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Background Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART. Methods Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500–599, 600–799, or ≥ 800 cells/mm3. After 36–44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. Results We enrolled 146 PWH, 36 in the 500–599, 60 in the 600–799, and 50 in the ≥ 800 CD4 strata. After 36–44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600–799 or 500–599 cells/mm3. The median level of HIV-DNA after 36–44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500–599 cells/mm3 (median [interquartile range]: 16.3 [7.0–117.6] vs 68.4 [13.7–213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females. Conclusions Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600–799 or 500–599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.

New South Wales has the greatest burden of HIV in Australia, with 2012 and 2013 recording the highest rates of new diagnoses in 20 years. Concurrently, there has been significant changes in antiretroviral treatments and testing paradigms. We compiled a statewide resistance database to characterize changes in HIV-1 resistance mutations over time. Genotypic antiretroviral resistance testing (GART) was performed on request at three reference laboratories using commercial and in-house methods. In total, 7629 HIV-1 polymerase sequences obtained from GART from 2004 to 2013 were retrospectively collated, reformatted, de-identified, and analyzed using Stanford HIVdb program 7.0 and the 2009 World Health Organization (WHO) surveillance drug resistance mutations (SDRMs). Analyses were performed on subgroups of known treatment naives, treatment experienced, and seroconverters. There has been a decrease in overall rates of prevalent drug resistance mutations from 57.8% in 2004 to 21% in 2013. Dual and triple class resistance mutations have decreased from 32.7% in 2004 to 5.8% in 2013 and 16.4% to 1.2%, respectively. In treatment-naive individuals (

Heterosexuals living with HIV report feeling additional HIV stigma compared to homosexual men, which may affect clinical outcomes. Yet, beyond routinely collected surveillance data, little is known about the characteristics of individuals who acquire HIV heterosexually and clinical outcomes by mode of sexual acquisition have not been directly compared. Using data from the Australian HIV Observational Database, we compared clinical characteristics of those with heterosexually-acquired (Het-HIV) to homosexually-acquired HIV (Hom-HIV) to investigate any differences and their implications for clinical management. 513 Het-HIV and 1467 Hom-HIV patients were included and contributed 3,127 and 9,457 person-years of follow-up, respectively. Compared with Hom-HIV, Het-HIV were more often born outside Australia (62.5% vs 39.9%, p

Human papillomavirus (HPV) causes anal warts and anal squamous cell carcinoma (SCC). A higher incidence of anal cancer has been found among individuals previously diagnosed with anogenital warts. We aimed to investigate the association between anal warts and the presumed anal SCC precursor high-grade squamous intraepithelial lesion (HSIL), among participants in the Study of the Prevention of Anal Cancer (SPANC). SPANC was a longitudinal study of anal HPV infections and related lesions among gay and bisexual men (GBM) age 35 years and older, in Sydney, Australia. Anal cytology and high-resolution anoscopy were performed. Logistic regression was used to investigate the association between clinically diagnosed anal warts and intra-anal composite-HSIL (cytology and/or histology) at the baseline visit. The prevalence of HSIL within biopsies from intra-anal warts was calculated. Laser capture microdissection (LCM) and HPV-genotyping was performed on HSIL lesions. Among 616 participants at study entry, 165 (26.8%) and 51 (8.3%) had intra-anal and perianal warts, respectively. Warts were associated with composite-HSIL, even after adjustment for HIV status, age, lifetime receptive anal intercourse partner number, and smoking (perianal: aOR 2.13, 95% CI 1.17-3.87

Objective(s) To evaluate changes in injecting and sexual risk behaviours, and hepatitis C virus (HCV) reinfection incidence among people with HIV/HCV coinfection following unrestricted access to direct-acting antiviral therapy in Australia. Design Prospective observational cohort study (2014-2018). Methods Among people enrolled in the Control and Elimination of HCV from HIV-infected individuals within Australia study, changes in injecting and sexual behaviour were evaluated, including injecting drug use (IDU) in the last 6 months and last month, frequency of IDU and equipment sharing, condom-less anal intercourse with casual male partner(s), and group sex. HCV reinfection incidence was evaluated with follow-up through May 2018. Results Overall, 272 HIV/HCV antibody-positive participants [median age; 50 years, 96% male, 83% identified as gay and bisexual men (GBM)] had behavioural data at enrolment and follow-up (median 2.91 years) available for analysis. The proportion reporting IDU in the last 6 months remained stable from enrolment (35%) to follow-up (39%). Among GBM, the proportion reporting condom-less anal intercourse with casual partner(s) at enrolment (48%) and follow-up (46%) was also similar. Reinfection was detected in five individuals (all GBM) during total follow-up of 474 person-years for an overall incidence of 1.05 per 100 person-years (95% confidence interval, 0.44-2.53). Conclusion No change was observed in levels of injecting or sexual risk behaviour for HCV infection following unrestricted access to direct-acting antiviral therapy in an Australian HIV/HCV cohort. Incidence of HCV reinfection was low potentially reflecting high levels of treatment coverage within this population. Continued screening and rapid retreatment of reinfection will be required to maintain progress towards elimination.

Medical comorbidities occur in more persons with HIV than without HIV. We used a nationally representative 10% sample of 2016 Pharmaceutical Benefits Scheme (PBS) dispensing data to compare the proportions of antiretroviral therapy (ART)-purchasing and non-ART-purchasing patients who also purchased prescriptions for medical comorbidities. Each patient who purchased ART was compared with two gender- and age group-matched patients who did not purchase ART in the same year. We calculated the proportions of patients who also purchased coprescriptions used for hypertension, dyslipidemia, diabetes, cancer, low bone mineral density, and mental health, defined using PBS medication coding categories, and the resulting odds ratios. A total of 1,973 ART-purchasing patients in our sample were matched to 3,946 non-ART-purchasing patients. Compared with non-ART-purchasing patients, a greater proportion of ART-purchasing patients also purchased medications for dyslipidemia (19.8% vs. 16.6%

IntroductionVaccines against human papillomavirus (HPV) are the key to controlling cervical cancer in low/middle-income countries (LMICs) where incidence is highest, but there have been limited data from these settings on programme impact on HPV prevalence, and none in a population with endemic HIV infection. Furthermore, for many LMICs, the currently recommended two-dose schedule is difficult to deliver at scale, so there is mounting interest in a single-dose schedule.Methods and analysisThe Human Papillomavirus One and Two-Dose Population Effectiveness Study is a hybrid impact evaluation of the national South African HPV vaccination programme, which has targeted grade 4 girls aged at least 9 years in public schools with two doses of vaccine since 2014, and a single-dose vaccine ‘catch-up’ programme delivered in one district in 2019. Impacts of both schedules on the prevalence of type-specific HPV infection will be measured using repeat cross-sectional surveys in adolescent girls and young women aged 17–18 years recruited at primary healthcare clinics in the four provinces. A baseline survey in 2019 measured HPV prevalence in the cohort who were ineligible for vaccination because they were already above the target age or grade under either the national programme or the single-dose programme in the selected district. HPV prevalence surveys are repeated in 2021 in the selected district, and in 2023 in all four provinces. We will calculate prevalence ratios to compare the prevalence of HPV types 16 and 18 in the single-dose (2021) and two-dose (2023) cohorts, with the vaccine-ineligible (2019) cohort.Ethics and disseminationThe project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC #181005), and the University of New South Wales HREC (#181-005). Findings will be disseminated through peer-reviewed journals, scientific meetings, reports and community forums.

