Dr Toni Hazell presents an overview of HIV prevalence, testing, treatments, and other issues relevant to primary care

Dr Toni Hazell

Dr Toni Hazell

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Read this article to learn more about:

  • HIV prevalence, testing, diagnosis, and treatment
  • contraception, fertility treatment, cervical screening, and breastfeeding
  • pre-exposure prophylaxis (PrEP).

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Human immunodeficiency virus (HIV) has a fascinating history—the condition used to be a death sentence but is now manageable as a chronic disease. While the prescribing and monitoring of antiretrovirals remains in secondary care, there are some aspects of HIV that GPs need to be aware of, which this article aims to cover.

Note: Some of the treatments discussed in this article currently (October 2018) do not have UK marketing authorisation for the indications mentioned. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s guidance on Good practice in prescribing and managing medicines and devices1 for further information.

Prevalence and testing

Public Health England (PHE) estimates that there are around 101,200 people living with HIV in the UK, 13% of whom are undiagnosed.2 Those diagnosed late (with a CD4 count of less than 350 cells/mm3) are 10 times more likely to die within a year of diagnosis than those diagnosed earlier,3 so one of the most useful things GPs can do in primary care is to increase the number of HIV tests requested. There is no need for lengthy pre-test counselling; the main issues that need be covered are the benefits of an HIV test and how the patient is going to get the result. Patients should also be made aware of the window period, that is, the concept that an HIV test may not be positive for 1–3 months after HIV has been transmitted.4,5

NICE and PHE advise that GPs in areas with high or extremely high prevalence of HIV (more than two per 1000 patients aged 15–59) offer an HIV test to all new patients. In some areas this is funded as a local enhanced service. Tests should also be offered in these areas to people having a blood test for another reason, who have not had an HIV test in the last year. If the area has an extremely high prevalence (more than five per 1000 patients aged 15–59 years), practitioners should consider offering an HIV test at every consultation, whether bloods are being taken for another reason or not. Prevalence in England is outlined in Figure 1; the whole of London is a high-prevalence area and most of central London is an area of extremely high prevalence. Testing should also be offered to those in the high-risk groups listed in Box 1. Global adult HIV prevalence is illustrated in Figure 2.

Figure 1 HIV prevalence in the UK JPEG

Figure 1: Diagnosed HIV prevalence (per 1000 population aged 15–59 years): England, 20152

Kirwan P, Chau C, Brown A et al. Public Health England. HIV in the UK—2016 report. Public Health England, 2016. Available at: assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/602942/HIV_in_the_UK_report.pdf
Reproduced under the terms of the Open Government Licence v3.0

Box 1: Groups at high risk of contracting HIV4

  • Men who have sex with men and their female partners
  • Sexual partners of those who are HIV positive
  • Intravenous drug users
  • Those from a country with a high prevalence of HIV infection (see Figure 2) and their sexual partners
  • Trans women who have sex with men and have not had an HIV test in the last year
  • Those who disclose high-risk sexual practices, such as ‘chemsex’ (the use of drugs to facilitate sex)
  • Anyone who requests a test for a sexually transmitted infection or has one diagnosed.

Figure 2 HIV prevalence by WHO region

Figure 2: Adult HIV prevalence (15–49 years), 2017 by World Health Organization region6

Reproduced with permission. Information Evidence and Research, World Health Organization. Prevalence of HIV among adults aged 15 to 49, 2017—by WHO region. WHO, 2018. Available at: www.who.int/gho/hiv/hiv_013.png?ua=1

Symptoms and incidental findings

Practitioners should also test people who have symptoms that are consistent with HIV.4 The British HIV Association (BHIVA) has a list of conditions that should prompt an HIV test; this is shown in Table 1 and includes common presentations to general practice (such as dementia, chronic diarrhoea, and weight loss) as well as incidental findings such as leucopenia and neutropenia.5

Table 1: Clinical indicator diseases for adult HIV infection5
 AIDS-defining conditionsOther conditions where HIV testing should be offered

British HIV Association, British Association for Sexual Health and HIV, British Infection Society. UK national guidelines for HIV Testing 2008. BHIVA, 2008. Available at: www.bhiva.org/file/RHNUJgIseDaML/GlinesHIVTest08.pdf

