Darren Russell

Seroprevalence of herpes simplex virus types 1 and 2 in HIV-Infected and uninfected homosexual men in a primary care setting

BACKGROUND Genital herpes is usually caused by herpes simplex virus type 2 (HSV-2), with infections often being unrecognised by patients and/or clinicians. HSV-2 infections may be a risk factor for the transmission of human immunodeficiency virus (HIV) infection. Reliable tests for type-specific HSV antibodies are now readily available. OBJECTIVES To determine the seroprevalence of HSV-1 and -2 in HIV-seronegative gay men in a primary care setting in Melbourne, Australia, and to compare it with the rate in HIV-infected gay men. To assess the utility in a clinical setting of a type-specific HSV enzyme linked immunosorbent assay (ELISA) as compared with western blot. STUDY DESIGN We recruited a total of 300 HIV-seronegative homosexual men attending for HIV antibody testing, and HIV-infected men attending for CD4 lymphocyte count and viral load estimation. The subjects completed a questionnaire, and sera were sent for total IgG HSV testing and testing by Gull type-specific HSV ELISA assay. Selected serum samples were retested by western blotting and the results analysed. RESULTS In total, 168 HIV-antibody negative men and 132 HIV-antibody positive men were recruited. Of all subjects, 73.3% had HSV-1 antibodies. This proportion did not differ between HIV-seronegative and seropositive men (P=0.48). About twenty percent of HIV-seronegative men and 61% of HIV-seropositive men had antibodies to HSV-2 (P<0.0001); 75.6% of HIV-seronegative men with antibodies to HSV-2 gave no history of genital herpes, as did 66.7% of HIV-seropositive men. Overall, in using the type-specific ELISA (Gull) assay, false negative, false positive or equivocal results were obtained in 33/300 (11%) of samples tested compared with western blot. CONCLUSIONS High rates of HSV-2 infection were found in homosexual males, with the rate for HIV-seropositive men being over twice that for HIV uninfected men. Most subjects were not aware of their infection with HSV-2. HIV-infected individuals were also older and had higher numbers of sexual partners, but we were unable to unambiguously establish that these variables contributed to the difference in HSV-2 seroprevalence rates. The Gull type-specific assay for HSV antibodies has significant problems with sensitivity and specificity at a discrepancy rate of 11%. Caution is advised in using this type-specific commercial assay for clinical purposes.

Long-Term Survival in HIV Positive Patients with up to 15 Years of Antiretroviral Therapy

Background Life expectancy has increased for newly diagnosed HIV patients since the inception of combination antiretroviral treatment (cART), but there remains a need to better understand the characteristics of long-term survival in HIV-positive patients. We examined long-term survival in HIV-positive patients receiving cART in the Australian HIV Observational Database (AHOD), to describe changes in mortality compared to the general population and to develop longer-term survival models. Methods Data were examined from 2,675 HIV-positive participants in AHOD who started cART. Standardised mortality ratios (SMR) were calculated by age, sex and calendar year across prognostic characteristics using Australian Bureau of Statistics national data as reference. SMRs were examined by years of duration of cART by CD4 and similarly by viral load. Survival was analysed using Cox-proportional hazards and parametric survival models. Results The overall SMR for all-cause mortality was 3.5 (95% CI: 3.0–4.0). SMRs by CD4 count were 8.6 (95% CI: 7.2–10.2) for CD4<350 cells/µl; 2.1 (95% CI: 1.5–2.9) for CD4 = 350–499 cells/µl; and 1.5 (95% CI: 1.1–2.0) for CD4≥500 cells/µl. SMRs for patients with CD4 counts <350 cells/µL were much higher than for patients with higher CD4 counts across all durations of cART. SMRs for patients with viral loads greater than 400 copies/ml were much higher across all durations of cART. Multivariate models demonstrated improved survival associated with increased recent CD4, reduced recent viral load, younger patients, absence of HBVsAg-positive ever, year of HIV diagnosis and incidence of ADI. Parametric models showed a fairly constant mortality risk by year of cART up to 15 years of treatment. Conclusion Observed mortality remained fairly constant by duration of cART and was modelled accurately by accepted prognostic factors. These rates did not vary much by duration of treatment. Changes in mortality with age were similar to those in the Australian general population.

