Epidemiology

The most recent UK statistics on HIV and late-stage HIV disease can be found on the Health Protection Agency (HPA) website.^[6] The most recent global statistics can be found on the Averting HIV and AIDS (AVERT) website.^[7]

Diagnosis in adults^[8]

• Is based on detecting anti-HIV antibodies in serum. Rapid testing is offered by some sexual health clinics and can produce a result in 20 minutes.
• Acute infection may be detected by the presence of P24 antigen or HIV RNA by polymerase chain reaction (PCR) and precedes the appearance of IgM and IgG. A combination test checking for the presence of HIV antibody and p24 antigen (the so-called 'fourth generation test') is provided by hospital and is very accurate. It takes about four weeks to get the result back.
• HIV counselling is essential both before and after testing.

Stages of human immunodeficiency virus infection

Groups are those in the Centers for Disease Control and prevention (CDC) 1993 Classification system.^[9]

• Seroconversion illness:
  • Occurs between 1 and 6 weeks after infection. 20-60% present with symptoms at this time.
  • Common symptoms are a glandular fever-type illness with fever, malaise, myalgia, pharyngitis, headaches, diarrhoea, neuralgia or neuropathy, lymphadenopathy and/or a maculopapular rash. Rarely, meningoencephalitis. Acute infection may be asymptomatic.
  • As HIV gets more treatable, so recognising this early phase becomes more important. Although clinical features are similar to infectious mononucleosis, consider HIV seroconversion illness if there are unusual signs, eg oral candidiasis, recurrent shingles, leukopenia, or CNS signs.
  • Although antibody tests are negative, viral P24 antigen and HIV RNA levels are elevated in early infection.
  • Patients who are diagnosed with seroconversion illness should be referred promptly for specialist assessment and initiation of treatment.
• Asymptomatic infection:
  • After seroconversion, virus levels are low, although replication continues slowly. CD4 and CD8 lymphocyte levels are normal. This situation may persist for many years.
• Persistent generalised lymphadenopathy (PGL):
  • Defined as nodes >1 cm diameter at two extra-inguinal sites, persisting for three months or longer, not due to any other cause.
  • Biopsy is not recommended, unless an alternative diagnosis needs to be excluded, as features are nonspecific.
• Symptomatic infection:
  • Nonspecific constitutional symptoms develop: fever, night sweats, diarrhoea, weight loss.
  • There may also be minor opportunistic infections, eg oral candida, oral hairy leukoplakia, herpes zoster, recurrent herpes simplex, seborrhoeic dermatitis, tinea infections.
  • This collection of symptoms and signs is referred to as the AIDS-related complex (ARC) and is regarded as a prodrome to AIDS.
• AIDS:
  • Severe immunodeficiency.
  • Evidence of life-threatening infections and unusual tumours: see related separate articles Complications of HIV Infection and HIV and Skin Disorders.

Investigations in adults^[10]

• Detection of HIV antibody: enzyme-linked immunosorbent assay (ELISA), Western blot.
• Assessment of viral load: detection of virus or viral antigen: HIV RNA or branched DNA (bDNA) assay.
• FBC: anaemia, thrombocytopenia, lymphocytopenia with reduced CD4 cell count.
• Raised ESR.
• Assessment of other infections: eg tuberculosis, hepatitis B, cytomegalovirus (CMV), toxoplasma, syphilis, varicella.
• Screening for co-existing sexually transmitted diseases (STDs).
• Baseline CXR and cervical smear.
• It may be appropriate to screen for glucose-6-phosphate dehydrogenase (G6PD) deficiency in appropriate racial groups (some drug treatments can cause haemolysis in these patients).^[11]

Investigation in children^[4]

Standard anti-HIV IgG antibody tests cannot be used before 18 months of age, as maternal antibodies may be detected. PCR and virus culture are the best investigations in children born to infected mothers. 38% of infected infants can be detected within the first 48 hours after birth, rising to 96% at four weeks .

1993 Centers for Disease Control and prevention Classification of HIV infection in adults

The initial assessment should also 'stage' the disease. The most widely used staging system is the 1993 revision of the CDC's AIDS Surveillance Case Definition for Adolescents and Adults.^[12] According to this system, individuals are assigned a stage according to both a CD4 cell count category and a clinical one (eg 'A1' or 'C2'). The CD4 cell count categories are as follows:

• CD4 count greater than or equal to 500 cells/mm³ or 29%.
• CD4 count equal to 200-499 cells/mm³ or 14%-28%.
• CD4 count less than 200 cells/mm³ or less than 14%.