Background South Africa implemented universal test and treat (UTT) in September 2016 in an effort to encourage earlier initiation of antiretroviral therapy (ART). Methods We therefore conducted an interrupted time series (ITS) analysis to assess the impact of UTT on mean CD4 count at ART initiation among adults aged ≥16 years attending 17 public sector primary care clinics in rural South Africa, between July 2014 and March 2019. Results Among 20 599 individuals (69% women), CD4 counts were available for 74%. Mean CD4 at ART initiation increased from 317.1 cells/μL (95% confidence interval [CI], 308.6 to 325.6) 1 to 8 months prior to UTT to 421.0 cells/μL (95% CI, 413.0 to 429.0) 1 to 12 months after UTT, including an immediate increase of 124.2 cells/μL (95% CI, 102.2 to 146.1). However, mean CD4 count subsequently fell to 389.5 cells/μL (95% CI, 381.8 to 397.1) 13 to 30 months after UTT but remained above pre-UTT levels. Men initiated ART at lower CD4 counts than women (–118.2 cells/μL, 95% CI, –125.5 to –111.0) throughout the study. Conclusions Although UTT led to an immediate increase in CD4 count at ART initiation in this rural community, the long-term effects were modest. More efforts are needed to increase initiation of ART early in those living with human immunodeficiency virus, particularly men.

Summary Background Most studies assessing the HIV care cascade have typically been cross-sectional analyses, which do not capture the transition time to subsequent stages. We aimed to assess the longitudinal HIV cascade of care in Australia, and changes over time in transition times and associated factors. Methods In this longitudinal cohort study, we included linked data for gay and bisexual men (GBM) with a new HIV diagnosis who attended clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance in New South Wales and Victoria between Jan 1, 2012, and Dec 31, 2019. We assessed three cascade transition periods: diagnosis to linkage to care (stage 1 transition); linkage to care to antiretroviral therapy (ART) initiation (stage 2 transition); and ART initiation to virological suppression (viral load ≤200 copies per mL; stage 3 transition). We also calculated the probability of remaining virologically suppressed after the first recorded viral load of less than 200 copies per mL. We used the Kaplan-Meier method to estimate transition times and cumulative probability of stage transition. Findings We included 2196 GBM newly diagnosed with HIV between 2012 and 2019 contributing 6747 person-years of follow-up in our analysis. Median time from HIV diagnosis to linkage to care (stage 1 transition) was 2 days (IQR 1–3). Median time from linkage to care to ART initiation (stage 2 transition) was 33 days (30–35). Median time from ART initiation to first recorded virological suppression (stage 3 transition) was 49 days (47–52). The cumulative probability of ART initiation within 90 days of linkage to care increased from 36·9% (95% CI 32·9–40·6) in the 2012–13 calendar period to 94·1% (91·2–96·0) in the 2018–19 calendar period and cumulative probability of virological suppression within 90 days of ART initiation increased from 54·3% (48·8–59·3) in the 2012–13 calendar period to 82·9% (78·4–86·4) in the 2018–19 calendar period. 91·6% (90·1–93·1) of GBM remained virologically supressed up to 2 years after their first recorded virological suppression event. Interpretation In countries with high cross-sectional cascade estimates such as Australia, the impact of treatment as prevention is better estimated using longitudinal cascade analyses. Funding National Health and Medical Research Council Australia.

To compare the incidence of dyslipidemia in people with HIV receiving integrase inhibitors (INSTI) versus boosted protease inhibitors (PI/b) and nonnucleoside reverse transcriptase inhibitors (NNRTI) within RESPOND consortium of prospective cohorts.Participants were eligible if they were at least 18 years, without dyslipidemia and initiated or switched to a three-drug antiretroviral therapy (ART)-regimen consisting of either INSTI, NNRTI, or PI/b for the first time, between 1 January 2012 and 31 December 2018. Dyslipidemia was defined as random total cholesterol more than 240 mg/dl, HDL less than 35 mg/dl, triglyceride more than 200 mg/dl, or initiation of lipid-lowering therapy. Poisson regression was used to determine the adjusted incidence rate ratios. Follow-up was censored after 3 years or upon ART-regimen discontinuation or last lipid measurement or 31 December 2019, whichever occurred first.Overall, 4577 people with HIV were eligible (INSTI = 66.9%, PI/b = 12.5%, and NNRTI = 20.6%), 1938 (42.3%) of whom were ART-naive. During 1.7 (interquartile range, 0.6-3.0) median years of follow-up, 1460 participants developed dyslipidemia [incidence rate: 191.6 per 1000 person-years, 95% confidence interval (CI) 182.0-201.7]. Participants taking INSTI had a lower incidence of dyslipidemia compared with those on PI/b (adjusted incidence rate ratio 0.71; CI 0.59-0.85), but higher rate compared with those on NNRTI (1.35; CI 1.15-1.58). Compared with dolutegravir, the incidence of dyslipidemia was higher with elvitegravir/cobicistat (1.20; CI 1.00-1.43) and raltegravir (1.24; CI 1.02-1.51), but lower with rilpivirine (0.77; CI 0.63-0.94).In this large consortium of heterogeneous cohorts, dyslipidemia was less common with INSTI than with PI/b. Compared with dolutegravir, dyslipidemia was more common with elvitegravir/cobicistat and raltegravir, but less common with rilpivirine.

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV

Background: We evaluated continuous quality improvement (CQI) targeting antenatal HIV care quality in rural South Africa using a stepped-wedge cluster-randomised controlled trial (Management and Optimisation of Nutrition, Antenatal, Reproductive, Child health, MONARCH) and an embedded process evaluation. Here, we present results of the process evaluation examining determinants of CQI practice and ‘normalisation.’ Methods: A team of CQI mentors supported public-sector health workers in seven primary care clinics to (1) identify root causes of poor HIV viral load (VL) monitoring among pregnant women living with HIV and repeat HIV testing among pregnant women not living with HIV, and (2) design and iteratively test their own solutions. We used a mixed methods evaluation with field notes from CQI mentors (‘dose’ and ‘reach’ of CQI, causes of poor HIV care testing rates, implemented change ideas); patient medical records (HIV care testing by clinic and time step); and semi-structured interviews with available health workers. We analysed field notes andsemi-structured interviews for determinants of CQI implementation and ‘normalisation’ using Normalisation Process Theory (NPT) and Tailored Implementation of Chronic Diseases (TICD) frameworks. Results: All interviewed health workers found the CQI mentors and methodology helpful for quality improvement. Total administered ‘dose’ was higher than planned but ‘reach’ was limited by resource constraints, particularly staffing shortages. Simple workable improvements to identified root causes were implemented, such as a patient tracking notebook and results filing system. VL monitoring improved over time, but not repeat HIV testing. Besides resource constraints, gaps in knowledge of guidelines, lack of leadership, poor clinical documentation, and data quality gaps reduced CQI implementation fidelity and normalisation. Conclusion: While CQI holds promise, we identified several health system challenges. Priorities for policy makers include improving staffing and strategies to improve clinical documentation. Additional support with implementing clinical guidelines and improving routine data quality are needed. Normalising CQI may be challenging without concurrent health system improvements.

