Christine Bowman

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

Asymptomatic herpes simplex virus shedding from the genital tract whilst on suppressive doses of oral acyclovir.

Forty-eight patients were recruited into a study of continuous oral acyclovir therapy for the suppression of recurrent genital herpes simplex virus (HSV) infection. Seven of these patients were shown to shed HSV in the absence of clinical signs or symptoms whilst on medication. The asymptomatic shedders did not differ significantly from the rest of the group in terms of age, interval from first attack to enrolment or number of recurrences prior to enrolment. Only one patient admitted to poor compliance as a trigger to asymptomatic HSV shedding. Failure to suppress asymptomatic shedding during prophylactic acyclovir therapy may have implications for sexual transmission to partners and vertical transmission to neonates and requires further study.

Safety, immunogenicity and efficacy assessment of HIV immunotherapy in a multi-centre, double-blind, randomised, Placebo-controlled Phase Ib human trial.

BACKGROUND Combination antiretroviral therapy (cART) is the main therapeutic management tool for HIV/AIDS. Despite its success in controlling viral load and disease progression, cART is expensive, associated with a range of significant side effects and depends for its efficacy on the patients life-long commitment to high levels of treatment adherence. Immunotherapeutic agents can provide potential solutions to these shortcomings. Here we describe a Phase Ib trial of HIV-v, a synthetic immunotherapy that elicits T- and B-cell effector responses against HIV infected cells. METHODS Fifty-nine cART-naive HIV-infected males aged 18-50 years with viral load of 5000-500,000 copies/ml and CD4 counts >350/μl were recruited for this multi-centre, randomised, double blind study. Volunteers received one low (250 μg) or high (500 μg) dose of HIV-v, either alone or adjuvanted (ISA-51). Safety, immunogenicity, CD4 count and viral load were monitored over 168 Days. RESULTS HIV-v was well tolerated and the adjuvanted formulations elicited IgG responses in up to 75% of volunteers. The high adjuvanted dose also elicited cellular responses in 45% of tested volunteers. In these responding subjects viral loads were reduced by over 1 log (p=0.04) compared to Placebo and non-responders. No changes in CD4 count were observed. CONCLUSIONS HIV-v is safe and can elicit T- and B-cell responses in ART-naive HIV patients that significantly reduce viral load. Improved dosing regimens and further research on long term efficacy are required, but HIV-v appears to have potential as an immunotherapeutic anti-viral agent. Trial registered as EudraCT-2009-010593-37 (ClinicalTrials.gov Identifier: NCT01071031).

The contribution of the HIV specialist nurse to HIV care: a scoping review

AIMS AND OBJECTIVES To systematically identify and critically examine the evidence of the contribution of the HIV nurse specialist to provision of HIV care in the UK and other developed countries. BACKGROUND The HIV clinical nurse specialist role has evolved over the past two decades in response to changes in two areas of HIV care: first, changes in the treatment and care of those with HIV and second, changes and development in advanced nursing practice. The challenges facing HIV care require the development of innovative services including a greater contribution of HIV specialist nurses. A review of current evidence is required to inform developments. DESIGN A review. METHODS A broad search strategy was used to search electronic databases. Grey literature was accessed through a variety of approaches. Preference was given to UK literature with inclusion of international publications from other developed countries where relevant. RESULTS Fourteen articles were included. Four themes were identified: the diversity of the clinical role; a knowledge and skills framework for HIV nursing practice; the education and training role of the HIV nurse specialist; and the effectiveness of the HIV nurse specialist. The findings mainly focus on the clinical aspects of the role with little evidence concerning other aspects. There is limited evidence to indicate clinical effectiveness. CONCLUSIONS HIV care is facing substantial challenges, and there is a clear need to develop effective and efficient services, including expanding the contribution of HIV nurse specialists. Such developments need to occur within a framework that optimises nursing contribution and measures their impact on HIV care. This review provides a baseline to inform such developments. RELEVANCE TO CLINICAL PRACTICE This review of the literature details current understanding of the role of HIV specialist nurses and the contribution that they make to HIV care.

The Investigation of Patients with Human Immunodeficiency Virus Infection

The first cases of acquired immunodeficiency syndrome (AIDS) in the United Kingdom were reported in 1983. Recent estimates suggest that 7600 cases of AIDS will be diagnosed in England and Wales between 1990 and 19931• As human immunodeficiency virus (HIV)-related disease increases, patients will seek advice and medical help from non-specialists. This article is intended to provide guidelines for the investigations of patients attending with asymptomatic HIV infection for routine follow-up and symptomatic patients with common presenting complaints.

How does specialist nursing contribute to HIV service delivery across England

This study aimed to examine what specialist nursing contributes to HIV service delivery across England and how it could be optimised. A three part multi-method qualitative study was undertaken, involving (1) interviews with 19 stakeholders representing professional or service user groups; (2) interviews with nurse/physician pairs from 21 HIV services; and (3) case studies involving site visits to five services. A framework analysis approach was used to manage and analyse the data. There was substantial variability in specialist nursing roles and the extent of role development. Most hospital-based HIV nurses (13/19) were running nurse-led clinics, primarily for stable patients with almost half (6/13) also managing more complex patients. Role development was supported by non-medical prescribing, a robust governance framework and appropriate workload allocation. The availability and organisation of community HIV nursing provision determined how services supported vulnerable patients to keep them engaged in care. Four service models were identified. The study showed that there is scope for providing a greater proportion of routine care through nurse-led clinics. HIV community nursing can influence health outcomes for vulnerable patients, but provision is variable. With limited financial resources, services may need to decide how to deploy their specialist nurses for best effect.

Respecting patient choice on access

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A workforce in jeopardy - identifying the challenges of ensuring a sustainable advanced HIV nursing workforce.

Background HIV services in England face substantial challenges arising from financial pressures and changes to commissioning. A sustainable HIV specialist nursing workforce will be vital to enable them to respond to those challenges. Aims This paper examines the current workforce situation in HIV services across the country. Methods This mixed-method study involved semi-structured interviews with 19 key stakeholders and with 44 nurses/physicians from 21 purposively selected HIV services across England. Data were interpreted using a framework analysis approach. Results ‘Building a career in HIV nursing’ identified problems associated with retention and recruitment. Changes in commissioning are disrupting common career routes from sexual health to HIV nursing, and a perceived lack of a clear career pathway was seen as a barrier to recruitment. ‘Developing a specialist workforce’ explored the professional development of the current workforce, which was hampered by poor access to funding or study time for advanced study and the absence of an HIV-specific advanced nursing qualification. Conclusions The HIV nursing workforce, which provides an increasing proportion of HIV care, is facing serious recruitment and retention challenges. A strategic approach to workforce development and training is essential to overcome systemic barriers and secure the next generation of skilled practitioners.