PEP, PrEP and all things HIV. St Emlyn’s

On the 1st December we marked world AIDS Day. This day was one of the first ever global health days and was introduced to increase awareness of the issue of HIV and AIDS in the 1980’s. The stigma and health concerns over HIV and AIDS have barely abated over this time and the day is as important as ever. I’ve previously blogged about HIV and was grateful to be part of the market place at the #StEmlynsLIVE conference where I waxed lyrical about my thoughts on HIV testing in the ED. Although testing is one aspect of HIV in the ED  (if you want to read about who you should be screening for HIV you can here).  I think HIV is more than just a blood test that we perform so I thought I might talk about my approach to HIV.

In Virchester we see quite a bit of HIV medicine however many UK emergency departments may not. I’m also aware we have a very wide readership from consultants to medical students so I am going to start with the basics and build up from there.  So here goes… (sorry to our South African friends who rock at this stuff)

What exactly is HIV?

(told you I was starting with the basics)

HIV is the human immunodeficiency virus. It’s a retrovirus and by that I mean its an RNA virus that uses an enzyme called reverse transcriptase to create a copy of DNA (the reverse of what normally happens in our bodies). This DNA then gets inserted in to the host cells genome by other enzymes one of which is called HIV integrase. These two enzymes are important (alongside others) because the drugs we prescribe in the ED as PEP work by stopping their function. There are two types of HIV virus. Type 1 and type 2. In the UK we are predominately concerned with Type 1 as it is this virus type that is the most virulent but also the one found world wide. Type 2 is found in West Africa and is less virulent than its type 1 cousin. Although there are only 2 types of virus there are many many strains of HIV and these all have varying degrees of virulence and resistance.

How does HIV infect? 

 HIV is spread predominately by sexual intercourse and blood. Vertical transmission during pregnancy, birth or though breast milk can can also occur. After initial exposure of the mucosal surface to the virus, dendritic cells become infected by the HIV attaching to specific co-receptors found on the cell surface. The receptor used is dependant on the strain of HIV. These dendritic cells then fuse to CD4 lymphocytes which get transported to regional lymph nodes. This process takes two or three days. From here the CD4 cells are released into the blood and the virus is disseminated throughout the body. The timing of this process can go someway in explaining why PEP works best when given quickly and really not at all after 72 hours as the virus has already started to spread to distant tissues.

What is the natural history of HIV?

In the first few months, in fact anytime from about day 5 after coming in contact with HIV, the person develops acute HIV. During this time there is a large increase in the number of RNA copies found in the blood and the patient is highly infectious. It’s often during this period of high viral 

load that onward transmission will occur. During this time the patient may exhibit features of a seroconversion illness. Following acute HIV the number of RNA copies falls and patients become asymptomatic and may stay so for a number of years. However at some point virus load begins to rise and the CD4 count falls. Eventually opportunistic infections such as those mentioned below develop. This of course is all dependant on not receiving antiretroviral therapies as these significantly improve survival to near normal life expectancy and is why testing is so important.

So that’s a (very) brief  explanation of HIV. I think at work there are probably five main groups of patients we might see in the ED and each needs a different approach.

1.Those requiring PEP/ PEPSE prior to the establishment of HIV infection

2. Those with an acute HIV illness

3. Those with HIV who are asymptomatic

4. Those with an AIDS defining illness

5. Those known to have HIV on ARVT

1. Those requesting PEP/ PEPSE

PEP is post exposure prophylaxis. This is a course of three drugs used to try and prevent HIV infection after exposure. This exposure could come following occupational exposure (e.g. needlestick), from wounding (e.g.multiple stab victims injured by a single knife) or as is the predominant reason for prescribing PEP in Virchester after potential sexual exposure.

Occupational Exposure

Those who require PEP following occupational exposure are those injured by something contaminated with fresh blood (not dried) from a donor known to be either HIV+ or from a high risk group (MSM/ IVDU/ sex worker). Old discarded needles from a community, random needles from the sharps bin etc. don’t warrant PEP.

Wounding

An unusual cause but something to consider with rising knife crime. Follow a similar thinking as per sexual exposure.

Sexual Exposure

PEPSE’s use is dependant on a  number of factors. The type of sexual exposure and with whom are important. For instance unprotected receptive MSM sex is a high risk act where as fellatio is not. If the donor status is unknown then the background prevalence of HIV in your area needs to be considered (Risk tables are below). If however we know the donor is HIV+ obtaining their viral load can help guide the decision as if they are on antiretroviral therapy (ARVT) and have a stable, undetectable viral load for 6 months there is no need for PEPSE. 