Reproduced with permission

Respiratory

Tuberculosis

Pneumocystis

Bacterial pneumonia

Aspergillosis

Neurology 

Cerebral toxoplasmosis

Primary cerebral lymphoma

Cryptococcal meningitis

Progressive multifocal leucoencephalopathy

Aseptic meningitis/encephalitis

Cerebral abscess

Space occupying lesion of unknown cause

Guillain–Barré syndrome

Transverse myelitis

Peripheral neuropathy

Dementia

Leucoencephalopathy

Dermatology 

Kaposi’s sarcoma

Severe or recalcitrant seborrhoeic dermatitis

Severe or recalcitrant psoriasis

Multidermatomal or recurrent herpes zoster

Gastroenterology 

Persistent cryptosporidiosis

Oral candidiasis

Oral hairy leukoplakia

Chronic diarrhoea of unknown cause

Weight loss of unknown cause

Salmonella, shigella, or campylobacter

Hepatitis B infection

Hepatitis C infection

Oncology 

Non-Hodgkin’s lymphoma

Anal cancer or anal intraepithelial dysplasia

Lung cancer

Seminoma

Head and neck cancer

Hodgkin’s lymphoma

Castleman’s disease

Gynaecology

Cervical cancer

Vaginal intraepithelial neoplasia

Cervical intraepithelial neoplasia Grade 2 or above

Haematology 

 

Any unexplained blood dyscrasia including:

  • thrombocytopenia
  • neutropenia
  • lymphopenia

Ophthalmology 

Cytomegalovirus retinitis 

Infective retinal diseases including herpes viruses and toxoplasma

Any unexplained retinopathy

ENT

 

Lymphadenopathy of unknown cause

Chronic parotitis

Lymphoepithelial parotid cysts

Other

 

Mononucleosis-like syndrome (primary HIV infection)

Pyrexia of unknown origin

Any lymphadenopathy of unknown cause

Any sexually transmitted infection

Over half of all patients with HIV will have seroconversion symptoms within 2–4 weeks of infection but making the diagnosis at this point is not easy in general practice.7,8 Symptoms include maculopapular rash, fever, sore throat, headache, malaise, lymphadenopathy, joint or muscle pain, mouth ulcers, and diarrhoea—all very common in primary care.8 One small study7 showed that a fever and typical rash was the strongest predictor for HIV seroconversion, so it is worth practitioners being alert to this combination as well as being aware of other symptoms. In a possible seroconversion situation, it is important that patients understand the risk of a false negative test soon after infection. Most modern tests will be positive before the traditional 3-month window period, but it is worth re-testing at 3 months to be certain of not missing a diagnosis.

Antiretroviral therapy

All patients with HIV should be offered antiretroviral therapy (ART) from diagnosis, a change to previous practice where ART was only used below a certain CD4 count.9 Practitioners are therefore likely to see more patients on ART, with the potential for drug interactions. Antiretroviral therapy should always be entered on to the computer record (as a hospital issue) so that the GP is alerted to possible interactions. If in doubt, the University of Liverpool has a useful website for checking interactions (www.hiv-druginteractions.org/checker).10

Contraception

Regarding contraception, HIV itself is generally not a contraindication to any specific methods. The 2016 UK Medical Eligibility Criteria for contraceptive use11 says only that intrauterine devices and systems are relatively contraindicated, but that the risks are likely to outweigh the benefits only when the CD4 count is less than 200 cells/mm3. The main problem with prescribing contraception is that many types of ART are enzyme-inducing and will therefore significantly reduce the activity of both oestrogen- and progesterone-based hormonal contraceptives. Women taking enzyme-inducing ART can use an intrauterine device or system, or the depot injection. They can of course also use condoms as a sole method of contraception, but this carries a high failure rate. For those who refuse all these methods, there are oral contraceptive regimens (usually involving an oestrogen dose of 50–70 mcg with a shortened pill-free interval) that have been designed for women taking enzyme-inducers. This type of use is unlicensed and has a high failure rate so should always be combined with condoms.12 Women who are taking enzyme-inducing drugs and need emergency contraception should have a double dose of levonorgestrel (3 mg)—this is also unlicensed. They should not use ulipristal.13

