardiovascular disease in the general population. It is unknown whether IgG antibody levels for periodontal pathogens are associated with the diagnosis of coronary artery disease (CAD) in HIV-positive individuals., Material and Methods: Twenty-four HIV-positive individuals (cases) with stored plasma available in the 12 months before CAD diagnosis were age- and sex-matched 1:2 with 46 HIV-positive individuals without CAD (controls). Antibody levels to whole cell extracts from periodontal pathogens Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum, as well as markers of inflammation sCD14, CXCL10 and high-sensitivity C-reactive protein, were compared between cases and controls using enzyme-linked immunosorbent assays., Results: P. gingivalis-specific IgG levels (μg/mL) were significantly higher in individuals with CAD (median 1.48 [IQR 1.06-2.05]) compared to controls (0.70 [IQR 0.35-1.24], P<.001), and remained significantly higher following adjustment for traditional cardiovascular risk factors and HIV viral load (OR 21.6 [95% CI 3.73-125.63] P=.001). There was a borderline association between A. actinomycetemcomitans IgG antibody levels (cases, median 3.86 [IQR 3.19-4.72]; controls, 3.34 [IQR 2.59-4.07], P=.050) and no association found between F. nucleatum antibody levels and CAD. sCD14 levels (μg/mL) were higher in cases compared with controls (median 3.45 [IQR 3.03-4.11] vs 2.65 [IQR 2.32-2.99] P<.001), while CXCL10 (median 127 pg/mL [IQR 88-157] vs 153 [IQR 90-244] P=.321) and high-sensitivity C-reactive protein (median 3.44 mg/L [1.98-5.32] vs 1.85 [1.13-6.88] P=.203) levels were not different between cases and controls., Conclusion: Periodontal bacteria may be contributing to CAD risk in HIV-positive individuals., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The widespread availability of direct-acting antivirals (DAAs) is expected to drastically improve the treatment uptake and cure rate of hepatitis C virus (HCV). In this paper, rates of and factors associated with HCV treatment uptake and cure in the HIV co-infected population in Australia were assessed before access to DAAs., Methods: The medical records of patients in the Australian HIV Observational Database who were reported to be HCV antibody positive from 1999 to 2014 were reviewed for HCV treatment data. Patients with detectable HCV RNA were included in this analysis. Logistic regression models were applied to identify factors associated with treatment uptake and HCV sustained virological response (SVR) 24 weeks' post treatment., Results: The median follow-up time of those with chronic HCV/HIV co-infection was 103 months (interquartile range 51-166 months). Of 179 HCV viraemic patients, 79 (44.1%) began treatment. In the adjusted model, a higher METAVIR score was the only significant factor associated with treatment uptake (odds ratio (OR) 8.87, 95% confidence interval (CI) 2.00-39.3, P=0.004). SVR was achieved in 37 (50%) of 74 treated patients. HCV genotypes 2/3 compared with 1/4 remained the only significant factor for SVR in an adjusted multivariable setting (OR 5.44, 95% CI 1.53-19.4, P=0.009)., Conclusions: HCV treatment uptake and SVR have been relatively low in the era of interferon-containing regimens, in Australian HIV/HCV coinfected patients. With new and better tolerated DAAs, treatment of HCV is likely to become more accessible, and identification and treatment of HCV in co-infected patients should become a priority.

Background: Progressively sensitive assays for plasma HIV RNA have led to increased detection of plasma HIV RNA between 20 and 200 copies/ml, known as low level viremia (LLV) when recurrent or persistent, in HIV-infected patients on antiretroviral therapy (ART). The aim of this study was to determine outcomes following initial detection of LLV in an Australian cohort., Methods: A retrospective study using the HIV Service Database (Alfred Hospital) included all patients on ART who recorded plasma HIV RNA 20-200 copies/mL following prior virological suppression (viral load (VL) HIV RNA <20 copies/mL) over 2 years (2010 to 2012), with follow-up to June 2013. Factors associated with subsequent virological outcome were assessed via univariate and multivariate analysis., Results: Of 919 patients managed by The Alfred HIV service, 207 (22.5%) met inclusion criteria. Mean age was 48.8 years, 91.3% were male. During follow-up, 54% patients recorded no further HIV RNA 20-200 copies/mL (viral blip); 39% had recurrent or persistent VL 20-200 copies/mL (LLV); and 7% progressed to virological failure with VL >200 copies/mL. Factors associated with LLV included co-morbid type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count. Clinician management of VL 20-200 copies/mL was generally conservative, with infrequent requests for genotypic analysis (3.3% cases) or change in ART (<1% cases)., Conclusions: LLV following virological suppression is common, and occurred as an isolated viral blip in half the patients. Those patients with persistent or recurrent LLV had higher rates of type 2 diabetes, shorter prior virological suppression and lower nadir CD4 cell count.

