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Summary A cascade of care model is central to contemporary approaches to HIV prevention. The model prioritizes strategies to increase rates of HIV testing and promote early and sustained uptake of antiretroviral treatment (ART) among people living with HIV (PLHIV). The model aims to prevent new HIV transmissions by increasing the number of PLHIV who have achieved HIV viral suppression. However, good quality of life (QoL) among PLHIV has been proposed as an additional goal. This prioritizes the basic right of PLHIV to lead meaningful lives and acknowledges the relationship between better QoL and consistent ART use. A better understanding of factors associated with the QoL can thus inform health promotion programmes for PLHIV. In this study, N=465 Australian participants, recruited through social media and various HIV community organizations, completed an online survey that included a measure of QoL and a range of demographic, health-related and social variables. Overall, social factors accounted uniquely for the most variance in QoL (18%), followed by health-related (11%) and demographic factors (2%). Social support, HIV-related discrimination and treatment convenience were among the strongest determinants of QoL. These findings reinforce the importance of a more holistic approach to health promotion among PLHIV. Specifically, our results indicate that to improve the QoL of PLHIV and to boost related public health benefits, community advocates and healthcare professionals must be responsive to the broader psychological, social and functional needs of PLHIV.

The most common reasons for switching HIV-1 therapy in patients with virologic suppression are treatment regimen simplification and resolving tolerability issues. Single-pill regimens that include an integrase inhibitor are recommended options. A retrospective clinical audit was performed to determine the motivations for switching to dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC) at high HIV-caseload general practice clinics in Australia. The most common reasons for switching from a prior suppressive therapy to DTG/ABC/3TC were simplification of regimen, resolving toxicity/intolerance and patient preference (73%, 13% and 12%, respectively). Kaplan–Meier analysis showed that the probability of patients remaining on DTG/ABC/3TC therapy at 12 months was 95.1%. Switching to DTG/ABC/3TC from a range of other regimens was associated with a discontinuation rate of 3.2%, with 2.5% of patients discontinuing due to adverse events and no patients discontinuing due to virologic failure. Switching to DTG/ABC/3TC was a viable treatment strategy in this cohort of Australian patients.

Syphilis is increasing in men who have sex with men and disproportionately affects HIV-infected men. Here we review the epidemiology, diagnostic techniques, treatment guidelines, follow-up procedures and control of syphilis. The difference in these factors in HIV-infected men and uninfected men and evidence for this is reviewed. We explain that HIV-infected men are at higher risk of syphilis acquisition as a result of different behavioral factors. Thus, some control strategies may be different for HIV-infected men owing to these factors and also because HIV-infected men are more closely linked with medical care. There is no strong evidence to suggest there should be any differences in diagnostic techniques, treatment guidelines or follow-up procedures between HIV-infected and uninfected men.

Objective: To assess the effects of decreased antiretroviral therapy exposure on body fat and metabolic parameters. Design: Substudy of the Strategies for Management of Anti-Retroviral Therapy study, in which participants were randomized to intermittent CD4-guided [Drug Conservation (DC) group] or to continuous [Viral Suppression (VS) group] antiretroviral therapy. Methods: Participants at 33 sites were coenrolled in the Strategies for Management of Anti-Retroviral Therapy Body Composition substudy. Regional fat was assessed annually by whole-body dual-energy X-ray absorptiometry and abdominal Computed tomography. Fasting metabolic parameters were assessed at months 4, 8, and annually. Treatment groups were compared for changes in fat and metabolic markers using longitudinal mixed models. Results: Two hundred and seventy-five patients were randomized to the DC (n = 142) or VS (n = 133) group and followed for a median of 2.0 years. By month 12, limb fat (DC-VS difference 9.8%, 95% confidence interval 3.5-16.1; P=0.003) and subcutaneous abdominal fat (DC-VS difference 14.3 cm(2), 95% confidence interval -0.1 to 28.7; P=0.05) increased in the DC group. There was no treatment difference in visceral abdominal fat (DC-VS difference -2.1%, 95% confidence interval -13.5 to 9.4; P=0.72). Lipids significantly decreased in the DC group by month 4 and treatment differences persisted throughout follow-up (P

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$36 million, while the total savings in lifetime-discounted costs for the new infections averted was A$22 million. 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.

