Norman Roth

Does the frequency of HIV and STI testing among men who have sex with men in primary care adhere with Australian guidelines

Objectives Australian guidelines recommend annual testing for HIV and sexually transmitted infections (STIs) for all men who have sex with men (MSM) and 3–6 monthly testing for those at higher risk as defined by behavioural criteria. We assessed HIV/STI re-testing rates among MSM attending primary care clinics. Methods We conducted a retrospective follow-up of HIV negative MSM tested for HIV or STIs (chlamydia or syphilis) at four primary care clinics in the 9-month period: April to December 2006. Re-testing rates for these infections were calculated over 18 months. Logistic regression was undertaken to identify predictors of guideline adherence. Results Of the MSM requiring annual HIV testing according to the guidelines, the re-testing rates at 1 y were 35% (762/2163). Among the higher risk MSM, 6-monthly HIV re-testing rates were 15% (283/1862). Within the subgroup who reported 11 or more male sexual partners within the past 6 months, HIV re-testing rates within 6 months were 19%. Independent predictors of HIV re-testing within 6 months in higher-risk MSM were reporting 11 or more male sexual partners in the last 6 months (AOR 3.1, 95% CI 1.8 to 4.8); being born overseas (AOR 2.0, 95% CI 1.2 to 3.4); and previous HIV testing more than 12 months earlier (AOR 3.3, 95% CI 1.9 to 5.5). Conclusion There is poor adherence to national guidelines that recommend regular re-testing of MSM for STIs, particularly among those at higher risk who require more frequent testing. Clinical strategies are urgently needed to encourage more frequent HIV/STI testing among MSM, especially in the higher risk subgroup.

Randomized, Open-Label, Comparative Trial to Evaluate the Efficacy and Safety of Three Antiretroviral Drug Combinations Including Two Nucleoside Analogues and Nevirapine for Previously Untreated HIV-1 Infection: The OzCombo 2 Study

Abstract PURPOSE: To assess and compare the efficacy and safety of three triple combination antiretroviral therapies in HIV-1-infected treatment-naive patients. METHOD: Seventy treatment-naive HIV-infected adults with CD4+ T-cell counts >50/μL were randomized to receive either zidovudine + lamivudine + nevirapine (AZT + 3TC + NVP), stavudine + didanosine + nevirapine (d4T+ddI+NVP), or stavudine + lamivudine + nevirapine (d4T+3TC+NVP) for 52 weeks. Patient assessments were conducted monthly and included measurement of plasma HIV RNA levels and CD4+ T-cell counts and evaluations for drug toxicity. RESULTS: The mean time-weighted reductions in plasma HIV RNA in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 1.29, 2.13, and 1.78 log10 copies/mL, respectively (p = .389). The proportions of patients with HIV RNA <50 copies/mL in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 73%, 68%, and 80%, respectively (p =.71). The mean time-weighted increases in CD4+ T-cell counts in the AZT+3TC+NVP, d4T+3TC+NVP, and d4T+ddI+NVP groups were 139, 113, and 174 cells/μL, respectively (p =.30). Three patients ceased assigned treatment due to rash (one from each treatment arm), and 5 of the 45 patients on d4T (3 from the d4T+3TC+NVP arm and 2 from the d4T+ddI+NVP arm) ceased assigned treatment due to neuropathy. CONCLUSION: All three-drug combinations were equally effective at suppressing viral load and increasing CD4+ T-cell counts. No significant differences were detected between the treatment groups in virological or immunological response or cessation of study drugs due to adverse events, although it is possible that the study was underpowered to detect differences. NVP was safe and efficacious in this setting, and efficacy was not influenced by nucleoside reverse transcriptase inhibitor backbone.

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.

Risk factors for HIV seroconversion in men who have sex with men in Victoria, Australia: Results from a sentinel surveillance system

