27th June 2023

Antiretroviral therapy

There are several objectives to antiretroviral therapy, including prevention of the mortality and morbidity from chronic HIV, and the prevention of people acquiring HIV infection, either in the form of pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP).

Antiretroviral medications

There are five classes of antiretroviral medications used in HIV, which act on different parts of the HIV life cycle:

• Entry inhibitors (EI) – maraviroc blocks the CCR5 receptor to reduce viral entry to cells.
• Integrase inhibitors (II) – raltegravir, elvitegravir and dolutegravir inhibit the integrase enzyme which prevents the viral DNA from being joined to the host DNA.
• Protease inhibitors (PI) such as atazanavir, darunavir, ritonavir, lopinavir and fosamprenavir block the protease enzyme needed to form mature virions.
• Nucleoside reverse transcriptase inhibitors (NRTI) such as tenofovir, lamivudine, emtricitabine, abacavir and zidovudine act by replacing a nucleoside causing termination of DNA production from RNA by viral reverse transcriptase.
• Non-nucleoside reverse transcriptase inhibitors (NNRTI) such as efavirenz, etravirine, nevirapine and rilpivirine also act to inhibit reverse transcriptase.

The current recommendations for ‘therapy naïve’ adults with newly diagnosed HIV involve:

• NRTI ‘backbone’ with tenofovir and emtricitabine.
• A third agent – atazanavir/darunavir, dolutegravir, elvitegravir, raltegravir or rilpivirine (elvitegravir and rilpivirine are recommended only in circumstances of poor renal function and raised viral load, respectively).
• An alternative to the NRTI ‘backbone’ is abacavir and lamivudine, which are recommended only if there is a sufficient viral load and in HLA-B57:01 negative individuals.
• Patients are recommended to be started on antiretroviral therapy as soon as they are diagnosed with HIV.

Pre-exposure prophylaxis

The most common PrEP regimen is tenofovir with emtricitabine. The following groups are currently recommended to have PrEP after consideration of risk assessment in conjunction with tertiary sexual health services:

• Men who have sex with men who are assessed to have high risk and have had recent ongoing condomless anal sex (i.e. within the previous six months).
• People who are having condomless sex with a partner who is HIV positive, unless the partner has been on ART for >6 months and has a viral load lower than 200 copies/mL.
• Others who on sexual history and medical history are assessed to have an increased risk of HIV otherwise.

PrEP is given with different dosing regimens can be considered in different patients:

• Daily dosing for insertive and receptive anal and vaginal sex
• On-demand dosing (4 or more tablets around sexual activity) for people involved in anal sex
• Intermittent dosing (4 or more tablets prior to and after sex) for people involved in anal sex

Post-exposure prophylaxis

PEP should be given to people who find themselves in the following circumstances:

• After receptive anal intercourse with a partner of unknown or positive HIV status unless undetectable viral load. (Considered following insertive anal intercourse under these circumstances).
• After receptive vaginal intercourse with a partner of unknown or positive HIV status unless undetectable viral load. (Considered following insertive vaginal intercourse under these circumstances).
• After a sharps or mucosal splash injury in the workplace with a person known to be HIV positive unless viral load is undetectable.

The first-line treatment for PEP is tenofovir disoproxil/emtricitabine and raltegravir. In pregnancy, raltegravir only is given twice daily in addition to tenofovir disoproxil and emtricitabine. The duration of PEP is generally 28 days.