Over the past decade antiretroviral drugs have dramatically improved the prognosis for HIV-1 infected individuals, yet achieving better access to vulnerable populations remains a challenge. The principal obstacle to the CCR5-antagonist, maraviroc, from being more widely used in anti-HIV-1 therapy regimens is that the pre-treatment genotypic “tropism tests” to determine virus susceptibility to maraviroc have been developed primarily for HIV-1 subtype B strains, which account for only 10% of infections worldwide. We therefore developed PhenoSeq, a suite of HIV-1 genotypic tropism assays that are highly sensitive and specific for establishing the tropism of HIV-1 subtypes A, B, C, D and circulating recombinant forms of subtypes AE and AG, which together account for 95% of HIV-1 infections worldwide. The PhenoSeq platform will inform the appropriate use of maraviroc and future CCR5 blocking drugs in regions of the world where non-B HIV-1 predominates, which are burdened the most by the HIV-1 pandemic.

Since 2000, infectious syphilis notifications have increased substantially among Australian gay men. We describe testing at a frequency lower than guidelines recommend.We examined data from a cross-sectional survey of gay men in 5 Australian cities in 2010. We used logistic regression to identify correlates of no lifetime syphilis test among HIV-uninfected men and2 tests per year in HIV-infected men and higher-risk HIV-uninfected men.Of 6329 HIV-uninfected men, 65% reported a syphilis test in the past year, and 86% in their lifetime, and factors associated with no lifetime syphilis test were lower social engagement with gay men, older age, fewer sexual partners, no anal sex with casual partners, and not being aware syphilis could be asymptomatic. Among higher-risk HIV-uninfected men (10 partners in the past 6 months), factors associated with2 syphilis tests in the past year were nonmetropolitan residence, older age, no anal sex or unprotected anal intercourse with casual partners, not aware syphilis could be acquired through oral sex, and testing at a nonregular general practitioner. Of the 580 HIV-infected, 87% reported a syphilis test in the past year, and 96% in their lifetime, and factors associated with2 syphilis tests in the past year were unprotected anal intercourse with HIV-uninfected casual partner and recruitment from social or sex-on-premises venues.Our analysis showed high lifetime and annual syphilis testing rates in Australian gay men, but low retesting rates. We identified factors associated with less frequent syphilis testing rates among Australian gay men to assist in developing targeted screening strategies.

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.

Over the last decade, syphilis epidemics have resurged around the world, particularly among gay men. An innovative public health response could be the use of chemoprophylaxis. We sought out to determine the acceptability of syphilis chemoprophylaxis and its likely population effectiveness if it were adopted.We conducted a mixed-methods study. An online survey (n = 2095 participants) and focus groups (n = 23 participants) were conducted to determine whether syphilis chemoprophylaxis is likely to be acceptable to gay men in Australia. We also developed an individual-based mathematical model that simulated a population of gay men, to explore the potential impact of introducing chemoprophylaxis.Of the 2095 gay men surveyed, 52.7% (95% confidence interval, 50.6%-54.8%) indicated that they would be very likely or slightly likely to use chemoprophylaxis to reduce their chance of acquiring syphilis, increasing to 75.8% (95% confidence interval, 74.0%-77.6%) if chemoprophylaxis would help reduce infections in the gay community. In this model, 70% use-effectiveness of chemoprophylaxis used by 50% of gay men is expected to reduce the number of syphilis cases by ∼50% after 12 months and 85% after 10 years. The majority of the prevention efforts can be gained by targeting subpopulations of men with higher sexual activity.Chemoprophylaxis offers promise as an acceptable and effective intervention for mitigating syphilis epidemics. The outcomes of a planned placebo-controlled syphilis chemoprophylaxis trial are eagerly anticipated.