Risk of HIV transmission = Risk of exposure x Risk HIV +


Example: the risk of unprotected MSM receptive anal intercourse in Manchester (see tables above)                                                                                                                    (8.6/100) x 1/65 = 1/756

In general you can consider using PEP when the risk is over 1:10,000 but when the risk is above 1:1000 it is absolutely recommended.

What exactly is PEP?

PEP in the UK consists of Truvada (Emtricitabine and Tenfovir) and Raltegravir. Truvada works by inhibiting nucleoside and nucleotide reverse transcriptase enzymes that produce DNA from the viral RNA (NRTI and NtRTI). Raltegravir is an HIV integrase inhibitor. This works but preventing the newly formed DNA from being inserted into the host genome. Kaletra is a combination protease inhibitor (another antiviral drug that stops DNA insertion) that is still used in some parts of the world. It has however been superseded by Raltegravir in the UK due to its better absorption rates and side effect profile. PEP is a 28 day course (often ED’s will only supply the first 5 days) so follow up with sexual health or occupational health services are mandatory. It’s also really important to say that if your patients stops taking the PEP for more than 48 hours its often advised that they stop taking it completely as it can lead to resistance. Liaise with your local friendly GUM team as they will be able to advise.

2. Those with acute HIV infection

Around 50% of patients with acute HIV may be asymptomatic or have very mild symptoms so depending on your background prevalence you may need to have high index of suspicion. Fever, tiredness sore throat are common. Sometimes there is weight loss or gastro type symptoms. You might find lymphadenopathy or a maculopapular rash when examining the patient. If considering HIV infection in a patient explain that this is a differential to the patient and request HIV testing. 

HIV detection time Laboratory Best Practice Blog: 

Modern HIV tests are very good and can detect HIV at very early stage. Traditional antibody tests were only useful at about a month or later after becoming infected however modern assays combined with p24 antigen testing has improved this. More recently RNA detection can now detect the presence of HIV genetic material in the first couple of weeks. This is really important as we can now diagnose HIV at the time of the large spikes in viral load. These newer tests when combined with treatment and preventative stratgeties such as PrEP (Pre-exposure prophylaxis and TasP (Treatment as Prevention) and strateies such as those outlined in the NICE guideline have resulted in large falls in new diagnoses of HIV in London.

New diagnoses of HIV 56 Dean St London (Twitter @56DeanStreet)

3. Asymptomatic Patients

I have previously blogged about HIV screening in the ED. I think it’s really important and so does NICE…so much so that they have created a great guideline on who to screen based on your local prevalence. Needless to say the large urban areas of the UK have higher rates of HIV than “the sticks” and thus inner city ED’s will require a different (and more expensive) approach to most smaller district hospitals. The NICE guideline can be found here. You can search Public Health England’s fingertips website to find your local prevalence here and my previous blog can be found here  I’m not gonna chat much more about this other than to say that screening in the ED although is public health medicine comes under the CCG with regards to funding (boring I know) so if you’re wanting to introduce this or apply for funding for it you need to have a dialogue with your urgent care commissioners. 

4. AIDS defining illnesses 

I would hope that most of us would recognise that the 40 year old Zimbabwean lady who presented with headaches, a fit and this CT requires a HIV test. It might be toxoplasmosis or a primary CNS lymphoma. Either way we kinda know that this lady is gonna need HIV testing.

Image courtesy of Dr Leong @ Radopaedia

Similarly, the 28 year old man with exertional breathlessness and this chest X-ray in keeping with Pneumocystis is getting an HIV test. These are late presentations of HIV and would be considered “AIDS defining”. These AIDS defining illnesses can be split into five groups: bacterial, fungal, viral, parasitic and oncological. There are a lot of them and a full list can be found here

 I can’t go through the management of every AIDS defining illness here but I thought I should mention a few things about this list. First of all is the that having a couple episodes of pneumonia within a year should raise suspicions. It’s a small thing but you don’t necessarily have to have an obvious disease like PJP to consider HIV as a diagnosis. Secondly it’s that seemingly innocuous diseases such as herpes when resistant to treatment or when recurrent might represent an immunocompromised individual. I can imagine being presented with a 1 month history of cold sores/ genital sores might not seem like an emergency but they’re in your ED and we have a responsibility to get this right. Finally sometimes HIV can just surprise you. I’ve personal experience of a case of HIV presenting as a perforated appendix. The person in question was diagnosed with lymphoma and were subsequently offered HIV testing which was positive!

