eHIVe Module

Introduction to HIV













Authors: Sharon Byrne and Lucy Hedley                                                 Approved by: HIVPA Expert Panel

Date: June 2019

HIVPA Training Module



For the reader to be able to further develop practical and clinical skills and competencies in the HIV specialty.

Recommended reading

  1. Clinical Pharmacist, Jul-Aug pg 149-153 10/7/14

  2. BNF – HIV / Infection, chapter 5

  3. BHIVA Treatment Guidelines 2015 (2016 interim update)

  4. BHIVA and British Infection Association Opportunistic Infection Guidelines 2011 

  5. HIV Infection 2005 – Hoffman, Rockstroh, Kamps

  6. BHIVA Standards of Care for people living with HIV 2018

  7. European Aids Clinical Society Treatment Guidelines 2018

Useful websites

  1. is the official website of the HIV Pharmacy Association (HIVPA) which has pharmacy focused information such as eHIVe, the online training modules (including this one) and recorded study days (go to eHIVe recorded study days). There are also specially written PILs which can be printed off for use in clinic. There are details of the HIVPA study days and conferences and links to related events and websites.

  2. This is the website for the British HIV association which has all the BHIVA guidelines and consultations plus dates for conferences.

  3. An essential resource for checking drug interactions with other medicines, herbs and recreational drugs.

  4. Another good website for drug interactions

  5. This is the central organisation for global management of HIV and has the latest epidemiology and data on the global picture of HIV

  6. It is written by people living with HIV (PLWHIV) for both other PLWHIV and healthcare professionals. This is useful for a general overview and basic information on the disease and treatments. Their patient leaflets are a very useful resource to use in clinic.


1- HIV – Human immunodeficiency virus

2-.AIDS – Acquired immunodeficiency syndrome.

3- Opportunistic Infection – Infections caused by pathogens which do not typically infect a patient with a healthy immune system

4- Primary prophylaxis – Primary prophylaxis are the measures used to prevent a disease occurring in a patient who has not previously been infected with the causative organism

5- Secondary prophylaxis – Prophylaxis to prevent an infection coming back after treatment is completed

6- Viral Load (VL) –The quantity of the virus present in the blood and is measured as the number of viral RNA copies per ml. Usually a plasma sample is used but it is also possible to measure the viral load in other body compartments such as CSF. A high viral load is defined as greater than 100,000 copies/ml.

Definitions cont/..

7- CD4 count – Is the number of CD4 cells, (otherwise known as helper T lymphocyte cells) per mm3 of blood. The range for a normal immune system is between 500 – 1200 cells/mm3, with <200cells/mm3 representing immune suppression. It is also expressed as a percentage of all white blood cells (CD4%) with a range of 20-40%.

8- ARVs – Antiretrovirals. Anti-viral medication that targets and halts the HIV cell entry and replication process.

9- ART – Antiretroviral therapy is a combination of drug classes used together to target different pathways of HIV cell entry and replication with a reduced risk of resistance.

10- Adherence – The degree to which the patient takes their medicines in accordance with the medical advice given. High levels of adherence are essential in the treatment of HIV as low levels of ARVs in the blood can lead to viral mutation and resistance.

11- Resistance – Resistance to ARV drugs occurs as a result of mutations within viral RNA. These mutations may confer resistance to individual drugs or entire drug classes meaning the drugs will not work against the virus.

Introduction to HIV

On June 5, 1981, a short article appeared in a medical journal that described an unusual situation – five young men in Los Angeles were all suffering from pneumocystis pneumonia and other diseases found in people who have severely suppressed immune systems. All five were men who have sex with men. The article was the first published report1 in the world on the condition later named acquired immune deficiency syndrome, or AIDS, although initially it was termed GRID (Gay related immune deficiency). Its lead author was Dr.Gottlieb and his later New England Journal paper 2 included the first description of the CD-4 T cell deficiency which is the immunologic hallmark of HIV infection.

The HIV Virus

HIV was first isolated in Paris in 1983 and belongs to the family of lentiviruses. It is a retrovirus which means its genetic information is encoded in RNA. It is composed of 2 single strands of RNA. The retrovirus genome needs to be reverse –transcribed into DNA by the viral reverse transcriptase enzyme before it can replicate. The enzymes needed for replication are contained within the capsid of the virus.