Among a subgroup of participants in the Strategies for Management of Antiretroviral Therapy (SMART) Trial that were naïve to antiretroviral therapy (ART) or off ART (6 months or longer) at study entry, risk of AIDS and serious non-AIDS events were increased for participants who deferred ART compared with those randomized to (re)initiate ART immediately. Our objective was to determine whether ART initiation in this group reduced markers of inflammation and coagulation that have been associated with increased mortality risk in SMART. Changes in these biomarkers have been described after stopping ART, but not after starting ART in SMART.Stored specimens for 254 participants (126 drug conservation [DC] and 128 viral suppression [VS]) who were naïve to ART or off ART (6 months or longer) were analyzed for interleukin-6, high sensitivity C-reactive protein, and D-dimer at baseline and Months 2 and 6.At Month 6, 62% of the VS group had HIV RNA less than 400 copies/mL and median CD4 count was 190 cells/mm3 higher than for the DC group (590 versus 400 cells/mm3). Compared with DC, the VS group had 32% (95% confidence interval, 19%-43%) lower D-dimer levels at Month 6 (P0.001); differences were not significant for high sensitivity C-reactive protein or interleukin-6 levels.In this randomized comparison of immediate versus delayed ART initiation, D-dimer, but not interleukin-6 and high sensitivity C-reactive protein, declined significantly after starting ART. Further studies are needed to determine whether improvements in D-dimer are associated with reduced risk of clinical disease and whether adjunct treatments used in combination with ART can reduce inflammation among individuals with HIV infection.

Objective: To determine factors associated with baseline neurocognitive performance in HIVinfected participants enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) neurology substudy. Methods: Participants from Australia, North America, Brazil, and Thailand were administered a 5-test neurocognitive battery. Z scores and the neurocognitive performance outcome measure, the quantitative neurocognitive performance z score (QNPZ-5), were calculated using US norms. Neurocognitive impairment was defined as z scores 2 in two or more cognitive domains. Associations of test scores, the QNPZ-5, and impairment with baseline factors including demographics and risk factors for HIV-associated dementia (HAD) and cardiovascular disease (CVD) were determined in multiple regression. Results: The 292 participants had a median CD4 cell count of 536 cells/mm 3 , 88% had an HIV viral load 400 copies/mL, and 92% were taking antiretrovirals. Demographics, HIV, and clinical factors differed between locations. The mean QNPZ-5 score was 0.72; 14% of participants had neurocognitive impairment. For most tests, scores and z scores differed significantly between locations, with and without adjustment for age, sex, education, and race. Prior CVD was associated with neurocognitive impairment. Prior CVD, hypercholesterolemia, and hypertension were associated with poorer neurocognitive performance but conventional HAD risk factors and the CNS penetration effectiveness rank of antiretroviral regimens were not. Conclusions: In this HIV-positive population with high CD4 cell counts, neurocognitive impairment was associated with prior CVD. Lower neurocognitive performance was associated with prior CVD, hypertension, and hypercholesterolemia, but not conventional HAD risk factors. The contribution of CVD and cardiovascular risk factors to the neurocognition of HIV-positive populations warrants further investigation. Neurology ® 2010;75:864–873

