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IntroductionStudies in heterosexual HIV serodiscordant couples have provided critical evidence on the role of HIV treatments in reducing HIV transmission risk. However, there are limited data regarding the effect of treatment on HIV transmission in homosexual male couples. We examined features of male homosexual HIV serodiscordant relationships that may impact upon the design of HIV treatment and transmission studies.MethodsData were from a prospective cohort study of HIV‐negative homosexual men in Sydney, Australia. Men were followed up with six‐monthly interviews and annual testing for HIV. Characteristics of men in HIV serodiscordant and seroconcordant relationships at baseline were compared, and a longitudinal analysis performed of rate of relationship break‐up and of HIV incidence.ResultsAt baseline, 5.5% of participants (n=79) had an HIV‐positive partner. Most (80.8%) of these relationships were non‐monogamous, and 36.7% of men reported recent unprotected anal intercourse (UAI) with casual partners. The rate of relationship break‐up was 29.5 per 100 person‐years. Half of men in serodiscordant relationships (49.4%) reported recent UAI with their regular partners. HIV incidence was 2.2 per 100 person‐years. It was substantially higher in relationships of less than one year's duration (6.1 per 100 person‐years) and in men who reported unprotected receptive anal intercourse with ejaculation with their regular partners (15.5 per 100 person‐years).ConclusionsLevels of HIV transmission risk and incidence were high, particularly in early relationships. Rates of relationship break‐up were high. These data suggest that studies of HIV treatments and transmission in homosexual serodiscordant couples should focus on early relationships so as not to underestimate risk, and sample sizes must allow for high rates of relationship break‐up.

AbstractIntroductionHIV pre‐exposure prophylaxis (PrEP) has been government subsidized in Australia since April 2018 and while uptake is high among men who have sex with men, rates of discontinuation are also high. The aims of this study were to examine the impact of discontinuation on overall PrEP usage, the proportion of PrEP users who discontinue and the predictors of discontinuation.MethodsWe used linked de‐identified dispensing records of all government subsidized PrEP in Australia between April 2018 and September 2021: a whole‐of‐population data set. Defining discontinuation as 180 days or more without PrEP after the final dispensed supply, we calculated the number of people who discontinued at each 6‐month interval during the study period, the proportion who had discontinued 2 years after the first supply and, using Cox regression, predictors of discontinuation.ResultsOf 49,164 people dispensed PrEP (98.5% male, median age 34 years), 40.3% (19,815) had discontinued by September 2021. Within 2 years of their first supply, 11,150 (37.7%) of 29,549 PrEP users had discontinued, including 10.0% after a single dispensed supply. Large variations were observed, particularly according to prescriber characteristics: discontinuation was higher among people prescribed PrEP by low caseload (≤10 patients) prescribers (61.2%) than by high caseload (>100 patients) prescribers (31.1%, p<0.001), and by prescribers practising in areas with low estimated prevalence (<1.0%) of gay men (64.1%) than high (>5%) prevalence (36.7%, p<0.001). Women and younger people were more likely to discontinue, while patients receiving a higher level of government subsidy were less likely. The independent predictors of discontinuation with the greatest effect size were female sex (adjusted hazards ratio [aHR] 2.99, p<0.001), low estimated gay prevalence of prescriber location (aHR 1.98, p<0.001) and low prescriber PrEP caseload (aHR 1.79, p<0.001).ConclusionsThere are high rates of PrEP discontinuation in Australia and some populations are at increased risk of discontinuation. Strategies are needed to support persistence on PrEP and the re‐starting of PrEP during periods of risk.

IntroductionHIV epidemics in the Asia‐Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre‐exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia‐Pacific region, including opportunities and barriers.DiscussionAwareness about PrEP in the Asia‐Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non‐existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger‐scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher‐, facility‐ and community‐led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific.ConclusionsCountries of the Asia‐Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes.