Objectives: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. Methods: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12±3months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL'200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4count '750cells/μL or a 33% increase where the baseline CD4 count was ≥500 cells/μL. Poisson regression compared clinical failures (AIDS/death≥14days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. Results: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged ' 50years, 2539 (49.4%) had CD4 counts '350 cells/μL and 1891 (36.8%) had VL'100000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40–50 and '50 years), CD4 count categories (≤ 350 vs. '350 cells/μL) and VL categories at ART initiation (≤ 100000 vs. '100000copies/mL), with all investigated interactions being nonsignificant (P'0.05). Conclusions: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

Background We investigate whether correct infant feeding knowledge and practice differ by maternal HIV status in an era of evolving clinical guidelines in rural South Africa. Methods This cohort study was nested within the MONARCH stepped-wedge cluster-randomised controlled trial (www.clinicaltrials.gov: NCT02626351) which tested the impact of continuous quality improvement on antenatal care quality at seven primary care clinics in KwaZulu-Natal, from July 2015 to January 2017. Women aged ≥18 years at delivery were followed up to 6 weeks postpartum. Clinical data were sourced from routine medical records at delivery. Structured interviews at early postnatal visits and the 6-week postnatal immunisation visit provided data on infant feeding knowledge and feeding practices respectively. We measured the relationship between maternal HIV status and (i) correct infant feeding knowledge at the early postnatal visit; and (ii) infant feeding practice at 6 weeks, using Poisson and multinomial regression models, respectively. Results We analysed data from 1693 women with early postnatal and 471 with 6-week postnatal interviews. HIV prevalence was 47% (95% confidence interval [CI] 42, 52%). Women living with HIV were more knowledgeable than women not living with HIV on correct infant feeding recommendations (adjusted risk ratio, aRR, 1.08, p p p Conclusions Many mothers in rural South Africa still do not practice exclusive breastfeeding. Women living with HIV were more knowledgeable but had lower overall uptake of breastfeeding, compared with women not living with HIV. Women living with HIV were also more likely to practice exclusive breastfeeding over mixed feeding if currently breastfeeding. Improved approaches are needed to increase awareness of correct infant feeding and exclusive breastfeeding uptake.

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.

Objectives: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM). Methods: We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional sample of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged >= 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities. Results: Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2%; stroke, 7.5 versus 4.2%; thrombosis, 10.5 versus 4.2%; and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99; P = 0.03] and thrombosis (aOR 2.87; P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM; P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score. Conclusions: HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population.

Objectives Cohort studies are often used as a national surveillance tool to monitor trends in HIV treatment and morbidity outcomes. However, there are limited studies validating the accuracy of using cohorts as a representation of the overall HIV-positive population. We compared data from a large Australian HIV-positive cohort study (Australian HIV Observational Database [AHOD]) and a 10% longitudinal sample from Australia's subsidized prescription medication scheme (Pharmaceutical Benefits Scheme [PBS]) to assess the use of cohorts for providing representative data for surveillance and monitoring purposes. Study Design and Setting Basic demographics and treatment information from July 1, 2013, to March 31, 2016, were divided into half-yearly periods to compare HIV trends between AHOD (n = 2,488) and PBS (n = 18,409) patients. Results In both data sets, most patients were men, aged above 50 years, and primarily resided in New South Wales. Both data sets revealed a significant shift toward the increased use of integrase strand transfer inhibitors and a gradual decline in the use of protease inhibitors and nonnucleoside reverse-transcriptase inhibitors among the treated population in Australia. Similarly, a substantial increase in the use of once daily, single-tablet, fixed-dose combination regimens was also observed. Conclusion Our results show that observational cohort studies can serve as useful surrogate surveillance tools for monitoring patient characteristics and HIV treatment trends.

OBJECTIVE To determine the long-term incidence of glucose disorders in treated HIV infection, associations with traditional and HIV-specific risk factors. METHODS Observational cohort of 104 men with treated HIV infection and without diabetes, aged 43 ± 8 years at baseline, with (mean ± SD) 11.8 ± 3.5 years follow-up. Ascertainment of glucose status by fasting glucose or, in a subset (n = 33), a 75 g oral glucose tolerance test by 10-12 years follow-up. A subset underwent sequential body composition measures (n = 58) to determine changes in total body and central abdominal adiposity. RESULTS The cumulative incidence of glucose disorders was 48.1% (prediabetes 35.6%, diabetes 12.5%), with an incidence rate of 34.5/1000 years of patient follow-up (PYFU) (prediabetes: 24.3/1000 PYFU; diabetes: 10.2/1000 PYFU). Incident glucose disorders were independently associated with higher age (44.9 ± 8.4 vs. 41.1 ± 7.5 years, P = 0.027), baseline C-peptide (2.9 ± 1.3 vs. 2.4 ± 1.1 ng/ml, P = 0.019) and baseline 2-h glucose (135 ± 41 vs. 95 ± 25 mg/dl, P

Objectives To compare virologic and immunologic outcomes of integrase inhibitor (INSTI)-containing, contemporary boosted protease inhibitor (PI/b)-containing and non-nucleotide reverse transcriptase inhibitor (NNRTI)-containing regimens in a real-life setting. Methods Using logistic regression, virologic and immunologic outcomes of INSTI use were compared to outcomes of PI/b or NNRTI treatment 12 months after treatment start or switch, for participants in the RESPOND cohort consortium. A composite treatment outcome (cTO) was used, defining success as viral load (VL), SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: Weight gain is common among people with HIV once antiretroviral treatment is commenced. We assess the effect of changes in body mass index (BMI), from different baseline BMI levels, on the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). METHODS: D:A:D participants receiving antiretroviral treatment were followed from their first BMI measurement to the first of either CVD or DM event, or earliest of January 2, 2016 or 6 months after last follow-up. Participants were stratified according to their baseline BMI, and changes from baseline BMI were calculated for each participant. Poisson regression models were used to assess the effects of changes on BMI on CVD or DM events. RESULTS: There were 2104 CVD and 1583 DM events over 365,287 and 354,898 person-years [rate: CVD 5.8/1000 (95% confidence interval: 5.5 to 6.0); DM 4.5/1000 (95% confidence interval: 4.2 to 4.7)]. Participants were largely men (74%), baseline mean age of 40 years, and median BMI of 23.0 (IQR: 21.0-25.3). A risk of CVD by change in BMI from baseline, stratified by baseline BMI strata showed little evidence of an increased risk of CVD with an increased BMI in any baseline BMI strata. An increase in BMI was associated with an increased risk of DM across all baseline BMI strata. CONCLUSIONS: Although increases in BMI across all levels of baseline BMI were not associated with an increased risk of CVD, such changes were consistently associated with an increased risk of DM. There was also some evidence of an increased risk of CVD with a decrease in BMI.

In Australia HIV notifications are increasing among overseas-born men who have sex with men (MSM) and particularly among Asian-born MSM.1 Despite the ‘test and treat early’ paradigm in Australia, a steady proportion of people are diagnosed with late HIV infection and a large proportion (35%) of these are from East Asian countries.1 Globally, marginalised populations are reported to experience inequalities in treatment uptake and response. Although these inequalities are not consistent across all ethnic subpopulations,2 and once accounting for CD4 count at diagnosis, ethnicity might not be a factor at all.3 Australian evidence suggests that culturally and/or linguistically diverse populations are less likely to start treatment early irrespective of CD4 cell count at diagnosis,4 but little is known about response once in care. The Australian HIV Observational Database (AHOD) is used to investigate treatment response in overseas-born MSM from non-English-speaking countries compared with Australian-born MSM, further categorised based on participation in the Australian Temporary Residents Access Study (ATRAS).5 The Australian government provides fully subsidised antiretroviral therapy (ART) through the Pharmaceutical Benefits Scheme, but to receive ART patients must be entitled to a Medicare card. ATRAS participants were temporary residents ineligible for Medicare and were chosen as the closest surrogate to identifying the newly arrived overseas-born MSM. Time to first virological suppression (VS) (viral load (VL)

Background Microelimination of hepatitis C virus (HCV) among people living with human immunodeficiency virus (HIV) may be feasible in Australia, given unrestricted access to direct-acting antiviral (DAA) therapy from 2016. Our aim was to evaluate progress towards elimination goals within HIV/HCV-coinfected adults in Australia following universal DAA access. Methods The CEASE prospective cohort study enrolled adults with HIV/HCV, irrespective of viremic status, from 14 primary and tertiary clinics in Australia. Annual and cumulative HCV treatment uptake, outcome, and HCV RNA prevalence were evaluated, with follow-up through May 2018 (median follow-up, 2.63 years). Factors associated with DAA uptake were analyzed. Results Between July 2014 and March 2017, 402 participants who were HIV/HCV antibody positive were enrolled (95% male [80% gay and bisexual men,], 13% cirrhosis, 80% history of injecting drug use [39% currently injecting]). Following universal DAA access, annual HCV treatment uptake in those eligible increased from 7% and 11% per year in 2014 and 2015, respectively, to 80% in 2016. By 2018, cumulative HCV treatment uptake in those ever eligible for treatment was 91% (336/371). HCV viremic prevalence declined from 82% (95% CI, 78–86%) in 2014 to 8% (95% CI, 6–12%) in 2018. Reinfection was reported in only 5 participants for a reinfection incidence of 0.81 per 100 person-years (95% CI, 0.34–1.94). Conclusions High uptake and effectiveness of unrestricted DAA therapy in Australia have permitted rapid treatment scale-up, with a dramatic reduction in HCV infection burden and low reinfection rate among people living with HIV, suggesting that microelimination is feasible. Clinical Trials Registration NCT02102451.