5. Known HIV on ARVT

With growing numbers of HIV+ patients and the trend to start ARVT as soon as possible we’re seeing more and more patients present to the ED on HIV meds. Clearly sometimes these meds stop working and these patient may present with AIDS defining illnesses as described above. If however presented with a patient who is unwell and on ARVT there is a simple rule to follow. On treatment with an undetectable viral load don’t think of opportunistic infections… manage them like everyone else. These are well people without a serious immune deficiency because they are on treatment. You do have to consider whether the presentation could be directly due to the ARVT though. Common side effects include gastro features (nausea, vomiting, diarrhoea) and tiredness although even these are becoming less of a feature. Traditionally we’re taught that ARVTs can affect liver function tests but this is quite rare with the newer drugs and we should consider other causes of deranged liver function tests including viral hepatitis prior to assuming the ARVT is the cause.

There is a small but growing group of people who find themselves on ARVT who don’t have HIV; those who take it prophylactically. Pre exposure prophylaxis or PrEP has become more and more common in the gay community as a way to obliterate the risk of contracting HIV whilst having unprotected sex. This has become more of an issue with the rise in Chemsex parties, To date there have been three sporadic cases of HIV being contracted whilst on the treatment but they were due to a highly resistant strain, failure to take the meds properly and in once case “remarkably high numbers of sex partners”. Although PrEP protects against HIV it doesn’t protect against other infections and STI rates among those given PrEP were significantly higher compared with the rates among MSM not on PrEP.  It’s even thought that ARVT may cause an immune modulation increasing syphilis susceptability. It’s worth noting however that people on PrEP will often have more regular health screening so this may explain some of this increase in STI rates. Another thing we must consider is that with growing numbers of MSM partaking in Chemsex there is an associated  nine fold increased risk of viral hepatitis in this group compared to MSM who do not attend chemsex parties as often the drugs will be injected or “slammed” so the presence of abnormal liver tests should make us thinking about testing for these (remember modern ARVTs are less likely to cause deranged tests)

So that’s about it. PEP, PrEP and all HIV. Hopefully it’s given you a brief run through of some of the things we might come across whilst at work. We might be the first people to suspect HIV due to the presenting illness. We might be asked to consider PEP for our patients or have a patient on PreP  and the possible implications that has, or we might have a HIV positive patient come in unwell and need to decided whether this is a HIV issue or not. 

vb

Gareth

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References

  • https://www.stemlynsblog.org/hiv-in-the-ed-when-who-and-why-st-emlyns/
  • https://www.stemlynsblog.org/on-post-exposure-prophylaxis-a-diet-pepse-served-on-ice/
  • https://www.slideshare.net/shruthipradeep/2-natural-history-of-hiv-and-who-clinical-staging-naco-lac-m
  • Khan JO, Walker BD :Acute Human Immunodeficiency Virus Type 1 Infection. N Engl J Med 1998; 339:33-39 available at https://www.nejm.org/doi/full/10.1056/NEJM199807023390107
  • Best Practices for HIV-1/2 Screening: When to Test and What to Test. Ying Liu, Nam Tran https://blog.ucdmc.ucdavis.edu/labbestpractice/index.php/2017/09/15/best-practices-for-hiv-12-screening-when-to-test-and-what-to-test/
  • NICE Guideline NG60: HIV testing: increasing uptake among people who may have undiagnosed HIV. available at https://www.nice.org.uk/guidance/ng60
  • Public Health Profiles:Manchester https://fingertips.phe.org.uk/search/HIV#page/1/gid/1/pat/6/par/E12000002/ati/101/are/E08000003/iid/91818/age/188/sex/4
  • https://radiopaedia.org/cases/pneumocystis-jiroveci-pneumonia-complicating-immune-reconstitution-inflammatory-syndrome-1
  • US Department of Veteran Affairs : AIDS Defining Illness https://www.hiv.va.gov/patient/diagnosis/oi-aids-defining-illnesses.asp
  • https://www.poz.com/article/prep-fails-third-man-time-hiv-drug-resistance-blame
  • https://www.poz.com/article/hiv-medications-possibly-including-prep-may-raise-susceptibility-syphilis
  • Pakianathan, M. , Whittaker, W. , Lee, M. , Avery, J. , Green, S. , Nathan, B. and Hegazi, A. (2018), Chemsex and new HIV diagnosis in gay, bisexual and other men who have sex with men attending sexual health clinics. HIV Med, 19: 485-490.
  • https://www.independent.co.uk/news/uk/crime/experts-warn-of-rise-in-gay-slamming-9069571.html

Posted by Gareth Roberts

Dr Gareth Roberts MB/ChB FRCEM MAcadMed is an editorial board member of the St Emlyn's blog and podcast. He is a senior trainee in Emergency Medicine at Manchester University Foundation Trust. His research interests are in communicable disease, public health, resuscitation and emergency medicine. You can find him on twitter as @drgarethroberts

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