1st August 2023

HIV Infection

Background

Human immunodeficiency virus (HIV) was first identified in the 1980s. Despite the remarkable progress in treatment and prevention strategies, it remains endemic in many places worldwide, including Eastern Europe, Asia and Sub-Saharan Africa. It is a major cause of morbidity and mortality worldwide and a key global public health concern. The prognosis of HIV has hugely improved since the virus was first identified, and it is now a manageable chronic disease. This is primarily due to the advent of antiretroviral therapy (ART).

Pathophysiology and virology

HIV is a retrovirus. Retroviruses infiltrate the cells of host organisms and use the enzyme reverse transcriptase to transcribe their viral RNA into DNA, which is then incorporated into the host cell genome. Once the virus has ‘taken over’ the host cell, it replicates, creating more HIV-infected cells that proliferate throughout the host organism.

HIV infects CD4 receptor-positive white blood cells. These are T-helper cells which communicate with antigen-presenting cells and are a key part of the cell-mediated immune response. Infection of these cells with HIV, therefore, weakens the immune system.

The amount of HIV-infected cells in the blood is measured as ‘viral load’ – the higher the viral load, the fewer healthy CD4 cells, and the greater burden of disease.

There are two types of HIV – HIV-1 and HIV-2. HIV-1 is the most common, with HIV-2 mainly confined to West Africa. HIV-1 is divided into four distinct strains – group M is by far the most common, with N, O and P much rarer.

Epidemiology

As of 2022, WHO estimates that 37.7 million people are infected with HIV worldwide, with Sub-Saharan Africa most affected.

Advances in treatment mean that survival rates of HIV are increasing, meaning that in countries such as the UK, where treatment is widely available, prevalence has increased whilst mortality decreases – people are living longer with the disease. Undiagnosed HIV (approximately one-quarter of UK cases) is the commonest cause of mortality.

Certain behaviours and conditions increase the risk of contracting HIV, which are as follows:

• Unprotected anal or vaginal sex
• Co-morbid sexually transmitted infections
• The use and sharing of contaminated needles and syringes for injecting intravenous drugs
• Needle stick injuries

HIV is transmitted via bodily fluids, such as blood, breast milk, semen, and vaginal secretions. HIV can also be transmitted vertically (from mother to child, during pregnancy or childbirth). The most common routes of spread are via sexual intercourse and through blood.

When first identified, HIV was thought of as a disease which affected the male homosexual population. In the UK, gay or bisexual men, Black Africans, and people born abroad are the three groups most at risk of HIV. However, heterosexual transmission is the most common cause of infection worldwide.

Prevention

Prevention is a key strategy for managing the rate of HIV infections. Risk factor reduction includes sexual health awareness and the provision of condoms to reduce infection risk, testing and counselling for those diagnosed with risk conditions such as STIs and tuberculosis, needle exchange programmes, and the use of antiretroviral drugs as post-exposure prophylaxis (PEP) for those potentially exposed to HIV.

PEP is offered to people who may have been exposed through sexual contact, needle sharing, or through occupational exposure – and has an evidence basis for reducing the risk of infection if started within 72 hours of potential exposure. Treatment consists of a four week course of dual therapy with the antiretrovirals tenofovir/emtricitabine and raltegravir.

Diagnosis

HIV infection can be symptomatic or asymptomatic and may be detected through screening or following investigation of suspicious clinical features.

Clinical features

Primary HIV infection (or seroconversion illness) refers to the non-specific flu-like illness that may present in the first six months following infection. It generally manifests within the first six weeks when the immune system reacts to the virus and produces antibodies. The common features are fever, sore throat, malaise, lethargy, arthralgia, myalgia, and a maculopapular rash.

Long-term HIV infection may cause constitutional features such as fever, weight loss, night sweats and lymphadenopathy.

HIV may also manifest with the features of associated illnesses as the initial presentations (see Complications section below).