Background: There have been improvements in combination antiretroviral therapy (cART) over the past 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome., Methods: Patients in the Australian HIV Observational Database who initiated treatment using mono/duo therapy prior to 1996, or using cART from 1996 onwards, were included in the analysis. Patients were stratified by era of ART initiation. Median changes in CD4(+) T-cell count and the proportion of patients with detectable HIV viral load (>400 copies/ml) were calculated over the first 4 years of treatment. Probabilities of treatment switch were estimated using the Kaplan-Meier method., Results: A total of 2,753 patients were included in the analysis: 28% initiated treatment <1996 using mono/duo therapy and 72% initiated treatment ≥1996 using cART (30% 1996-1999, 12% 2000-2003, 11% 2004-2007 and 19% ≥2008). Overall CD4(+) T-cell count response improved by later era of initiation (P<0.001), although 2000-2003 CD4(+) T-cell count response was less than that for 1996-1999 (P=0.007). The average proportion with detectable viral load from 2 to 4 years post-treatment commencement by era was: <1996 mono/duo 0.69 (0.67-0.71), 1996-1999 cART 0.29 (0.28-0.30), 2000-2003 cART 0.22 (0.20-0.24), 2004-2007 cART 0.09 (0.07-0.10) and ≥2008 cART 0.04 (0.03-0.05). Probability of treatment switch at 4 years after initiation decreased from 53% in 1996-1999 to 29% after 2008 (P<0.001)., Conclusions: Across the five time-periods examined, there have been incremental improvements for patients initiated on cART, as measured by overall response (viral load and CD4(+) T-cell count) and also increased durability of first-line ART regimens.

Background: Tenofovir (TDF) is effective for treatment of hepatitis B virus (HBV) in human immunodeficiency virus (HIV) infection; however, some individuals have ongoing HBV viremia, the reasons for which are unclear. We determined the patterns and factors associated with detectable HBV DNA in HIV-HBV-coinfected subjects on highly active antiretroviral therapy (HAART)., Methods: One hundred sixty-five HIV-HBV-coinfected individuals from the United States, Australia, and Thailand, the majority of whom were on HAART at study entry, were prospectively followed semiannually for a median of 2.8 years. Logistic regression was used to determine factors associated with detectable HBV DNA., Results: Anti-HBV regimens were TDF/emtricitabine (57%), lamivudine or emtricitabine (19%), or TDF monotherapy (13%). During follow-up, HBV DNA was detected at 21% of study visits and was independently associated with hepatitis B e antigen (HBeAg), HAART <2 years, CD4 <200 cells/mm(3), detectable HIV RNA, reporting <95% adherence, and anti-HBV regimen. TDF/emtricitabine was less likely to be associated with detectable HBV than other regimens, including TDF monotherapy (odds ratio, 2.79; P = .02). In subjects on optimal anti-HBV therapy (TDF/emtricitabine) and with undetectable HIV RNA, HBeAg, CD4 <200 mm(3), and reporting <95% adherence remained associated with detectable HBV DNA. Three main patterns of HBV viremia were observed: persistent HBV viremia, viral rebound (>1 log from nadir), and viral blips. No TDF resistance was identified., Conclusions: Tenofovir/emtricitabine was superior to other anti-HBV regimens in long-term HBV suppression. HBV viremia on therapy was identified in 1 of 3 main patterns. Suboptimal adherence was associated with detectable HBV DNA during therapy, even when HIV was undetectable.