Fertility treatment

People with HIV may also approach their GP for help with subfertility. It would be inappropriate to deny fertility treatment to a patient with HIV based solely on their HIV status, assuming that they fit other local criteria. Discordant couples (those where only one of the couple has HIV) may need help to try and conceive while avoiding unprotected sex. If the man has HIV then sperm washing14 can be used. This separates the sperm (which does not carry HIV) from the surrounding fluids (which do carry HIV) and then the sperm is used in assisted conception. If the woman is HIV positive then the couple can have intrauterine insemination, either done themselves at home or in a clinic. Funding for these procedures is likely to vary from area to area. Some discordant couples, particularly those for whom sperm washing or intrauterine insemination is not available on the NHS, may try to conceive naturally by having targeted unprotected sex around the time of ovulation. BHIVA’s comment on this is that, where the HIV positive partner has an undetectable viral load for the last 6 months, ‘the risk to the uninfected partner is difficult to quantify but can certainly not be quoted as zero. Mathematical models cite a risk of 1 in 100,000 per act of intercourse.’ Various studies of several hundred patients have shown no transmission of HIV using this method of conception, however data is limited and sample sizes are small so caution should always be advised. These discussions should really be had with the patient’s HIV physician rather than in primary care.15

Pregnancy, birth, and breastfeeding

Pregnant women with HIV will always have shared consultant-led care; previous practice has been to offer a caesarean although in women with an undetectable viral load and in the absence of obstetric complications it is now considered safe to attempt a vaginal delivery. Current advice is still that women with HIV should not breastfeed, although BHIVA says that if women insist on breastfeeding, they should be supported to make it as safe as possible. This involves making sure the woman has an undetectable viral load, good adherence to ART, and agrees to monthly viral load checks for themselves and testing for their infant throughout breastfeeding and for 2 months afterwards. Any woman who continues to breastfeed while their viral load is detectable, or who does not attend for these checks, should be referred to social services as a child protection concern. BHIVA also advises that those who choose to breastfeed should do so exclusively and should finish breastfeeding by the time the infant is 6 months old.16

Cervical smear tests

Another potential challenge for primary care is managing the cervical smear test requirements of women with HIV. These women have a higher prevalence of cervical cancer and of oncogenic forms of human papillomavirus (HPV) than the general population. Women with HIV should all have a smear and colposcopy at the time of their diagnosis with HIV, and thereafter should have lifelong annual smears,17,18 with repeat colposcopy only if recommended on the smear report. GPs should check whether the HIV clinic is arranging annual smears and the initial colposcopy—if not, the GP could consider asking their local cytology lab whether they will adjust the screening interval to yearly if informed that a woman has HIV. If this is not possible then the practice will need to have an internal system to ensure that these women are recalled annually rather than every 3 years as standard.

Pre-exposure prophylaxis (PrEP)

A relatively new concept in the world of HIV is that of pre-exposure prophylaxis (PrEP)—the idea that a person who is confirmed to be HIV negative but at high risk of transmission takes a single daily dose of ART, in combination with safer sex practices, to prevent this transmission. PrEP reduces the relative risk of transmission by 44­–86%, giving a number needed to treat (in 1 year) in order to prevent one transmission, of 13–68.19 PrEP may be appropriate for discordant couples, where the negative partner does not want to have to take post-exposure prophylaxis every time they have a condom accident, or for those with multiple partners who do not use condoms, particularly men who have sex with men. In 2016, an AIDS charity took NHS England (NHSE) to court after NHSE argued that PrEP funding should come from public health not from NHSE. The charity won20 and at the time of writing (September 2018), NHSE is funding PrEP for some patients as part of a large-scale trial.21,22 The court case was particularly interesting due to NHSE’s contention that funding PrEP would mean that other treatments may not be funded.23 This was the first time that NHSE had publicly stated that the funding of one drug may affect the availability of another, something that may become more apparent in years to come. The relevance of this to GPs is that some patients may now be taking PrEP as part of a trial and others may be buying it privately—GPs should be made aware of this and the drugs should be entered in the computer notes to pick up interactions.22,24

GPs are often uniquely placed in that they know a patient’s family and home situation—this can cause uncertainty if they discover that a patient with HIV has not told their partner about their diagnosis. The General Medical Council is clear, stating that:25

You may disclose information to a person who has close contact with a patient who has a serious communicable disease if you have reason to think that:

a. the person is at risk of infection that is likely to result in serious harm

b. the patient has not informed them and cannot be persuaded to do so.’

As in any case of breaching confidentiality, the patient must be informed in advance if it is practical and safe to do so (and it may be worth letting them know that they are at risk of criminal prosecution for knowingly passing on HIV26); also, it would be sensible to discuss the matter with a medical defence organisation.

