Anna McNulty

Increasing role of herpes simplex virus type 1 in first-episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992–2006

Objectives: Herpes simplex virus (HSV) type 1 is causing an increasing proportion of anogenital herpes; however, it is unclear which populations are affected. We describe the contribution of HSV-1 to first-episode anogenital herpes and its associations. Methods: For all cases of first-episode anogenital herpes diagnosed at the Sydney Sexual Health Centre from 1992 to 2006, medical record review was used to confirm the type and anatomical site. Age, sex, HIV status and sexual behaviour data were extracted from the clinic database. Results: Overall, among 1845 confirmed cases of first-episode anogenital herpes the proportion attributable to HSV-1 increased from 29% to 42% (odds ratio (OR) per 3-year band 1.19; 95% CI 1.11 to 1.27). When stratified by gender of sexual partners the proportion of first-episode anogenital herpes due to HSV-1 increased over time, but only achieved significance in heterosexual women (p<0.01). Among men who have sex with men (MSM), HSV-1 only increased for those less than 28 years of age, 17% in 1992–4 to 76% in 2004–6 (OR per 3-year band 1.58; 95% CI 1.14 to 2.19). The proportion attributable to HSV-1 was higher for anal than genital herpes and MSM were much more likely to have anal disease. Conclusions: The proportion of first-episode anogenital herpes due to HSV-1 significantly increased among younger MSM and heterosexual women over the 15-year period. In some clinical populations, such as young MSM and women or patients with anal disease, HSV-1 may now account for the majority of first-episode anogenital herpes.

Lack of consistency between five definitions of nonprogression in cohorts of HIV-infected seroconverters

Objective:To identify appropriate criteria for characterizing HIV-infected nonprogressors. Design:Five definitions were compared as follows: (1) last CD4 count > 500×106/l; (2) two most recent CD4 counts > 500×106/l; (3) calculated CD4 count based on linear regression > 500×106/l; (4) CD4 slope ≥ 0 with no antiretroviral use; (5) all CD4 counts > 500×106/l, decline in CD4 slope < 5 cells per year, no antiretroviral use. Participants:Five prospective cohorts of homosexual men with documented dates of HIV-1 seroconversion. Main outcome measures:Proportions of nonprogressors were calculated 7, 8, 9 and 10 years following seroconversion (n = 285). Definitions were evaluated with respect to consistency over time and across sites. Subjects lacking CD4 counts within 3 years preceding end of follow-up were excluded. Results:Across sites, proportions of nonprogressors ranged from 1% (definition 5) to 17.5% (definition 1) 10 years after seroconversion. Definitions based on absolute CD4 counts (definitions 1–3) had higher proportions and were less consistent than those based on stable slopes (definitions 4 and 5). For each definition, proportions decreased as follow-up increased, but were most stable for definition 4 (3%). Site differences decreased as follow-up increased, but remained nearly threefold for definitions 1–3. None of the definitions classified the same subjects as nonprogressors at any timepoint. Conclusions:Observations regarding nonprogression are highly dependent on the definition and the duration of follow-up. Our findings highlight methodological challenges which will need to be overcome in natural history studies of nonprogression.

SMS reminders improve re-screening in women and heterosexual men with chlamydia infection at Sydney Sexual Health Centre: a before-and-after study

Background In 2009, Sydney Sexual Health Centre implemented a short message service (SMS) reminder system to improve re-screening after chlamydia infection. SMS reminders were sent at 3 months recommending the patient make an appointment for a re-screen. Methods Using a before-and-after study, the authors compared the proportion re-screened within 1–4 months of chlamydia infection in women and heterosexual men who were sent an SMS in January to December 2009 (intervention period) with a 18-month period before the SMS was introduced (before period). The authors used a χ2 test and multivariate regression. Visitors and sex workers were excluded. Results In the intervention period, 141 of 343 (41%) patients were diagnosed with chlamydia and sent the SMS reminder. In the before period, 338 patients were diagnosed as having chlamydia and none received a reminder. The following baseline characteristics were significantly different between those sent the SMS in the intervention period and the before period: new patients (82% vs 72%, p=0.02), aged <25 years (51% vs 33% p<0.01), three or more sexual partners in the last 3 months (31% vs 27%, p<0.01) and anogenital symptoms (52% vs 38%, p<0.01). The proportion re-screened 1–4 months after chlamydia infection was significantly higher in people sent the SMS (30%) than the before period (21%), p=0.04, and after adjusting for baseline differences, the OR was 1.57 (95% CI 1.01 to 2.46). Conclusions SMS reminders increased re-screening in patients diagnosed as having chlamydia at a sexual health clinic. The clinic now plans to introduce electronic prompts to maximise the uptake of the initiative and consider strategies to further increase re-screening.

Is azithromycin adequate treatment for asymptomatic rectal chlamydia

Rectal chlamydia is a common sexually transmissible infection (STI) in men who have sex with men (MSM) that is predominantly asymptomatic. The recommended treatment of azithromycin 1 g as a single oral dose has not been subject to randomized trials and so its efficacy is unknown. We conducted a retrospective case-note review of all MSM diagnosed at the Sydney Sexual Health Centre with asymptomatic rectal chlamydia in 2009. We identified 116 MSM who received azithromycin; 85 (73%) attended for the recommended re-test at varying times (median 78 days, range 21–372 days). Of the men who returned, 11 (13%) had a persistently positive result; we reviewed behavioural data to classify these men as probable re-infections (6/11) or possible treatment failures (5/11), suggesting an efficacy of 94%. Until a randomized controlled trial (RCT) is conducted, patients with rectal chlamydia should be encouraged to attend for a re-test at 6–12 weeks.