BackgroundThe SMART trial found a raised risk of cardiovascular disease (CVD) events in patients undergoing CD4+T cell-count guided intermittent antiretroviral therapy (ART) compared with patients on continuous ART. Exploratory analyses were performed to better understand the reasons for this observation.MethodsA total of 5,472 patients with CD4+T-cell counts >350 cells/mm3were recruited and randomized to either continuous ART (the viral suppression arm; VS) or CD4+T-cell count-guided use of ART (the drug conservation arm; DC).ResultsMajor CVD events developed in 79 patients. The hazard ratio (HR) for risk of CVD events for DC versus VS was 1.57 (95% confidence interval 1.00–2.46; P=0.05). There was no evidence that being off ART or a higher current HIV viral load were associated with increased CVD risk. Total cholesterol and low-density lipoprotein cholesterol were reduced as a result of ART interruption in DC patients but so was high-density lipoprotein (HDL) cholesterol, leading to a net unfavourable change in the total/HDL cholesterol ratio.ConclusionsReasons for the higher risk of CVD for DC compared with VS patients remain unclear. There was no clear evidence to suggest that ART interruption per se or a higher HIV viral load were associated with an increased CVD risk in the DC group. Lipid changes were less favourable among DC compared with VS patients, which could offer a partial explanation.

Introduction Human immunodeficiency virus (HIV) infects immune system cells by binding cell-surface CD4 and one of two coreceptors, CCR5 or CXCR4. Maraviroc (MVC) is an anti-HIV drug that binds to CCR5 and blocks HIV entry. Because MVC is ineffective against CXCR4-using viruses, it is only prescribed to patients shown to exclusively harbour CCR5-using viruses. The major obstacles to MVC being more widely used in anti-HIV therapies are (i) traditional pre-treatment prognostic “tropism tests” to determine CCR5- or CXCR4-usage are expensive and time consuming, and (ii) cheaper and rapid genotypic tropism tests have been developed only for subtype B viruses, which account for only 10% of infections worldwide. We developed PhenoSeq, a suite of reliable genotypic tropism tests for the major HIV subtypes; A, B, C, D and circulating recombinant forms of AE (CRF01_AE) and AG (CRF02_AG), which together account for 95% of infections worldwide. Methods Development of genotypic tropism tests was informed by analysis of all previously published HIV genetic sequences with corresponding coreceptor usage and subtype data (n = 2257; 630 CXCR4-using and 1637 CCR5-using), to elucidate statistically significant mutations that distinguish CXCR4- from CCR5-using viruses. The accuracy of PhenoSeq was validated against independent HIV sequences from patients previously enrolled in phase III MVC clinical trials (A4001064 and MERIT), relative to phenotypic tropism tests results. Results PhenoSeq genotypic algorithms exhibited more favourable sensitivity and specificity profiles for establishing CCR5- or CXCR4-usage of HIV subtypes A, B, C, D, CRF01_AE and CRF02_AG than alternative algorithms, including in-use algorithms geno2pheno and WebPSSM (two tailed t-test, p ≤ 0.05 considered significant). Conclusion As the only platform of algorithms that reliably infer tropism of all major global HIV subtypes, PhenoSeq may inform the use of MVC and future CCR5 blocking drugs, in particular for regions burdened most by the HIV pandemic, where non-B HIV predominates. Disclosure of interest statement JFD and FD are employees of ViiV Healthcare. PRG is a former member of the ViiV Australia scientific advisory board and has received honoraria. KC and PRG have received funding from ViiV Healthcare Australia for conference travel. KC and PRG presently receive research funding from ViiV Healthcare to further develop PhenoSeq algorithms. PRH is supported by CIHR/GSK Research Chair in Clinical Virology and has consulted and/or received grant funding from a variety pharmaceutical diagnostic companies and has received grants from, served as an ad hoc advisor to, or spoke at various events sponsored by: Pfizer, Glaxo-Smith Kline, Abbott, Merck, Selah, Tobira, Virco and Quest Diagnostics.

