Revolution in prevention and treatment of HIV

Recent decades have seen great advances in the medical management of HIV, including HIV prevention. In 2019, people diagnosed with HIV who are on antiretroviral therapy (ART) can expect to have a near-normal life expectancy.¹ Further, a person living with HIV virologically suppressed on ART will not transmit the virus through sexual contact.^2,3,4,5 This is publicised through The U=U Campaign (undetectable = untransmittable), which empowers people diagnosed with HIV to live uninterrupted lives without fear of transmission to their partner(s). ART is free to all people living with HIV in Ireland. The HSE recommends that all people with HIV in Ireland are offered ART as soon as possible after diagnosis, and are informed of its benefits in reducing HIV infectiousness and improving their personal health.⁶ HIV is a preventable infection through well-defined strategies, including structural, behavioural and biomedical interventions. 

Rates of HIV diagnosis are relatively high in Ireland (11.1 per 100,000 compared to the EU/EEA average of 6.2 per 100,000 in 2017).^7,8 Even excluding those previously diagnosed abroad (32%), this figure remains above the EU/EEA average at 6.4 per 100,000.^7,9

Of the new HIV diagnoses in 2017 which were not previously diagnosed abroad, 55% presented with late infection (CD4 count < 350 cells/µL).¹⁰ Missed opportunities for early diagnosis have previously been described.^11,12 There is a clear need for improved HIV prevention and earlier detection and treatment of HIV in Ireland.

This article focuses on biomedical interventions for HIV prevention as it relates to GPs, particularly regarding HIV testing, and the newest HIV prevention strategy, PrEP. 

What is HIV prevention?

• HIV prevention includes structural, behavioural and biomedical interventions. 
• Structural interventions relate to public policy 
• Behavioural interventions focus on risk recognition and behavioural modification. For example, single consultation patient education interventions on sexual health have been shown to reduce the risk of an STI by 35%¹³
• Biomedical interventions include condom use, HIV testing, and the use of ART as prevention.  

HIV testing

It is estimated that approximately 10% of people living with HIV in Ireland are undiagnosed.³ This group may fuel both unknown onward transmission and late presentations.^11,12,14,15 One Irish study found that people with late HIV presentations in Ireland have frequent contact with healthcare services, particularly with GPs.¹¹ Of these contacts, 60% occur as a consequence of symptoms which could be deemed HIV-related.¹¹

England has witnessed a dramatic decline in new HIV diagnoses since 2008.¹⁶ Central to this was increasing HIV testing rates between 2007 and 2014, which were associated with a decline in HIV diagnoses from 2014 onwards.¹⁷ Other contributing factors include early ART initiation and introduction of PrEP through the IMPACT public health trial.^17,18 In San Francisco, a decline in HIV incidence began in the early 2000s, coupled with increased HIV testing, earlier asymptomatic detection and treatment and availability of PrEP.¹⁹ Based on international experiences, we in Ireland need to redouble our efforts for the early identification and treatment of undiagnosed HIV to reduce transmission and late presentations.

In Ireland, systematic HIV testing occurs in STI clinics and drug treatment clinics.¹¹ Routine opt-out screening occurs in the antenatal population, and in certain emergency departments.^11,20 HIV testing is recommended in all sexually active people from countries with a HIV rate of > 1%.²¹ HIV testing is also recommended in people with suspected acute retroviral syndrome, with a suspected or diagnosed HIV indicator illness/condition, and as part of routine asymptomatic screening in people with risk factors for HIV infection.^22,23

Acute retroviral syndrome (HIV seroconversion illness) is the earliest clinical manifestation of HIV infection.^24,25 It occurs in the first 42 days of HIV infection, in the interval between the appearance of HIV RNA and the development of HIV antibodies.²⁵ It can present with fever, headache, malaise, cough and lymphadenopathy, in addition to fatigue, myalgia, weight loss, night sweats, skin rash, pharyngitis, gastrointestinal symptoms, and oral ulcers.^25,26 Laboratory investigations may demonstrate leukopenia, thrombocytopenia and elevation of liver enzymes.^25,27 More specific findings include aseptic meningitis, encephalitis, facial nerve palsies, and opportunistic infections.^27,28 In those with presentations consistent with acute retroviral syndrome, prompt specialist referral for appropriate assessment is recommended.^25,29