In Australia, the non-occupational post-exposure prophylaxis service in Victoria (VNPEPS) maintains a database of non-occupational post-exposure prophylaxis (NPEP) use throughout the state. Through the database the service can monitor and respond to patterns of NPEP presentation, re-presentation and follow-up as well as those who test positive for HIV. We describe a cohort of NPEP individuals from the commencement of the service to 31 December 2009. During this time, 1864 individuals presented for NPEP on 2396 occasions. The majority (85%) were men who have sex with men (MSM) presenting after receptive anal intercourse (56.1%). Repeat NPEP presentations were high (17.5%) and follow-up testing at week 12 post-NPEP was low (34%). Twenty-two patients (1.2%) tested positive for HIV at baseline presentation and six patients seroconverted to HIV during follow-up. The VNPEPS has initiated strategies to encourage behaviour change for those who re-present for NPEP, and to improve rates of week 12 follow-up.

Objective: To describe the clinical outcomes for all HIV-serodiscordant couples attending an assisted reproduction program., Design, Setting and Participants: Retrospective review of demographic, clinical and outcome data for all HIV-serodiscordant couples who attended an assisted reproduction program at a tertiary hospital in Melbourne, between its commencement in 2003 and June 2010., Main Outcome Measures: Pregnancies, miscarriages, births, HIV transmission to the HIV-negative partner, semen quality and detection of HIV (HIV RNA and HIV DNA) in semen., Results: As of June 2010, 39 HIV-positive clients had proceeded to assisted reproduction after the initial consultation in the program. There were 162 completed cycles, with 26 pregnancies (clinical pregnancy rate per cycle, 16.2% for HIV-positive men with an HIV-negative partner, and 15.4% for HIV-positive women). Of all 222 tested semen samples, 18 (8%) had HIV RNA detected despite these men receiving antiretroviral therapy and having an undetectable HIV viral load in plasma. Sperm velocity was significantly lower in HIV-positive clients receiving combination antiretroviral therapy than in a control group of recipient-recruited sperm donors (P = 0.01); there were no other significant differences in sperm quality between the two groups. No HIV transmission to babies or HIV-negative partners occurred., Conclusion: Our findings show detectable HIV in 8% of semen samples from men with an undetectable HIV viral load in plasma, but confirm the safety of assisted reproduction for HIV-serodiscordant couples within a program with strict protocols for HIV treatment and testing of all semen before use.

Background: The rise in serious complications of early syphilis, including neurosyphilis, particularly in those with HIV infection and in men who have sex with men (MSM), is of concern., Objectives: To review the manifestations and management of neurosyphilis in a population of HIV-infected MSM., Methods: Retrospective review of patients with HIV and early neurosyphilis in three centres in Melbourne, Australia, in 2000-07., Results: Eighteen male HIV patients met the criteria for diagnosis of early neurosyphilis. Thirteen patients (72.2%) had neurological symptoms: six with headache (33.3%), four with tinnitus (22.2%) and five with impaired vision (27.8%), and one patient each with ataxia, leg weakness and anal discharge with faecal incontinence. Five patients (27.8%) reported no neurological symptoms. All had serum rapid plasma reagin (RPR) titres ≥1:32 and all except one had cerebrospinal fluid positive for syphilis fluorescent treponemal antibodies-absorbed. After treatment with 14-15 days of 1.8 g intravenous benzylpenicillin 4-hourly, 12 of 17 patients (71%) demonstrated a four-fold drop in serum RPR titre over 6-12 months and were considered successfully treated. A rise in RPR was noted in three patients during the 12-month follow-up period, suggesting re-infection or recurrence., Conclusion: HIV-infected patients found to have syphilis either because of symptoms or by routine screening should be carefully assessed for neurological, ophthalmic and otological symptoms and signs. A low threshold for a diagnostic lumbar puncture to exclude the diagnosis of neurosyphilis enables appropriate administration and dose of penicillin for treatment, which appears successful in ~75% of cases.