BACKGROUND Prevalence of anxiety and mood disorders (AMDs) in HIV-infected individuals has varied widely because of the variety of measurements used and differences in risk factor profiles between different populations. We aimed to examine the relationship between HIV status and hospitalization for AMDs in gay and bisexual men (GBM). DESIGN AND METHODS HIV-infected (n = 557) and HIV-uninfected (n = 1325) GBM recruited in Sydney, Australia were probabilistically linked to their hospital admissions and death notifications (2000-2012). Random-effects Poisson models were used to assess HIV risk factors for hospitalization. Cox regression methods were used to assess risk factors for mortality. RESULTS We observed 300 hospitalizations for AMDs in 15.3% of HIV-infected and 181 in 5.4% of HIV-uninfected participants. Being infected with HIV was associated with a 2.5-fold increase in risk of hospitalization for AMDs in GBM. Other risk factors in the HIV-infected cohort included previous hospitalization for HIV-related dementia, a more recent HIV diagnosis, and a CD4 T-cell count above 350 cells per cubic millimeter. Being hospitalized for an AMD was associated with a 5.5-fold increased risk of mortality; this association did not differ by HIV status. An association between substance use and mortality was observed in individuals hospitalized for AMDs. CONCLUSIONS There is a need to provide more effective strategies to identify and treat AMDs in HIV-infected GBM. This research highlights the importance of further examination of the effects of substance use, neurocognitive decline, and AMDs on the health of HIV-infected individuals.

Background Previous studies suggest that nonnucleoside reverse-transcriptase inhibitors (NNRTIs) cause faster virologic suppression, while ritonavir-boosted protease inhibitors (PI/r) recover more CD4 cells. However, individual trials have not been powered to compare clinical outcomes. Methods We searched databases to identify randomized trials that compared NNRTI- vs PI/r-based initial therapy. A metaanalysis calculated risk ratios (RRs) or mean differences (MDs), as appropriate. Primary outcome was death or progression to AIDS. Secondary outcomes were death, progression to AIDS, and treatment discontinuation. We calculated RR of virologic suppression and MD for an increase in CD4 cells at week 48. Results We included 29 trials with 9047 participants. Death or progression to AIDS occurred in 226 participants in the NNRTI arm and in 221 in the PI/r arm (RR, 1.03; 95% confidence interval, .87-1.22; 12 trials; n = 3825), death in 205 participants in the NNRTI arm vs 198 in the PI/r arm (1.04; 0.86-1.25; 22 trials; n = 8311), and progression to AIDS in 140 participants in the NNRTI arm vs 144 in the PI/r arm (1.00; 0.80-1.25; 13 trials; n = 4740). Overall treatment discontinuation (1.12; 0.93-1.35; 24 trials; n = 8249) and from toxicity (1.21; 0.87-1.68; 21 trials; n = 6195) were comparable, but discontinuation due to virologic failure was more common with NNRTI (1.58; 0.91-2.74; 17 trials; n = 5371). At week 48, there was no difference between NNRTI and PI/r in virologic suppression (RR, 1.03; 0.98-1.09) or CD4(+) recovery (MD, -4.7 cells; -14.2 to 4.8). Conclusions We found no difference in clinical and viro-immunologic outcomes between NNRTI- and PI/r-based therapy.

The aim of this study was to understand factors associated with increased mortality in a cohort of primary HIV infection (PHI) in New South Wales (NSW) over three decades. Six hundred and two patients with PHI were enrolled from 1984 to 2009. Probabilistic data linkage was performed to NSW Registry of births deaths and marriages and Australian Bureau of Statistics mortality database. Mortality was measured by crude death rate. Pre highly active antiretroviral therapy (pre-HAART) era was defined as before January 1, 1997. A Cox proportional hazard model was used to identify factors associated with death. One hundred and thirty-eight deaths occurred during 6,223 person years (PY) follow-up. Overall crude death rate was 2.2 per 100 PY (95% confidence interval [CI], 1.9–2.6), 3.6 (95% CI, 3.1–4.3)in pre-HAART era and 0.20 (95% CI, 0.08–0.47) in post-HAART era. AIDS was the most frequent cause of death (52%, 72/138), all occurring in the pre-HAART era. Of non-AIDS deaths, the leading known cause was non-AIDS cancer 8% (11/138) followed by suicide 4% (6/138). On multivariate analysis, estimated date of infection in pre-HAART era and time to commencement of ART greater than 1 year post diagnosis were more likely to be associated with death (p

Background Current antiretroviral therapy is effective in controlling HIV-1 infection. However, cessation of therapy is associated with rapid return of viremia from the viral reservoir. Eradicating the HIV-1 reservoir has proven difficult with the limited success of latency reactivation strategies and reflects the complexity of HIV-1 latency. Consequently, there is a growing need for alternate strategies. Here we explore a “block and lock” approach for enforcing latency to render the provirus unable to restart transcription despite exposure to reactivation stimuli. Reactivation of transcription from latent HIV-1 proviruses can be epigenetically blocked using promoter-targeted shRNAs to prevent productive infection. We aimed to determine if independent and combined expression of shRNAs, PromA and 143, induce a repressive epigenetic profile that is sufficiently stable to protect latently infected cells from HIV-1 reactivation when treated with a range of latency reversing agents (LRAs). Results J-Lat 9.2 cells, a model of HIV-1 latency, expressing shRNAs PromA, 143, PromA/143 or controls were treated with LRAs to evaluate protection from HIV-1 reactivation as determined by levels of GFP expression. Cells expressing shRNA PromA, 143, or both, showed robust resistance to viral reactivation by: TNF, SAHA, SAHA/TNF, Bryostatin/TNF, DZNep, and Chaetocin. Given the physiological importance of TNF, HIV-1 reactivation was induced by TNF (5 ng/mL) and ChIP assays were performed to detect changes in expression of epigenetic markers within chromatin in both sorted GFP− and GFP+ cell populations, harboring latent or reactivated proviruses, respectively. Ordinary two-way ANOVA analysis used to identify interactions between shRNAs and chromatin marks associated with repressive or active chromatin in the integrated provirus revealed significant changes in the levels of H3K27me3, AGO1 and HDAC1 in the LTR, which correlated with the extent of reduced proviral reactivation. The cell line co-expressing shPromA and sh143 consistently showed the least reactivation and greatest enrichment of chromatin compaction indicators. Conclusion The active maintenance of epigenetic silencing by shRNAs acting on the HIV-1 LTR impedes HIV-1 reactivation from latency. Our “block and lock” approach constitutes a novel way of enforcing HIV-1 “super latency” through a closed chromatin architecture that renders the virus resistant to a range of latency reversing agents. Electronic supplementary material The online version of this article (10.1186/s12977-018-0451-0) contains supplementary material, which is available to authorized users.

