Cascade of care and rapid treatment pathway at Auckland City Hospital for patients with a new diagnosis of HIV infection, 2015-2019.

AIMS: Legislative changes in 2017 enabled subsidised HIV care for all people living with HIV in New Zealand. This enabled a rapid treatment pathway (RTP) to be developed at Auckland City Hospital (ACH). Our aims were to document the cascade of care for people referred with newly diagnosed HIV infection and evaluate the effect of the RTP. METHODS: People with newly diagnosed HIV infection in New Zealand referred to ACH between 2015 and 2019 were included in the cascade of care. The 2-year periods before (2015 and 2016) and after (2018 and 2019) the RTP were compared for initiation of antiretroviral therapy (ART) and attainment of HIV viral suppression. RESULTS: There were 240 people with newly diagnosed HIV infection referred. Of these, 197/200 (98.5%) were on ART and 195/197 (99%) had documented viral suppression. ART was initiated within 6 weeks of referral for 41/120 (34.2%) in the pre-RTP and 76/79 (96.2%) in the RTP periods (p<0.0001). Viral suppression was achieved within 6 months of diagnosis for 66/118 (55.9%) in the pre-RTP and 73/75 (97.3%) in the RTP periods (p<0.0001). CONCLUSIONS: A high proportion of people referred with newly diagnosed HIV infection were commenced on ART and achieved viral suppression. The RTP facilitated earlier initiation of ART and achievement of viral suppression.

Pediatric Invasive Meningococcal Disease, Auckland, New Zealand (Aotearoa), 2004-2020.

New Zealand (Aotearoa) experienced a Neisseria meningitidis serogroup B epidemic during 1991-2006, and incidence remains twice that of other high-income countries. We reviewed clinical, laboratory, and immunization data for children <15 years of age with laboratory-confirmed invasive meningococcal disease in Auckland, New Zealand, during January 1, 2004-December 31, 2020. Of 319 cases in 318 children, 4.1% died, and 23.6% with follow-up data experienced sequelae. Children of Maori and Pacific ethnicity and those living in the most deprived areas were overrepresented. Eighty-one percent were positive for N. meningitidis serogroup B, 8.6% for serogroup W, 6.3% for serogroup C, and 3.7% for serogroup Y. Seventy-nine percent had bacteremia, and 63.9% had meningitis. In New Zealand, Maori and Pacific children are disproportionately affected by this preventable disease. N. meningitidis serogroup B vaccine should be included in the New Zealand National Immunization Schedule to address this persistent health inequity.

Outcomes of adults with invasive meningococcal disease with reduced penicillin susceptibility in Auckland 2004-2017.

PURPOSE: The purpose of this study was to assess the clinical outcomes of adults with invasive meningococcal disease (IMD) and to compare the outcomes of patients with IMD caused by a penicillin susceptible isolate (minimum inhibitory concentration (MIC) ≤ 0.06 mg/L) with patients with IMD caused by an isolate with reduced penicillin susceptibility (MIC > 0.06 mg/L). We also assessed the outcomes of patients with IMD caused by an isolate with reduced penicillin susceptibility who were treated exclusively with intravenous (IV) benzylpenicillin. METHODS: Retrospective study of all culture positive IMD in adult patients (age ≥ 15 years) in the Auckland region from 2004 to 2017. RESULTS: One hundred and thirty-nine patients were included; 94 had penicillin susceptible isolates (88 cured, 6 died), and 45 had an isolate with reduced penicillin susceptibility (41 cured, 1 possible relapse, 3 died). The median benzylpenicillin/ceftriaxone treatment duration was 3 days for both groups. There was no difference in the patient outcomes of both groups. Eighteen patients with IMD caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone and were cured. CONCLUSIONS: This study provides further support to existing data that has shown that short duration IV beta-lactam treatment is effective for IMD in adults. Only a small number of patients with meningitis caused by an isolate with reduced penicillin susceptibility received benzylpenicillin alone, limiting its evaluation. For Neisseria meningitidis meningitis, we recommend ceftriaxone as empiric treatment and as definitive treatment when this is caused by an isolate with reduced penicillin susceptibility.

Infective endocarditis in patients with rheumatic heart disease: a single-centre retrospective comparative study.

