Damian P. Conway

Multi-Centre Evaluation of the Determine HIV Combo Assay when Used for Point of Care Testing in a High Risk Clinic-Based Population

Background Determine HIV Combo (DHC) is the first point of care assay designed to increase sensitivity in early infection by detecting both HIV antibody and antigen. We conducted a large multi-centre evaluation of DHC performance in Sydney sexual health clinics. Methods We compared DHC performance (overall, by test component and in early infection) with conventional laboratory HIV serology (fourth generation screening immunoassay, supplementary HIV antibody, p24 antigen and Western blot tests) when testing gay and bisexual men attending four clinic sites. Early infection was defined as either acute or recent HIV infection acquired within the last six months. Results Of 3,190 evaluation specimens, 39 were confirmed as HIV-positive (12 with early infection) and 3,133 were HIV-negative by reference testing. DHC sensitivity was 87.2% overall and 94.4% and 0% for the antibody and antigen components, respectively. Sensitivity in early infection was 66.7% (all DHC antibody reactive) and the DHC antigen component detected none of nine HIV p24 antigen positive specimens. Median HIV RNA was higher in false negative than true positive cases (238,025 vs. 37,591 copies/ml; p = 0.022). Specificity overall was 99.4% with the antigen component contributing to 33% of false positives. Conclusions The DHC antibody component detected two thirds of those with early infection, while the DHC antigen component did not enhance performance during point of care HIV testing in a high risk clinic-based population.

A Laboratory-Based Evaluation of Four Rapid Point-of-Care Tests for Syphilis

Background Syphilis point-of-care tests may reduce morbidity and ongoing transmission by increasing the proportion of people rapidly treated. Syphilis stage and co-infection with HIV may influence test performance. We evaluated four commercially available syphilis point-of-care devices in a head-to-head comparison using sera from laboratories in Australia. Methods Point-of-care tests were evaluated using sera stored at Sydney and Melbourne laboratories. Sensitivity and specificity were calculated by standard methods, comparing point-of-care results to treponemal immunoassay (IA) reference test results. Additional analyses by clinical syphilis stage, HIV status, and non-treponemal antibody titre were performed. Non-overlapping 95% confidence intervals (CI) were considered statistically significant differences in estimates. Results In total 1203 specimens were tested (736 IA-reactive, 467 IA-nonreactive). Point-of-care test sensitivities were: Determine 97.3%(95%CI:95.8–98.3), Onsite 92.5%(90.3–94.3), DPP 89.8%(87.3–91.9) and Bioline 87.8%(85.1–90.0). Specificities were: Determine 96.4%(94.1–97.8), Onsite 92.5%(90.3–94.3), DPP 98.3%(96.5–99.2), and Bioline 98.5%(96.8–99.3). Sensitivity of the Determine test was 100% for primary and 100% for secondary syphilis. The three other tests had reduced sensitivity among primary (80.4–90.2%) compared to secondary syphilis (94.3–98.6%). No significant differences in sensitivity were observed by HIV status. Test sensitivities were significantly higher among high-RPR titre (RPR≥8) (range: 94.6–99.5%) than RPR non-reactive infections (range: 76.3–92.9%). Conclusions The Determine test had the highest sensitivity overall. All tests were most sensitive among high-RPR titre infections. Point-of-care tests have a role in syphilis control programs however in developed countries with established laboratory infrastructures, the lower sensitivities of some tests observed in primary syphilis suggest these would need to be supplemented with additional tests among populations where syphilis incidence is high to avoid missing early syphilis cases.

Effect of availability of HIV self-testing on HIV testing frequency in gay and bisexual men at high risk of infection (FORTH): a waiting-list randomised controlled trial