Background Treatment guidelines for antiretroviral therapy (ART) have evolved to emphasize newer regimens that address ageing-related comorbidities. Using national Australian dispensing data we compare ART regimens with Australian HIV treatment guidelines in the context of treated comorbidities. Methods The study population included all individuals in a 10% sample of national data from the Australian Pharmaceutical Benefits Scheme (PBS) who purchased a prescription of ART during 2016. We defined each patient’s most recently dispensed ART regimen and characterized them to evaluate regimen complexity and adherence to national HIV treatment guidelines. We then analyzed ART regimens in the context of other co-prescriptions purchased for defined comorbidities. Results The 1995 patients in our sample purchased 212 different ART regimens during 2016; 1524 (76.4%) purchased one of the top ten most common regimens of which 62.3% were integrase strand transfer inhibitor-based. Among the 1786 (90%) patients that purchased the most common regimens, 83.7% purchased a regimen recommended by the guidelines for initial antiretroviral therapy and 11.4% purchased antiretrovirals that are not recommended for initial therapy

OBJECTIVES: To determine trends in and predictors of early treatment for people newly diagnosed with human immunodeficiency virus (HIV) infection in Australia. DESIGN, SETTING: Retrospective cohort analysis of routinely collected longitudinal data from 44 sexual health clinics participating in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) program. PARTICIPANTS: Patients diagnosed with HIV infections, January 2004 - June 2015. MAIN OUTCOME MEASURES: Commencement of antiretroviral therapy within 6 months of HIV diagnosis (early treatment); demographic, clinical, and risk group characteristics of patients associated with early treatment; trends in early treatment, by CD4+ cell count at diagnosis. RESULTS: 917 people were diagnosed with HIV infections, their median age was 34 years (interquartile range [IQR]: 27-43 years), and 841 (92%) were men; the median CD4+ cell count at diagnosis was 510 cells/μL (IQR, 350-674 cells/μL). The proportion of patients who received early treatment increased from 17% (15 patients) in 2004-06 to 20% (34 patients) in 2007-09, 34% (95 patients) in 2010-12, and 53% (197 patients) in 2013-15 (trend, P

Objectives There is evidence that HIV-positive patients are suffering from a greater burden of morbidity as they age due to nonAIDS-related complications. To date it has been difficult to determine what part of this excess risk is due to the health effects of HIV, its treatment or to lifestyle factors common to gay and bisexual men (GBM). We calculated overall and cause-specific hospitalisation rates and risk factors for hospitalisations in HIV-negative and HIV-positive cohorts of GBM and compare these with rates in the general male population. Methods We conducted a record linkage study, linking two cohorts of HIV-negative (n = 1325) and HIV-positive (n = 557) GBM recruited in Sydney, New South Wales (NSW), Australia with the NSW hospital discharge data register. We compared rates of hospitalisation in the two cohorts and risk factors for hospitalisation using random-effects Poisson regression methods. Hospitalisation rates for each cohort were further compared with those in the general male population using indirect standardisation. Results We observed 2032 hospitalisations in the HIV-negative cohort during 13 016 person-years (PYs) [crude rate: 15.6/100PYs (95% CI: 14.9–16.3)] and 2130 hospitalisations in the HIV-positive cohort during 5571 PYs [crude rate: 38.2/100PYs (95% CI: 36.6–39.9)]. HIV-positive individuals had an increased risk of hospitalisation compared with the HIV-negative individuals [adjusted-IRR: 2.34 (95% CI: 1.91–2.86)] and the general population [SHR: 1.45 (95% CI: 1.33–1.59)]. Hospitalisation rates were lower in the HIV-negative cohort compared with the general population [SHR: 0.72 (95% CI: 0.67–0.78)]. The primary causes of hospitalisation differed between groups. Conclusions HIV-positive GBM continue to experience excess morbidity compared with HIV-negative GBM men and the general population. HIV-negative GBM had lower morbidity compared with the general male population suggesting that GBM identity does not confer excess risk.

Multimorbidity and unplanned admissions are common among people with human immunodeficiency virus (PWH).To determine factors predictive of unplanned admission among PWH in regional New South Wales and compare care coordination between people with and without unplanned admissions.A prospective cohort study of PWH attending a regional human immunodeficiency virus (HIV) service was conducted. Baseline HIV-specific results and multimorbidity markers including Cumulative Illness Rating Scale (CIRS) were assessed as predictors of time to first unplanned admission using Cox regression analysis. Care coordination markers were compared between people with and without unplanned admission, using χA cohort of 181 PWH was followed for a maximum of 5 years. During a total of 739 person-years of follow up, 39 (20.6%) patients reached the endpoint of unplanned admission. In multivariate analysis, the baseline CIRS score was predictive of unplanned admission (P0.001). Age, HIV-specific markers and missed visits were not predictive of unplanned admission. For patients with an unplanned admission, discharge summaries were documented for 22/39 (56.4%). Of 180 PWH with a visit after baseline, 131 (72.8%) had a letter to a general practitioner and 79 (43.7%) had two or more prescribers. Having two or more prescribers was more common in people with an unplanned admission than in those without (64.1% vs 38.0%, P = 0.004).Unplanned admission among PWH is predicted by multimorbidity. Care for PWH should include coordinated management of other health conditions in order to reduce their severity and prevent unplanned admissions.

AIM: To examine data from the Australian HIV Observational Database (AHOD) to, firstly, describe the incidence of chronic kidney disease (CKD) and rate of loss of renal function in HIV-infected individuals living in Australia, and then to examine the risk factors contributing to CKD in this population. METHODS: AHOD patients over 18 years of age were eligible if they had at least two serum creatinine measurements from 1 April 2008 until 31 March 2016 and an initial estimated glomerular filtration rate (eGFR) greater than 60mL/min/1.73m(3). Cox proportional hazards models were used to assess risk factors for CKD, which included key patient demographic data and antiretroviral therapy (ART) exposure. RESULTS: Of 1924 patients included in the analysis between April 2008 and March 2016, 81 (4.2%) developed CKD (confirmed eGFR of less than 60mL/min/1.73m(3) through two consecutive eGFR measurements at least three months apart). Of the examined risk factors, baseline age, baseline eGFR, and the route of HIV acquisition were statistically significant predictors of development of CKD. ART exposure, viral hepatitis co-infection, high viral load and low CD4 lymphocyte count were not found to be significant risk factors for CKD. CONCLUSION: This is the first study to investigate the risk factors for development of CKD amongst Australian HIV-infected patients using cohort data. It highlights the need for awareness of renal risk factors, particularly amongst older patients or in those with pre-existing renal dysfunction. Further research is required to explore the discrepancy between patients who have acquired HIV through different means of exposure.

Background In the era of effective antiretroviral treatment (ART) CD4:CD8 ratio is proposed as a potential marker for HIV-positive (HIV+) patients at increased risk for non-AIDS comorbidities. The current study aims to compare CD4:CD8 ratio between Asian and Caucasian HIV+ patients. Methods HIV+ patients from the Australian HIV Observational Database (AHOD) and the TREAT Asia HIV Observational Database (TAHOD) meeting specific criteria were included. In these analyses Asian and Caucasian status were defined by cohort. Factors associated with a low CD4:CD8 ratio (cutoff 1) at 12 and 24 months post ART commencement were assessed using logistic regression. Results There were 591 patients from AHOD and 2,620 patients from TAHOD who met the inclusion criteria. TAHOD patients had a significantly ( P1 ( P=0.475). Conclusions We found a significantly lower CD4:CD8 ratio prior to commencing ART in TAHOD compared to AHOD even after adjusting for confounders. However, after adjustment, there was no significant difference between the cohorts in odds of achieving normal ratio. Baseline CD4+ and CD8+ counts seem to be the main driver for this difference between these two populations.