HIV indicator infections include AIDS defining conditions and conditions which are associated with a prevalence of undiagnosed HIV in excess of 0.1%.^29,30

AIDS-defining conditions include:

Neoplasms: cervical cancer, non-Hodgkin’s lymphoma and Kaposi’s sarcoma

Bacterial infection: TB; mycobacterium avium complex; recurrent pneumonia (more than two episodes in 12 months); salmonella septicaemia

Viral infections: CMV retinitis; CMV infection (not including liver, spleen, glands); herpes simplex ulcers for more than one month; bronchitis; pneumonitis; progressive multifocal leucoencephalopathy

Parasitic infections: cerebral toxoplasmosis; cryptosporidiosis diarrhoea (more than one month); isosporiasis (more than one month); atypical disseminated leishmaniasis; reactivation of American trypanosomiasis (meningoencephalitis or myocarditis)

Fungal infections: pneumocystis carinii pneumonia; oesophageal candidiasis; respiratory candidiasis; extrapulmonary cryptococcus; disseminated histoplasmosis; disseminated coccidiomycosis; disseminated penicilliosis.

Conditions which are associated with an undiagnosed HIV prevalence of > 0.1% include^29,30:

• STIs 
• Malignant lymphoma 
• Anal and cervical cancer/dysplasia 
• Herpes zoster 
• Hepatitis B and C
• Mononucleosis-like illness
• Unexplained leucocytopenia/thrombocytopenia for more than four weeks 
• Seborrhoeic dermatitis/exanthema 
• Invasive pneumococcal disease
• Unexplained fever
• Candidaemia
• Visceral leishmaniasis.

HIV testing should be considered where not identifying the presence of HIV could have significant adverse consequences, particularly in people on immunosuppressive therapy for cancer, transplantation or autoimmune disease treatment.²⁹

Asymptomatic HIV testing is recommended in the following groups^23,29,31: 

• People from countries with high HIV prevalence
• Men who have sex with men (MSM)
• Commercial sex workers
• People who inject drugs 
• People with ≥ 3 partners in the past six months
• People with a partner in one of these high-risk groups. 

While relevant to all sexually active individuals in the GP setting, HIV testing is particularly relevant to sub-groups within the general population, such as people with complex substance misuse, and immigrants from countries of high HIV prevalence when first registering with the practice. It is recommended as part of routine STI screening. In Ireland, most late diagnoses occur in heterosexual men and people from Sub-Saharan Africa.¹¹

ART as prevention

ART as prevention is an exciting and novel aspect of medicine. It includes TAsP, PEP and PrEP. 

• Treatment as Prevention (TAsP): Treating individuals living with HIV to an undetectable viral load, and thus preventing further transmission. In Ireland, 98% of people attending HIV services are on ART, of whom 95% are virologically suppressed³²
• Post-Exposure Prophylaxis (PEP): A 28-day course of ART started within 72 hours of potential HIV exposure. PEP is recommended when the risk of HIV is estimated to be ≥ 1 in 1,000. Guidelines on indications for PEP across a range of various potential clinical exposure scenarios are available at www.emitoolkit.ie
• Pre-Exposure Prophylaxis (PrEP): Pre-emptive use of ART in HIV-negative individuals to prevent HIV acquisition. PrEP is now provided for free through the HSE in approved centres, on the basis of risk of HIV acquisition.

