oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
- 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.
- In 1985 HIV-II was identified in AIDS patients with West African connections and is currently still uncommon outside that region.
- 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.
- The success of antiretroviral therapy (ART, formerly highly-active retroviral therapy or HAART) has revolutionised the way we think about HIV infection. Far fewer patients now progress to AIDS, which - due to the stigma surrounding the diagnosis - is increasingly being known as late-stage HIV disease. Both terms are used interchangeably throughout this article, as the term AIDS is still used by some authorities (eg, the Centers for Disease Control and prevention (CDC) in America).
- The number of circulating viruses (viral load) predicts progression to late-stage HIV disease.
The most recent UK statistics on HIV and late-stage HIV disease can be found on the Health Protection Agency (HPA) website. The most recent global statistics can be found on the Averting HIV and AIDS (AVERT) website.
Diagnosis in adults
- 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.
- 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.
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.
- 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).
Investigation in children
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. 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%.
- 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.
- Symptomatic disease, conditions not listed in clinical Category C, including conditions that are:
- 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.
|AIDS-defining conditions in adults|
|Candidiasis of bronchi, trachea or lungs.||Lymphoma, Burkitt's (or equivalent term).|
|Candidiasis, oesophageal.||Lymphoma, immunoblastic (or equivalent term).|
|Cervical carcinoma, invasive.||Lymphoma, primary, of brain.|
|Coccidioidomycosis, disseminated or extrapulmonary.||Mycobacterium avium complex (MAC) or M. kansasii, disseminated or extrapulmonary.|
|Cryptococcosis, extrapulmonary.||Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary).|
|Cryptosporidiosis, chronic intestinal (>1 month's duration).||Mycobacterium, other species or unidentified species, disseminated or extrapulmonary.|
|Cytomegalovirus (CMV) disease (other than liver, spleen or nodes).||Pneumocystis jirovecii pneumonia.|
|CMV retinitis (with loss of vision).||Pneumonia, recurrent.|
|Encephalopathy, HIV-related.||Progressive multifocal leukoencephalopathy.|
|Herpes simplex: chronic ulcer(s) (>1 month's duration); or bronchitis, pneumonitis or oesophagitis.||Salmonella septicaemia, recurrent.|
|Histoplasmosis, disseminated or extrapulmonary.||Toxoplasmosis of brain.|
|Isosporiasis, chronic intestinal (>1 month's duration).||Wasting syndrome due to HIV.|
There is a similar 1994 CDC classification of HIV infection in children, 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.
- 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.
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.
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).
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.
- Other drugs are used in particular circumstances (see treatment guidelines).
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.
- Primary chemoprophylaxis is used when the CD4 lymphocyte count drops below a certain level, making opportunistic infection likely.
- Secondary chemoprophylaxis is used to prevent the recurrence of an infection that has already occurred.
- Early disease (World Health Organization (WHO) stages 1-3). The type of infection will depend on local disease prevalence. The advent of antiretroviral therapy (ART, formerly known as highly-active retroviral therapy or HAART) has dramatically reduced the risk of developing AIDS (increasingly being known as late-stage HIV disease). Some idea of UK prevalence can be obtained from statistics of diseases which indicate possible development of late-stage HIV disease (so-called 'indicator diseases'). UK data commonly feature pneumocystis pneumonia (PCP), tuberculosis (TB), atypical mycoplasma, candidiasis, cytomegalovirus (CMV) and toxoplasma. Recent years have seen TB overtake PCP as the most common indicator disease. Globally, the important infections are TB, pneumococcal pneumonia, shingles, malaria, staphylococcal skin infections and septicaemia. Of these, TB is the most prevalent and WHO is pursuing joint prevention/treatment interventions, providing care in homes, communities and hospitals.
- Late disease (WHO stage 4 - equivalent to AIDS). Common recurring infections are pneumocystis, cryptococcus, toxoplasma and TB.
Antiretroviral drugs are now available to inhibit the replication of the human immunodeficiency virus (HIV). This helps to prolong life, restore the patient's immune system to something approaching normal activity and reduce the chances of opportunistic infection developing. Combinations of three or more drugs are given to lessen the possibility of resistance.
See separate article Antiretroviral Agents for more details.
Where there is no prevalent UK policy, the WHO or US policy is adopted.
- TB - this is 30-50 times more likely to develop in HIV-positive patients than in those who do not have the virus. The WHO guidance issued in 2010 recommends that the decision to prescribe isoniazid preventative therapy (IPT) can be based on a symptom algorithm. It is no longer necessary to perform tuberculin skin tests or CXRs before isoniazid is instituted. These guidelines have been slow to percolate through the developed world but have been rapidly adopted in resource-poor countries.
- In South Africa (TB is the most common opportunistic infection, and most patients will have a positive skin test) isoniazid is offered to all patients with HIV who do not have signs or symptoms of active TB..
- In the UK, the success of ART has made the routine use of IPT unnecessary for the indigenous population. However, it should still be considered for those at high risk (eg, immigrants on ART with a CD count less than 300 cells/μL).
