See also separate articles on Management of HIV in Pregnancy and Post HIV Exposure Prophylaxis.

Human immunodeficiency virus (HIV) is a retrovirus that was first identified in 1983:¹

• Initially named lymphadenopathy associated virus (LAV), it was the third identified in a family of human T-lymphotropic viruses (HTLV-III) finally renamed as HIV-I, and causes acquired immune deficiency syndrome (AIDS)-related disease in most parts of the world.²
• In 1985 HIV-2 was identified in AIDS patients with West African connections and is currently still uncommon outside that region.³
• HIV binds to CD4 receptors on helper T-lymphocytes, monocytes, macrophages and neural cells. CD4 cells migrate to the lymphoid tissue where the virus replicates and then infects new CD4-positive cells. As the infection progresses, depletion or impaired function of CD4 cells predisposes to the development of immune dysfunction.⁴
• The number of circulating viruses (viral load) predicts progression to AIDS.⁵

Epidemiology

The most recent UK statistics on HIV and AIDS were published by the Health Protection Agency (HPA) in August 2009.⁶ These showed that in the UK:

• An estimated 83,000 people were living with HIV in 2008; more than a quarter (27%) were unaware of their infection.
• There were 7,298 new diagnoses of HIV by the end of 2008, contributing to a cumulative total of 105,625 cases reported by the end of June 2009.
• There was a significant increase in the number of women reported as HIV positive (37% in 2008 compared with 13% in1993), mainly due to heterosexual contact.
• 382 new diagnoses of people with AIDS were made in 2008 and 525 AIDS-related deaths occurred.
• The screening of blood donors and sterilising blood products in developed countries have greatly reduced the risk of HIV infection by this route.
• The UK cities with the largest numbers of people with HIV infection are London, Brighton and Manchester.⁵
• Historically, the highest rates of infection have been in London, Brighton, Bournemouth, Eastbourne, Manchester and Blackpool.⁷

Statistics provided by the United Nations Programme on HIV/AIDS (UNAIDS) reported that globally in 2008:⁸

• 31.3 million adults and 2.1 million children were living with HIV.
• 2.7 million people became infected.
• 2 million people died from AIDS. This figure peaked in 2004 and has only reduced since then slowly, despite the advent of highly active antiretroviral therapy (HAART).
• Approximately 11% of HIV infections occurred in babies due to infection from their mothers.
• 10% were acquired from injectable drug use.
• 5-10% occurred in healthcare settings.
• 5-10% were caused by sex between men.
• The remaining incidences were due to heterosexual transfer (approximately two thirds of new infections).
• Two-thirds of all infected people live in Sub-Saharan Africa. The second highest number live in South and South-East Asia.
• HIV prevalence varies considerably across the region, ranging from less than 1% in Madagascar to over 30% in Swaziland.
• In Sub-Saharan Africa, AIDS killed approximately 1.4 million people in 2008. Antiretroviral drugs remain unavailable to most Africans.
• Unlike women in most other regions in the world, African women are more likely to be infected with HIV than men. The reasons for this include the greater efficiency of male-to-female HIV transmission through sex and the younger age at initial infection for women.

Diagnosis in adults

• Is based on detecting anti-HIV antibodies in serum.
• 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. The P24 test can give a result after 3 weeks compared to 3 months with the IgM and IgG tests.
• During the asymptomatic period there are high titres of IgG to core and envelope proteins. As immunodeficiency develops, IgG titre to core protein falls and P24 antigenaemia recurs.
• HIV counselling is essential both before and after testing.

Stages of HIV 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, e.g. 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 many years.
• Persistent generalised lymphadenopathy:
  • Defined as nodes >1 cm diameter at 2 extra-inguinal sites, persisting for 3 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, e.g. 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 on Complications of HIV Infection and HIV and Skin Disorders.