OBJECTIVES HIV diagnosis rates in men who have sex with men (MSM) began increasing in Australia 10 years ago, and there has been a major resurgence of syphilis. We determined predictors of HIV positivity and seroconversion among MSM in Victoria, Australia. METHODS We conducted a retrospective longitudinal analysis of data from MSM who underwent HIV testing between April 2006 and June 2009 at three primary care clinics. Logistic regression was used to determine predictors of HIV positivity and seroconversion. RESULTS During the study period, 7857 MSM tested for HIV. Overall HIV positivity was 1.86% (95% confidence interval (CI): 1.6-2.2). There were 3272 repeat testers followed for 4837 person-years (PY); 60 seroconverted and HIV incidence was 1.24 (95% CI: 0.96-1.60) per 100 PY. Independent predictors of HIV seroconversion were: an infectious syphilis diagnosis within the last 2 years (adjusted hazard ratio (AHR)=2.5, 95% CI: 1.1-5.7), reporting six or more anal sex partners in the past 6 months (AHR=3.3, 95% CI: 1.8-6.3), reporting an HIV-positive current regular partner (AHR=3.4, 95% CI: 1.1-10.6) and reporting inconsistent condom use with casual partners in the past 6 months (AHR=4.4, 95% CI: 1.7-11.5). CONCLUSION Our results call for HIV prevention to target high-risk MSM, including men with a recent syphilis diagnosis or a high numbers of partners, men who have unprotected anal sex with casual partners and men in serodiscordant relationships. The HIV incidence estimate will provide a baseline to enable public health officials to measure the effectiveness of future strategies.

Opt-Out and Opt-In Testing Increases Syphilis Screening of HIV-Positive Men Who Have Sex with Men in Australia

Background Since 2005, Australian clinicians were advised to undertake quarterly syphilis testing for all sexually active HIV-positive men who have sex with men (MSM). We describe differences in syphilis testing frequency among HIV-positive MSM by clinic testing policies since this recommendation. Methods Three general practices, two sexual health clinics and two hospital HIV outpatient clinics provided data on HIV viral load and syphilis testing from 2006–2010. Men having ≥1 viral load test per year were included; >95% were MSM. We used Chi-2 tests to assess changes in syphilis testing frequency over time, and differences by clinic testing policy (opt-out, opt-in and risk-based). Results The proportion of men having HIV viral loads with same-day syphilis tests increased from 37% in 2006 to 63% in 2007 (p<0.01) and 68–69% thereafter. In 2010, same-day syphilis testing was highest in four clinics with opt-out strategies (87%, range:84–91%) compared with one clinic with opt-in (74%, p = 0.121) and two clinics with risk-based strategies (22%, range:20–24%, p<0.01). The proportion of men having ≥3 syphilis tests per year increased from 15% in 2006 to 36% in 2007 (p<0.01) and 36–38% thereafter. In 2010, the proportion of men having ≥3 syphilis tests in a year was highest in clinics with opt-out strategies (48%, range:35–59%), compared with opt-in (39%, p = 0.121) and risk-based strategies (8.4%, range:5.4–12%, p<0.01). Conclusion Over five years the proportion of HIV-positive men undergoing syphilis testing at recommended frequencies more than doubled, and was 5–6 times higher in clinics with opt-out and opt-in strategies compared with risk-based policies.

The rise of infectious syphilis in Victoria and the impact of enhanced clinical testing

Objective: Passive surveillance indicates a clear increase in infectious syphilis cases in Victoria, but trends are likely to be influenced by changes in testing. We therefore used testing data from two Melbourne clinics with a high caseload of men who have sex with men to examine infectious syphilis prevalence, time trends and risk factors for infection.

A new surveillance system for monitoring HIV infection in Victoria, Australia

OBJECTIVES To establish a new mechanism for monitoring patterns of HIV infection, in the context of a sustained increase in HIV diagnosis among men who have sex with men (MSM) in Victoria. METHODS Between April 2004 and August 2005, a linked voluntary HIV sentinel surveillance system was implemented at five medical clinics with a high case load of MSM. Using a questionnaire, doctors collected HIV testing history, demographic and sexual risk behaviour information from all clients undergoing voluntary HIV testing. Questionnaires were linked with HIV test results. Logistic regression analysis was conducted to determine factors associated with HIV infection. RESULTS Of 3435 MSM tested for HIV at participating sites, 1.7%, (95% CI = 1.2-2.2) were newly diagnosed with HIV; between 2004 and 2005 the proportion increased from 1.3% (95% CI = 1.2-1.5) to 2.0% (95% CI = 1.8-2.2), P = 0.107. There was no significant change in the number of HIV tests conducted per month or in demographic characteristics, testing history and sexual behaviour characteristics between time periods. In multivariate analysis, reporting unprotected anal intercourse (UAI) with any partner, UAI with a HIV-positive partner/s and being aged 30-39 years or 40 years or greater were significantly associated with HIV infection. CONCLUSION This new surveillance mechanism, based on linked testing at participating clinics, indicates that the increase in HIV notifications in 2005 was unrelated to changes in testing and data from a Melbourne sexual behavioural survey suggests the increase was more likely to be attributed to increases in transmission within the past few years. The sentinel system highlighted UAI, especially with HIV positive partner/s are important transmission factors.

