Human Immunodeficiency Virus (HIV) is a species of lentivirus that can infect humans and subsequently causes Acquired Immunodeficiency Syndrome (AIDS). At the end of 2018, 37.9 million people were living with HIV worldwide.

Infection

HIV is spread via the transmission of bodily fluids, such as blood or semen. Routes of transmission include:

• Sexual contact (particularly between homosexual men).
• Needle sharing in IV drug users.
• Mother to child during pregnancy or breastfeeding.
• (Historically) by transfusion using infected blood.

Replication

Once inside the human body, HIV targets T-cells via the CD4 receptor. Within the cell, HIV has a positive sense ssRNA genome that uses reverse transcriptase in order to copy itself into a DNA intermediate which is then integrated into the host genome using the viral protein, integrase. From here, the now integrated HIV DNA is transcribed in the same manner as host DNA, producing RNA copies of the HIV genome previously integrated which can leave the host cell and infect other cells.

Initial Presentation

Following exposure and infection by HIV, patients may experience a flu-like illness (fever, fatigue) 2 to 6 weeks later. This process is known as seroconversion and is the point at which HIV antibodies become detectable. Following these initial symptoms, patients may not have any further symptoms for years as the virus slowly damages and reduces their immune system.

Who to test?

While it is important to not stereotype certain patient groups, there are groups that are more likely to be exposed to possible HIV infection ⁽¹⁾:

• If they are male, engaging in unprotected sexual intercourse with another man.
• Having unprotected intercourse in, or with a person who had been exposed in a country where transmission of HIV through sexual intercourse between men and women is common.
• Sharing injecting equipment while using drugs.
• Having a significant occupational exposure to HIV infected material in any circumstances.
• Engaging in invasive medical, surgical, dental or midwifery procedures, either as a practitioner or patient, in parts of the world where infection control precautions may have been inadequate, or where the population prevalence of HIV infection is high.
• Engaging in unprotected sexual intercourse with someone who may have been exposed to HIV through any of the above categories.
• People accessing healthcare in areas with high (>2/1,000; if undergoing venepuncture) and extremely high (>5/1,000; all attendees) HIV seroprevalence.

Where a patient belongs to a high-risk group and presents feeling generally unwell, particularly with flu-like symptoms, HIV infection should be considered and a focussed history should be taken to stratify their risk, for example, they may be able to pinpoint a specific event (such as unprotected sexual intercourse) within the last few weeks.

Where there is clinical suspicion, HIV should be tested for with the patient’s consent. At this time, it is good practice to explain that while HIV may not necessarily be suspected in this patient, it is something important to rule out. Patients may need to be counselled from this point with their prospective diagnosis. When investigating for HIV, especially if a recent sexual contact is the potential source of infection, a full STI screen should be carried out.

Presentation of known HIV patients

It is important when consulting with HIV positive patients that you always remain respectful and not show any prejudice towards them and their diagnosis. Most aspects of your clinical interactions with these patients will not be changed due to their infection however a few things will need to be considered:

• Any procedure involving needles that result in a needle stick injury will be more likely to result in the clinician being prescribed PEP.
• Where patients are immunocompromised, especially in the context of COVID-19, it may be necessary to wear further protective equipment to minimise the introduction of other infections.

Treatment of HIV patients should be started as with any other individual, however, it is important to be mindful as to their HIV medications which often are unfamiliar to juniors and have a long list of side effects. If you are unsure when prescribing for HIV positive patients on therapy, it is important to check the BNF, discuss with a GUM doctor/HIV specialist or consult websites such as hiv-druginteractions.org to help guide you.

Diagnosis and Infection Monitoring

There are a number of ways in which HIV can be tested for in patients and prior to any testing taking place, patients should be consented for testing and if already suspected of being exposed to HIV, be advised to take precautions such as the use of condoms until test results are received.

p24 and p24 antibodies:

p24 antigen is the earliest method to detect HIV infection and can be detected from around 2 weeks of suspected exposure, however, levels will begin to decrease as p24 antibodies are produced, with them being detectable from 3-4 weeks. p24 antigen can also be detected in CSF in the investigation of HIV-related dementia or encephalopathy.

Once a diagnosis has been made and a patient is found to be HIV positive, their infection progression can be monitored by observing their viral load and CD4 count.

Viral load:

Viral load detects the number of HIV particles (copies) within an ml of blood and is a marker of infectivity; below 20 copies per ml of blood, HIV is ‘undetectable’ and therefore untransmittable (commonly referred to as U=U).

CD4:

A patient’s CD4 count is a measure of their infection severity and can be a useful way to monitor progression. An uninfected individual’s CD4 count will range from 450-1500 cells/mm³ however it is important to remember that even HIV positive patients may have an in-range CD4 count, at which point a trend over time is more useful. In an untreated HIV positive patient, CD4 count may reduce by up to 80 cells per year but can be kept stable or increased with good HIV management.

