18th June 2024

HIV

Background

Human immunodeficiency virus (HIV) affected an estimated 37.7 million worldwide in 2020, with 1.5 million people becoming newly infected, as per the UNAIDS statistics published in 2021. The UK AIDS Trust estimated that there were approximately 105,200 people living with HIV in the UK in 2019.

HIV is a single-stranded RNA retrovirus which is spread predominantly through penetrating sexual contact, blood exposure and perinatally. HIV’s main negative impact on health is through progressive destruction of patients’ CD4+ helper T cell population, resulting in serious illness from pathogens not otherwise anticipated in a healthy patient (opportunistic infections). Other features include enhanced susceptibility to various cancer types (most notably non-Hodgkin Lymphoma and Kaposi sarcoma), organ-specific complications associated with viraemia (i.e. thrombocytopenia and HIV-associated nephropathy) and chronic conditions exacerbated through increased atherosclerosis (i.e. cardiovascular and cerebrovascular disease).

Clinical features

Seroconversion illness

Following exposure to HIV, patients undergo a latency period before symptoms manifest or a diagnosis can be readily made through conventional testing. Symptoms usually appear 2-4 weeks following infection and can occur as late as three months after. The HIV seroconversion illness typically consists of fevers, sore throat, rash and lymphadenitis.

Natural History of HIV Infection

The stages of HIV infection have been defined by the CDC. Following the Seroconversion illness (Stage 1), a patient enters an asymptomatic phase (Stage 2), lasting for usually 5 or even 10 or more years, although some variants are associated with a more-rapid progression. Stage 3, previously (and no longer) referred to as the Acquired Immunodeficiency Syndrome (AIDS), occurs when the absolute CD4+ T cell count falls below 200 cells per mm³. Without treatment, this stage of HIV typically has a life expectancy of 2-3 years.

Diagnosis

HIV-specific antibodies do not appear until at 2-12 weeks following infection, with >90% of patients being antibody positive at four weeks. Modern 4th generation ELISA testing can detect the p24 antigen as well as HIV1/2 antibody, conferring greater sensitivity in the early phases of the infection. Positive antibody testing is confirmed via western blot (also called immunoblot). Other methods, such as salivary testing for HIV antibody, and point-of-care 4ᵗʰ generation tests are also in common use, with comparable sensitivity and specificity.

Opportunistic Infections

A normal CD4+ count typically ranges from between 500 to 1,500 cells per mm³. The majority of opportunistic infections occur at CD4+ counts of 200 cells per mm³ or fewer. The various opportunistic pathogens associated with HIV are often grouped into the range of CD4+ count at which they are most expected to cause disease

< 200 cells per mm³: Pneumocystis jirovecii, oesophageal candidiasis

<100 cells per mm³ Cryptococcus neoformans, Toxoplasma gondii, Cryptosporidium parvum

<50 cells per mm³ Mycobacterium avium complex, cytomegalovirus

HIV Treatment

Advances in antiretroviral therapy (ART) have transformed HIV into a manageable condition with an overall-normal life expectancy, provided the disease is promptly diagnosed and the treatment regimen is rigidly adhered to. Following the results of the INSIGHT START Trial in 2015, rather than waiting for the CD4+ count to fall to a certain threshold, ART is now recommended to commence as soon as possible. Typical regimens contains three drugs, usually two nucleoside reverse transcriptase inhibitors (NRTIs) (e.g. tenofovir disoproxyl fumarate, emtricitabine) plus a third agent belonging to one of the following categories:

• Non-nucleoside reverse transcriptase inhibitors (NNRTIs): commonly selected agents, earlier generations are associated with neuropsychiatric side effects. Examples include efavirenz and rilpivirine
• Protease inhibitors (PIs): agents with high barriers to resistance, however a common cause of drug-drug interactions and diarrhoea.  Examples include darunavir and lopinavir
• Integrase strand transfer inhibitors (ISTIs): very well-tolerated agents with a high barrier to resistance. They are becoming increasingly popular. Examples include dolutegravir and bictegravir

References

• UNAIDS. UNAIDS Data 2020. New York: UNAIDS; 2020.  Available from: https://www.unaids.org/sites/default/files/media_asset/2020_aids-data-book_en.pdf
• National AIDS Trust. UK HIV Statistics. London: National AIDS trust; 2022. Available from: https://www.nat.org.uk/about-hiv/hiv-statistics
• INSIGHT START Study Group, Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer G, Llibre JM, Molina JM, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795-807. doi: 10.1056/NEJMoa1506816. Epub 2015 Jul 20. PMID: 26192873; PMCID: PMC4569751
• Cohen J, Powderly W, Opal S. Infectious diseases. Amsterdam: Elsevier; 2017
• European AIDS Society. Guidelines version 11.0. October 2021