- 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.
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- 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.
- There are four main groups:
- New classes and new combinations are being developed all the time. Sequencing the drugs so that the one with the least cross-resistance is used first, seems to be the most effective approach.
- There is a growing body of evidence to suggest that ART may obviate the need to remain on lifelong chemoprophylaxis, providing the CD count remains high. It is , however, still necessary for patients who do not sustain immune recovery.
- ART should be differentiated from post-exposure prophylaxis (PEP). In this, a 28-day regime of drugs is given to prevent infection in non-HIV individuals after suspected exposure - eg healthcare workers who have been in a situation in which exposure is possible. It should be given as soon as possible, and certainly within 72 hours. See separate article HIV Post-exposure Prophylaxis for more details.
Expansion of ART into the community is important in resource-poor areas where physicians and clinical services are few. Prevention of transmission from mother to child is of particular significance.
See separate Human Immunodeficiency Virus (HIV) article and 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.
Further reading & references
- Mayer KH, Krakower D; Antiretroviral Medication and HIV Prevention: New Steps Forward and New Ann Intern Med. 2012 Jan 16.
- Celum CL; HIV preexposure prophylaxis: new data and potential use. Top Antivir Med. 2011 Dec;19(5):181-5.
- 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
- Treatment of opportunistic infection in HIV-seropositive individuals, British HIV Association (2011)
- 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.
- Martinez-Cajas JL, Wainberg MA; Antiretroviral therapy : optimal sequencing of therapy to avoid resistance. Drugs. 2008;68(1):43-72.
- Mermin J, Were W, Ekwaru JP, et al; Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study. Lancet. 2008 Mar 1;371(9614):752-9.
- Ndirangu J, Newell ML, Tanser F, et al; Decline in early life mortality in a high HIV prevalence rural area of South AIDS. 2010 Jan 11.
- 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)
- Seasonal flu vaccine, Terence Higgins Trust, 2011
|Original Author: Dr Laurence Knott||Current Version: Dr Laurence Knott||Peer Reviewer: Dr John Cox|
|Last Checked: 14/03/2012||Document ID: 300 Version: 4||© EMIS|
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