Background: Despite widespread prescription of non-occupational post-exposure prophylaxis (NPEP) in Victoria, little is known about subsequent HIV acquisition among NPEP users. We linked the Victorian NPEP Service (VNPEPS) database and the Victorian HIV Surveillance Registry to determine the number, incidence rate and predictive factors of HIV seroconversions among users of the VNPEPS., Methods: Records from male patients that received NPEP in the VNPEPS database (n = 1420) between January 2001 and February 2008 were linked with all entries in the Victorian HIV Surveillance Registry up to May 2008., Results: Sixty-one men who presented to the VNPEPS were identified as HIV seropositive; 16 of these were diagnosed at initial presentation for NPEP. The incidence of HIV seroconversion in males who were HIV seronegative at first presentation for NPEP was 1.27 (95% confidence interval 0.95-1.70) per 100 person-years. There was no association between HIV seroconversion and number of NPEP presentations or age. The median age of seroconversion was 34.6 years., Conclusion: The incidence of HIV infection among men presenting to the VNPEPS is slightly lower than the HIV incidence in NPEP users in a recent Australian cohort study of men who have sex with men, but higher than HIV incidence in general gay male populations. Frequency of NPEP use was not associated with risk of HIV seroconversion. Examination of risk behaviour before and after NPEP use in this population is required to further assess the impact of NPEP availability and use on HIV incidence rates and risk behaviour in Australia.

Background: both the current NHMRC guidelines of Australia and the USPHS/IDSA guidelines recommend pneumococcal vaccine be given to all patients with HIV infection despite a paucity of data to support these recommendations., Objectives: the aim of this study was to assess the incidence of invasive pneumococcal disease and use of pneumococcal vaccine in HIV-infected patients at The Alfred Hospital, Melbourne, Australia, and to review the evidence for the current recommendations., Study Design: a case record review of all HIV-infected patients followed at The Alfred Hospital diagnosed with pneumonia between 1 June 1996 and 1 June 2000 was performed. Main outcome measures were the incidence of invasive pneumococcal disease and the proportion of these individuals who received pneumococcal vaccination., Results: Invasive pneumococcal disease was a relatively infrequent event with an incidence of 1.9 per 1000 person years. This rate is lower than the 8.2 per 1000 person years reported for confirmed disease by CDC. Of the 34 patients with either definite invasive, presumptive or possible pneumococcal disease, 16 (47%) had received pneumococcal vaccine, seven of these within 5 years prior to the episode of pneumonia. In 15 cases, the vaccine was administered when the CD4 cell count was <500 per microl., Conclusion: lack of efficacy data, rarity of invasive disease plus evidence of infrequent administration delivered predominantly to those who are least likely to benefit, has prompted us to question the value of routinely vaccinating all our HIV-infected patients with pneumococcal vaccine. Review of the published literature provides conflicting data in support of the current recommendations for administration of pneumococcal vaccine in HIV patients. It may be more cost-effective to concentrate efforts on strategies to improve adherence to ARV therapy, as this has unequivocally been shown to be associated with a reduction in the incidence of pneumococcal disease.

Objectives: This study's objective was to determine the prevalence of body shape changes and metabolic abnormalities in an ambulant population with HIV infection. Three different definitions of lipodystrophy were used to assess these changes. Patients' anthropometric measures and dual-energy X-ray absorptiometry (DEXA) scans were compared in order to estimate fat distribution in this population. We sought to evaluate potential predictors for lipodystrophy according to each of the three definitions., Methods: We performed a cross-sectional study in the outpatient clinic of a tertiary referral hospital in Melbourne, Australia. We enrolled a total of 167 HIV-infected ambulatory patients over 3 months in mid-1998. Data on 159 males, 149 of whom were receiving triple combination antiretroviral therapy, were evaluated. Anthropometric measures, clinical examination, self-report of body shape changes, biochemical measures and DEXA scan were used to assess lipodystrophy and risk factors for cardiovascular disease. Patients described body shape changes in the face, trunk, arms and legs. Laboratory parameters measured included fasting triglyceride (TG), cholesterol, high-density lipoproteins (HDL), glucose, insulin, CD4 cell count and plasma HIV RNA. Current and past antiretroviral therapies were ascertained., Results: According to one proposed Australian national definition of lipodystrophy (LDNC), the prevalence of lipodystrophy in this population was 65%. This definition included an objective assessment with major and minor criteria. Patient-defined lipodystrophy (LDP), which involved a subjective assessment of thinning arms and legs and central adiposity, occurred in 19%. Patient-defined lipoatrophy (LAP), which involved a subjective assessment of thinning arms and legs without central adiposity, occurred in 21.3%. No change in body habitus was noted by 37% of the cohort. Hypercholesterolaemia was recorded in 44%, hypertriglyceridaemia in 52% and elevated insulin levels in 23%. Anthropometry was predictive of the per cent total body fat recorded by DEXA scan, but produced consistently lower values. In multivariate analysis, LDP and LAP were significantly associated with stavudine (d4T) use, while LAP was also associated with zidovudine (ZDV) treatment. There were no treatment associations with LDNC. Protease inhibitor (PI) exposure was associated with metabolic changes but not patient perceived body shape changes, while d4T and ZDV exposure was associated with increased triglycerides and reduced peripheral fat stores., Conclusions: The prevalence of body shape changes in a single population varied depending on the definition applied. The LDNC definition overestimated body shape abnormalities in comparison with patient perception. LAP was associated with significantly lower fat stores measured by anthropometry and DEXA scan than those identified under the LDNC definition. In contrast to LDNC, LAP was associated with d4T exposure, nucleoside reverse transcriptase inhibitor (NRTI) and ZDV duration of use, but not PI use. Until a consensus definition for lipodystrophy is developed, including agreement on objective measurement and thresholds for abnormality, careful description of the individual components of the syndrome is required to enable cohort comparisons so that predictors of the syndrome can be assessed more accurately and outcome studies made feasible.