BACKGROUND: Recent studies suggest higher cumulative HIV viremia exposure measured as viremia copy-years (VCY) is associated with increased all-cause mortality. The objectives of this study are (1) report the association between VCY and all-cause mortality and (2) assess associations between common patient characteristics and VCY. METHODS: Analyses were based on patients recruited to the Australian HIV Observational Database (AHOD) who had received ≥24 weeks of antiretroviral therapy (ART). We established VCY after 1, 3, 5, and 10 years of ART by calculating the area under the plasma viral load time series. We used survival methods to determine the association between high VCY and all-cause mortality. We used multivariable mixed-effect models to determine predictors of VCY. We compared a baseline information model with a time-updated model to evaluate discrimination of patients with high VCY. RESULTS: Of the 3021 AHOD participants who initiated ART, 2073 (69%), 1667 (55%), 1267 (42%), and 638 (21%) were eligible for analysis at 1, 3, 5, and 10 years of ART, respectively. Multivariable-adjusted hazard ratio association between all-cause mortality and high VCY was statistically significant, hazard ratio 1.52 (1.09, 2.13), P = 0.01. Predicting high VCY after 1 year of ART for a time-updated model compared with a baseline information model, the area under the sensitivity/specificity curve was 0.92 vs. 0.84; and at 10 years of ART, area under the sensitivity/specificity curve was 0.87 vs. 0.61, respectively. CONCLUSION: A high cumulative measure of viral load after initiating ART is associated with increased risk of all-cause mortality. Identifying patients with high VCY is improved by incorporating time-updated information. © 2013 by Lippincott Williams and Wilkins.

Objective: Combination antiretroviral therapy (cART) has greatly improved the life expectancy of people living with HIV (PLHIV). Our study aims to project the life expectancy of PLHIV in a resource-rich setting in the context of the currently available antiretroviral treatments. Methods: Patient antiretroviral treatment data were sourced from an observational cohort of 3434 predominantly male (94.2%) PLHIV in Australia over the period 1997– 2010. These data were analyzed in a computer simulation model to calculate the distribution of time until exhaustion of all treatment options and expected effect on mortality. Standardized mortality ratios were used to simulate expected survival before and after treatment exhaustion. Results: We estimated that the median time until exhaustion of currently available treatment options is 45.5 years [interquartile range (IQR) 34.0–61.0 years]. However, 10% of PLHIV are expected to exhaust all currently available cART options after just 25.6 years. PLHIV who start currently available cART regimens at age 20 years are expected to live to a median age of 67.4 (IQR 53.2–77.7) years. This is a substantial improvement on no cART [27.7 (IQR 23.8–32.0) years] but is still substantially less than the median general population mortality age [82.2 (IQR 74.0–87.8) years]. The life expectancy gap between PLHIV and the general population is greatest for those infected at younger ages. Conclusion: As treatment options are exhausted, a substantial difference in life expectancy between PLHIV and the general population could be expected even in resourcerich settings, particularly for people who acquire HIV at a younger age or who are currently highly treatment experienced. 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2013, 27:1245–1251

Background: Australia has increased coverage of antiretroviral treatment (ART) over the past decade, reaching 73% uptake in 2014. While ART reduces AIDS-related deaths, accumulating evidence suggests that it could also bolster prevention efforts by reducing the risk of HIV transmission ('treatment as prevention'). While promising, evidence of community-level impact of treatment as prevention on reducing HIV incidence among gay and bisexual men is limited. We describe a study protocol that aims to determine if scale up of testing and treatment for HIV leads to a reduction in community viraemia and, in turn, if this reduction is temporally associated with a reduction in HIV incidence among gay and bisexual men in Australia's two most populous states. Methods: Over the period 2009 to 2017, we will establish two cohorts making use of clinical and laboratory data electronically extracted retrospectively and prospectively from 73 health services and laboratories in the states of New South Wales and Victoria. The 'positive cohort' will consist of approximately 13,000 gay and bisexual men (>90% of all people living with HIV). The 'negative cohort' will consist of at least 40,000 HIV-negative gay and bisexual men (approximately half of the total population). Within the negative cohort we will use standard repeat-testing methods to calculate annual HIV incidence. Community prevalence of viraemia will be defined as the proportion of men with a viral load ≥200RNA copies/mm3, which will combine viral load data from the positive cohort and viraemia estimates among those with an undiagnosed HIV infection. Using regression analyses and adjusting for behavioural and demographic factors associated with infection, we will assess the temporal association between the community prevalence of viraemia and the incidence of HIV infection. Further analyses will make use of these cohorts to assess incidence and predictors of treatment initiation, repeat HIV testing, and viral suppression. Discussion: This study will provide important information on whether 'treatment as prevention' is associated with a reduction in HIV incidence at a community level among gay and bisexual men.

Purpose of review In the era of effective antiretroviral therapy, HIV-positive patients experience an increase in non-AIDS associated comorbidities. Causes of death are now more frequently associated with ageing and smoking; alcohol and drug use are strongly linked to many of these causes. Recent findings An almost equal life expectancy among HIV-positive people compared with HIV-negative population has been recently reported. However, life expectancy is reduced among HIV-positive smokers by at least 16 years and further reduced for people who have a history of excessive alcohol and drug use. Cohort studies report between a 1.5- and two-fold or greater increased mortality risk as a result of smoking. In a Danish population study, 61% of deaths in HIV-positive people were associated with smoking. Excessive alcohol and drug use are also elevated among specific HIV subpopulations and significantly impact morbidity and mortality. In the Veteran Affairs cohort study, moderate and excessive alcohol use increased mortality by 25-35% compared with low alcohol use. Summary Despite the effective therapy, smoking, alcohol and drug use have a significant role in increased mortality and reduced life expectancy among HIV-positive people. These factors need to be in continued focus for the management and care of HIV-positive people.

Objectives We established a subcohort of HIV-positive individuals from 10 sexual health clinics within the Australian HIV Observational Database (AHOD). The aim of this study was to assess demographic and other factors that might be associated with an incident sexually transmitted infection (STI). Methods The cohort follow-up was from March 2010 to March 2013, and included patients screened at least once for an STI. We used survival methods to determine time to first new and confirmed incident STI infection (chlamydia, gonorrhoea, syphilis or genital warts). Factors evaluated included sex, age, mode of HIV exposure, year of AHOD enrolment, hepatitis B or C coinfection, time-updated CD4 cell count, time-updated HIV RNA viral load, and prior STI diagnosis. Results There were 110 first incident STI diagnoses observed over 1015 person-years of follow-up, a crude rate of 10.8 [95% confidence interval (CI) 9.0–13.0] per 100 person-years. Factors independently associated with increased risk of incident STI included younger age [≥ 50 vs. 30–39 years old, adjusted hazards ratio (aHR) 0.4; 95% CI 0.2–0.8; P < 0.0001]; prior STI infection (aHR 2.5; 95% CI 1.6–3.8; P < 0.001), and heterosexual vs. men who have sex with men (MSM) as the likely route of exposure (aHR 0.2; 95% CI 0.1–0.6; P < 0.001). Conclusions In this cohort of individualsbeing treated with antiretroviral drugs, those who were MSM, who were 30–39 years old, and who had a prior history of STI, were at highest risk of a further STI diagnosis.