Clinical categories

• Category A:
  • Documented HIV infection, asymptomatic, including persistent generalised lymphadenopathy (PGL) - a condition in which HIV continues to produce chronic painless swellings in the lymph nodes during the latency period - or acute HIV infection.
• Category B:
  • Symptomatic disease, conditions not listed in clinical Category C, including conditions that are:
    • attributed to HIV infection or indicative of a defect in cell-mediated immunity; or
    • considered to have a clinical course or management that is complicated by HIV infection.
  • Conditions such as: bacillary angiomatosis, persistent or recurrent oral or vaginal candidiasis, moderate-to-severe cervical dysplasia; constitutional symptoms such as fever (38.5°C) or diarrhoea for over one month, oral hairy leukoplakia, herpes zoster (>1 episode or >1 dermatome), idiopathic thrombocytopenic purpura (ITP), listeriosis, pelvic inflammatory disease and peripheral neuropathy.
• Category C:
  • AIDS indicator condition (see below): once a Category C condition has occurred, the individual remains in Category C.

Any individual with stage A3, B3, C1, C2 or C3 infection has AIDS by the CDC definitions.

There is a similar 1994 CDC classification of HIV infection in children^[13], where infected children are classified - according to three parameters - into mutually exclusive categories: a) infection status, b) clinical status and c) immunological status.

Monitoring human immunodeficiency virus infection

• Clinical assessment.
• Monitoring the CD4 count.
• Plasma HIV RNA levels strongly predict progression to AIDS and death but the CD4 count may be sufficient in the later stages in resource-poor countries.^[14]
• Clinical benefit from anti-HIV agents depends not only on improving the CD4 count but also from decreasing HIV RNA by at least 70%. This is now possible with combination therapy.

Management^[15]

People with HIV infection (and their families) need a great deal of support, as well as monitoring and drug treatment for the patient. Management also includes the treatment of any specific complications of HIV infection. See separate article Managing HIV-positive Individuals in Primary Care.

The following guidance is taken from the British HIV Association (BHIVA) guidelines.^[16]

Antiretroviral therapy is recommended for all patients with established HIV infection if they have a CD4 cell count of ≤350 cells/mm³ or signs of nervous system involvement or an AIDS-defining condition present.

Those with established HIV infection with a CD4 cell count of between 351-500 cells/mm³ should be treated if they have:

• Hepatitis B infection, where treatment is indicated.
• Hepatitis C infection in some cases, where treatment for hepatitis is deferred.
• Low CD4 percentage (<14%).
• Established or high risk of cardiovascular disease.

Late-stage HIV patients should have treatment (except in the presence of tuberculosis when CD4 >350 cells/mm³).

Drug treatment^[16]

Antiretroviral treatment may cause lipodystrophy syndrome which includes fat redistribution, insulin resistance and dyslipidaemia.

• Preferred initial therapy is usually three drugs: efavirenz plus tenofovir or abacavir, plus lamivudine or emtricitabine.^[16]
• Other drugs are used in particular circumstances (see treatment guidelines).

Other measures^[15][17]

• Immunise against hepatitis B, pneumococcal disease and Haemophilus influenzae type b (and possibly influenza and hepatitis A).
• Because of immunosuppression, HIV patients should not receive BCG vaccination, yellow fever, oral typhoid or live oral polio immunisations.
• Aim for prompt treatment of any infection and vigorous primary and secondary prophylaxis for pneumocystosis and toxoplasmosis. See separate article Chemoprophylaxis in HIV for further details.

Preventing human immunodeficiency virus spread^[15][18]

• Promote lifelong safer sex, barrier contraception and reduction in the number of partners. Videos, followed by interactive discussions, are one way to double the use of condoms. Another way is the 100% condom programme involving distribution of condoms to brothels, with enforcement programmes enabling monitoring and encouraging of condom use at any sex establishment. Such programmes are estimated to have prevented 2 million HIV infections in Thailand.
• Warn heterosexuals about the dangers of sexual tourism/promiscuity.
• Tell drug users not to share needles. Use needle exchange schemes.
• Vigorous control of other STDs can reduce HIV incidence by 40%.
• Strengthen awareness of clinics for STDs.
• Reduce unnecessary blood transfusions.
• Encourage pregnant women to have HIV tests.
• Post-exposure prophylaxis after occupational and sexual exposure also helps to limit HIV spread. See separate HIV Post-exposure Prophylaxis article for more details.
• Pre-exposure prophylaxis has been mooted in some areas where HIV prevalence is very high, eg sub-Saharan Africa.^[19]