Future initiatives

What of the future? An effective vaccine is badly needed but sadly it will be a while before there is one available for routine use. However, phase II trials are underway, looking at patients from the general population as well as those who are at high risk of acquisition of HIV27,28 and there must surely be a Nobel prize or two waiting for the scientists who crack this particular conundrum.

Summary

The treatment of HIV has come a long way in the last few decades and what used to be a universally fatal condition is now a chronic disease. Provision of antiretroviral therapy will always come from secondary care but there are many issues that GPs need to be aware of for their patients with HIV, including drug interactions, contraception, and issues of confidentiality.

Dr Toni Hazell

Part-time GP, Greater London

Diploma in genitourinary medicine

Dr Hazell works as a GP in Tottenham, North London. She holds the Diploma in genitourinary medicine and worked for 8 years as a clinical assistant in GU and HIV medicine. Her other interests are in contraception and medical education.

Key points

  • GPs in areas with high or extremely prevalence of HIV are advised to offer HIV testing to all new patients and to those who are having blood tests for another reason and have not had an HIV test in the last year
  • An HIV test should be arranged for those presenting with indicator conditions, including dementia and unexplained weight loss. There is no need for extensive pre-test counselling before HIV testing—the only point to cover is the risk of a false negative test during the window period
  • A maculopapular rash and a fever should prompt consideration of HIV seroconversion
  • HIV itself is generally not a contraindication to contraceptive methods, but drug interactions may limit the woman’s choices of contraception
  • Antiretroviral therapy has significant drug interactions and should be entered on the computer record as a hospital issue
  • Patients with HIV should not be refused fertility treatment solely on the basis of their HIV-positive status
  • Some women with HIV can be supported to breastfeed, but those who breastfeed with a detectable viral load or without undergoing regular testing for themselves and/or their child should be considered for a child protection referral
  • Women with HIV need colposcopy at diagnosis, and lifelong annual smears
  • GPs may need to breach confidentiality if they become aware that a patient with HIV has not told their partner.

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources. 

  • Establish a local STP group led by public health officers to identify any areas with high or very high prevalence of HIV in the local area
  • Define all actions required to address the risk of HIV in the local health improvement plan, including education, prevention, screening, and access to diagnosis and treatment services
  • Agree a care pathway for people diagnosed with HIV to include maternity services
  • Ensure the pathway clearly defines who is responsible for providing each part of the service
  • Commission services required to implement this pathway from various providers and agree what is funded by public health and NHS budgets (or pool budgets)
  • Provide diagnostic prompts to primary care clinicians to stimulate more appropriate HIV testing and explore whether these can be built into GP computing systems.

