Section 1: Epidemiology and aetiology
There has been a reduction in the proportion of undiagnosed HIV but, of the 101,200 people estimated to be living with HIV in the UK, 13% remain unaware of their status.1 This figure rises to 1 in 5 among non-black African heterosexuals. In 2015, of the 87,700 individuals with diagnosed HIV in the UK, 47% were men who have sex with men (MSM), 29% were black African heterosexuals and 19% were non-black African heterosexuals; injecting drug users account for a small proportion of HIV cases (2.5%). There were just over 6,000 new diagnoses in 2015, a figure that has remained fairly static over time.2 Provisional figures for 2016 show a downturn in new diagnoses in MSM for the first time since the mid-1980s, likely due to a combination of increased testing, use of pre-exposure prophylaxis (PrEP) and the impact of effective HIV treatment on transmission risk.3
Important! An estimated 13% of people with HIV are unaware of their status.
HIV data collection
Data on the number of HIV patients accessing care is collected by the HIV and AIDS reporting system, which informs HIV prevention and care strategies.
A number of data sources, including positivity rates in antenatal, drug dependency and prison settings, are used to estimate the number of undiagnosed infections. See figure 1.
Figure 1: Estimated number of people living with HIV (both diagnosed and undiagnosed) using the MPES model, all ages: UK, 2015 (click to view)
HIV is a retrovirus which replicates within, and ultimately destroys, CD4 T-cells. The mechanisms by which HIV evades the body's immune defences are manifold, and include the error-prone viral reverse transcriptase enzyme, which accounts for a high diversity of HIV.
Total CD4 counts and percentages are the surrogate markers used to monitor immune function.
During acute or primary HIV infection high levels of viraemia are common, but as the immune system mounts a response this tends to plateau to a lower level. Subsequent immune decline is gradual - typically five to eight years from infection to reach a CD4 count less than 200, the threshold at which the risk of opportunistic conditions rises dramatically - because of partial control of the virus.
However, immunological decline is variable; some individuals maintain reasonable immune function for many years, others progress rapidly. The patient may be asymptomatic but able to transmit to others. Without treatment, immune exhaustion and inexorable decline followed by death from HIV-related or AIDS conditions are almost inevitable (see figure 2).
Figure 2: Typical CD4 trajectory in untreated HIV infection (click to view)
Section 2: Making the diagnosis
HIV may present in primary care as either primary HIV infection or as one of the many HIV indicator conditions associated with chronic infection. NICE HIV testing guidelines, published in 2016, recommend that primary care staff are able to recognise symptoms that may signify primary HIV infection or illnesses that often coexist with HIV and that, in such cases, they should recommend an HIV test.4
Combined HIV antibody/antigen tests (fourth-generation tests) are the gold standard of testing. Antibodies are usually not detected until seroconversion. Historically the 'window period' from initial infection to antibody detection was three months, but a fourth-generation test will be positive within four weeks in most newly infected individuals.
Rapid, near-patient HIV tests are now widely used. A venous fourth-generation test remains the preferred test for individuals with recent possible exposure. In addition, home sampling (sample collected at home, returned to lab or clinic and result texted or phoned) and, more recently, home testing (immediate result at home) provide additional testing options.
Important! Combined HIV antibody/antigen tests are the gold standard.
HIV RNA testing is not recommended routinely because of the potential for false positive tests but can be useful on a case-by-case basis if there is a high suspicion of acute HIV. It is also used to screen blood donations.
NICE guidelines recommend that testing strategies are based on local prevalence, defined as follows:4
- High prevalence - local authorities with a diagnosed HIV prevalence of between two and five per 1,000 people aged 15 to 59 years.
- Extremely high prevalence: local authorities with a diagnosed HIV prevalence of five or more per 1,000 people aged 15 to 59 years.
Around two thirds of late diagnoses are made in high or extremely high prevalence local authority areas, so following NICE guidance4 could dramatically reduce the proportion of diagnoses made late.
Recommendations for testing in general practice are summarised in table 1. If a venous blood sample is declined, offer a less invasive form of specimen collection, such as a mouth swab or finger-prick. All pregnant women should be offered HIV testing as part of an opt-out package in antenatal care, regardless of background risk, because of the significant implication of undiagnosed HIV in pregnancy.