AIMS: We reviewed the baseline characteristics and outcomes of patients with infective endocarditis (IE) and compared those with and without rheumatic heart disease (RHD). METHODS: We retrospectively reviewed patients ≥15 years with IE treated at Auckland City Hospital between January 2016 and December 2018 and excluded device-related IE and complex congenital heart disease. RHD status was based on echocardiographic features or previous history of rheumatic fever with valvular disease. Microbiologic and echocardiographic results, treatment modalities and complications were recorded. Demographics and outcomes were compared based on RHD status. RESULTS: There were 155 patients with IE. Twenty-two had RHD. The mean age at admission was 45 years for RHD patients, which was 19 years younger than for non-RHD patients. There were significantly more Pacific patients with RHD (55% vs 14%). Previous IE and prosthetic valve endocarditis (PVE) were more common in RHD patients (27% vs 5%, and 77% vs 29%, respectively). After a median follow-up of 29 months, there was no significant difference in all-cause mortality between the two groups. However, 25/155 patients (16%) had died from IE-related causes (septic or cardiogenic shock post cardiac surgery, or embolic complications), with a significantly higher mortality in patients with RHD (7/22 (32%) patients, HR: 2.5) on univariate analysis. On multivariable analysis, PVE, heart failure, Staphylococcus aureus infection, diabetes, stroke and cardiac abscess were all associated with increased mortality, whereas RHD was not independently associated with increased mortality. CONCLUSIONS: In this retrospective single-centre audit, patients with RHD experienced IE at a younger age, had a higher incidence of prosthetic valve endocarditis and a prior history of IE. Although there was no difference in all-cause mortality, mortality in patients with RHD was almost exclusively secondary to complications of IE. This highlights the need for prevention strategies against endocarditis in the RHD population, including use of antibiotic prophylaxis¬, accessible dental health care and a high clinical suspicion for IE in RHD by healthcare providers.

Delayed diagnosis of HIV infection in women in the Auckland and Northland regions.

AIMS: We aimed to describe the epidemiology of women with HIV infection in the Auckland and Northland regions, and to assess whether there were missed opportunities for an earlier diagnosis of HIV infection. METHODS: We undertook a retrospective cohort analysis of women diagnosed with HIV infection between July 2011 and June 2021 under the care of the Infectious Disease Unit, Auckland City Hospital. RESULTS: Fifty-six women (54 cis and 2 trans) were diagnosed during the period. Eleven (20%) were diagnosed following a presentation with one or more AIDS-defining illnesses. Three (6%) died within six months of diagnosis. Fifteen of 44 (34%) women residing in New Zealand prior to their diagnosis of HIV infection had identifiable healthcare interactions that could have resulted in an earlier diagnosis of this infection. CONCLUSIONS: Women account for one in eight of the total population of people diagnosed with HIV infection in the Auckland and Northland regions. There are currently inadequate levels of HIV testing for women in the Auckland and Northland regions. There is a need for targeted HIV screening efforts for women. HIV screening needs to be optimised to maximise coverage, normalise testing and reduce the stigmatisation associated with testing.

In Vitro Synergism of Penicillin and Ceftriaxone against Enterococcus faecalis.

Enterococcus faecalis infective endocarditis is commonly treated with intravenous ampicillin/ceftriaxone combination therapy. Ampicillin, however, is unsuitable for outpatient parenteral antibiotic therapy (OPAT) regimens due to its instability in 24 h continuous infusors, and has been successfully replaced by benzylpenicillin used together with ceftriaxone in a few small case series. Since in vitro synergy data of penicillin/ceftriaxone against E. faecalis are still lacking, checkerboard assays were performed for 28 clinical E. faecalis isolates and one laboratory standard strain. Synergistic effects (both lowest and median FICI) were observed for penicillin/ceftriaxone in 15/29 isolates, while ampicillin/ceftriaxone exhibited synergism in 22/29 isolates. For isolates with ceftriaxone MICs ≤ 256 mg/L, the addition of free ceftriaxone trough concentrations to penicillin or ampicillin resulted in comparable synergistic effects for both combinations. In contrast, for isolates with ceftriaxone MICs ≥ 512 mg/L free ceftriaxone trough concentrations were only sufficient to exhibit synergistic effects in combination with ampicillin, but not penicillin. This study suggests that benzylpenicillin/ceftriaxone would be expected to be suitable for the OPAT treatment of enterococcal endocarditis for E. faecalis isolates with ceftriaxone MICs ≤ 256 mg/L. However, combination therapy would be expected to provide no advantage over benzylpenicillin monotherapy for isolates with ceftriaxone MICs ≥ 512 mg/L. Further investigation is required to analyse the relationship between ceftriaxone susceptibility and penicillin/ceftriaxone synergy, especially for isolates with ceftriaxone MICs of 64 to 512 mg/L.

Synchronous and metachronous malignant melanomas arising in a human immunodeficiency virus-positive patient after the commencement of highly active antiretroviral therapy treatment: a case report.

BACKGROUND: We present an unusual case of a patient who developed four melanomas within a few months of diagnosis with human immunodeficiency virus and commencement of highly active antiretroviral therapy therapy. The patient had no previous history of melanoma, and previous skin checks were normal. CASE PRESENTATION: A 50-year-old Caucasian male drainlayer with Fitzpatrick type 2 skin presented for a routine skin examination. He had been diagnosed with human immunodeficiency virus 4 months earlier and commenced on highly active antiretroviral therapy therapy. He was found to have three melanomas (melanoma in situ stage) on excision biopsies, and when he presented for wider excisions of these sites a few weeks later, another new melanoma in situ was found. He had no other medical history of note, and no symptoms to report. He is being followed up 3-monthly. CONCLUSIONS: This case of a human immunodeficiency virus-positive person presenting with four cutaneous melanomas-occurring in both synchronous and metachronous fashion within a 4-month period-is being presented both for its uniqueness and also to highlight the increased need for close skin surveillance in human immunodeficiency virus-positive patients.

Outpatient continuous-infusion benzylpenicillin combined with either gentamicin or ceftriaxone for enterococcal endocarditis.

BACKGROUND: Treatment regimens requiring multiple daily dosing for enterococcal endocarditis are challenging to deliver in the outpatient setting. Continuous-infusion benzylpenicillin via a 24 h elastomeric infusor, combined with either once-daily gentamicin or ceftriaxone, requires only one nursing encounter daily and is commonly used in New Zealand. OBJECTIVES: To assess the therapeutic success and adverse antibiotic effects of these regimens. METHODS: A retrospective observational case series from multiple hospitals of patients aged 15 years or over with enterococcal endocarditis diagnosed between July 2013 and June 2019 who received at least 14 days of outpatient continuous-infusion benzylpenicillin combined with either gentamicin or ceftriaxone for synergy. RESULTS: Forty-three episodes of enterococcal endocarditis in 41 patients met inclusion criteria. The primary synergy antibiotic was gentamicin in 20 episodes and ceftriaxone in 23 episodes. For the 41 initial treatment courses, 31 (76%) patients were cured, 3 (7%) patients developed relapsed endocarditis during or following antibiotic treatment and 7 (17%) patients continued with long-term suppressive oral amoxicillin following IV antibiotic treatment. There was no difference in the relapse rate between the two groups (P = 0.59). Seven (35%) adverse antibiotic effects were documented in the gentamicin group and none in the ceftriaxone group (P < 0.01). Two deaths (5%) occurred within the 6 month follow-up period. CONCLUSIONS: Outpatient treatment of enterococcal endocarditis with continuous-infusion benzylpenicillin combined with either once-daily gentamicin or ceftriaxone following a period of inpatient treatment is usually effective. A significantly higher rate of adverse effects was seen with gentamicin, favouring ceftriaxone as the initial synergy antibiotic.

An observational study of high- and low-abundance anti-retroviral resistance mutations among treatment-naïve people living with HIV in New Zealand between 2012 and 2017.

HIV resistance genotyping detects drug resistance mutations (DRMs) in ≥20% of circulating virus within an infected individual (high-abundance DRMs). Deep sequencing also detects DRMs in smaller viral subpopulations (low-abundance DRMs), although these are of uncertain importance. In this retrospective analysis of 292 treatment-naïve patients, high-abundance DRMs were present in 30/292 (10%) patients, but only one (0.3%) had resistance to first-line anti-retrovirals. Low-abundance DRMs were present in 36/247 (15%) patients, but none who received anti-retrovirals for which these were present had virologic failure. These findings demonstrate that starting first-line therapy in treatment-naïve patients need not be delayed while awaiting resistance testing.

Rheumatic fever recurrences in New Zealand 2010-14.

AIM: To describe the epidemiology and clinical characteristics of recurrences of acute rheumatic fever (ARF) in New Zealand 2010-14. METHOD: Retrospective hospital chart review for ARF with repeat hospital admissions from 2010-14, to identify recurrences of ARF. Definitions of recurrence as per NZ Heart Foundation Guidelines. RESULTS: There were 65 episodes of recurrent ARF among 60 patients. Maori 51%, Pacific 49%. Arthritis and carditis were the most common major manifestations. Median age at recurrence 21.6 years, (8-42 years), with 83% patients over 15 years. There were 841 first episodes of ARF in New Zealand in 2010-4. Overall New Zealand ARF recurrence rate was 7.2% (CI 5.5-8.9%). The recurrence rate was 4% for those under 16 years, 16% for those aged 16-20 and 25% for those >20 years (p<0.05). Seventy-three percent of recurrences occurred in the Auckland region. Recurrences of ARF were strongly associated with RHD progression. CONCLUSION: The risk of recurrence of ARF in New Zealand is low for children. In contrast, recurrences of ARF in New Zealand occur predominantly after age 15, and disproportionately in the Auckland DHBs. Current medical systems and registers may not be meeting the needs of adolescents and adults requiring secondary prophylaxis.