To assess time trends in incidence of AIDS illnesses in Australia, a retrospective cohort of people diagnosed with AIDS from January 1, 1983 to December 31, 1994 in three HIV medicine units in Sydney, Melbourne, and Perth was established. Data on initial and subsequent AIDS illnesses were available for 2580 AIDS cases, or 45% of Australian AIDS notifications over the study period. Males represented 97.2% of the cohort, and HIV exposure category was homosexual contact for 89.9%. Subcohorts were formed by interval of AIDS diagnosis: 1983 through 1987, 1988 through 1990, and 1991 through 1994, with estimation of cumulative risk for each AIDS illness by the Kaplan-Meier method. The cumulative risk declined for Pneumocystis carinii pneumonia (PCP) (p < 0.0001) and for Kaposi's sarcoma (KS) (p < 0.0001); PCP cumulative risk estimates 2 years following AIDS diagnosis were 70% for people diagnosed with AIDS in 1983 through 1987 and 48% in 1991 through 1994, and KS cumulative risk estimates 2 years following AIDS diagnosis were 44% in 1983 through 1987 and 32% in 1991 through 1994. In contrast, cumulative risk increased from 34% to 40% for cytomegalovirus (CMV) disease (p = 0.005), from 47% to 50% for Mycobacterium avium complex (MAC) (p < 0.0001), and from 26% to 33% for esophageal candidiasis (p < 0.0001). Corresponding to this changing spectrum of AIDS illness has been an increase in severity of immunodeficiency at AIDS, with median CD4 cell count declining from 54 cells/mm3 in 1983 through 1987 to 34/mm3 in 1991 through 1994 (p = 0.002).

Objective: To explore trends in cumulative incidence of Kaposi's sarcoma (KS) and the level of immunodeficiency at KS diagnosis among people with AIDS in Australia., Setting: Three hospital-based HIV units., Study Population: Retrospective cohort of 2580 people diagnosed with AIDS over the period 1983-1994, representing 45% of cases of AIDS in Australia over this period., Methods: Data including date and CD4 T-lymphocyte count of KS diagnosis was abstracted from medical records. KS occurring as both an initial and subsequent AIDS illness was included. Three subcohorts were defined based on interval of AIDS diagnosis: 1983-1987, 1988-1990, 1991-1994. Cumulative risk estimates for KS development were calculated by the Kaplan-Meier method., Results: KS was diagnosed in 716 people (27.8%), and in 451 (63%) of these as the initial AIDS illness. There was a decline over time in cumulative incidence of KS (P < 0.0005); the cumulative risk of KS at 1 year after AIDS diagnosis declined from 35% for those diagnosed with AIDS during 1983-1987 to 25% for 1991-1994. This decline was not due to a decline in homosexual HIV exposure category, and was independent of CD4 T-lymphocyte count at AIDS. In multivariate analysis independent risk factors for KS development were year of AIDS diagnosis (P = 0.003), male homosexuality (P = 0.003), and CD4 T-lymphocyte count at AIDS greater than 150 x 10(6)/l (P = 0.02). A decline in median CD4 T-lymphocyte count at KS diagnosis was seen, from 67 x 10(6)/l in 1984-1987 to 20 x 10(6)/l for 1991-1994 (P < 0.0005)., Conclusion: The decline in incidence and later occurrence of KS suggest several hypotheses, including declining prevalence or reduced virulence of a KS cofactor.