Background Despite HIV/STI testing rates being high (∼60%) on an annual basis in gay men in Australia, the proportion of “high risk” gay men having two or more HIV/STI tests per year, as specified in clinical guidelines, appears quite low (20%). Mathematical modelling predicts that increasing the frequency of HIV/STI testing among gay men with high numbers of sexual partners to 3–6 monthly would effectively stop the HIV and syphilis epidemics over a ten year period. We developed a multi-faceted intervention package based on information technology which aims to increase STI/HIV testing in high-risk men gay men. We describe the process and outcomes of the development stage of the intervention. Methods The intervention will be conducted over 2 years at 10–15 general practice clinics which see a high case load of gay men. These clinics provide both general healthcare and specialist sexual health and HIV management. All of these clinics utilise different patient management systems. We engaged a software company to develop a program adaptable to multiple clinic systems which aims to increase clinic efficiency and enhance sexual health testing. The process was undertaken over 12-month period in 2010 and involved extensive consultation with clinicians, stakeholders and information technology specialists. Results The program has now been developed and has four key elements: (i) passive prompts to remind clinicians when the next HIV/STI test is due based on the patient9s risk assessment profile, testing guidelines and clinic record of past testing; (ii) SMS-based recalls which are automatically sent to patients when HIV/STI testing is overdue; (iii) a sexual health resource tool bar on the computer desktop of primary care providers to provide partner notification websites, up-to-date education brochures and referral systems that support collaboration between providers; and (iv) a reporting enhancement which allows practice staff to look at their data for the achievement of best practice and data quality targets. Further details of the system and functionality will be provided in the poster. Conclusion The program is the first clinical intervention we are aware of that addresses a range of important barriers to HIV/STI testing in a single information technology program. The system is currently being rolled out into the 10–15 clinics in Sydney and the impact of this intervention will be assessed by measuring the change in HIV/STI testing rates before-and-after the program. Interviews will also be conducted with clinicians and practice managers before and after the intervention to assess barriers to testing and acceptability and transferability of the intervention.

Background Azithromycin is the recommended first-line therapy for asymptomatic rectal chlamydia. However a recent European study reported significant numbers of treatment failures, with higher failure rates in HIV positive men. In 2009, the Sydney Sexual Health Centre instituted a 6 week re-test policy for all cases of asymptomatic rectal chlamydia to assess the extent of azithromycin treatment failures. Methods We conducted a retrospective audit of all men who have sex with men (MSM) diagnosed with asymptomatic rectal chlamydia in 2009. MSM with anal symptoms were excluded from this analysis, due to the possibility of lymphogranuloma venereum. We then categorised the infections present at re-testing as probable re-infections (men reported ongoing sexual activity with an untreated partner) or probable treatment failures (men did not have any obvious ongoing exposure, either because they did not report any further anal sex with any existing partners or because condoms were used consistently with all partners). Results In the 12-month period there were 116 asymptomatic MSM treated for rectal chlamydia with 1 gram azithromycin as a single dose. Fourteen (12%) of the men were HIV positive. The median age was 33 years (range 20–64 years). Of the 116 men, 85 (73%) returned at varying times; median time of 10 weeks (78 days, range 21–372 days. Of the 85 men who returned, 11 (13%) were persistently positive and the median time to re-test was 11 weeks (78 days, range 47–209 days). Six of the 11 men were classified as probable re-infection and five as probable treatment failures, equating to an efficacy of 94%. None of the men classified as probable treatment failures were HIV positive. Conclusions Interpreted conservatively, the azithromycin treatment failure rate could have been as high as 13% in our study. However most of these cases could be explained by re-infection suggesting an actual treatment failure rate of 6%. There was no evidence azithromycin is an ineffective first-line therapy for asymptomatic rectal chlamydia in MSM, but prospective studies would be welcome.

To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients.Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts50/microL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP), stavudine + didanosine + nevirapine (d4T+ddI+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity.The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 1.29, 2.13, and 1.78 log(10) copies/mL, respectively (p =.389). The proportions of patients with HIV RNA50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 73%, 68%, and 80%, respectively (p =.71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 139, 113, and 174 cells/microL, respectively (p =.30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddI+NVP arm) ceased assigned treatment due to neuropathy.All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone.