Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) is highly effective in men who have sex with men (MSM) at the individual level, but data on population-level impact are lacking. We examined whether rapid, targeted, and high-coverage roll-out of PrEP in an MSM epidemic would reduce HIV incidence in the cohort prescribed PrEP and state-wide in Australia's most populous state, New South Wales. METHODS: The Expanded PrEP Implementation in Communities-New South Wales (EPIC-NSW) study is an implementation cohort study of daily co-formulated tenofovir disoproxil fumarate and emtricitabine as HIV PrEP. We recruited high-risk gay men in a New South Wales-wide network of 21 clinics. We report protocol-specified co-primary outcomes at 12 months after recruitment of the first 3700 participants: within-cohort HIV incidence; and change in population HIV diagnoses in New South Wales between the 12-month periods before and after PrEP roll-out. The study is registered with ClinicalTrials.gov, number NCT02870790. FINDINGS: We recruited 3700 participants in the 8 months between March 1, 2016, and Oct 31, 2016. 3676 (99%) were men, 3534 (96%) identified as gay, and 149 (4%) as bisexual. Median age was 36 years (IQR 30-45 years). Overall, 3069 (83%) participants attended a visit at 12 months or later. Over 4100 person-years, two men became infected with HIV (incidence 0·048 per 100 person-years, 95% CI 0·012-0·195). Both had been non-adherent to PrEP. HIV diagnoses in MSM in New South Wales declined from 295 in the 12 months before PrEP roll-out to 221 in the 12 months after (relative risk reduction [RRR] 25·1%, 95% CI 10·5-37·4). There was a decline both in recent HIV infections (from 149 to 102, RRR 31·5%, 95% CI 11·3 to 47·3) and in other HIV diagnoses (from 146 to 119, RRR 18·5%, 95% CI -4·5 to 36·6). INTERPRETATION: PrEP implementation was associated with a rapid decline in HIV diagnoses in the state of New South Wales, which was greatest for recent infections. As part of a combination prevention approach, rapid, targeted, high-coverage PrEP implementation is effective to reduce new HIV infections at the population level. FUNDING: New South Wales Ministry of Health, Gilead Sciences.

Non-AIDS complexity amongst patients living with HIV in Sydney: risk factors and health outcomes.

OBJECTIVE: To assess the prevalence of non-AIDS co-morbidities (NACs) and predictors of adverse health outcomes amongst people living with HIV in order to identify health needs and potential gaps in patient management. DESIGN: Retrospective, non-consecutive medical record audit of patients attending a publicly funded HIV clinic in metropolitan Sydney analysed for predictors of adverse health outcomes. We developed a scoring system based on the validated Charlson score method for NACs, mental health and social issues and confounders were selected using directed acyclic graph theory under the principles of causal inference. RESULTS: 211 patient files were audited non-consecutively over 6 weeks. 89.5% were male; 41.8% culturally and linguistically diverse and 4.1% were of Aboriginal/Torres Strait Islander origin. Half of patients had no general practitioner and 25% were ineligible for Medicare subsidised care. The most common NACs were: cardiovascular disease (25%), hepatic disease (21%), and endocrinopathies (20%). One-third of patients had clinical anxiety, one-third major depression and almost half of patients had a lifetime history of tobacco smoking. Five predictors of poor health outcomes were identified: (1) co-morbidity score was associated with hospitalisation (odds ratio, OR 1.58; 95% CI 1.01-2.46; p = 0.044); (2) mental health score was associated with hospitalisation (OR 1.79; 95% CI 1.22-2.62; p = 0.003) and poor adherence to ART (OR 2.34; 95% CI 1.52-3.59; p = 0.001); (3) social issues score was associated with genotypic resistance (OR 2.61; 95% CI 1.48-4.59; p = 0.001), co-morbidity score (OR 1.69; 95% CI 1.24-2.3; p = 0.001) and hospitalisation (OR 1.72; 95% CI 1.1-2.7; p = 0.018); (4) body mass index < 20 was associated with genotypic resistance (OR 6.25; 95% CI 1.49-26.24; p = 0.012); and (5) Medicare eligibility was associated with co-morbidity score (OR 2.21; 95% CI 1.24-3.95; p = 0.007). CONCLUSION: Most HIV patients are healthy due to effective antiretroviral therapy; however, NACs and social/mental health issues are adding to patient complexity. The current findings underpin the need for multidisciplinary management beyond routine viral load and CD4 count monitoring.