Investigations in adults

• 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
• Full blood count: anaemia, thrombocytopenia, lymphocytopenia with reduced CD4 cell count
• Raised ESR
• Assessment of other infections: e.g. tuberculosis, hepatitis B, cytomegalovirus (CMV), toxoplasma, syphilis, varicella
• Screening for coexisting sexually transmitted diseases
• Baseline chest X-ray 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)

Investigation in children¹⁰

Standard anti-HIV IgG antibody tests cannot be used before 18 months of age, as maternal antibodies may be detected. Polymerase chain reaction (PCR) and virus culture are the best investigations in children born to infected mothers. 30-50% of infected infants can be detected at birth and 100% can be picked up by the age of 3-6 months.

1993 CDC 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.⁹ According to this system, individuals are assigned a stage according to both a CD4 cell count category and a clinical one (e.g. '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 1 month, oral hairy leucoplakia, 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 children¹⁰, where infected children are classified according to three parameters into mutually exclusive categories: a) infection status, b) clinical status and c) immunologic status.

Monitoring HIV infection

• Clinical assessment.
• Monitoring the CD4 count.
• Plasma HIV RNA levels strongly predict progression to AIDS and death, whatever the CD4 count. This test typically involves quantitative reverse transcriptase PCR to amplify DNA copies of the target RNA. HIV patients in the lowest quartile of viral load (HIV RNA = 4530 copies/ml) have an 8% chance of progressing to AIDS in 5 years compared with 62% in those in the highest quartile (>36,270 copies/ml).
• 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

A thorough review of the management of HIV infection can be found in the recommendations of the HIV Medicine Association of the Infectious Diseases Society of America.¹¹ People with HIV infection and their families, need a great deal of support as well as monitoring and drug treatment. 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 guidelines.¹²

Antiretroviral therapy is recommended for all patients with established HIV infection if they have a CD4 cell count of ≤350 cells/mm or signs of nervous system involvement or an AIDS-defining condition present.¹²
Those with established HIV infection with CD4 cell count of between 351-500 cells/mm 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

AIDS patients should have treatment (except in the presence of tuberculosis when CD4 >350 cells/mm).¹²

Drug treatment

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

• Preferred initial therapy is usually 3 drugs: efavirenz plus tenovofir or abacavir, plus lamivudine or emtricitabine.¹²
• Other drugs are used in particular circumstances (see treatment guidelines).¹²

Other measures

• Immunise against hepatitis B, pneumococcus and haemophilus (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.

Preventing HIV spread

• Promote lifelong safer sex, barrier contraception and reduction in the number of partners. Videos, followed by interactive discussions, is 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 sexually transmitted diseases.
• Reduce unnecessary blood transfusions.
• Encourage pregnant women to have HIV tests.

Document references

1. Mortimer J, Evans B, Goldberg D; The surveillance of HIV infection and AIDS in the United Kingdom Communicable Disease Review Vol 7 (Review No 9)
2. Szczypinska, E, Wallace M, Booth Wainscoat, DO et al; Human T-Cell Lymphotrophic Viruses 2009.
3. Marlink R; Lessons from the second AIDS virus, HIV-2. AIDS. 1996 Jun;10(7):689-99.
4. Rivera D, Fry R; HIV Infection, eMedicine.com, 2010
5. HIV and Sexually Transmitted Infections, Health Protection Agency; (reports)
6. HIV Statistics 2009, Health Protection Agency
7. Ladva S; HPA statistics: HIV in the UK 2008.
8. AVERT; Worldwide AIDS Statistics 2010
9. Centers for Disease Control and Prevention; 1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults.
10. CDC Revised classification system for HIV infection in children <13 years (1994); CDC Paediatric HIV staging
11. Aberg JA, Gallant JE, Anderson J, et al; Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2004 Sep 1;39(5):609-29. Epub 2004 Aug 11.
12. Guidelines for the treatment of HIV-infected adults with antiretroviral therapy, The British HIV Association (2008)

Internet and further reading

• Management of sexual and reproductive health (SRH) of people living with HIV infection, British HIV Association (2008)
• HIV and STIs, Health Protection Agency

Acknowledgements