IntroductionAnal cancer in men who have sex with men (MSM) living with HIV is an important issue but there are no consistent guidelines for how to screen for this cancer. In settings where screening with anal cytology is unavailable, regular anal examinations have been proposed in some guidelines but their cost‐effectiveness is unknown.MethodsOur objective was to estimate the cost‐effectiveness of regular anal examinations to screen for anal cancer in HIV‐positive MSM living in Australia using a probabilistic Markov model. Data sources were based on the medical literature and a clinical trial of HIV‐positive MSM receiving an annual anal examination in Australia. The main outcome measures for calculating effectiveness were undiscounted and discounted (at 3%) lifetime costs, life years gained, quality‐adjusted life years (QALY) gained and incremental cost‐effectiveness ratio (ICER).ResultsBase‐case analysis estimated the average cost of screening for and management of anal cancer ranged from $195 for no screening to $1,915 for lifetime annual screening of men aged ≥ 50. Screening of men aged ≥ 50 generated ICERs of $29,760 per QALY gained (for screening every four years), $32,222 (every three years) and $45,484 (every two years). Uncertainty for ICERs was mostly influenced by the cost (financially and decrease in quality of life) from a false‐positive result, progression rate of anal cancer, specificity of the anal examination, the probability of detection outside a screening program and the discount rate.ConclusionsScreening for anal cancer by incorporating regular anal examinations into routine HIV care for MSM aged ≥ 50 is most likely to be cost‐effective by conventional standards. Given that anal pap smears are not widely available yet in many clinical settings, regular anal exams for MSM living with HIV to detect anal cancer earlier should be implemented.

IntroductionThe incidence of anal cancer is significantly higher in men who have sex with men (MSM) living with HIV when compared to the general population. We aimed to assess their awareness, knowledge and perceived level of personal risk for anal cancer to help inform educational strategies targeting this group.MethodsA cross‐sectional study of 327 HIV positive MSM in Melbourne, Australia, attending clinical settings (a sexual health centre, tertiary hospital HIV outpatients and high HIV caseload general practices) completed a written questionnaire in 2013/14. Poor knowledge was defined as those who had never heard of anal cancer, or scored 5 or less out of 10 in knowledge questions amongst those who reported ever hearing about anal cancer. Underestimation of risk was defined as considering themselves as having the same or lower risk for anal cancer compared to the general population.ResultsOf 72% (95% confidence interval (CI): 67–77) who had heard of anal cancer, 47% (95% CI: 41–53) could not identify any risk factors for anal cancer. Of total men surveyed, 51% (95% CI: 46–57) underestimated their risk for anal cancer. Multivariate analysis showed that men who underestimated their risk were older (OR 1.04 (per year increase in age), 95% CI: 1.01–1.07), had poor anal cancer knowledge (OR 2.06, 95% CI: 1.21–3.51), and more likely to have ever had an anal examination (OR 2.41, 95% CI: 1.18–4.93). They were less likely to consult a physician if they had an anal abnormality (OR 0.54, 95% CI: 0.31–0.96), to have had receptive anal sex (OR 0.12, 95% CI: 0.02–0.59) or speak English at home (OR 0.28, 95% CI: 0.09–0.90).ConclusionsThis survey of MSM living with HIV demonstrated limited awareness, knowledge level and estimation of risk for anal cancer. Further educational and public health initiatives are urgently needed to improve knowledge and understanding of anal cancer risk in MSM living with HIV.