Objective: To determine the efficacy of high-dose oral acyclovir in preventing cytomegalovirus (CMV) and other herpesvirus disease in patients with advanced HIV disease and to evaluate its effect on patient survival., Design: Double-blind, placebo-controlled randomized trial of up to 1 year's therapy., Setting: Outpatient clinics in 16 hospitals in Europe and Australia., Participants: A total of 302 patients with Centers for Disease Control and Prevention stage IV HIV disease, seropositive for CMV and with CD4+ lymphocyte counts < or = 150 x 10(6)/l., Interventions: Oral acyclovir (800 mg, four times daily) or matching placebo for 48 weeks., Main Outcome Measures: Time to development of CMV and other herpesvirus disease. Following the results of another study, the protocol was amended to make survival a second major endpoint., Results: Acyclovir failed to reduce the incidence of CMV disease: the probability of developing CMV disease at 1 year was 0.24 and 0.23 in the placebo and acyclovir groups, respectively (P = 0.53). However, acyclovir significantly reduced the probability of dying at 1 year of follow-up (from 0.39 to 0.23; P = 0.018). As expected, acyclovir significantly reduced the incidence and frequency of herpes simplex virus disease. There were no notable differences between treatment groups in clinically adverse experiences and no changes in haematological parameters to indicate clinically significant drug-induced toxicity., Conclusions: High-dose acyclovir failed to reduce the incidence of CMV disease, but significantly reduced the probability of dying at 1 year of follow-up.

Infection with the human immunodeficiency virus (HIV) results in progressive depletion of the CD4 subset T-lymphocytes and the development of opportunistic infections and certain malignancies. Charts were reviewed for 185 HIV-infected individuals with 265 AIDS-defining illnesses (ADIs) who had T-lymphocyte subset analyses performed within 2 months prior to or 1 month following the diagnosis. Also included were 22 HIV-infected patients with oral candidiasis and 20 with asymptomatic infection. Significant differences in CD4 lymphocyte numbers were observed between the 12 ADIs, oral candidiasis, and asymptomatic infection, allowing them to be grouped into five general categories, based on mean CD4 count: (a) asymptomatic infection, CD4 greater than 500/mm3; (b) oral candidiasis and tuberculosis, range 250-500/mm3; (c) Kaposi's sarcoma, lymphoma, and cryptosporidiosis, range 150-200/mm3; (d) Pneumocystis carinii pneumonitis, disseminated Mycobacterium avium complex, herpes simplex ulceration, toxoplasmosis, cryptococcosis, and esophageal candidiasis, range 75-125/mm3; (e) cytomegalovirus retinitis, less than 50/mm3. Our data concur with clinical impressions and provide a basis for interim treatment and prophylaxis recommendations.

In the period from January 1971 to June 1983, 46 of 5477 patients (0.84%) admitted to Fairfield Hospital, Melbourne, with acute viral hepatitis died of fulminant hepatic failure. The case-fatality rate for patients with hepatitis A was 0.14%; for patients with hepatitis B, 0.84%; and for patients with non-A non-B (NANB) hepatitis, 2.29%. The highest case-fatality rates were observed in patients with post-transfusion hepatitis B (18.8%), and in patients with NANB hepatitis aged less than 5 years (50%) and 40 years and over (10%).

Evidence of infection with delta agent was sought in 284 patients with acute hepatitis B referred to Fairfield Hospital, Melbourne, between July 1, 1981, and June 30, 1982 and in 127 hepatitis B surface antigen (HBsAg) carriers. Acute and convalescent serum samples from the patients with acute hepatitis B and single or multiple sera from the HBsAg carriers were tested for delta antigen (delta ag) and/or antibody (anti-delta) by solid-phase radioimmunoassay (SPRIA). Evidence of infection was detected in 14.4% of patients with acute hepatitis B and 7.1% of chronic HBsAg carriers. Eighty-eight percent of those in whom delta agent infection was demonstrated were intravenous drug users.