Long-Term Stable Bone Mineral Density in HIV-Infected Men Without Risk Factors for Osteoporosis Treated with Antiretroviral Therapy.

INTRODUCTION: Most prospective studies of bone mineral density (BMD) in HIV-infected cohorts taking antiretroviral therapy (ART) have been of short duration, typically < 3 years. Such studies have reported short-term stable or increasing BMD. We assessed whether this BMD stability persists for > 10 years in middle-aged and older men established on ART. METHODS: A 12-year, prospective, longitudinal study in 44 HIV-infected men treated with ART who had measurements of BMD at the lumbar spine, proximal femur and total body at baseline, 2, 6 and 12 years. RESULTS: At baseline, the mean age of participants was 49 years, the mean duration of HIV infection was 8 years, and the mean duration of ART was 50 months. After 12 years, BMD increased by 6.9% (95% CI 3.4 to 10.3) at the lumbar spine, and remained stable (range of BMD change: - 0.6% to 0.0%) at the total hip, femoral neck and total body. Only two individuals had a decrease of > 10% in BMD at any site during follow-up and both decreases in BMD were explained by co-morbid illnesses. CONCLUSIONS: BMD remained stable over 12 years in middle-aged and older HIV-infected men treated with ART. Monitoring BMD in men established on ART who do not have risk factors for BMD loss is not necessary.

Effects of Intravenous Zoledronate on Bone Turnover and Bone Density Persist for at Least 11 Years in HIV-Infected Men.

Previously we reported the results of a 4-year extension of a 2-year randomized placebo-controlled trial showing that the antiresorptive effects of two annual 4-mg doses of zoledronate in HIV-infected men persisted for at least 5 years after the second dose. We set out to determine whether the effects on BMD and bone turnover persist beyond 10 years. We invited all participants in the original trial known to be alive and living in New Zealand to attend an additional visit approximately 12 years after trial entry and 11 years after their second dose of study medication. The outcome measures were BMD at the lumbar spine, proximal femur, and total body, and markers of bone turnover. Twenty-five of the 43 men originally enrolled in the trial attended the final visit, representing 25 of 31 (81%) participants alive and residing in New Zealand at the time. The average duration of follow-up was 12.4 years. At the final visit, BMD remained higher in the zoledronate group than the placebo group (lumbar spine 3.7%, 95% CI, 0.1 to 7.3; total hip 3.7%, 95% CI, 1.2 to 6.2; femoral neck 5.0%, 95% CI, 2.1 to 7.9; total body 2.4%, 95% CI, 0.7 to 4.0), and the between-group differences in BMD remained stable between 6 and 12 years. Serum CTx remained lower in the zoledronate group than the placebo group between 6 and 12 years and, at the final visit, was 45% lower (95% CI, 25 to 64) than the placebo group. P1NP was 26% (95% CI, 4 to 48) lower in the zoledronate group than the placebo group at the final visit. In summary, two annual 4-mg doses of zoledronate have effects on bone turnover and BMD in men that persist for at least 11 years after the second dose. © 2019 American Society for Bone and Mineral Research.

Missed opportunities for earlier diagnosis of human immunodeficiency virus infection among adults presenting to Auckland District Health Board hospital services.

BACKGROUND: Earlier diagnosis of human immunodeficiency virus (HIV) infection improves health outcomes and reduces transmission. In New Zealand, half of new HIV diagnoses between 2005 and 2010 had a cluster of differentiation 4 count below 350 cells/mm3 . HIV screening is already offered in antenatal settings in New Zealand, but not universally in hospital settings. AIMS: To assess the impact of missed opportunities to diagnose HIV infection in adults presenting to hospital services at Auckland District Health Board (ADHB). METHODS: Retrospective cohort analysis of all new diagnoses of HIV infection in adults aged 15-64 years residing within the ADHB catchment area over a 7-year period. Those who had contact with hospital services prior to diagnosis, but within their estimated window of undiagnosed infection, were compared with those without such contact. RESULTS: Of 201 newly diagnosed patients, 68 had prior hospital contact within their estimated window of HIV infection, 68% of whom were men who have sex with men. These patients could potentially have been diagnosed earlier by a median of 12 months (range 1-84). Missed opportunity visits occurred across a wide range of hospital services, and included visits for conditions that indicated risk for, or actual, HIV infection. Thirteen patients had HIV-associated illnesses at the time of diagnosis that could have been prevented if diagnosed earlier. CONCLUSION: Our current risk-based HIV screening strategy commonly results in late diagnosis, negative health impacts and possibly avoidable transmissions. Further study is warranted to model the feasibility and potential impact of universal HIV screening at ADHB.