IntroductionAlthough prostate cancer (PCa) incidence is lower in HIV+ men than in HIV− men, the usefulness of prostate‐specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV− men. We aimed to describe the kinetics and predictive value of PSA in HIV+ men.MethodsMen with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed models were used to describe kinetics.ResultsSixty‐one men were included with a median six (IQR 2–9) years follow‐up. Time between last sample and PCa was seven (4–11) months. Cases and controls were well matched at first sample, with a median age of 51 (IQR 48–57) and CD4 of 437 (243–610) cells/mm3. Median tPSA [2.8 (IQR: 1.6–4.6) and 0.8 (0.5–1.2) µg/L] and fPSA [0.4 (0.2–0.8) and 0.3 (0.2–0.4) µg/L] levels were higher in cases than controls at first sample. Both tPSA and fPSA increased significantly over time in cases (Figure 1), to a median at last sample of 6.1 (4.7–9.5) and 0.9 (0.6–1.3) µg/L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5–1.4) and 0.2 (0.2–0.4) µg/L (Figure). Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2‐fold higher 4.7 (CI: 1.7–12.9) and 5.4 (1.7–17.4)]. Elevated tPSA values in cases were detectable ≥5 years before PCa (p<0.01). Testosterone [overall median 19.4 (IQR 15.3–23.9) nmol/L at first sample) and SHBG [50.0 (34.0–66.0) nmol/L] levels were similar in cases and controls at first and last sample (all p>0.7). The most informative predictor of PCa was tPSA (AUC=0.9), followed by fPSA (0.8). Testosterone (AUC = 0.5) and SHBG (0.5) were poor predictors of PCa. Overall, tPSA level >4 µg/L had 99% specificity and 37% sensitivity. Performance was best in the year prior to PCa (specificity: 99%, sensitivity: 88%).ConclusionsPSA was highly predictive of PCa in HIV+ men. Our results indicate that PSA screening in HIV+ men may be useful, and further work is needed to identify potentially age‐related cut‐offs to maximize sensitivity and specificity to identify those for further evaluation at early stages of PCa.

AbstractIntroductionNew South Wales (NSW) has one of the world's highest uptake rates of HIV pre‐exposure prophylaxis (PrEP). This uptake has been credited with sharp declines in HIV transmission, particularly among Australian‐born gay and bisexual men. Concerns have been raised around the potential for the emergence of tenofovir (TFV) and XTC (lamivudine/emtricitabine) resistance in settings of high PrEP use. Such an emergence could also increase treatment failure and associated clinical outcomes among people living with HIV (PLHIV). Despite low levels of nucleoside reverse‐transcriptase inhibitor (NRTI) resistance relating to PrEP use in clinical settings, there are few published studies describing the prevalence of NRTI resistance among people newly diagnosed with HIV in a setting of high PrEP use.MethodsUsing HIV antiretroviral drug resistance data linked to NSW HIV notifications records of people diagnosed from 1 January 2015 to 31 December 2021 and with HIV attributed to male‐to‐male sex, we described trends in TFV and XTC resistance. Resistance was identified using the Stanford HIV Drug Resistance genotypic resistance interpretation system. To focus on transmitted drug resistance, resistance prevalence estimates were generated using sequences taken less than 3 months post‐HIV diagnosis. These estimates were stratified by timing of sequencing relative to the date of diagnosis, year of sequencing, birthplace, likely place of HIV acquisition, and stage of HIV at diagnosis.ResultsAmong 1119 diagnoses linked to HIV genomes sequenced less than 3 months following diagnosis, overall XTC resistance prevalence was 1.3%. Between 2015 and 2021, XTC resistance fluctuated between 0.5% to 2.9% and was 1.0% in 2021. No TFV resistance was found over the study period in any of the sequences analysed. Higher XTC resistance prevalence was observed among people with newly acquired HIV (evidence of HIV acquisition in the 12 months prior to diagnosis; 2.9%, p = 0.008).ConclusionsIn this Australian setting, TFV and XTC resistance prevalence in new HIV diagnoses remained low. Our findings offer further evidence for the safe scale‐up of PrEP in high‐income settings, without jeopardizing the treatment of those living with HIV.