The role of GPs in HIV prevention

All GPs and practice nurses have an important role to play in HIV prevention. There is a demand for GP-led sexual health services among certain at-risk groups; 23% of Irish MSM would like HIV testing through GPs.³³ Among young Irish people, there is a strong desire to make STI services as normal as any other health check-up.³⁴ Further, GP-led services can be provided in rural areas, where there is significant demand for HIV prevention services.³⁵

There is a resource and training gap for some GPs with regard to HIV prevention. For instance, GPs who offer STI screening services to MSM are less likely to complete a comprehensive assessment, including a three-site swab.³³ Evidence suggests that appropriate HIV testing in STI consultations is not included by GPs, and that HIV testing is often ordered to reassure patients, rather than out of concern for infection.^31,33

Obstacles that may impede STI and HIV testing and prevention in primary care include lack of support for partner notification, time pressures, and reluctance to discuss sexual health, particularly when it doesn’t directly relate to the patient’s presenting complaint.³⁴

HIV PrEP 

HIV PrEP is effective for primary prevention of sexually acquired HIV. Currently, PrEP is dispensed as two drugs in a single tablet, tenofovir disoproxil fumarate and emtricitabine (245mg/200mg). In 2017, Scotland was the first country worldwide to provide free PrEP as part of routine state-funded need-based care.³⁶ HIV incidence among service users between July 2017 to June 2018 was 1-4 per 1,000, which is an encouraging result.³⁶ The number of new STIs seen has increased; however this may relate to more frequent testing and asymptomatic detection, and a causal link has not been established.^36,37

In Ireland, PrEP is now available for free through approved services on the basis of risk. Further information on approved PrEP services is available online at www.sexualwellbeing.ie – search for ‘where to get prep’.

National guidelines and standards for PrEP provision have been developed and are also available on the website by searching for ‘national standards’.³⁹ Information is also provided on how to become an approved PrEP service. 

PrEP should be provided as part of a combination HIV (and STI) prevention approach within services that meet national standards. The following section provides a summary of guidelines that should be referenced for more comprehensive information.³⁹

Who is eligible for free PrEP?

HIV-negative individuals who are aged 17 years or older, have a PPSN, and fall into one of the following categories: 

• MSM (includes transgender), or transgender women who have sex with men, who are sexually active and likely to remain sexually active in the next three months, with one of the following: 

   – report condomless anal sex with ≥ 2 partners over the past six months

   – episode(s) of acute STI over the past 12 months

   – documented or reported use of HIV PEP following sexual exposure in the past 12 months 

   – report engagement in chemsex over the past six months

• Individuals having condomless sex with a HIV-positive person who is not stably suppressed on ART.

Contraindications and cautions with PrEP

Unknown HIV status is an absolute contraindication to PrEP, as are allergies to tenofovir or emtricitabine. Other contraindications are relative, based on individual case evaluation, and include impaired renal function (at baseline or while taking PrEP), and insufficient compliance to medications such that there is a risk of HIV infection with added risk of antiretroviral resistance. 

PrEP pharmacology

PrEP is currently licensed to be taken once-daily. In certain specific circumstances, it can be taken when risk occurs (event-based dosing). Common side-effects include mild nausea, diarrhoea, bloating and headache, which usually resolve within one month. Declining renal function and reversible bone mineral density loss are potential adverse effects. Drug-drug interactions are rare, but exposure to other nephrotoxins should be avoided. 

PrEP dosing

PrEP can be offered to all people who meet eligibility criteria. Event-based dosing (EBD) is effective for MSM, and can be considered where sex is ≤ 2 times per week, and where the individual is able to allow adequate time to take the first dose before sex (see below). 

• EBD is not recommended for women (including transgender women), transgender men having vaginal sex, or men having sex with women
• EBD is contraindicated in people who have hepatitis B. 

Daily dosing: anal sex

• Starting: Two tablets between two and 24 hours before sex
• While on PrEP take one tablet every 24 hours
• Stopping: continue one tablet every 24 hours until two tablets have been taken after last sexual episode.

Daily dosing: vaginal sex

• Starting: One tablet daily for seven days before vaginal sex
• While on PrEP take one tablet every 24 hours
• Stopping: continue one tablet every 24 hours for seven days after last sexual episode.

