Human Immunodeficiency Virus (HIV)

See also separate article on Management of HIV in Pregnancy.

HIV is a retrovirus that was first identified in 1983:

• Initially named LIV (lymphadenopathy associated virus). It was the third identified in a family of human T-lymphotropic viruses (HTLV-III) finally renamed as HIV-I and causes AIDS related disease in most parts of the world.
• In 1985 HIV-2 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 number of circulating viruses (viral load) predicts progression to AIDS (acquired immune deficiency syndrome).¹

• The current estimate of worldwide disease prevalence is more than 38 million HIV infections. Ninety-five percent of these cases are in developing countries, mainly Sub-Saharan Africa and South-East Asia.
  • Sub-Saharan Africa is by far the worst-affected in the world by the AIDS epidemic. The region has just over 10% of the world's population, but is home to over 60% of all people living with HIV. An estimated 2.8 million adults and children became infected with HIV during 2006, bringing the total number of people living with HIV/AIDS in the region to 24.7 million.
  • 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 2.1 million people in 2006. 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.
• At the end of 2005 an estimated 63,500 adults aged over 15 years were living with HIV in the UK, 20,100 (32%) of whom were unaware of their infection.¹
• HIV predominantly affects younger adults. In 2003, 74% of individuals were aged 15-39 years at diagnosis.¹
• With a reduction in HIV associated deaths with new treatments and an increase in the number of new diagnoses, there has been a marked increase in the number of people requiring long-term treatment.
• Sex between men remains the group in the UK at highest risk of acquiring HIV.
• 76% of heterosexually acquired HIV infections diagnosed in the UK in 2002/2003 were in people from Africa, or were associated with exposure there.¹
• There is no evidence of significant current HIV spread amongst intravenous drug users in the UK.
• The proportion of maternal HIV infections detected in pregnancy has increased but congenital HIV infection is still occurring in women whose HIV infection has not been detected.
• The screening of blood donors and sterilizing blood products in developed countries has 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.¹

• Is based on detecting anti-HIV antibodies in serum.
• Acute infection may be detected by the presence of P24 antigen or HIV RNA by PCR and precedes the appearance of IgM and IgG (within 3 months).
• 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.

Groups are those in the CDC 1993 Classification system.²

• 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 recognizing 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, leucopenia, 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 >1cm 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 non-specific.
• Symptomatic infection:
  • Non-specific 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 articles on complications of HIV infection and HIV and skin disorders.

• Detection of HIV antibody: ELISA, Western blot
• Assessment of viral load: detection of virus or viral antigen: HIV RNA or bDNA assay
• Full blood count: anaemia, thrombocytopenia, lymphocytopenia with reduced CD4 cell count
• Raised ESR
• Assessment of other infections: e.g. tuberculosis, hepatitis B, CMV, toxoplasma, syphilis, varicella
• Screening for co-existing sexually transmitted diseases
• Baseline chest x-ray and cervical smear
• It may be appropriate to screen for G6PD deficiency in appropriate racial groups (some drug treatments can cause haemolysis in these patients)

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.² 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 PGL; 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 > one month; oral hairy leukoplakia; herpes zoster (> 1 episode or > one dermatome); 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.

• 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.

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.³ 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. The following guidance is taken from the British HIV association guidelines.⁴

• The best time to start treatment remains controversial but is based on clinical symptoms, CD4 count and HIV RNA viral load.
• Triple therapy is recommended. There are three groups of antiretroviral drugs:⁴
  • Nucleoside reverse transcriptase inhibitors: e.g. zidovudineabacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir and zalcitabine.
  • Non-nucleoside reverse transcriptase inhibitors: e.g. efavirenz, nevirapine.
  • Protease inhibitors: indinavir, lopinavir, nelfinavir, ritonavir, saquinavir.
• The preferred initial regimen includes two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.
• Switching therapy or another antiviral drug may need to be added if there is any clinical or virological deterioration.
• Antiretroviral treatment may cause lipodystrophy syndrome which includes fat redistribution, insulin resistance and dyslipidaemia.⁴

Other measures

• Immunize against hepatitis B, pneumococcus and haemophilus (and possibly influenza and Hep A).
• Because of immunosuppression, HIV patients should not receive BCG vaccination, yellow fever, oral typhoid or live oral polio immunizations.
• Aim for prompt treatment of any infection, and vigorous primary and secondary prophylaxis for pneumocystosis and toxoplasmosis.

Local guidelines should be followed. The Department of Health published revised guidelines in February 2004:⁵

• Post-exposure prophylaxis (PEP) should be recommended to health care workers if they have had a significant occupational exposure to blood or another high risk body fluid (amniotic fluid, CSF, human breast milk, pericardial fluid, peritoneal fluid, pleural fluid, saliva in association with dentistry, synovial fluid, unfixed human tissues and organs, any other body fluid if visibly bloodstained, exudative or other tissue fluid from burns or skin lesions, vaginal secretions).
• PEP should be commenced as soon as possible after the event, but it may still be worth considering starting PEP even if up to 2 weeks have elapsed since the exposure.
• PEP should normally be continued for 4 weeks. Regular medical follow-up during the period of PEP is necessary to monitor acceptability and possible toxicity of the drugs.
• At least 6 months should elapse after cessation of PEP before a negative antibody test is used to reassure the individual that infection has not occurred.
• Drugs used for PEP
  • Zidovudine is the only drug which has been properly studied and for which there is evidence of a reduction in risk of HIV transmission following occupational exposure.
  • No antiretroviral drug has been licensed for post-exposure prophylaxis.
  • The recommended drugs for PEP starter packs are now zidovudine 250mg or 300mg b.d., with lamivudine 150mg b.d., and nelfinavir 1250mg b.d. (or 750mg t.d.s).

• Promote life-long safer sex, barrier contraception, and reduction in the number of partners. Videos, followed by inter-active 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.