HIV-related stigma and discrimination in the New Zealand healthcare setting: a mixed-methods study.

Background People living with HIV (PLHIV) assume that healthcare workers have an adequate knowledge of HIV and expect that they will be treated with respect and compassion in the healthcare setting. Despite the remarkable advances in HIV treatment in the past two decades, PLHIV have continued to experience HIV-related stigma and discrimination by healthcare workers worldwide. The aim of this study was to explore the prevalence and nature of stigma and discrimination experienced by PLHIV in the healthcare setting in New Zealand. METHODS: This study involved a mixed-methods approach, using a questionnaire to collect quantitative and qualitative data from PLHIV recruited from the HIV Clinic at Auckland City Hospital and from two national HIV peer-support organisations between August 2012 and February 2013. RESULTS: Two hundred and thirteen PLHIV participated in the study. One hundred PLHIV (47%) reported that they had ever experienced HIV-related discrimination by a healthcare worker. The types of discrimination included confidentiality problems (19%), additional infection control measures (19%) and rudeness (18%). Healthcare settings where most of the discrimination had been experienced were other (non-infectious diseases) hospital wards, dental clinics, other (non-HIV) outpatient clinics and general practice clinics. CONCLUSION: Almost half of the PLHIV in New Zealand have experienced stigma and discrimination in a healthcare setting. The findings of this study show that there is a need to continue to normalise the care of HIV and increase HIV education for healthcare workers.

Increased uptake of cervical screening by women with HIV infection in Auckland regardless of ethnicity, requirement for an interpreter or level of education.

BACKGROUND: Current guidelines recommend that women with HIV infection receive annual cervical smears. METHODS: We evaluated the uptake of annual cervical smears by women with HIV infection under the care of the Infectious Disease Service at Auckland City Hospital. In an attempt to identify potential barriers to regularly receiving an annual cervical smear, we invited the women to complete a questionnaire. The responses from women who had regularly received an annual cervical smear were compared with those who had not. RESULTS: The proportion of women who had received a cervical smear increased from 44% in 2001, to 73% in 2010 (p=0.001). Ninety-three women (76%) completed the study questionnaire. No statistically significant differences were found in the questionnaire responses between the women who had regularly received an annual cervical smear and those who had not. CONCLUSION: The proportion of women in this cohort who received a cervical smear in 2010 is comparable with other studies of women with HIV infection in New Zealand and overseas. We have not been able to identify barriers that prevent women with HIV infection in Auckland regularly receiving an annual cervical smear. We plan to encourage women who have not received a cervical smear in the previous 2-year period to have a cervical smear performed when they attend the Infectious Disease Clinic, and will continue to notify the National Cervical Screening Programme that all women who are newly diagnosed with HIV infection should have an annual recall code attached to future cervical smear reports. We expect that these interventions will further increase the proportion of women with HIV infection in Auckland who receive an annual cervical smear.

HIV-associated tuberculosis in Auckland.

AIM: New Zealand has low rates of disease caused by to Mycobacterium tuberculosis (TB) and Human Immunodeficiency Virus (HIV). This study is the first to describe a New Zealand cohort of patients with HIV-associated TB. METHOD: We retrospectively reviewed the clinical records, laboratory data and chest radiographs of all patients who were diagnosed with HIV-associated TB and who commenced treatment for TB disease at Auckland City Hospital between January 1997 and July 2009. RESULTS: During the 12-and-a-half year study period, 40 patients were diagnosed with HIV-associated TB. The median age was 37 years and the median CD4 count was 130 cells/mm3. Only 2 patients were New Zealand born. Twenty-four (60%) patients had known HIV infection prior to their diagnosis of TB disease. Two patients with known HIV infection and positive tuberculin skin tests had not received treatment for latent tuberculosis infection (LTBI). Twenty-three (58%) patients received antiretroviral treatment during their TB treatment. There were 21 episodes of treatment interruption or immune reconstitution inflammatory syndrome. Three (8%) patients died. CONCLUSIONS: New Zealand continues to have a low incidence of HIV-associated TB. Early HIV diagnosis with universal screening and the treatment of LTBI in persons living with HIV infection is key to minimising the disease burden.