Diagram taken from the National Institute of Allergy and Infectious Disease

HIV Lifecycle

The diagram below describes step by step how the virus enters the host cell and through multiple stages uses it to replicate itself and the subsequent release of more viruses back out into the blood stream. HIV can infect numerous cells but its main target cells are lymphocytes that express the protein CD4, known as CD4 cells. Once infected the CD4 cell then dies by apoptosis, though the exact mechanism is unknown. There are theories that cell death is caused by the activation of DNA dependent protein kinase (a central integrator of DNA damage response) during viral integration.3

The virus replicates at a very rapid rate, which can be up to a billion new viruses a day. However, this is an error prone process and millions are not functional and do not survive, therefore the viral load does not match the replication rate.

The purpose of antiretroviral therapy (ART) is to stop viral replication, reducing the amount of HIV in the body below the limit of detection, usually <50copies/ml. It does not eradicate the virus from the body completely, as there are “hidden” viral residues in resting memory cells. If ART is taken correctly every day the HIV virus cannot replicate to cause further damage to the immune cells. In simplier words the ARVs have “put the virus to sleep”.

Click below:

Diagrammatic representation of the HIV replication cycle

Stages of HIV Infection

Just after infection there is a surge in viral replication and this is referred to as seroconversion. Some patients may experience a short flu-like illness that is mainly characterised by lymphadenopathy, fever, maculopapular rash and myalgia and can last a few weeks. A small minority of patients can experience a severe illness with potential CNS symptoms. However, many patients do not have any noticeable symptoms at the time of infection and will be unaware that they are carrying the virus.

Transmission risk is at its highest during this period of seroconversion as the concentration of HIV RNA is very high. At the onset of infection, the CD4 cell count can fall rapidly as initially the immune system is not ready for the viral assault, eventually it mounts a strong response and is able to bring the viral load down dramatically to less than 1% of the value at seroconversion. This then remains at a relatively steady level for several years and is referred to as a patient’s viral set point or CD4 nadir. The CD4 count will then decline from a normal value (range 500-1200 cells/ mm3) at different rates for each patient. The destruction of CD4 cells impairs cell mediated immunity which increases the risk of opportunistic infections and some cancers There is a great variability between individuals with some losing CD4 cells rapidly and others retaining near normal values for many years.

Stages of HIV Infection

This stage of clinical latency may last anything from a few months to several years where a person has no outward signs of infection. Some patients experience persistent swollen lymph nodes but otherwise feel well. The immune system has regained some control and the viral load has dropped from its initial peak in primary infection and is replicating at a slower rate.

In most cases the immune system will become weakened as the CD4 count declines to such an extent that serious ‘AIDS-defining’ opportunistic infections (OIs) or malignancies can occur. Signs and symptoms suggestive of a declining immune function include lymphadenopathy, oral candidiasis, herpes zoster infection, diarrhoea, fatigue, fever and blood dyscrasias. In the UK an AIDS diagnosis is confirmed if a person with HIV develops one or more of a specific number of opportunistic infections or cancers. These can be organisms, pathogens or certain cancers which would otherwise not cause problems in someone with a healthy immune system but are able to take advantage of a weakened immune system. Normally AIDS defining illnesses occur when the CD4 count has dropped below 200 cells/ mm3. It is worth noting that someone can be very unwell with HIV but not have an AIDS-defining diagnosis. Conversely, someone with an AIDS-defining diagnosis (particularly if they are established on ART and the opportunistic infections are managed) can continue to lead a full and healthy life.

Opportunistic infections (OIs)

Below is a list of more than 20 OIs that are considered AIDS-defining conditions—the occurrence of one of the listed OIs will result in an AIDS diagnoses no matter what the CD4 count happens to be:

Opportunistic infections (OIs)

Opportunistic infections (OIs)

OIs can be relatively localised or disseminated and the risk of getting an OI is usually related to the CD4 count. Below are some examples of the OIs that occur at different CD4 counts. Once the CD4 count drops to a certain level the patient may contract any of the OIs that occur from that point onwards so a patient with a very low CD4 count may have multiple OIs at the same time which presents a challenging scenario from a drug interaction and monitoring perspective.

If the CD4 count is greater than 500 cells/mm3

In general, people with CD4 counts greater than 500 cells/mm3 are not at risk of opportunistic infections. The exception being tuberculosis which can occur in HIV positive patients with a CD4 cell count above 500 cells/mm3. For people with CD4 counts around 500, however, the daily fluctuations in CD4 cell levels can leave them vulnerable to minor infections, such as candidal vaginitis or yeast infections.

If the CD4 count is between 200 cells/mm3 and 500 cells/mm3

Some OIs can occur as the CD4 count drops towards 200cells/mm3 such as Candidiasis (Thrush) and Kaposi’s Sarcoma (KS).
Kaposi’s Sarcoma is caused by Human Herpes Virus-8. Before the introduction of antiretroviral therapy, as many as 1 in 5 patients with AIDS had Kaposi’s Sarcoma. It can cause lesions on the body and in the mouth with distinctive brown or purple colouring. In addition, this virus can affect internal organs and disseminate to other parts of the body without any external signs.

