IAS-USA 2024 guidelines for HIV treatment and prevention: some differences to EACS and UK

5 December 2024. Related: Guidelines.

Simon Collins, HIV i-Base

The latest update to the IAS-USA HIV consensus guidelines are based on 110 new studies and were published on 1 December 2024 in JAMA. [1]

We review this update in the context of other guidelines to highlight both positive changes, and differences compared to recent EACS and UK guidelines. [2, 3, 4, 5]

This shows how expert panels can sometimes reach different conclusions with access to the same body of evidence.

The IAS-USA guidelines are a concise 16 pages with four pages of references. Key recommendations or changes to this edition are boxed within each of the 10 sections.

Standard sections cover starting and switching ART, considerations about significant OIs and cancer, and routine monitoring. This year the section on metabolic complications includes weight gain and a new section has been on substance use disorders and HIV.

The guidelines include a four-page section on HIV and STI prevention, including PEP, PrEP and doxyPEP and finish with a short summary of what to expect in the near future.

The following points summarise the recommendations but please refer to the full online document for full details.

Summary and comments on the 2024 changes

Early treatment after diagnosis is recommended within seven days and includes same-day ART, unless there are clinical reasons to delay.
The three combinations for initial ART are B/F/TAF or DTG + TXF/XTC or DTG/3TC, with the dual therapy option not recommended with HBV coinfection or a viral load >500,000.
Notably, DTG/ABC/3TC is not included.
Alternative combinations are included in Table 2 based on specific factors.
Although DTG + TAF/FTC or TXF/XTC is recommended during pregnancy, BIC/F/TAF is an alternative and can be continued.
Switching therapy is discussed separately depending on whether or not this is in the context of viral failure, which is defined as being >200 copies/mL, when genotypic resistance testing is also recommended before changing ART. Management of persistent low level viraemia at 20-200 copies/mL is discussed but changing ART is not recommended.
Long-acting cabotegravir/rilpivirine is discussed in detail as one of the switch options that will help specific groups, with a caution that 1-2% of participants can experience viral failure despite good adherence, and that this risks resistance to both INSTI and NNRTIs.
Importantly, CAB/RPV-LA is also recommended as a switch option within a supported setting for people with detectable viral load linked to difficulties with adherence to daily oral ART. Monica Gandhi has produced the largest dataset supporting this off-label use, and is also chair of the guidelines panel. Injectable ART is included as appropriate in other sections of the guidelines.
Monitoring guidelines are largely unchanged, still recommending viral load testing 4 to 6 weeks after starting or switching ART, and then 3-monthly until suppressed, then 6-monthly. CD4 count is still recommended at diagnosis, start of ART and then 6-monthly until the count has been >250 cells/mm³ for a year, and then stopped.
Weight gain on ART is given a separate section and includes a box with eight general recommendations, three of which are on statins. Although this section includes the standard lifestyle advice it doesn’t go beyond these to comment in detail on more proactive management. The guidelines recognise that some ARVs can increase weight, but switching ART is still not recommended (other than stopping abacavir with CVD risk) even if the gain is excessive, and also not for management of diabetes or hypertension. Similarly, weight and BMI at baseline and every 6 months is only recommended for ART containing an INSTI or TAF, when this could routinely be included for everyone on ART, and could also include waist circumference and height.
GLP-1 agonists for weight loss are included, based on similar expected responses to those seen in non-HIV studies (HIV was an exclusion criteria in most if not all registrational studies). Cautions include loss of muscle mass, especially in older people, and that overall visceral and subcutaneous body fat could worsen facial lipoatrophy.
The management of cardiovascular disease, diabetes and hypertension is also discussed in detail and includes recommendations for broader statin use based on the REPRIEVE study. Diet, exercise and other lifestyle changes are recommended.
The guidelines include a new section on substance use and related disorders in people living with or at risk of HIV, also with a box of eight recommendations. This section is mainly concerned with opioids, fentanyl, and to some extent alcohol and tobacco. However, it is difficult to understand the lack of reference to drugs that are widely used for chemsex, including crystal meth, mephedrone and GHB/GBL, as these are also significantly associated with HIV incidence in the US and this would have been an ideal time to highlight the need for appropriate resources. This year the EACS guidelines added a new section on chemsex.
The final section of the guidelines continues to be on HIV and STI prevention, including PEP, PrEP and doxyPEP. This is perhaps the most problematic section in terms of both language and the way it differs to both EACS and UK guidelines. IAS-USA recommends everyone start oral PrEP with a double dose, whether using TD/FTC or TAF/FTC, but unlike BASHH they don’t recommend that the two oral formulations can effectively be dosed and used in the same way as each other. TAF/FTC is also still restricted to use by cisgender gay and bisexual men and transgender women. Although IAS-USA emphasises that HIV prevention should be non-judgemental, they still recommend condoms be used every time anyone has sex, even when using PrEP, and most significantly fail to recognise U=U as a way to reduce HIV transmission. It is also disappointing that many of the studies used to support the recent BASHH recommendations for PrEP don’t seem to have been considered by IAS-USA.
The sections on ageing and on mpox from the 2022 guidelines are no longer included in the 2024 update.

comment

Treatment guidelines establish evidence-based medical consensus for a minimum standard of care. Although primarily written for doctors they can also be used by people living with HIV if we are not receiving optimal care.

When guidelines panels disagree with each other, it would help if they addressed important differences directly.

For example, US guidelines took many years before recommending on-demand dosing for PrEP and the latest IAS-USA update still restricts this option to some people. The recent BASHH guidelines on PrEP are notable for using evidence from a wider set of studies in their recommendation to broaden access.

Although guidelines technically only offer advice, they are commonly used as a proscriptive framework, and so any differences are important to explain.

References

Gandhi RT et al. Antiretroviral drugs for treatment and prevention of HIV in adults: 2024 recommendations of the International Antiviral Society–USA Panel. JAMA. doi:10.1001/jama.2024.24543. (01 December 2024).
https://jamanetwork.com/journals/jama/fullarticle/2827545
EACS guidelines: New format and contents includes chemsex. HTB (26 November 2024).
https://i-base.info/htb/49481
EACS HIV Guidelines 2024, v12.1.
https://www.eacsociety.org/guidelines/eacs-guidelines/
Major update of UK PrEP guidelines online for public consultation. HTB (1 October 2024).
https://i-base.info/htb/48804
BASHH and BHIVA. BHIVA/BASHH guideline on the use of HIV pre-exposure prophylaxis – 2024: Draft out for consultation. (27 September 2024).
https://www.bashh.org/resources/126/bhivabashh_guideline_on_the_use_of_hiv_preexposure_prophylaxis_2024_draft_out_for_consultation (web page)
https://www.bashh.org/_userfiles/pages/files/draft_bashh_bhiva_prep_guidelines_240924_v30_final.pdf (PDF direct link)