Sex differences in the significance of isolated reactive treponemal chemiluminescence immunoassay results.

OBJECTIVES: The significance of sera with isolated reactive treponemal chemiluminescence immunoassay (IRTCIA) results is unclear. Women have this phenotype more commonly than men. Most cohorts examining this phenotype have included predominantly men and have demonstrated evidence of past or subsequently confirmed syphilis infection in a significant proportion of cases. We hypothesised that a proportion of sera with IRTCIA results would be positive on immunoblot testing and that sera from women with IRTCIA would have different results in immunoblot testing than men. METHODS: IRTCIA sera from a tertiary referral serology laboratory serving multiple clinical sites were analysed with a syphilis line immunoblot assay (LIA) and analysed by sex. Logistic regression was undertaken to assess factors associated with LIA status. Medical record review and descriptive analysis of a separate cohort of women with the IRTCIA phenotype from a single campus was also undertaken. RESULTS: Overall, 19/63 (30.1%) subjects with the IRTCIA phenotype were positive in the LIA, including 13 men and 6 women. Women were significantly less likely to have definitive results (positive or negative) than men (p=0.015). Pregnant women were less likely than non-pregnant women to have a negative LIA result (OR 0.57; p=0.03). Record review of 22 different women with IRTCIA reactivity showed that 2/22 (9.1%) had HIV and previous syphilis infection, 15/22 (68.2%) were pregnant and 3 (13.6%) had autoimmune disease. CONCLUSIONS: A significant proportion of sera with IRTCIA results on serological tests are reactive on LIA testing and some may not be false positive results. The interpretation of IRTCIA results should be undertaken in conjunction with an assessment of factors such as sex, pregnancy, a history of syphilis and other STIs and syphilis risk.

Antiretroviral Use in the CEASE Cohort Study and Implications for Direct-Acting Antiviral Therapy in Human Immunodeficiency Virus/Hepatitis C Virus Coinfection.

Background. Interferon-free direct-acting antiviral (DAA) regimens for hepatitis C virus (HCV) provide a major advance in clinical management, including in human immunodeficiency virus (HIV)/HCV coinfection. Drug-drug interactions (DDIs) with combination antiretroviral therapy (cART) require consideration. This study aimed to characterize the cART regimens in HIV/HCV-coinfected individuals and assess the clinical significance of DDIs with DAAs in a real-world cohort. Methods. This analysis included participants enrolled in CEASE-D, a prospective cohort of HIV/HCV-coinfected individuals in Sydney, Australia, between July 2014 and December 2015. A simulation of potential DDIs between participants' cART and interferon-free DAA regimens was performed using www.hep-druginteractions.org and relevant prescribing information. Results. In individuals on cART with HCV genotype (GT) 1 and 4 (n = 128), category 3 DDIs (contraindicated or not recommended) were noted in 0% with sofosbuvir/ledipasvir, 0% with sofosbuvir plus daclatasvir, 17% with sofosbuvir/velpatasvir, 36% with ombitasvir/paritaprevir/ritonavir ± dasabuvir, 51% with grazoprevir/elbasvir, and 51% with sofosbuvir plus simeprevir; current cART regimens were suitable for coadministration in 100%, 100%, 73%, 64%, 49%, and 49%, respectively. In individuals with HCV GT 2 or 3 (n = 53), category 3 DDIs were evident in 0% with sofosbuvir plus daclatasvir, 0% with sofosbuvir and ribavirin, and 13% with sofosbuvir/velpatasvir; current cART regimens were suitable in 100%, 100%, and 81%, respectively. Conclusions. Potential DDIs are expected and will impact on DAA prescribing in HIV/HCV coinfection. Sofosbuvir in combination with an NS5A inhibitor or ribavirin appeared to be the most suitable regimens in this cohort. Evaluation of potential DDIs is required to prevent adverse events or treatment failure.