Guidelines on HIV treatment
HIV treatment recommendations
The advent of antiretroviral treatment (ART) in the mid-1990s revolutionised the management and prognosis of HIV1.
The goal of HIV treatment is to suppress viral load to undetectable levels, preserve or improve immune function and, consequently, reduce the risk of opportunistic infections and cancers commonly associated with HIV while simultaneously preventing viral transmission2,3.
ART is recommended for all people living with HIV, regardless of CD4 count. Genotypic resistance testing should not delay treatment initiation3-5. The aim of treatment is to reduce associated morbidity and mortality and improve quality of life, ideally achieving an undetectable viral load, which prevents sexual transmission of the virus3-5.
The latest European AIDS Clinical Society (EACS) guidelines define virological response to treatment as follows6:
- Virological suppression: HIV viral load (HIV-RNA) below 50 copies/mL for at least 6 months3
- Virological failure:
- Incomplete suppression: Generally, HIV-RNA above 50 copies/mL at 6 months after commencing an initial course of ART, although the guidelines note suppression may be delayed in people with very high baseline levels (>100,000 copies/mL)3
- Virological rebound: HIV-RNA above 50 copies/mL in a person with previously undetectable HIV-RNA3
The US guidelines, from the Department of Health and Human Services (DHHS), are similar but use an HIV-RNA threshold of 200 copies/mL for incomplete response and rebound4. They also include a separate category for virological failure, defined as the inability to either achieve or maintain HIV-RNA below 200 copies/mL.
The US guidelines contain two additional definitions:
- Virological blip: An isolated detectable HIV-RNA level in a person with otherwise suppressed HIV-RNA4
- Low-level viraemia: Detectable HIV-RNA level below 200 copies/mL4
There are many key areas for clinicians to consider when talking to people with HIV prior to initiation of therapy (Figure 1).
Figure 1. What to review prior to initiation of antiretroviral therapy4-6.
International guidelines recommend that ART is initiated as soon as possible after HIV diagnosis and genotypic resistance testing should not delay treatment initiation4-6.
The eight different classes of HIV treatments are4:
- nucleoside reverse transcriptase inhibitors (NRTIs)
- protease inhibitors (PIs)
- non-nucleoside reverse transcriptase inhibitors (NNRTIs)
- fusion inhibitors
- CCR5 coreceptor antagonists (entry inhibitors)
- integrase strand transfer inhibitors (INSTIs)
- entry inhibitors (gp120 attachment inhibitor and CD4 post-attachment inhibitor)
- capsid inhibitors (lenacapavir – approved in the USA and Europe in 2022)
The key considerations when choosing an ART regimen should be4:
- virologic efficacy
- toxicity
- pill burden
- dosing frequency
- drug–drug interactions
- comorbidities
- access
- cost
- drug resistance
Potential first-line ART regimens for a treatment-naive patient generally consist of two NRTIs in combination with an INSTI, NNRTI or boosted PI4-6.
NRTIs currently recommended in guidelines are4-6:
- lamivudine
- abacavir
- emtricitabine
- tenofovir
Recommended INSTIs are4-6:
- bictegravir
- dolutegravir
- elvitegravir
- raltegravir
- cabotegravir
Recommended NNRTIs are4-6:
- doravirine
- efavirenz
- rilpivirine
Recommended PIs are4-6:
- atazanavir
- darunavir
For many PIs, adequate plasma levels cannot be achieved without coadministration of a booster (P450 CYP3A inhibitor)7.
For people who have achieved viral suppression with a daily oral regimen, a long-acting injectable regimen (cabotegravir plus rilpivirine) is approved for injection every 2 months in Europe and monthly or bimonthly in the USA6,8. Lenacapavir, a twice-yearly subcutaneous injection for multi-drug resistant HIV, has also been approved9.
The NRTI abacavir is contraindicated in people who are HLA-B*5701-positive. Even if HLA-B*5701-negative, counselling on the risk of hypersensitivity reaction (HSR) is critical4,6. Abacavir should be used with caution or avoided in persons with a high CVD risk4,6.
There is a need to screen for potential barriers to ART adherence, including depression, stigma, cultural or social reasons, cognitive impairment, harmful alcohol use or recreational drug use, and discuss these with patients4,5
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Developed by EPG Health, for Medthority. This content has been developed in collaboration with the sponsor ViiV Healthcare and has been independently reviewed by an HIV specialist physician. EPG Health received funding from the sponsor to help provide its healthcare professional members with access to the highest quality medical and scientific information, education and associated relevant content.
Job code: NP-GBL-2DR-WCNT-230001
Date of preparation: November 2024