STP=sustainability and transformation partnership; ICS=integrated care system

References

  1. General Medical Council. Good practice in prescribing and managing medicines and devices. GMC, 2013. Available at: www.gmc-uk.org/Prescribing_guidance.pdf_59055247.pdf
  2. Kirwan P, Chau C, Brown A et al. HIV in the UK—2016 report. Public Health England, 2016. Available at: assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/602942/HIV_in_the_UK_report.pdf
  3. Harris J, Khatri R. Late diagnosis of HIV in the United Kingdom: an evidence review. Centre for Public Health, Liverpool John Moores University, December 2015. Available at: www.cph.org.uk/wp-content/uploads/2015/12/Late-HIV-diagnosis-rapid-evidence-review_final_covers.pdf
  4. NICE, Public Health England. HIV testing: increasing uptake among people who may have undiagnosed HIV. NICE Guideline 60. NICE, December 2016. Available at: www.nice.org.uk/ng60
  5. British HIV Association, British Association for Sexual Health and HIV, British Infection Society. UK national guidelines for HIV testing 2008. BHIVA, 2008. Available at: www.bhiva.org/file/RHNUJgIseDaML/GlinesHIVTest08.pdf
  6. Information Evidence and Research, World Health Organization. Prevalence of HIV among adults aged 15 to 49, 2017—by WHO region. WHO, 2018. Available at: www.who.int/gho/hiv/hiv_013.png?ua=1
  7. Hecht F Busche M, Rawale B et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS 2002; 16 (8): 1119–1129.
  8. Chelsea and Westminster Hospital. HIV symptoms. www.chelwest.nhs.uk/services/hiv-sexual-health/hiv-symptoms (accessed 25 September 2018).
  9. British HIV Association. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015 (2016 interim update). BHIVA, 2016. Available at: www.bhiva.org/file/RVYKzFwyxpgiI/treatment-guidelines-2016-interim-update.pdf
  10. University of Liverpool. HIV drug interactionswww.hiv-druginteractions.org/checker (accessed 3 October 2018).
  11. Faculty of Sexual and Reproductive Healthcare. UK medical eligibility criteria for contraceptive use. FSRH, 2016. Available at: www.fsrh.org/standards-and-guidance/external/ukmec-2016-digital-version/
  12. Faculty of Sexual and Reproductive Healthcare. Combined hormonal contraception. FSRH, 2011 updated 2012. Available at: www.fsrh.org/standards-and-guidance/documents/combined-hormonal-contraception/
  13. Faculty of Sexual and Reproductive Healthcare. Drug interactions with hormonal contraception. FSRH, 2017. Available at: www.fsrh.org/standards-and-guidance/documents/ceu-clinical-guidance-drug-interactions-with-hormonal/
  14. Chelsea and Westminster Hospital NHS Foundation Trust. Sperm washing. http://www.chelwest.nhs.uk/services/womens-health-services/fertility-treatment/treatment-options/treatment-options-1/sperm-washing (accessed 3 October 2018).
  15. Fakoya A, Lamba H, Mackie N et al. British HIV Association, BASHH and FSRH guidelines for the management of the sexual and reproductive health of people living with HIV infection 2008. HIV Med 2008; 9 (9): 681–720.
  16. de Ruiter A, Taylor G, Claydon P et al. British HIV Association guidelines for the management of HIV infection in pregnant women 2012 (2014 interim review). HIV Med 2014; 15 (Suppl 4): 1–77.
  17. NICE. Cervical screening. NICE Clinical Knowledge Summary. NICE, 2017. Available at: cks.nice.org.uk/cervical-screening#!scenario
  18. Bower M, Palfreeman A, Alfa-Wali M et al. British HIV Association guidelines for HIV-associated malignancies 2014. HIV Med 2014; 15 (Suppl 2): 1–92.
  19. NICE. Pre-exposure prophylaxis of HIV in adults at high risk: Truvada (emtricitabine/tenofovir disoproxil). Evidence Summary 78. NICE, 2016. Available at: www.nice.org.uk/advice/esnm78/chapter/key-points-from-the-evidence
  20. National AIDS Trust. Final PrEP HIV drug case win for National AIDS Trust at Court of Appeal. www.nat.org.uk/press-release/final-prep-hiv-drug-case-win-national-aids-trust-court-appeal (accessed 3 October 2018).
  21. NHS England. NHS England announces major extension of national HIV prevention programme with Public Health England and funding for ten new specialised treatments. www.england.nhs.uk/2016/12/hiv-prevention-pregramme/ (accessed 3 October 2018).
  22. NHS England. NHS commissioning-specialised services. F03. HIV. www.england.nhs.uk/commissioning/spec-services/npc-crg/blood-and-infection-group-f/f03/ (accessed 3 October 2018).
  23. Boseley S. PrEP HIV drugs: fight for limited NHS funds takes unedifying turn. The Guardian, 2016. www.theguardian.com/society/2016/aug/03/prep-hiv-drugs-fight-for-limited-nhs-funds-takes-unedifying-turn (accessed 3 October 2018).
  24. Gilead Sciences Ltd. Truvada film-coated tablets—summary of product characteristics. Available at: www.medicines.org.uk/emc/product/3890
  25. General Medical Council. Confidentiality: disclosing information about serious communicable diseases. GMC, 2017. Available at: www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/confidentiality—disclosing-information-about-serious-communicable-diseases
  26. NAM aidsmap. Timeline of developments in the criminalisation of HIV and STI transmission in the UK. www.aidsmap.com/Timeline-of-developments-in-the-criminalisation-of-HIV-and-STI-transmission-in-the-UK/page/1504201/ (accessed 3 October 2018).
  27. Choi E, Michalski C, Choo S et al. First Phase I human clinical trial of a killed whole-HIV-1 vaccine: demonstration of its safety and enhancement of anti-HIV antibody responses. Retrovirology 2016; 13  (1): 82.
  28. US National Library of Medicine—ClinicalTrials.gov. A phase II clinical trial to evaluate the immunogenicity and reactogenicity of the recombinant HIV-1 envelope vaccines SF-2 rgp120 (CHO) [Chiron Vaccines] in MF59 adjuvant and MN rgp120/HIV-1 [VaxGen] in alum adjuvant in healthy adults. clinicaltrials.gov/ct2/show/NCT00001031 (accessed 3 October 2018).