Increasing chlamydia test of re-infection rates using SMS reminders and incentives

Background Clients diagnosed and treated for Chlamydia trachomatis are a recognised high-risk group for subsequent infection. An estimated 8% of clients treated for chlamydia at Cairns Sexual Health Service return for re-testing within the recommended 3–4-month period. There is no recall or reminder system in place. This study assesses the effectiveness of using short messaging service (SMS) reminders with and without incentive payments to increase re-testing rates. Methods Eligible consenting clients were randomly allocated to one of three groups. Group 1 (controls) received the standard advice from the clinician to return for re-testing in 3–4 months. Group 2 received the standard advice and an SMS reminder at 10–12 weeks post-treatment. Group 3 received the standard advice and the SMS reminder, which also offered an incentive payment on clinic attendance. Results 32 participants were recruited to groups 1 and 2 and 30 participants to group 3. 62 SMS reminders were sent with 13 (21.0%) reported as undelivered. Re-testing rates were 6.3%, 28.1% and 26.7% for groups 1, 2 and 3, respectively. Conclusion SMS reminders with or without an incentive payment increased re-testing rates in our clients who were diagnosed and treated for chlamydia. However, re-testing remained less than ideal, and the high rate of undelivered SMS reminders suggest that this intervention alone will not achieve desired re-testing rates and that a range of strategies will be required to increase re-testing in this population.

Experiences and outcomes of partner notification among men and women recently diagnosed with chlamydia and their views on innovative resources aimed at improving notification rates.

Objective: To describe the partner notification experiences of individuals diagnosed with chlamydia and to determine what supports might best assist them. Goal: To determine what supports might best assist chlamydia infected individuals to notify their partners. Study Design: A telephone survey was undertaken with men and women recently diagnosed with chlamydia across 3 Australian jurisdictions between August 2007 and January 2008. Results: Of the 286 individuals who agreed to be contacted about the study, 202 (71%) completed the survey. Twenty-three percent (333/1458) of recent partners were notified: men who had sex with men (MSM) notified 15% (133/880) of their partners, heterosexual men 31% (114/370), and women 46% (86/188) of their partners (P < 0.001). Overall, 84% (169/202) of individuals notified at least one partner. The main reasons for informing partners were out of concern for them (44%) or because it was considered “the right thing to do” (37%). The preferred methods for contacting partners were telephone (52%) and face-to-face (30%). E-mail (8%) and short message service (SMS) (11%) were less commonly used; however, if offered a website with anonymous e-mail and SMS services, nearly half of individuals indicated they would find this useful. Of those who had not informed all partners with known contact details (n = 94), 34% reported that if web-based tools were available they would have contacted more partners. Over half of participants would like to have been given antibiotics to give to their partner. Conclusion: The availability of tailored resources may assist in improving partner notification for chlamydia.

Mycoplasma genitalium: a review

Mycoplasma genitalium (M. genitalium) was first isolated from the urethral swabs of two symptomatic men with urethritis in 1980. Published prevalence rates vary greatly between populations studied. A number of urogenital conditions have been ascribed to M. genitalium, which is recognised to cause a sexually transmitted infection. The association of M. genitalium with non-specific urethritis is now well established, but the evidence supporting its role in both male and female infertility remains inconclusive. Laboratory methods are challenging and there is a lack of test standardisation. The recommended treatment of the infection is azithromycin as a single 1 gm dose. However, in recent years macrolide resistance has been observed. More studies are required to establish the clinical importance of M. genitalium in urogenital conditions, particularly infertility, and to establish the role for screening and treatment in high-risk populations.