At a CD4 count of <200 cells/mm³, a diagnosis of AIDS is made. It is worth noting that at any CD4 count, a number of conditions are classed as AIDS-defining and therefore a diagnosis of AIDS includes a range of infections and cancers. 

Once a patient has been diagnosed as being HIV positive, it is important that they are referred onto a GUM or HIV specialist for treatment and follow up.

Other investigations to consider:

In any patient suspected of having HIV, it is important to consider requesting the following investigations:

• Hepatitis serologies (Hepatitis A, B & C)
• Full STI screen
• Screen for latent opportunistic infections (TB, toxoplasma gondii, varicella-zoster, CMV)
• HPV testing and investigation of cervical/anal dysplasia if indicated

Management of HIV positive patients:

The goal of treatment in HIV therapy is to maintain a patient’s CD4 count whilst reducing the amount of detectable HIV within the blood.

Highly Active Anti-Retroviral Therapy (HAART) is a method of combination therapy used to treat HIV positive patients, typically by selecting at least 3 drugs from at least 2 of the following classes (commonly 2 NRTIs and an NNRTI, II or PI):

• Nucleoside reverse transcriptase inhibitors (NRTIs) e.g. tenofovir, zidovudine
• Non-Nucleoside reverse transcriptase inhibitors (NNRTIs) e.g. nevirapine, efavirenz
• Integrase inhibitors (IIs) e.g. raltegravir
• Protease inhibitors (PIs) e.g. saquinavir
• Fusion inhibitors (FIs) e.g. enfuvirtide, maraviroc

HIV patient will also need to be vaccinated against Hepatitis B, Haemophilus influenzae B, pneumococcal disease and influenza. Due to their immunosuppressed state, patients should not receive vaccination against TB (BCG), yellow fever, oral typhoid or live oral polio vaccines. HIV patients should also be followed up regularly with routine blood tests (FBCs, U&Es, LFTs to monitor for any complications from their medications or illness).

Exposure prophylaxis:

HIV can be treated prophylactically both pre- and post-exposure to HIV. Pre-exposure prophylaxis (PrEP) is given to individuals considered to be at a high risk for being infected with HIV to reduce infection risk should they be exposed. Post-exposure prophylaxis is given to individuals following an exposure, for example following a needle stick injury in a healthcare setting.

Counselling and Psychological management:

Patients may often feel that their diagnosis is a ‘death sentence’ whereas this is no longer the case. Due to the development of medications previously mentioned, there is no reason that an HIV positive patient with a well-controlled viral load and CD4 count cannot live a full life. Counselling and psychological management should also be considered in patients being diagnosed with HIV and it is important that they receive this regarding their diagnosis in either a formal setting, with their HIV consultant or a psychiatrist, or informally, with peer support amongst other patients. The Terence Higgins Trust is a UK charity that offers support and information to HIV patients and is an excellent first point of contact for anyone with questions.

HIV positive patients that are not healthcare workers do not need to tell their employer and cannot be discriminated against by employers under the Equality Act 2010.

Healthcare workers who are HIV +ve

Healthcare workers that perform Exposure Prone Procedures (EPPs) are required to tell their employer and will be allowed to continue to perform EPPs if:

Either:

• Be on effective combination Anti-Retroviral Therapy (cART) + Have a plasma viral load <200 copies/ml.
• Be an elite controller (an elite controller is defined as a person living with HIV who is not receiving antiretroviral therapy and who has maintained their viral load below the limits of assay detection for at least 12 months, based on at least three separate viral load measurements).

And meet the following requirements:

• Be subject to plasma viral load monitoring every three months.
• Be under joint supervision of a consultant occupational physician and their treating physician.
• Be registered with the UKAP Occupational Health Monitoring Register (UKAP-OHR).

Complications of HIV and opportunistic infections

As the number of CD4 T-cells reduce with infection progression, the complications of HIV become a greater issue for patients.

These can include several opportunistic infections (see below) as well as Kaposi Sarcoma, a type of malignancy caused by Human Herpes Virus 8 (HHV8). If you suspect that an HIV positive patient is experiencing a complication of their HIV then it is important to discuss their case with a GUM doctor/HIV specialist.

Opportunistic infections can occur at any point during HIV infection but are more likely to occur with particular organisms when CD4 counts are reduced beyond a certain level ^(2):

References

1. Public Health England. PHE gateway number: 2013439. The Management of HIV infected Healthcare Workers who perform exposure prone procedures: updated guidance, January 2014. London: PHE; 2014 [available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/333018/Management_of_HIV_infected_Healthcare_Workers_guidance_January_2014.pdf]
2. HIV-1 Associated Opportunistic Infections. Angel A. Justiz Vaillant; Roopa Naik.

Useful Links

1. https://www.nhs.uk/conditions/hiv-and-aids/
2. https://www.tht.org.uk/
3. https://www.hiv-druginteractions.org/

Written by Dr Callum Verran (FY2)
Editing by Aos Al-Hassani (Y3 Medical Student)