If the CD4 Count is between 100 cells/mm3 and 200 cells/mm3

Pneumocystis Jirovecii (Carinii) Pneumonia (PCP)
PCP is classified as a fungal infection and is the most common presenting OI in patients with HIV. Although a fungal infection, it is treatable with antibiotic therapy and close monitoring. Prophylaxis therapy with co-trimoxazole is recommended for patients with low CD4 counts i.e. less than 200 cells/mm3.

Histoplasmosis and Coccidioidomycosis
These are fungal infections that often present as severe, disseminated illnesses in patients with low CD4 counts. Histoplasmosis is an infection caused by the fungus Histoplasma. The fungus lives in the environment, particularly in soil that contains large amounts of bird or bat droppings.  People can get histoplasmosis after breathing in the microscopic fungal spores from the air, often after participating in activities that disturb the soil. Coccidioidomycosis, also called valley fever is an infection caused by the fungus Coccidioides. The fungus is known to live in the soil in the southwestern United States and parts of Mexico and Central and South America. They are both treated with antifungals and duration of treatment depends on the severity of the illness and the patient’s CD4 count.

Progressive Multifocal Leukoencephalopathy (PML) is a severe neurological condition that is caused by the JC (John Cunningham) virus and typically occurs in patients with CD4 counts below 200. While there is no definitive treatment for this disease, it has been shown to be responsive to antiretroviral therapy. In some cases, the disease resolves without any treatment.

If the CD4 count is between 50 cells/mm3 and 100 cells/mm3

Toxoplasmosis is caused by the parasite Toxoplasma gondii that can cause encephalitis and neurological disease. The parasite is carried by cats, birds, and other animals and is also found in soil contaminated by cat faeces and in meat, particularly pork. Toxoplasmosis is treatable with aggressive therapy, and prophylaxis is recommended for patients with low CD4 counts i.e. less than 200 cells/mm3. Co-trimoxazole used prophylactically for PCP will also cover for toxoplasmosis

Cryptosporidiosis is a diarrhoeal disease caused by the protozoa Cryptosporidium, and it can become chronic for people with low CD4 counts. Symptoms include abdominal cramps and severe chronic diarrhoea. Infection with this parasite can occur through: swallowing water that has been contaminated with faecal material (in swimming pools, lakes, or public water supplies); eating uncooked food (like oysters) that are infected; or by person-to-person transmission, including soiled nappies or exposure to faeces during sexual contact.

Cryptococcal Infection
Cryptococcal infection is caused by a fungus that typically enters the body through the lungs and can spread to the brain, causing cryptococcal meningitis. In some cases, it can also affect the skin, skeletal system, and urinary tract. This can be a very deadly infection if not caught and properly treated with antifungal medication. Although this infection is found primarily in the central nervous system, it can disseminate to other parts of the body, especially when a person has a CD4 count of less than 50 cells/mm3.

Cytomegalovirus (CMV)
CMV is an extremely common virus that is present in all parts of the world. It is estimated that a majority of the population have had CMV by the time they are 40 years-old. CMV can be transmitted by saliva, blood, semen and other bodily fluids. It can cause mild illnesses when first contracted and many people may never have symptoms. However, it does not leave the body when someone is infected. In patients with low CD4 counts it can cause infections in the gastrointestinal system and in the eye which if left untreated can lead to blindness.

If the CD4 count is less than 50 Cells/mm3

Mycobacterium Avium Complex (MAC)
MAC is a mycobacterium that can be found in soil, water, and many places in the environment. The bacteria can infect the lungs or the intestines, or in some cases, can become “disseminated”. If this occurs, it can be a life-threatening infection.

Some patients may develop cancers such as Kaposi’s sarcoma and non-Hodgkin’s lymphoma which are also classified as AIDS defining illnesses.

Opportunistic infections and their treatment are covered in more depth in the “British HIV Association and British Infection Association Guidelines for the Treatment of Opportunistic Infection in HIV-seropositive Individuals 2011” which is available on

There are also lectures on OIs from HIVPA study days which can be accessed on eHIVe.

With the current antiretrovirals, most patients, if diagnosed before their CD4 count drops below 350mm3 go on to have a normal life expectancy.

Please refer to the BHIVA and BIA guidelines for treatment of Opportunistic Infections for information on treatment and dosing schedules.

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