Adherence to HIV treatment guidelines for comorbid disease assessment and initiation of antiretroviral therapy.

Background:There are limited data on adherence to HIV treatment guidelines. We assessed adherence to US Department of Health and Human Services guidelines with Australian Commentary for adults initiating antiretroviral therapy (ART). Methods:Data were recorded regarding “when to start”, “what to start” and pre-ART comorbid disease assessment for consecutive adults initiating ART at primary care and hospital clinics in Sydney and Melbourne from 2004 through 2008. Independent predictors of adherence to guidelines were calculated by stepwise logistic regression. Results:For the 500 subjects (95.9% male, mean 40.2 years, median CD4 count 270 cells/&mgr;L) “when to start” adherence was 87.6%, and was less likely with initiation in a clinical trial [0.25 (95% CI: 0.13 to 0.49); P < 0.0001] and previous, short-term nontherapeutic antiretroviral exposure [0.08 (0.03 to 0.25); P < 0.0001]. “What to start” adherence was 69.0% for guideline-“preferred” regimens (85.8% for guideline-“preferred” or “alternative” regimens) and more likely with ART initiated in 2008 versus pre-2008 [OR: 2.69 (1.64 to 4.61); P = 0.0001]. Median comorbid disease assessment adherence was 56.8%, ranging from 25.6% for urinalysis to 99.2% for white blood cell count, and was more likely in patients with AIDS, and initiating ART in hospital or in a clinical trial. Hospital clinics were more likely to perform antiretroviral resistance testing (71.2% vs. 46.4%, P < 0.0001), to use “preferred” ART regimens (76.8% vs. 62.2%, P = 0.0002) but less likely to promote healthy diet and lifestyle (63.4% vs. 36.4%, P < 0.0001). Conclusions:“When to start” and “what to start” guidelines have been largely adhered to in Australia, but pre-ART comorbid disease assessment requires greater attention.

Rosuvastatin vs. protease inhibitor switching for hypercholesterolaemia: a randomized trial

The aim of the study was to compare the efficacy and safety of rosuvastatin initiation with those of switching of ritonavir‐boosted protease inhibitors (PI/rs) in HIV‐1‐infected adults with hypercholesterolaemia and increased cardiovascular risk scores.

A Randomized Trial of Nelfinavir, Ritonavir, or Delavirdine in Combination with Saquinavir-SGC and Stavudine in Treatment-Experienced HIV-1-Infected Patients

Abstract Purpose: To evaluate the 24-week impact of saquinavir-enhancing antiretroviral therapy on viral replication in patients previously treated with nucleoside analogues with or without prior saquinavir hard-gel capsules (HGC). Method: Patients were randomized in three groups to receive the following: Group 1—nelfinavir (750 mg tid), saquinavir soft-gel capsule (SGC) (800 mg tid), and stavudine (40 mg bid); Group II—ritonavir (400 mg bid), saquinavir-SGC (400 mg bid), and stavudine (40 mg bid); or Group III—delavirdine (400 mg tid), saquinavir-SGC (800 mg tid), and stavudine (40 mg bid). Viral loads, CD4 count, and safety were assessed over a 24-week period with an additional 6-month follow-up. Results: 73 patients received randomized therapy; 14 of whom were SQV naïve, with a median baseline viral load of 3.6 log10 and a CD4 count of 370 cells/mm3. By 6 months, the median decreases in plasma viral loads were 0.26, 0.71, and 0.29 log10 copies/mL for groups I, II, and III, respectively. The median increases in CD4 counts, for groups I, II, and III, were 52, 40, and 69 cells/mm3 at 6 months, respectively. Changes in viral load and CD4 counts at 6 months and 1 year were not significantly different between the treatment groups. More patients discontinued therapy in the ritonavir arm (35%) for drug intolerance or toxicity compared to either the nelfinavir or delavirdine arms (15% and 5%, respectively). In a multivariate analysis, baseline viral load, younger age, and baseline saquinavir resistance were significantly associated with detectable viral load at 24 weeks. Conclusion: The use of antiretroviral agents that pharmacokinetically boost saquinavir levels has a modest benefit in saquinavir-experienced patients.