- Pneumocystis jirovecii pneumonia - UK recommendations are to offer co-trimoxazole to all patients with a CD count below 200/mm3 or who have a history of oral candidiasis, a CD4 T-cell percentage of all lymphocytes <14%, or a previous AIDS-defining illness. Discontinue if CD count remains above 200/mm3 for 3-6 months.
- Bacterial pneumonia - offer pneumococcal vaccine to all patients with CD count above 200/mm3 who have not had vaccine within five years.
- Mycobacterium avium-intracellulare (MIA) - the British HIV Association (BHIVA) recommends azithromycin for individuals with CD4 counts <50 cells/μL. Patients receiving ART can stop prophylaxis once the CD4 count rises above 50 cells/μL and the viral load is <50 copies per ml for at least three months. Clarithromycin is sometimes used as an alternative.
- Toxoplasma - offer co-trimoxazole for toxoplasma-positive patients with counts below 100/mm3 or test at regular intervals. Dapsone plus pyrimethamine can be used in cases of co-trimoxazole allergy.
- Varicella zoster - if susceptible (no history of chickenpox, shingles, or detectable antibody) - offer varicella immune globulin within 96 hours of exposure.
- CMV and herpes simplex - primary prophylaxis is not routinely offered in the UK.
- Microsporidiosis, cryptosporidiosis - there is no known prophylaxis available.
- The combined influenza/swine flu vaccine is routinely offered in the UK to all individuals living with HIV, especially those with a CD count below 200/mm3.
- Cytomegalovirus (CMV) - use ganciclovir to prevent retinitis. Long-acting drug-release intravitreous implants have been shown to be cost-effective.
- Herpes simplex - may require temporary daily suppressive treatment with oral aciclovir. There are limited safety data for famciclovir and valaciclovir.
- Oral candidiasis - may require suppressive treatment with an antifungal agent.
- Salmonella - long-term therapy may be required to prevent septicaemia - ciprofloxacin is the first choice.
- Toxoplasma - give co-trimoxazole to prevent relapse (pyrimethamine plus dapsone if allergic); discontinue if the CD4 cell count increases above 200/mm3 and is sustained for at least six months. Resume if the count subsequently falls below 200/mm3.
- 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.
Further reading & references
- Management of sexual and reproductive health of people living with HIV infection, British HIV Association (2008)
- Mayer KH, Krakower D; Antiretroviral Medication and HIV Prevention: New Steps Forward and New Ann Intern Med. 2012 Jan 16.
- HIV and STIs, Health Protection Agency
- 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)
- Marlink R; Lessons from the second AIDS virus, HIV-2. AIDS. 1996 Jun;10(7):689-99.
- HIV and Sexually Transmitted Infections, Health Protection Agency; (reports)
- HIV Statistics 2012, Health Protection Agency
- Worldwide AIDS Statistics 2010, AVERT
- UK national guidelines for HIV testing, British HIV Association (September 2008)
- Curran JW, Jaffe HW; AIDS: the early years and CDC's response. MMWR Surveill Summ. 2011 Oct 7;60 Suppl 4:64-9.
- Adalja AA, Vergis EN; Chart Review: Prophylaxis of Pneumocystis Pneumonia at a Large Metropolitan HIV P T. 2009 Jul;34(7):389-90.
- Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults, Centers for Disease Control & Prevention (1993)
- Revised classification system for HIV infection in children <13 years="" a="">; Revised classification system for HIV infection in children <13 years="" centers="" for="" disease="" control="" and="" prevention="" 1994="" li="">
- Korenromp EL, Williams BG, Schmid GP, et al; Clinical prognostic value of RNA viral load and CD4 cell counts during untreated PLoS One. 2009 Jun 17;4(6):e5950.
- HIV in Primary Care; Medical Foundation for AIDS & Sexual Health (2011)
- Guidelines for the treatment of HIV-infected adults with antiretroviral therapy, The British HIV Association (2012)
- Treatment of opportunistic infection in HIV-seropositive individuals; British HIV Association (2011)
- Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults, World Health Organization (2006); recommendations for a public health approach
- What is HIV antiretroviral treatment? AVERT.org
- Joint HIV/TB Interventions, World Health Organization, 2012
- Kaplan JE, Benson C, Holmes KH, et al; Guidelines for prevention and treatment of opportunistic infections in MMWR Recomm Rep. 2009 Apr 10;58(RR-4):1-207; quiz CE1-4.
- Smart T; New joint guidelines on Isoniazid preventive therapy, HIV & AIDS Treatment in Practice, 2010
- HIV Related Opportunistic Infections: Prevention and Treatment, AVERT.org, 2012
- Guidelines for the treatment of TB/HIV coinfection, British HIV Association (2011)
- Guidelines for Tuberculosis Preventive Therapy in HIV Infected Individuals in South Africa, Health Department, Republic of South Africa, 2010
- Chemopreventative therapy - HAART or antituberculosis drugs? British HIV Association (2005)
- Can you get HIV from....?, AVERT, 2012
- Celum CL; HIV preexposure prophylaxis: new data and potential use. Top Antivir Med. 2011 Dec;19(5):181-5.
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.
Dr Colin Tidy
Dr Laurence Knott
Dr John Cox