Event-based/on demand dosing: one sexual episode

• Take two tablets between two and 24 hours before sex
• Take one tablet 24 hours later
• Take one more tablet 24 hours after that.

Event-based/on-demand dosing: multiple sexual episodes over a number of days

• Take two tablets between two and 24 hours before sex
• Take one tablet 24 hours later
• Continue taking one tablet every 24 hours until two tablets have been taken after the last sexual encounter.

PrEP consultations

The first consultation 

The first consultation should include a full medical and sexual history, to determine eligibility and identify contraindications to PrEP.

People who have completed PEP and are commencing PrEP should be seen in a specialist centre. A prescription for PrEP can be given where there is a confirmed negative fourth generation test within four weeks, or negative point of care test with a fourth generation test in progress. 

Patients should be seen four weeks after commencement on PrEP if they are in the window period at time of testing. Patients should be counselled around seroconversion illness syndromes at time of commencement and advised to attend urgently if they develop such symptoms. All people receiving PrEP should complete an appropriate vaccine schedule.

Chemsex is associated with increased risks of STI and HIV transmission. In a study at the Gay Men’s Health Service in Dublin, over a quarter of people attending reported engaging in chemsex, with gamma-hydroxybutyrate (GHB) being the most commonly reported drug.⁴⁰

All patients who misuse illicit substances should receive counselling and an offer of continuing care and follow-up. People using GHB should receive additional counselling, including written information and a G-card to alert emergency medicine services about GHB use in the event of overdose.

The follow-up consultation

People on PrEP should be assessed at least every three months – or four weeks after initiation if in the HIV window period – for HIV and STI testing and assessment of renal function. STIs should be managed promptly, as delayed detection may increase onward transmission.⁴¹

Special situations

Patients with renal impairment will require management by an appropriately trained specialist with experience in using these medications in patients with renal impairment. Patients who develop renal impairment on PrEP may also merit specialist referral, including nephrology referral. Discontinue PrEP and refer patients if eGFR falls below 60mL/min.

People who contract HIV while on PrEP should be referred urgently to a specialist centre for appropriate care. 

Conclusion

GPs and practice nurses are regularly consulted by people in relation to sexual health. Many practices have well established interests in sexual and reproductive health.⁴² There is progress to be made in improving primary prevention and early detection of HIV in Ireland. There is a role for increased involvement of general practice in this context.

There may be ongoing research on HIV prevention and sexual health services in primary care. If you are a GP or practice nurse with an interest in participating in sexual health service development research, including HIV testing and providing PrEP, and would like to contribute, please email gpsexualhealth@gmail.com

Acknowledgements

The HSE Dublin Southeast Academic Track Internship Programme is gratefully acknowledged for the academic support which contributed to this article.

Useful resources for GPs

• STI management guidelines: www.hse.ie/eng/services/list/
• 2/gp/antibiotic-prescribing/conditions-and-treatments/genital/
• PEP guidelines: www.emitoolkit.ie 
• PrEP guidelines and standards: www.sexualwellbeing.ie/
• for-professionals/prep-information-for-service-providers/
• #guidelines
• ICGP STI e-learning module (requires ICGP login):
• www.icgp.ie/go/courses/e_learning
• European Centre for Disease Control HIV (and hepatitis) testing guidelines: www.ecdc.europa.eu/sites/portal/files/documents/hiv-hep-testing-guidance.pdf

Useful resources for patients

• STI information: www.sexualwellbeing.ie/sexual-health/sexually-transmitted-infections/
• HIV testing and treatment information: www.sexualwellbeing.ie/sexual-health/sexually-transmitted-infections/information-on-hiv/ (order free patient information booklets from www.healthpromotion.ie/ )
• PEP information: www.hivireland.ie/living-with-hiv/hiv-and-you/pep/ 
• PEP availability: www.hivireland.ie/wp-content/uploads/
• 000.-PEP-availability-in-ireland-june2019.pdf
• PrEP information: www.sexualwellbeing.ie/sexual-health/sexually-transmitted-infections/information-on-hiv/hiv-prep-in-ireland.pdf

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