Important! All pregnant women should be offered HIV testing.
|Table 1: NICE HIV testing recommendations for general practice4|
|A: In all practices offer an HIV test to….|
|B: In areas of high and extremely high prevalence, also offer and recommend HIV testing to….|
|C: In areas of extremely high prevalence….|
|For all people listed in categories A and B, recommend annual testing to people in groups or communities with a high rate of HIV, and more frequently if they are at high risk of exposure|
The British HIV Association (BHIVA) suggests that newly diagnosed patients should be seen by a specialist within two weeks of receiving a positive diagnosis.
New patients are tested for lymphocyte subsets to include a total CD4 T-cell count and percentage, HIV viral load, HIV resistance, viral hepatitis infection/immunity (hepatitis A, B and C), measles/varicella immunity (depending on vaccination and infection history), full blood count, renal, liver and bone profiles and urinalysis for proteinuria.
Additional recommended baseline assessments include QRISK for over 40s, FRAX for over 50s, interferon-gamma release assays for TB where indicated (according to BHIVA TB guidelines6) and, in women, cervical cytology if not screened in the last 12 months and rubella serology where indicated.
CD4 counts and HIV-RNA quantification
CD4 percentage and CD4 count are used in conjunction with the patient's clinical state to assess immune status, need for opportunistic infection prophylaxis and, until recently, as guidance for starting antiretroviral treatment (ART). Since 2015, BHIVA has recommended offering ART to all people living with HIV, regardless of CD4 count. At the time of writing, ART at all CD4 is not routinely commissioned in England but a policy is expected in 2017.
Late HIV diagnosis is defined as being diagnosed with a CD4 less than 350. Very late diagnosis is being diagnosed with a CD4 less than 200 or presenting with an opportunistic illness. People diagnosed late have a two-fold higher risk of dying in the year after diagnosis than those diagnosed sooner and some chronic comorbidities are associated with a history of profound immunosuppression.
HIV-RNA quantification or viral load (VL) quantifies circulating HIV in peripheral blood. Peak VL is seen during the seroconversion period, after which it plateaus to a relatively stable level known as the viral set point, usually (without treatment) for a number of years. Higher VL set points have been linked with faster disease progression. HIV VL is a vital tool for monitoring success of ART. The goal of treatment is to reach and maintain an undetectable VL, that is, viraemia below the lower limit of quantification of the assay used (typically less than 20-50 copies/mL). Once viral suppression has been achieved, VL is routinely measured six monthly or as indicated by adherence.
Primary HIV infection
Primary HIV infection is symptomatic in fewer than 50% of patients and presents with fever, lethargy, muscle and joint aches and lymphadenopathy. A minority will have signs of maculo-papular rash, genital or oral ulceration and, rarely, meningism. Patients can have a significant enough CD4 count decline to present with opportunistic illnesses.
Symptoms typically occur two to six weeks after a sexual contact. The VL peaks during the seroconversion illness and this is associated with an increased risk of HIV transmission. Treatment with antiretrovirals should be discussed and offered in primary HIV because of the high risk of onward transmission and evidence that early treatment initiation enhances immune recovery and limits the magnitude of the HIV reservoir. This may have benefits for long-term health and potential treatment response in future.
Important! Primary HIV infection is symptomatic in fewer than 50% of patients.
Chronic HIV infection
Evidence suggests that many patients present to GPs with HIV indicator diseases in the years preceding their diagnosis.
Key indicator conditions include the following.