We aimed to compare rates of illicit drug-related hospitalisations in HIV-negative (HIV−ve) (n = 1325) and HIV-positive (HIV+ve) (n = 557) gay and bisexual men (GBM) with rates seen in the general male population and to examine the association between self-reported illicit drug use and drug-related hospitalisation. Participants were asked how often they used a range of illicit drugs in the previous 6 months at annual interviews. Drug-related hospital admissions were defined as hospital admissions for mental or behavioural disorders due to illicit drug use (ICD 10: F11–16, F18, F19), drug poisoning (T40–T45, T50) or toxic effect of gases (T53, T59, T65). Drug-related hospitalisations were 4.8 times higher in the HIV−ve cohort [SIR 4.75 (95 % CI 3.30–6.91)] and 3.5 times higher in the HIV+ve cohort [SIR 3.51 (1.92–5.88)] compared with the general population. Periods of weekly drug use [IRR 1.86 (1.01–3.46)], poly-drug use [IRR 2.17 (1.07–4.38)] and cannabis use [low use-IRR 1.95 (1.01–3.77), high use-IRR 2.58 (1.29–5.16)] were associated with drug-related hospitalisation in both cohorts, as was being a consistently high meth/amphetamine user throughout follow-up [IRR 3.24 (1.07–9.83)] and being an inconsistent or consistent injecting drug user throughout follow-up [IRR 3.94 (1.61–9.66), IRR 4.43(1.04–18.76), respectively]. Other risk factors for drug-related hospitalisation indicated the likelihood of comorbid drug and mental health issues in GBM hospitalised for drug use.

Liver diseases are among the most frequent causes of non-AIDS–related deaths in human immunodeficiency virus (HIV)-positive persons [1–4]. Most deaths result from hepatitis C (HCV) or hepatitis B virus (HBV) coinfections or alcohol use; little is known about other causes [5]. Results of 2 prospective observational cohorts suggest that prolonged exposure to antiretroviral therapy (ART) may increase the risk for fatal liver failure. The Data Collection on Adverse Events of Anti-HIV Drug (D:A:D) cohort, which includes many HCV-coinfected persons, found an increased rate of liver-related deaths per year of ART in multivariable analyses that were also adjusted for the latest CD4 cell counts [1]. The EuroSIDA observational cohort showed similar results [6]. The role of ART in liver-related mortality in patients without chronic viral hepatitis is less well defined. In the Swiss HIV Cohort Study (SHCS), elevated alanin aminotransferase (ALT; reported as adverse events to antiretrovirals), was associated with a higher mortality, independent of chronic hepatitis virus coinfections [7]. In contrast, mortality was not increased in participants with chronic ALT elevation and without viral hepatitis in another SHCS analysis; however, the observation period was shorter and the patient number smaller [8]. Recently, new hepatic syndromes related to ART have emerged in HIV-infected persons. Noncirrhotic portal hypertension, a potentially life-threatening liver disease, has been linked to didanosine use [9, 10]. In addition, steatosis and steatohepatitis are common in HIV-positive persons with and without chronic viral hepatitis [11, 12] and are associated with advanced liver fibrosis and cirrhosis [13]; ART as a risk factor has been discussed. The aims of this study were to (1) assess liver-related mortality in HIV-positive persons without chronic viral hepatitis in the D:A:D cohort and (2) provide comprehensive clinical details of these events. The role of ART in death was of particular interest.

Summary Background Men who have sex with men (MSM) are at greatly increased risk of human papillomavirus (HPV)-associated anal cancer. Screening for the presumed cancer precursor, high-grade anal intraepithelial neoplasia (AIN), followed by treatment in a manner analogous to cervical screening, has been proposed. We aimed to assess available data for anal HPV disease that can inform pre-cancer screening programmes. Methods We searched PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, AIN, and anal cancer in MSM. We calculated summary estimates using random-effects meta-analysis. Findings 53 studies met the inclusion criteria, including 31 estimates of HPV prevalence, 19 estimates of cytological abnormalities, eight estimates of histological abnormalities, and nine estimates of anal cancer incidence. Data for incident HPV and high-grade AIN were scarce. In HIV-positive men, the pooled prevalence of anal HPV-16 was 35·4% (95% CI 32·9–37·9). In the only published estimate, incidence of anal HPV-16 was 13·0% (9·6–17·6), and clearance occurred in 14·6% (10·2–21·2) of men per year. The pooled prevalence of histological high-grade AIN was 29·1% (22·8–35·4) with incidences of 8·5% (6·9–10·4) and 15·4% (11·8–19·8) per year in two estimates. The pooled anal cancer incidence was 45·9 per 100 000 men (31·2–60·3). In HIV-negative men, the pooled prevalence of anal HPV-16 was 12·5% (9·8–15·4). Incidence of HPV-16 was 11·8% (9·2–14·9) and 5·8% (1·9–13·5) of men per year in two estimates. The pooled prevalence of histological high-grade AIN was 21·5% (13·7–29·3), with incidence of 3·3% (2·2–4·7) and 6·0% (4·2–8·1) per year in two estimates. Anal cancer incidence was 5·1 per 100 000 men (0–11·5; based on two estimates). There were no published estimates of high-grade AIN regression. Interpretation Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM. Funding Australian Government Department of Health and Ageing.

Objectives: To explore the relationship between elevated triglyceride levels and the risk of myocardial infarction (MI) in HIV-positive persons after adjustment for total cholesterol (TC), high-density lipoprotein–cholesterol (HDL-C) and nonlipid risk factors. Background: Although elevated triglyceride levels are commonly noted in HIVpositive individuals, it is unclear whether they represent an independent risk factor for MI. Methods: The incidence of MI during follow-up was stratified according to the latest triglyceride level. Multivariable Poisson regression models were used to describe the independent association between the latest triglyceride level and MI risk after adjusting for TC and HDL-C, nonlipids cardiovascular disease (CVD) risk factors, HIV and treatment-related factors. Results: The 33 308 persons included in the study from 1999 to 2008 experienced 580 MIs over 178 835 person-years. Unadjusted, the risk of MI increased by 67% [relative risk (RR) 1.67, 95% confidence interval 1.54–1.80] per doubling in triglyceride level. After adjustment for the latest TC and HDL-C level, the RR dropped to 1.33 (95% confidence interval 1.21–1.45); this effect was further attenuated by other CVD risk factors and the RR was reduced to 1.17 (95% confidence interval 1.06–1.29). In models that additionally adjusted for HIV and treatment factors, the risk was further diminished, although remained significant (RR 1.11, 95% confidence interval 1.01–1.23). Conclusion: Higher triglyceride levels were marginally independently associated with an increased risk of MI in HIV-positive persons, although the extent of reduction in RR after taking account of latest TC, latest HDL-C and other confounders suggests that any independent effect is small. 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2011, 25:1497–1504

The CTL response in HLA-B*27+ HIV-infected individuals is characterized by an immunodominant response to a conserved epitope in gag p24 (aa 263–272, KRWIILGLNK; KK10). Mutations resulting in substitution of the arginine (R264) at position 2 of this epitope have been identified as escape mutations. Nineteen HLA-B*27+ long-term nonprogressors were identified from an Australian cohort with an average follow-up of 16 y following infection. Viral and host genetic factors impacting on disease progression were determined at multiple time points. Twelve of 19 had wild-type sequences at codon 264 at all time points; 7 of 19 carried CTL escape variants. Median viral load and CD4+ T cell counts were not significantly different between these groups at enrollment. Viral load, as judged by levels at their last visit (1,700 and 21,000 RNA copies/ml, respectively; p = 0.01) or by time-weighted area under the curve was higher in the escape group (p = 0.02). Escape mutants at other HLA-B*27–restricted epitopes were uncommon. Moreover, host polymorphisms, such as CCR5Δ32, CCR2-64I, and SDF1-3′A, or breadth of TCR repertoire responding to KK10 did not segregate to wild-type or escape groups. Host and viral factors were examined for a relationship to viral load. The only factor to affect viral load was the presence of the R264 escape mutations at the immunodominant epitope. CTL escape at R264 in the KK10 epitope is a major determinant of subsequent viral load in these HLA-B*27+ individuals.