BACKGROUND Frequent testing of individuals at high risk of HIV is central to current prevention strategies. We aimed to determine if HIV self-testing would increase frequency of testing in high-risk gay and bisexual men, with a particular focus on men who delayed testing or had never been tested before. METHODS In this randomised trial, HIV-negative high-risk gay and bisexual men who reported condomless anal intercourse or more than five male sexual partners in the past 3 months were recruited at three clinical and two community-based sites in Australia. Enrolled participants were randomly assigned (1:1) to the intervention (free HIV self-testing plus facility-based testing) or standard care (facility-based testing only). Participants completed a brief online questionnaire every 3 months, which collected the number of self-tests used and the number and location of facility-based tests, and HIV testing was subsequently sourced from clinical records. The primary outcome of number of HIV tests over 12 months was assessed overall and in two strata: recent (last test ≤2 years ago) and non-recent (>2 years ago or never tested) testers. A statistician who was masked to group allocation analysed the data; analyses included all participants who completed at least one follow-up questionnaire. After the 12 month follow-up, men in the standard care group were offered free self-testing kits for a year. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12613001236785. FINDINGS Between Dec 1, 2013, and Feb 5, 2015, 182 men were randomly assigned to self-testing, and 180 to standard care. The analysis population included 178 (98%) men in the self-testing group (174 person-years) and 165 (92%) in the standard care group (162 person-years). Overall, men in the self-testing group had 701 HIV tests (410 self-tests; mean 4·0 tests per year), and men in the standard care group had 313 HIV tests (mean 1·9 tests per year); rate ratio (RR) 2·08 (95% CI 1·82-2·38; p<0·0001). Among recent testers, men in the self-testing group had 627 tests (356 self-tests; mean 4·2 per year), and men in the standard care group had 297 tests (mean 2·1 per year); RR 1·99 (1·73-2·29; p<0·0001). Among non-recent testers, men in the self-testing group had 74 tests (54 self-tests; mean 2·8 per year), and men in the standard care group had 16 tests (mean 0·7 per year); RR 3·95 (2·30-6·78; p<0·0001). The mean number of facility-based HIV tests per year was similar in the self-testing and standard care groups (mean 1·7 vs 1·9 per year, respectively; RR 0·86, 0·74-1·01; p=0·074). No serious adverse events were reported during follow-up. INTERPRETATION HIV self-testing resulted in a two times increase in frequency of testing in gay and bisexual men at high risk of infection, and a nearly four times increase in non-recent testers, compared with standard care, without reducing the frequency of facility-based HIV testing. HIV self-testing should be made more widely available to help increase testing and earlier diagnosis. FUNDING The National Health and Medical Research Council, Australia.

Barriers to HIV testing and characteristics associated with never testing among gay and bisexual men attending sexual health clinics in Sydney

HIV diagnoses among gay and bisexual men have increased over the past decade in Australia. HIV point‐of‐care testing (POCT) was introduced in Australia in 2011 as a strategy to increase HIV testing by making the testing process more convenient. We surveyed gay and bisexual men undergoing POCT to assess barriers to HIV testing and characteristics associated with not having previously tested for HIV (never testing).

Health Care Services for men who have sex with men in different Australian states and territories since the emergence of HIV

The purpose of this article is to describe sexual health services available in Australia across the different states and territories for gay men and men who have sex with men (MSM) and their utilisation. An assessment of services available in different states is made, then the evidence about how MSM and people living with HIV/AIDS access health care in Australia is presented. This demonstrates that the number and location of sexual health services has changed over time. It also demonstrates that services available differ by state and territory. The availability of non-occupational post-exposure prophylaxis for HIV infection has been different in each state and territory, as has its utilisation. The majority of care for sexual health-related issues and for MSM and people living with HIV/AIDS is delivered in general practice settings in Australia, with hospital outpatient settings, including sexual health clinics, utilised commonly.

Rapid HIV Testing Is Highly Acceptable and Preferred among High-Risk Gay And Bisexual Men after Implementation in Sydney Sexual Health Clinics

Background Rapid HIV testing (RHT) is well established in many countries, but it is new in Australia. We assessed the acceptability of RHT and its associations among gay, bisexual and other men who have sex with men (GBM) after implementation of RHT in Sydney sexual health clinics. Methods GBM were invited to complete an acceptability questionnaire before and after provision of the result of finger-prick blood RHT, comparing their experience of RHT with conventional HIV testing (CHT) involving venipuncture. Logistic regression was used to assess associations between patient characteristics and the preference for RHT over CHT next time they tested for HIV. Results Of 1061 GBM who received non-reactive RHT results, 59% found RHT less stressful than CHT and 34% reported no difference, and 61% found RHT more comfortable than CHT and 26% reported no difference. Nearly all men were satisfied with RHT result delivery (99%) and the RHT process overall (99%). Most men (79%) preferred RHT for their next HIV test and this preference was stronger in men who were aged 35-44 years (adjusted odds ratio [AOR] 2.49, p<0.01), reported they would test more often if RHT was available (AOR 1.66, p=0.01), found returning for results annoying (AOR 1.67, p=0.01), and found RHT less stressful (AOR 2.37, p<0.01) and more comfortable (AOR 1.62, p=0.02) than CHT. Men concerned about the reliability of RHT were less than half as likely to prefer RHT for their next HIV test (AOR 0.44, p<0.01). Conclusions Most GBM preferred RHT to CHT next time and this preference was associated with finding RHT more convenient, more comfortable and less stressful than CHT. These findings suggest that in a clinic setting RHT should be considered to improve the patient experience and may potentially increase uptake and frequency of HIV testing.