- AIDS-defining conditions
- Cervical cancer, non-Hodgkin lymphoma, Kaposi’s sarcoma
- Mycobacterial infections, recurrent bacterial pneumonia, recurrent salmonella septicaemia
- Pneumocystis pneumonia (always consider HIV if respiratory symptoms with few clinical findings on examination)
- Cytomegalovirus retinitis, oesophageal or respiratory tract candidiasis
- Non-AIDS indicator conditions associated with undiagnosed local HIV prevalence of >1/1000
- Sexually transmitted infections
- Any malignant lymphoma
- Anal cancer/dysplasia, cervical dysplasia
- Herpes zoster
- Hepatitis B or C (acute or chronic)
- Mononucleosis-like illness
- Unexplained leukocytopenia/thrombocytopenia lasting >4 weeks
- Seborrheic dermatitis/exanthema
- Invasive pneumococcal disease
- Unexplained fever
- Visceral leishmaniasis
- Non-AIDS indicator conditions considered likely to have an undiagnosed HIV prevalence >1/1000
- Primary lung cancer
- Lymphocytic meningitis
- Oral hairy leukoplakia
- Severe or atypical psoriasis
- Guillain–Barré syndrome, mononeuritis, subcortical dementia, multiple sclerosis-like disease, peripheral neuropathy
- Unexplained weight loss
- Unexplained lymphadenopathy
- Unexplained oral candidiasis
- Unexplained chronic diarrhoea
- Unexplained chronic renal impairment
- Hepatitis A
- Community-acquired pneumonia
- Conditions where undiagnosed HIV prevalence is <1/1000 but there are significant clinical implications if HIV is missed
- Conditions requiring aggressive immunosuppressive therapy:
- Primary space occupying lesion of the brain
- Idiopathic/thrombotic thrombocytopenic purpura
- Conditions requiring aggressive immunosuppressive therapy:
Section 3: Managing the condition
Collaboration between GPs and specialist HIV clinics is crucial in tackling HIV and many GPs may already be involved in shared care.
An awareness of HIV treatments, their potential complications and common drug interactions will help GPs who have patients with HIV.
Some complications of HIV or its treatments, such as cardiovascular disease and dyslipidaemias, are best managed by GPs. Other complications, such as co-infection with hepatitis B or C, need specialist input.
Since 2015, BHIVA guidelines have recommended ART for all people with HIV, regardless of CD4. Priorities for treatment include people with CD4 less than 350, people with HIV-negative partner(s), people with primary HIV, people with clinical manifestations of HIV and people co-infected with hepatitis B or C (HIV treatment allays the worse liver prognosis for co-infected patients).
Adherence to treatment is paramount to success and even adherence below 95% risks virological failure and the development of drug resistance. Once established, resistance is lifelong, and despite the progress made in antiretroviral drug development it can be difficult to construct suppressive regimens in people with extensive resistance. Thankfully, because of better-tolerated, simpler drugs and the availability of drugs with higher barriers to resistance development, new resistance is uncommon.
The first-line therapy recommended in guidelines, including BHIVA7, is a combination of three drugs; two nucleoside or nucleotide reverse transcriptase inhibitors with a third drug from a different class, a protease inhibitor, non-nucleoside reverse transcriptase inhibitor or an integrase inhibitor. This has been the cornerstone of therapy since the mid to late 1990s but there has been marked improvement in the drugs used. Most modern drugs are given once daily and short- and long-term tolerability and toxicity are far better than with earlier agents, which better supports the high levels of adherence required. In addition to national recommendations for preferred and alternative first-line therapy, there are regional guidelines based on cost. Many first-line agents are, or soon will be, available as generics offering significant reductions in ART-related costs.
Drug interactions are a common occurrence and as the population of people with HIV ages, prescribing of concomitant medications will increase.
A summary of each drug class and key information about individual agents is given in table 2.
|Table 2: Antiretroviral drug classes and key information|
|Nucleoside and nucleotide reverse transcriptase inhibitors (NRTI)|
|Non-nucleoside reverse transcriptase inhibitors (NNRTI)|
|Protease inhibitors (PI)|
|Integrase inhibitors (INI)|
Comorbidities in people living with HIV
Many cohorts show an increased risk of age-related comorbidities. Typically the prevalence of conditions like cardiovascular disease, chronic kidney disease and osteoporosis are similar to those observed in HIV-negative individuals a decade older. Contributing factors include traditional risk factors (smoking rates are higher in most HIV cohorts), drug side effects and the fact that even effective treatment does not normalise the inflammation and immune activation associated with HIV. Despite the association between some HIV drugs and comorbidity risk, the negative impact is outweighed by the benefit of viral suppression. Thresholds for investigation need to be amended for people with HIV and routine monitoring includes screening for renal impairment and performing DEXA based on FRAX scores and age. Because of a higher risk of cervical abnormalities, annual cervical cytology has long been a recommendation. But British guidelines are likely to change such that women with no history of cervical abnormality, good CD4 and who are negative for high-risk HPV can be offered screening in line with the general population.