AbstractIntroductionThere are few data about the range of strategies used to prevent sexual HIV transmission within gay male serodiscordant couples. We examined HIV prevention strategies used by such couples and compared differences between countries.MethodsOpposites Attract was a cohort study of male serodiscordant couples in Australia, Brazil and Thailand, from May 2014 (Australia) or May 2016 (Brazil/Thailand) to December 2016. At visits, HIV‐positive partners had viral load (VL) tested; HIV‐negative partners reported sexual behaviour and perceptions of their HIV‐positive partner's VL results. Within‐couple acts of condomless anal intercourse (CLAI) were categorized by strategy: condom‐protected, biomedically protected (undetectable VL and/or pre‐exposure prophylaxis [PrEP]), or not protected by either (HIV‐negative partners engaging in insertive CLAI, receptive CLAI with withdrawal, or receptive CLAI with ejaculation).ResultsA total of 343 couples were included in this analysis (153 in Australia, 93 in Brazil and 97 in Thailand). Three‐quarters of HIV‐positive partners were consistently virally suppressed (<200 copies/mL) during follow‐up, and HIV‐negative partners had correct perceptions of their partner's VL result for 76.5% of tests. One‐third of HIV‐negative partners used daily PrEP during follow‐up. Over follow‐up, 73.8% of couples had CLAI. HIV‐negative partners reported 31,532 acts of anal intercourse with their HIV‐positive partner. Of these, 46.7% were protected by condoms, 48.6% by a biomedical strategy and 4.7% of acts were not protected by these strategies. Australian couples had fewer condom‐protected acts and a higher proportion of biomedically protected acts than Brazilian and Thai couples. Of the 1473 CLAI acts where the perceived VL was detectable/unknown and were not protected by PrEP (4.7% of all acts), two‐thirds (n = 983) were when the HIV‐negative partner was insertive (strategic positioning). Of the 490 acts when the HIV‐negative partner was receptive, 261 involved withdrawal and 280 involved ejaculation. Thus, <1% of acts were in the highest risk category of receptive CLAI with ejaculation.ConclusionsCouples used condoms, PrEP or perceived undetectable VL for prevention in the majority of anal intercourse acts. Only a very small proportion of events were not protected by these strategies. Variation between countries may reflect differences in access to HIV treatment, education, knowledge and attitudes.

AbstractIntroductionMen who have sex with men (MSM) living with HIV have a high risk of anal cancer, which is often detected at late stages, when morbidity and mortality are high. The objective of this study was to describe the feasibility and challenges to incorporating regular digital anorectal examination (DARE) into routine HIV care for MSM living with HIV, from the perspective of patients, physicians and the health service.MethodsIn 2014, we recruited 327 MSM living with HIV, aged 35 and above from one major sexual health centre (n = 187), two high HIV caseload general practices (n = 118) and one tertiary hospital (n = 22) in Melbourne, Australia. Men were followed up for two years and DARE was recommended at baseline, year 1 and year 2. Data were collected regarding patient and physician experience, and health service use. An ordered logit model was used to assess the relationship between sociodemographic factors and the number of DAREs performed.ResultsMean age of men was 51 (SD ± 9) years, 69% were Australian born, 32% current smokers, and mean CD4 was 630 (SD ± 265) cells per mm3, with no significant differences between clinical sites. Overall, 232 (71%) men received all three DAREs, 71 (22%) received two DAREs, and 24 (7%) had one DARE. Adverse outcomes were rarely reported: anal pain (1.2% of total DAREs), bleeding (0.8%) and not feeling in control of their body during the examination (1.6%). Of 862 DAREs performed, 33 (3.8%) examinations resulted in a referral to a colorectal surgeon. One Stage 1 anal cancer was detected.ConclusionIncorporation of an early anal cancer detection programme into routine HIV clinical care for MSM living with HIV showed high patient acceptability, uncommon adverse outcomes and specialist referral patterns similar to other cancer screening programmes.