NICE recommends that HIV be suspected in patients presenting with prolonged or recurrent infections, any conditions recognised as complications, unexplained weight loss, unexplained lymphadenopathy, or pyrexia of unknown origin.

Testing

The first line HIV test in the UK is a dual test for the HIV antibody and p24 antigen (HIV viral material). Point-of-care antibody tests can give results within minutes, but should always be followed up by confirmatory serological testing.

There is a roughly six week latency period between the initial infection and the time at which the serological test becomes positive. Therefore, if an individual has been exposed and initially tests negative, repeat tests at this time interval may be indicated. Currently, the window period in which HIV tests may be negative despite the individual being infected is 45 days – therefore, negative tests before this interval may be inaccurate.

All individuals with symptoms suspicious of HIV infection should be tested, and screening tests also offered opportunistically to at-risk individuals, such as men who have sex with men (MSM), female sexual contacts of MSM, sex workers, intravenous drug users, prisoners, people from countries with a high prevalence of HIV, and people reporting sexual contact with individuals from a country with a high prevalence of HIV.

Specific verbal consent must be given for an HIV test, and a patient cannot be tested without their consent. Permission to disclose positive test results to other healthcare professionals – such as a patient’s GP – must also be specifically sought and can be refused.

Management

Antiretroviral therapy

The first line treatment for established HIV infection is antiretroviral therapy (ART). ART directly targets the underlying pathophysiology by limiting viral replication and has drastically changed the management of HIV. The goal of treatment is to reduce viral load to undetectable levels.

There are five classes of ART drugs, which are categorised by their mechanism. Examples are listed in the table below, along with common side effects, and the most frequently used drugs highlighted in bold.

Due to the tendency of the HIV virus to mutate, drug resistance is high, so ART is typically given as combination therapy of three or more drugs to reduce resistance. Typically, regimens consist of two nucleoside reverse transcriptase inhibitors (NRTI), with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Integrase inhibitors (II) and entry inhibitors (EI) are newer drugs with less long-term evidence available in regard to side effects. They are more expensive than the first line treatments, so they are generally reserved for resistant infections.

Current guidance states that ART should be started as soon as the infection is confirmed, as early treatment is a key positive prognostic factor.

Table 1: Classes and side effects of antiretroviral therapy (ART)

Monitoring

Disease monitoring consists of CD4 count and HIV viral load. The two are linked – a falling CD4 count is associated with a rising HIV viral load and is indicative of disease progression. A falling CD4 count may also suggest a lack of treatment adherence.

Monitoring blood tests for patients on ART include FBC, U&Es, LFTs, lipid profiles and glucose levels to assess for toxicity. Regular reviews of therapeutic compliance and monitoring for the development of any complications is also indicated, with specialist services available to facilitate this.

Patients with CD4 counts below 200 are most at risk of opportunistic infections (see AIDS and Other Complications).

Patient education and support

HIV is a chronic illness that has the potential to cause significant morbidity and a variety of complications, and remains associated with social stigma. As such, education and support are crucial aspects of management. Specialist services exist nationwide, through which patients can access specialist medical care, but also support groups and other forms of psychosocial input to help them live with their disease.

It is crucial that patients with HIV are educated on the risk of infections and fully immunised. Patients with HIV should also not receive live attenuated vaccines. Information on sexual health, and in particular, barrier methods of contraception to reduce transmission risk, is key.

HIV and Pregnancy

ART is the first line treatment for pregnant women with HIV, and the risk of vertical transmission correlates directly with viral load, which means ART is the single most important intervention for reducing the risk of vertical transmission. If a woman is on effective ART, then vaginal delivery is preferred to a C-section.

In the UK, breastfeeding is not recommended due to the risk of transmission. However, breastfeeding is preferred in the developing world due to the other benefits it provides.

Babies born to HIV-positive mothers should receive four weeks of treatment with zidovudine (AZT) postpartum.