People with HIV should be offered vaccination for hepatitis A and B, annual flu vaccine and pneumococcal vaccine. For the latter, BHIVA recommends PPV-13 for all people with HIV and PPV-23 in line with Green Book guidelines; the two types of vaccine should not be given within three months. HPV vaccine is likely to be beneficial, although in England is limited to MSM aged 45 years or less as part of a Public Health England (PHE) and NHS England pilot. Some live vaccines remain contraindicated and full vaccine recommendations can be accessed at www.bhiva.org.
Important! Offer vaccination for hepatitis A and B, flu and pneumococcal vaccine.
Preventing onward transmission
Treatment as prevention
Suppressive HIV therapy reduces the risk of onward transmission to zero in trials and observational cohorts. In a randomised trial of immediate versus deferred ART in heterosexual couples there was no HIV transmission where the positive person was undetectable on HIV therapy. In an observational cohort no transmissions were observed between sero-different MSM and heterosexual couples after a total of 58,000 condomless sex acts where the HIV-positive partner has an undetectable virus on treatment.8
Using HIV drugs in HIV-negative individuals
Post-exposure prophylaxis (PEP) is an established method to reduce the risk of HIV acquisition after a potential exposure and is recommended where the risk of HIV acquisition exceeds 1/1000. A month of triple therapy is started within 72 hours of exposure (ideally within 24 hours) and should be accessible through all GU services and emergency departments.
Pre-exposure prophylaxis (PrEP) is the use of dual HIV medication prior to potential exposure and is highly effective (86% reduction in HIV incidence in two large trials in MSM). PrEP can be taken daily or, for MSM, in an event-based manner before/after potential exposure. PrEP is available on the NHS in Scotland and Wales for high-risk individuals, plans in Ireland are pending and in England an implantation project led by PHE will start in 2017.
Condoms remain an effective method to reduce HIV transmission. Condoms should also be encouraged for individuals at risk of acquiring other STIs.
Education and risk-reduction advice are important. Behavioural interventions significantly reduce rates of condomless anal sex in MSM.
Section 4: Prognosis
ART use has resulted in huge reductions in morbidity and mortality and well-treated patients with HIV have a normal life expectancy.
Late diagnosis accounts for the highest mortality in the UK and starting antiretrovirals at a CD4 count less than 200 is associated with an increase in disease progression and death.
Initially, patients are usually followed up every three to four months in HIV specialist clinics. Once stable on therapy, six-monthly or sometimes annual follow-up is usual.
Section 5: Case study
A 68-year-old Caucasian man presented with a one-week history of productive cough.
His medical history included dyspepsia and high cholesterol. He was taking lansoprazole and simvastatin. He was prescribed antibiotics for the cough and recovered. Six months later, he presented with a vesicular rash on his chest affecting the T4/5 dermatome. He was diagnosed with shingles.
Later he complained of increased lethargy and weight loss. An FBC showed mild anaemia and lymphopaenia.
This was explained by his dyspepsia, which had increased in severity. He was admitted to hospital with a three-week history of worsening shortness of breath, dry cough and further weight loss.
Chest X-ray suggested pneumocystis pneumonia, which was confirmed by cytology of bronchial washings, and the patient was confirmed HIV positive. He was commenced on antiretrovirals.
This was a late presentation of HIV, with a low CD4 at 40 cells/microlitre and a high VL at >500,000 copies/mL.
The patient's most likely risk factor was when he worked in Nigeria for 10 years, where he had several episodes of unprotected heterosexual sex.
HIV is being increasingly diagnosed among older patients who are more likely to present late. This patient presented on three occasions with HIV indicator diseases providing an earlier opportunity for HIV testing.