AbstractIntroductionThe HIV Strategy in New South Wales (NSW) Australia aims to virtually eliminate HIV transmission by 2020. We estimated the 2016 HIV diagnosis and care cascade for the state of NSW, with a focus on introducing population‐based data to improve data quality and assess progress towards the UNAIDS 90‐90‐90 targets.MethodsTo estimate the number of people living with diagnosed HIV (PLDHIV) we used NSW data from the Australian National HIV Registry, enhanced by surveillance among people recently diagnosed with HIV to improve migration estimates. The number of undiagnosed PLHIV was estimated using back‐projection modelling by CD4 count at diagnosis. De‐duplicated prescription claims data were obtained from the Australian Pharmaceutical Benefits Scheme (PBS), and were combined with an estimate for those ineligible, to determine the number of PLDHIV on antiretroviral therapy (ART). Data from a clinic network with 87% coverage of PLDHIV in NSW enabled the estimation of the number on ART who had HIV suppression.Results and discussionWe estimated that 10,110 PLHIV resided in NSW in 2016 (range 8400 to 11,720), among whom 9230 (91.3%) were diagnosed, and 8490 (92.0% of those diagnosed) were receiving ART. Among PLDHIV receiving ART, 8020 (94.5%) had suppressed viral load (<200 HIV‐1 RNA copies/mL). Overall, 79.3% of all PLHIV had HIV virological suppression.ConclusionNSW has met each of the UNAIDS 90‐90‐90 targets. The enhanced surveillance methods and data collection systems improved data quality. Measuring and meeting the 90‐90‐90 targets is feasible and could be achieved in comparable parts of the world.

BackgroundThis retrospective survey describes types of cancers diagnosed in HIV‐infected subjects in Asia, and assesses risk factors for cancer in HIV‐infected subjects using contemporaneous HIV‐infected controls without cancer.MethodsTREAT Asia HIV Observational Database (TAHOD) sites retrospectively reviewed clinic medical records to determine cancer diagnoses since 2000. For each diagnosis, the following data were recorded: date, type, stage, method of diagnosis, demographic data, medical history, and HIV‐related information. For risk factor analyses, two HIV‐infected control subjects without cancer diagnoses were also selected. Cancers were grouped as AIDS‐defining cancers (ADCs), and non‐ADCs. Non‐ADCs were further categorized as being infection related (NADC‐IR) and unrelated (NADC‐IUR).ResultsA total of 617 patients were included in this study: 215 cancer cases and 402 controls from 13 sites. The majority of cancer cases were male (71%). The mean age (SD) for cases was 39 (10.6), 46 (11.5) and 44 (13.7) for ADCs, NADC‐IURs and NADCs‐IR, respectively. The majority (66%) of cancers were ADCs (16% Kaposi sarcoma, 40% non‐Hodgkin's lymphoma, and 9% cervical cancer). The most common NADCs were lung (6%), breast (5%) and hepatocellular carcinoma and Hodgkin's lymphoma (2% each). There were also three (1.4%) cases of leiomyosarcoma reported in this study. In multivariate analyses, individuals with CD4 counts above 200 cells/mm3 were approximately 80% less likely to be diagnosed with an ADC (p < 0.001). Older age (OR: 1.39, p = 0.001) and currently not receiving antiretroviral treatment (OR: 0.29, p = 0.006) were independent predictors of NADCs overall, and similarly for NADCs‐IUR. Lower CD4 cell count and higher CDC stage (p = 0.041) were the only independent predictors of NADCs‐IR.ConclusionsThe spectrum of cancer diagnoses in the Asia region currently does not appear dissimilar to that observed in non‐Asian HIV populations. One interesting finding was the cases of leiomyosarcoma, a smooth‐muscle tumour, usually seen in children and young adults with AIDS, yet overall quite rare. Further detailed studies are required to better describe the range of cancers in this region, and to help guide the development of screening programmes.

AbstractIntroductionThe human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV‐1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV‐1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW‐specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi‐Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2‐fold increase in the number of NSW‐specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above‐average growth rate (>1.5 sequences / 6‐months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.