One confirmed and one suspected case of pharyngeal gonorrhoea treatment failure following 500mg ceftriaxone in Sydney, Australia.

Emerging antimicrobial resistance within Neisseria gonorrhoeae (NG) is a significant global public health threat. Detection and investigation of treatment failures is a crucial component of the World Health Organisations response to this challenge. We report the cases of two homosexual men, both treated for pharyngeal NG with 500mg intramuscular ceftriaxone, in whom a test of cure 1 week after treatment showed persisting infection. Both men denied further sexual activity. In the first case, treatment failure was confirmed, since the isolates before and after treatment were identical by auxotype, antibiogram, multilocus sequence type (MLST) and multi-antigen sequence type (NG-MAST). In the second case, the MLSTs before and after treatment were identical, but NG-MAST results were similar but not indistinguishable. These cases underline the importance of test-of-cure and molecular investigations in identifying treatment failure, but also highlight the complexity of distinguishing treatment failure from reinfection when relying on highly variable molecular targets that may be subject to drug pressure.

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.

Raltegravir-emtricitabine-tenofovir as HIV nonoccupational post-exposure prophylaxis in men who have sex with men: safety, tolerability and adherence.

Three‐drug nonoccupational post‐exposure prophylaxis (NPEP) typically includes co‐formulated emtricitabine‐tenofovir (FTC‐TDF) and a protease inhibitor. However, protease inhibitors can cause significant toxicities, can interact with prescribed and illicit drugs, and work late in the viral cycle. Agents that act before viral integration into host DNA may have efficacy advantages. Raltegravir (RAL) is a good candidate for NPEP as it has few side effects or drug interactions and acts prior to HIV integration. The objective of this study was to investigate the use of RAL in 3‐drug NPEP in terms of safety, adherence and tolerability.

2-day versus 5-day famciclovir as treatment of recurrences of genital herpes: results of the FaST study

Background: The brief period of viral replication in recurrent genital herpes lesions suggests shorter therapeutic regimens may be as effective as standard 5-day courses. Objective: To demonstrate that a 2-day course of famciclovir 500 mg statim, then 250 mg twice daily was non-inferior to the standard 5-day course of 125 mg twice daily. Methods: Patients were randomly assigned either the 2-day or 5-day famciclovir course and initiated therapy within 12 h of onset of prodromal symptoms. They were instructed to complete daily questionnaires on herpes-related symptoms and functioning and to attend the clinic for assessment of healing 5.5 days after initiating therapy. Results: A total of 873 patients were randomised at least once and 1038 recurrences were treated. The proportion of evaluable recurrences with lesions present at 5.5 days was less in the 2-day arm (24%) than in the 5-day (28%) arm. The upper 97.5% confidence limit (CL) for this difference in favour of the 2-day arm was 2% in favour of the 5-day arm, well within the 10% predefined for non-inferiority. The upper 97.5% CL was similar in the intent-to-treat, evaluable and per-protocol recurrence populations and when adjusted for baseline differences (in gender, age, herpes history and HIV infection) or for clustering of recurrences within patients. Both treatments had similar side-effects; proportion of lesions aborted; time to next recurrence; patient-reported symptoms; and impact on daily functioning. Conclusions: The 2-day course was as safe and effective as the standard 5-day course and can only enhance patient convenience and compliance.

Herpes zoster and the stage and prognosis of HIV-1 infection.

OBJECTIVES: To examine the incidence of herpes zoster in HIV-1 infection. To assess the prognostic significance of the occurrence of herpes zoster and progression to AIDS or death DESIGN AND METHODS: 146 homosexually active men with known times of HIV-1 seroconversion were identified through the Sydney AIDS Prospective Study and the clinic records of a private medical practice with large caseload of HIV infected homosexual men. Medical records were reviewed for a history of herpes zoster, CD4+ lymphocyte counts, and HIV-1 disease status. Coxs proportional hazards model was used to determine whether herpes zoster predicted progression to AIDS or death. RESULTS: After a mean follow up of 54 months, 30 men (20%) had an episode of herpes zoster and three of these men had one recurrence. The overall incidence of herpes zoster was 44.4 episodes per 1000 person years (95% CI 30.0-63.5). Herpes zoster was not found to be a marker of deteriorating immune functions as measured by CD4+ lymphocyte counts. CD4+ counts did not differ significantly between those with and without zoster at 1 year (551 v 572.10(6)/1, p = 0.79), 2 years (451 v 557, p = 0.11), and 3 years (424 v 481, p = 0.50) following HIV-1 seroconversion. There was no statistically significant difference in progression to AIDS (RR = 1.89, 95% CI 0.80-4.46, p = 0.15) or death (RR = 0.90, 95% CI 0.31-2.65, p = 0.85) from HIV-1 sero-conversion in those who did and those who did not develop herpes zoster. CONCLUSION: The incidence of herpes zoster was consistent with the findings of other studies. There was no association between the occurrence of herpes zoster and progression of HIV-1 disease.

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.