An earlier test may have prevented hospital admission and avoided the increased morbidity and mortality associated with a late diagnosis.
Section 6: Evidence base
Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren J, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006; 355(22): 2283-96.
The SMART trial looked at CD4-guided treatment interruptions versus continued therapy. Outcomes (HIV and non-HIV related) were significantly better in the continuous therapy arm so treatment interruption is not recommended.
INSIGHT START Study Group, Lundgren JD, Babiker AG et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015; 373(9): 795-807.
The START trial investigated starting first-line ART at CD4 >500 versus deferred treatment. Significantly fewer AIDS/death/serious non-AIDs events in the earlier treatment arm, hence ART is now being recommended at all CD4.
McCormack S, Dunn DT, Desai M et al. 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. Lancet. 2016; 387(10013): 53–60.
PROUD is a UK trial of immediate versus deferred HIV PrEP demonstrating 86% reduction in HIV incidence amongst MSM offered daily PrEP.
Molina JM, Capitant C, Spire B, et al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. N Engl J Med. 2015; 373(23): 2237-46.
IPERGAY is a French trial of event-driven PrEP (active versus placebo) showing 86% reduction in HIV incidence among MSM in the active drug arm.
HPTN052. A randomized trial to evaluate the effectiveness of antiretroviral therapy plus HIV primary care versus HIV primary care alone to prevent the sexual transmission of HIV-1 in serodiscordant couples. Available from:
https://hptn.org/research/studies/hptn052 (accessed 26 June 2017). This is a randomised controlled trial of immediate versus deferred ART for people with HIV and an HIV-negative partner. A 93% reduction in HIV transmission was seen in the immediate ART arm, with no reported transmission in the context of viral suppression.
Rodger AJ, Cambiano V, Bruun T et al. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. JAMA. 2016; 12;316(2):171-81.
The PARTNER trial is an observational cohort of serodifferent couples where the HIV-positive person is taking suppressive ART. There was no transmission after 58,000 condomless sex acts in heterosexuals and MSM.
NICE. HIV testing: increasing uptake among people who may have undiagnosed HIV. NG60. 2016.
BHIVA guidelines - available from: http://www.bhiva.org/guidelines.aspx.
Madge S, Matthews P, Singh S et al. HIV in Primary Care. Medical Foundation for AIDS and Sexual Health.
- Dr Charlotte Hopkins and Dr R Monica Lascar, consultants in HIV and genitourinary medicine at Whipps Cross University Hospital, London.
- This is an updated version of an article that was first published in November 2010. It was updated by Dr Laura Waters, HIV & hepatitis lead, Central and North West London.
- Terrence Higgins Trust. HIV in the UK. Available from: http://www.tht.org.uk/our-charity/Facts-and-statistics-about-HIV/HIV-in-the-UK (accessed 26 June 2017).
- Kirwan PD, Chau C, Brown AE et al. HIV in the UK - 2016 report. December 2016. Public Health England, London.
- Delpech V. Oral abstract BHIVA Spring Conference, Liverpool, April 2017.
- NICE. HIV testing: increasing uptake among people who may have undiagnosed HIV. NG60. 2016.
- HIV in Europe. HIV Indicator Conditions:Guidance for Implementing HIV Testing in Adults in Health Care Settings. Available from http://hiveurope.eu/Portals/0/Guidance.pdf.pdf (accessed 26 June 2017).
- AL Pozniak, KM Coyne, RF Miller et al. British HIV Association guidelines for the treatment of TB/HIV coinfection 2011. HIV Medicine 2011; 12: 517-24.
- BHIVA. BHIVA guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015 (2016 interim update). Available from: http://www.bhiva.org/HIV-1-treatment-guidelines.aspx (accessed 26 June 2017).
- Rodger AJ, Cambiano V, Bruun T et al. Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. JAMA. 2016; 12;316(2):171-81.
Terrence Higgins Trust is the UK’s leading HIV and sexual health charity, offering support, information and advice services for those living with HIV and affected by HIV or poor sexual health.
Our vision is a world where people with HIV live healthy lives free from prejudice and discrimination, and good sexual health is a right and reality for all.