An Evaluation of a Novel Dual Treponemal/Nontreponemal Point-of-Care Test for Syphilis as a Tool to Distinguish Active From Past Treated Infection

BACKGROUND Most syphilis point-of-care (POC) tests detect treponemal antibodies, which persist after successful treatment. Subsequent POC tests are positive, despite no active infection, and can lead to unnecessary treatment. We evaluated a new POC test, incorporating a nontreponemal component, to distinguish active from past infection. METHODS Sera stored at 2 Australian laboratories were tested with DPP Screen and Confirm Assay. Treponemal and nontreponemal test lines were compared to corresponding conventional treponemal and nontreponemal reference test results: immunoassays and rapid plasma reagin (RPR), respectively, with RPR quantification by endpoint titration. POC test outcome concordance with conventional test results was assessed according to serological and clinical categories. RESULTS Among 1005 serum samples tested, DPP treponemal line sensitivity was 89.8% (95% confidence interval [CI], 87.3%-91.9%) and specificity was 99.3% (95% CI, 97.0%-99.9%). DPP nontreponemal line sensitivity was 94.2% (95% CI, 91.8%-96.0%) and specificity was 62.2% (95% CI, 57.5%-66.6%). DPP test outcome (pair of test lines) was concordant with both reference test results for 94.3% of 404 high-titer infections, 90.1% of 121 low-titer infections, 27.5% of 211 past/treated infections, and 78.1% of 242 infections classified as not syphilis. Among 211 past/treated infections, 49.8% were incorrectly identified as active infection and a further 22.8% as not syphilis. CONCLUSIONS DPP test use would result in identification of >93% of active syphilis infections, whereas just over half of past infections would be diagnosed as past or not syphilis, avoiding unnecessary treatment compared with other POC tests. This may be at the expense of missing some active infections; thus, its potential benefits will depend on the prevalence of past vs active infection in a population.

Potential public health benefits of HIV testing occurring at home in Australia.

In many countries, including Australia, policies have recently changed to support HIV self‐testing. The decision has created much debate about the public health benefits of the strategy versus the risks. Self‐testing for HIV was approved in the US on the basis that it would facilitate greater HIV testing uptake, despite having a lower sensitivity than laboratory HIV immunoassays. We calculated the frequency of self‐testing that would be required among Australian gay and bisexual men at high‐risk for there to be a public health benefit (detection of HIV infections that would have otherwise remained undiagnosed). At a population level, if access to HIV self‐testing led to men supplementing their usual sexual health check‐ups (involving a laboratory HIV immunoassay) with one or more self‐tests at home, or self‐tests led to untested gay and bisexual men having an HIV test for the first time, there would be a public health benefit. If men replaced their average of one laboratory HIV immunoassay per year with self‐testing at home, then three self‐tests would be needed to counteract the lower sensitivity of the self‐test (so zero infections would be missed). If four self‐tests were undertaken then additional infections would be detected (ie, there would be a public health benefit). Additional public health benefits include a reduction in the period of undiagnosed infection, which is known to be a period of relatively high infectiousness.

Validation of participant eligibility for pre-exposure prophylaxis: Baseline data from the PRELUDE demonstration project

Background In Australia, pre-exposure prophylaxis (PrEP) is targeted to individuals at high risk for HIV infection. We describe the HIV risk profile and characteristics of PRELUDE participants, and evaluate the population validity of the sample in representing high-risk gay and bisexual men (GBM) eligible for PrEP. Methods PRELUDE is an on-going, open-label, single-arm observational study. Participants were identified in clinics and screened for eligibility using a paper-based risk assessment tool which followed the New South Wales (NSW) PrEP guidelines. Selection was validated using an independent online behavioural survey, completed by study participants upon enrolment. Demographic information was analysed using descriptive statistics, and kappa tests were used to determine agreement between reporting of high-risk practices in the risk assessment and behavioural survey. Results During 2014–15, 471 individuals were targeted for enrolment; 341 were assessed for PrEP eligibility and 313 were enrolled. Of these, 303 (97%) identified as GBM. Overall, 85% of GBM met at least one high-risk criterion; 68% reported receptive intercourse with an HIV-positive or unknown status casual male partner, and 37% reported methamphetamine use in the three months preceding enrolment. The remaining 15% were enrolled based on medium-risk behaviours, or at the clinicians’ discretion. We found an 82% total agreement between self-reported high-risk behaviour and clinicians’ categorisation of GBM as being at high risk for HIV based on PrEP eligibility criteria. Conclusions Behavioural eligibility criteria used by clinicians successfully identified individuals at high risk for HIV infection. This targeted approach ensures that the greatest public health and HIV prevention benefits can be derived in a setting without universal access to PrEP.

Effect of testing experience and profession on provider acceptability of rapid HIV testing after implementation in public sexual health clinics in Sydney

Rapid HIV testing (RHT) is well established in many countries, but it is new in Australia since a policy change in 2011. We assessed service provider acceptability of RHT before and after its implementation in four Sydney public sexual health clinics.