It is not fully elucidated whether patients who receive antiretroviral therapy (ART) can maintain continued CD4 count increases. Previous studies suggested a plateau 2-4 years after treatment initiation. We aimed to characterize the evolution of CD4 counts in HIV-infected individuals receiving long-term suppressive ART, by performing a retrospective study of patients who maintained viral suppression (HIV RNA400 copies/ml) foror =5 years. We used linear regression models to determine for each individual whether the CD4 count continued to increase or plateau. Furthermore, we estimated whether the slope of the CD4 count for each individual became zero, which we defined as the CD4 set-point. We assessed factors associated with continued CD4 count rise, reaching a CD4 set-point and time to the CD4 set-point. Fifty-nine patients were included. The median baseline CD4 count was 238 (IQR, 120-360) cells/microl and the median duration on ART was 7.6 (IQR, 5.9-9.3) years. On ART, CD4 count continued to increase in 37 subjects (63%). Significant predictors of continued CD4 count increase included a lower baseline log10 HIV RNA (OR, 0.35; 95% CI, 0.14-0.89; p=0.026) and a shorter duration on ART (OR, 0.65; 95% CI, 0.47-0.91; p=0.021). Twenty-four (41%) subjects reached a set-point after a median 4.3 (IQR 1.8-6.4) years on ART. A lower baseline CD4 percentage was associated with both a longer time to reach the CD4 set-point and a lower CD4 count at the CD4 set-point. These findings suggest that CD4 count may continue to increase in some patients after several years of ART. Our results point to an advantage to commencing ART at higher CD4+ T cell strata. These data should be considered when estimating the optimal time to initiate ART.

Objectives: To determine the prevalence and predictors of an incomplete immune response in patients with sustained viral suppression after starting their first or second combination antiretroviral treatment (cART) regimen. Methods: All patients were recruited to the Australian HIV Observational Database (AHOD) by March 2006. Data were analyzed to assess the prevalence of an incomplete immune response (,350 cells/mL) in the 12–24 months after starting the first or second cART regimen. Factors associated with an incomplete immune response were assessed using logistic regression and time to AIDS/death was assessed using survival analysis. Results: Of the 2493 patients recruited to AHOD by March 2006, 590 were eligible for the analysis. Twenty-eight percent of patients with a baseline CD4 count, 350 cells per microliter had an incomplete immune response 12–24 months after starting their first or second cART regimen. Lower baseline CD4 count before starting the cART regimen was predictive of an incomplete immune response. There was a nonsignificant trend toward faster AIDS or death in incomplete immune responders. Conclusions: An incomplete immune response in patients with sustained viral suppression is associated with poorer immune function before starting cART. Type of cART or individual antiretroviral drug was not associated with an incomplete immune response.

We performed a retrospective review of cases of human immunodeficiency virus-associated progressive multifocal leucoencephalopathy in four hospitals (three in Australia and one in Hong Kong) between 1987 and 2003 in order to describe the local experience with this disease and to evaluate parameters impacting upon survival. Eighty-seven cases were identified and demographic details, baseline parameters and treatment methods and response were described. Survival was substantially increased in the post-highly active antiretroviral therapy (HAART) era with a median survival increase from 14 to 64 weeks. On multivariate analysis, variables associated with prolonged survival included a CD4 count of > 100 cells/μl at diagnosis and the use of HAART post-diagnosis, with no significant additional advantage from the use of neuroactive antiretrovirals.

Toxicity and resistance may limit the use of HIV nucleoside reverse transcriptase inhibitors (NRTIs). We assessed the safety and activity of regimens that did not include an NRTI.We analysed NRTI-sparing regimens using pooled data from three cohorts in Australia and France where HIV RNA viral load, CD4 lymphocyte count and metabolic parameters are assessed prospectively. The inclusion criterion was the commencement of any antiretroviral combination excluding NRTIs.A total of 334 (3.9%) of 8477 patients were included in the present study for a median follow-up time of 105 weeks. Therapeutic combinations were one nonnucleoside reverse transcriptase inhibitor (NNRTI) plus one protease inhibitor (PI) (58%), two PIs (26%), one PI (16%), and one NNRTI plus two PIs (8%). At baseline, the median CD4 lymphocyte count was 264 cells/muL (interquartile range 164-446 cells/muL) and 25% of patients had plasma HIV RNA below 500 HIV-1 RNA copies/mL. In intent-to-treat analysis, 64% of patients had HIV RNA500 copies/mL at 6 months and 68% at 24 months. The mean CD4 lymphocyte count increase was 60 cells/microL (95% confidence interval 41-76 cells/microL) at 6 months and 111 cells/microL (95% confidence interval 82-140 cells/microL) at 24 months. Prognostic factors for having HIV RNA500 copies/mL at 6 months included independently having undetectable HIV RNA at baseline and being naïve for NNRTIs. The proportion of patients with triglycerides2.3 mmol/L increased from 32% to 63% at 6 months and to 62% at 24 months (P-trend=0.002), and those with total cholesterol6.2 mmol/L increased from 18% to 38% at 6 months and to 44% at 24 months (P-trend0.001), with an increased risk for patients treated with NNRTI+PIs. Forty-one per cent of patients discontinued their NRTI-sparing regimen.In these antiretroviral-experienced patients, NRTI-sparing therapy appeared to have satisfactory virological and immunological efficacy. However, hyperlipidaemia was frequent and requires monitoring of cardiovascular risk factors.

Background There are few data regarding clinical care and outcomes of Indigenous Australians living with HIV and it is unknown if these differ from non-Indigenous HIV-positive Australians. Methods AHOD commenced enrolment in 1999 and is a prospective cohort of HIV-positive participants attending HIV outpatient services throughout Australia, of which 20 (74 %) sites report Indigenous status. Data were collected up until March 2013 and compared between Indigenous and non-Indigenous participants. Person-year methods were used to compare death rates, rates of loss to follow-up and rates of laboratory testing during follow-up between Indigenous and non-Indigenous participants. Factors associated with time to first combination antiretroviral therapy (cART) regimen change were assessed using Kaplan Meier and Cox Proportional hazards methods. Results Forty-two of 2197 (1.9 %) participants were Indigenous. Follow-up amongst Indigenous and non-Indigenous participants was 332 & 16270 person-years, respectively. HIV virological suppression was achieved in similar proportions of Indigenous and non-Indigenous participants 2 years after initiation of cART (81.0 % vs 76.5 %, p = 0.635). Indigenous status was not independently associated with shorter time to change from first- to second-line cART (aHR 0.95, 95 % CI 0.51-1.76, p = 0.957). Compared with non-Indigenous participants, Indigenous participants had significantly less frequent laboratory monitoring of CD4 count (rate:2.76 tests/year vs 2.97 tests/year, p = 0.025) and HIV viral load (rate:2.53 tests/year vs 2.93 tests/year, p

Introduction : HIV-positive (HIV+) temporary residents living in Australia legally are unable to access government subsidized antiretroviral treatment (ART) which is provided via Medicare to Australian citizens and permanent residents. Currently, there is no information systematically being collected on non-Medicare eligible HIV+ patients in Australia. The objectives of this study are to describe the population recruited to the Australian HIV Observational Database (AHOD) Temporary Residents Access Study (ATRAS) and to determine the short- and long-term outcomes of receiving (subsidized) optimal ART and the impact on onwards HIV transmission. Methods : ATRAS was established in 2011. Eligible patients were recruited via the AHOD network. Key HIV-related characteristics were recorded at baseline and prospectively. Additional visa-related information was also recorded at baseline, and updated annually. Descriptive statistics were used to describe the ATRAS cohort in terms of visa status by key demographic characteristics, including sex, region of birth, and HIV disease status. CD4 cell count (mean and SD) and the proportion with undetectable (

Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC : HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC : HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC : HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.

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.