Innovative Resources Could Help Improve Partner Notification for Chlamydia in Primary Care

Objective: To examine practices of general practitioners’ (GPs) in relation to partner notification for chlamydia and identify the supports they would find most useful to assist them. Goal: To identify innovative resources that could improve partner notification for chlamydia in primary care. Study Design: A postal survey was undertaken that involved GPs from several jurisdictions across Australia between August and December 2007. GPs were randomly selected from a national database. Results: Of 521 eligible GPs, 234 (45%) returned a completed questionnaire. Ninety-five percent (n = 223) felt that it was their role to discuss partner notification with patients diagnosed with chlamydia; however, only 45% (105/232) were sure how best to assist their patients with this. Considerable variation was shown in the way partner notification was undertaken, including how far back in time GPs recommended contacting partners. GPs considered a wide range of possible resources useful, including a website supporting patients (90%), information sheets generated by practice software when chlamydia is diagnosed (90%), printed information packs for patients (85%), a website designed to assist GPs (80%), and referral to these websites via positive laboratory results (85%). Forty-three percent currently undertook patient delivered partner therapy for chlamydia. Conclusion: GPs want and need greater guidance and resources to assist them with partner notification for chlamydia. Resources utilizing the internet and practice software and mechanisms where GPs are automatically directed to these when chlamydia is diagnosed have wide appeal and the potential to improve the effectiveness of partner notification for chlamydia.

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.

Interaction of imipenem with erythromycin and tetracycline assessed by microdilution checkerboard techniques.

Microdilution methodology was used to study the interaction of imipenem with erythromycin and tetracycline, a combination therapy that might be used for the treatment of serious pelvic inflammatory disease. The combination of imipenem and erythromycin showed no antagonism for Escherichia coli and Haemophilus influenzae but was antagonistic for Staphylococcus aureus, Enterococcus faecalis, and group B streptococci; the combination of imipenem and tetracycline was antagonistic for all strains except H. influenzae. Correlation between the results of kill curves and the measurement of fractional bactericidal concentration (FBC) indices was good, although FBC indices showed less antagonism than kill curves. Fractional inhibitory concentration indices showed poor correlation, rarely showing antagonism, and indeed showed synergy in three cases. If erythromycin or tetracycline is considered necessary in addition to imipenem in the treatment of pelvic inflammatory disease, it is probably more effective when given after the course of imipenem has been completed.

Increased Syphilis Testing of Men Who Have Sex With Men: Greater Detection of Asymptomatic Early Syphilis and Relative Reduction in Secondary Syphilis

Background Syphilis rates have increased markedly among men who have sex with men (MSM) internationally. We examined trends in syphilis testing and detection of early syphilis among MSM in Australia. Methods Serial cross-sectional analyses on syphilis testing and diagnoses among MSM attending a national sentinel network of 46 clinics in Australia between 2007 and 2014. Results 359313 clinic visits were included. The proportion of MSM serologically tested for syphilis annually increased in HIV-negative (48% to 91%; Ptrend < .0001) and HIV-positive MSM (42% to 77%; Ptrend < .0001). The mean number of tests per man per year increased from 1.3 to 1.6 in HIV-negative MSM (Ptrend < .0001) and from 1.6 to 2.3 in HIV-positive MSM (Ptrend < .0001). 2799 and 1032 syphilis cases were detected in HIV-negative and HIV-positive MSM, respectively. Among HIV-negative MSM, the proportion of infections that were early latent increased from 27% to 44% (Ptrend < .0001), while the proportion that were secondary decreased from 24% to 19% (Ptrend = .030). Among HIV-positive MSM, early latent infections increased from 23% to 45% (Ptrend < .0001), while secondary infections decreased from 45% to 26% (Ptrend = .0003). Among HIV-positive MSM, decreasing secondary syphilis correlated with increasing testing coverage (r = -0.87; P = .005) or frequency (r = -0.93; P = .001). Conclusions Increases in syphilis screening were associated with increased detection of asymptomatic infectious syphilis and relative falls in secondary syphilis for both HIV-positive and HIV-negative MSM nationally, suggesting interruption of syphilis progression.

Measuring performance to drive improvement: development of a clinical indicator set for general medicine

Background: There are delays in implementing evidence about effective therapy into clinical practice. Clinical indicators may support implementation of guideline recommendations.