US guidelines updated: new section on metabolic complications (2025)
30 September 2025. Related: Early access, Guidelines.
Simon Collins, HIV i-Base
The latest update to the leading US DHHS HIV guidelines was published this month.
One of the main changes includes a new 46-page chapter on cardiovascular and metabolic complications.
This includes an introduction overview and the four sections below. However, other important metabolic complications such as insulin resistance, diabetes, metabolic syndrome, MASLD, heart and cardiac failure and bone disease are not currently covered, as management is not different in people living with HIV.
Immune activation and inflammation on ART
Although this section reviews the evidence that residual inflammation on ART increases the risk of cardiovascular disease and metabolic complications, specific choice of ART, use of anti-inflammatory treatment or routine monitoring of related biomarkers are not recommended, other than in a research setting.
Cardiovascular complications
This detailed section with over 100 references is focussed on reducing the risk of atherosclerotic cardiovascular disease (ASCVD) – which has higher rates in women – including choice of ART, lipid management, statin therapy, behavioural changes and optimal management of comorbidities.
Statin therapy
This 10-page section presents latest US recommendations on use of statin therapy for primary prevention, based on the REPRIEVE study, including for people only at low and intermediate risk.
Weight gain on ART
This important new section includes the alarming result that more than 1 in 8 people starting ART have >10% increase in body weight within the first year, irrespective of ART regimen or baseline BMI.
However, the guidelines recommend management based on monitoring, counselling and weight loss strategies similar to the general population. Weight gain is also complicated by lipohypertrophy as a separate side effect of ART and an obesity epidemic in the general population in many countries.
Even though excessive weight gain has serious clinical consequences and often significantly impacts quality of life, the guidelines do not recommend individualised decisions to use ART or selecting specific HIV regimens to avoid weight gain in people who are most seriously affected.
The section includes the impact of different ARVs, and pharmacotherapy options for weight loss.
GLP-1 and dual GLP-1/GIP receptor agonists are already becoming widely used in people living with HIV, despite very limited data. The guidelines’ recommendations match those for the general population, although information about optimal and alternative dosing, long-term use and stopping these drugs is unclear for everyone.
Sections with key updates
The following sections have important changes.
Laboratory testing for initial assessment and monitoring
This section is mainly updated to cover concerns with same-day ART, stressing that treatment can be started without needing to wait for results first. Vaccine history should include COVID-19. New references in this section include providing information about U=U when viral load is <200 copies/mL and including INSTI resistance testing if this is a concern, especially after using cabotegravir-LA for treatment or prevention, noting that mutations might develop many months after a final dose.
Viral load and CD4 monitoring
Although the guidelines include the option for reduced CD4 and viral load monitoring once on stable ART, low baseline CD4 count is still emphasised as being the most important predictor of mortality and as being essential for prescribing OI prophylaxis.
This is one of the major differences between current management in high- compared to low- and middle-income countries.
Initiating ART
The updates to this section include new discussions about rapid ART, starting treatment during acute/primary infection and starting treatment during advanced hospitalised HIV.
ART is still recommended for elite controllers despite limited data to show this might reduce chronic inflammation in this populatioon. Closer monitoring is recommended in anyone deferring ART, for any reasons.
Suboptimal CD4 recovery despite viral suppression
The updated section on poor CD4 recovery has been largely rewritten and draws on 44 new references (out of 74) that produce a detailed review of this unexplained suboptimal response in a small percentage of people living with HIV.
Cost considerations
This section comments on the complexity of healthcare coverage in the US, especially in the ten US States that have not expanded Medicaid in line with the Affordable Care Act.
It also discusses drug pricing, changes and lapses in health insurance, difficulties when moving State, treatment interruptions for people involved in the criminal justice system, cost considerations with Medicare, injectable and generic ART.
comment
These guidelines are an essential reference on the latest developments in ART. At a time when funding has become less secure, this latest revision is welcomed, especially the expanded section on weight gain and ART.
The guideline panel meets monthly to review any new data and publishes any interim guidance online until it can be reviewed by the full committee. Each update always highlights changes in yellow in the PDF version so these are easy to see – a practice that should be routine in all guidelines, although this isn’t a feature in online pages. The guidelines (both PDF and online versions) also really helpfully include hyperlinks for all references.
Although 4-5 community representatives are included in the panel of roughly 50 voting panel members, it is not clear whey there are no community members on the writing panel. This year however, Richard Jefferys from TAG is credited as a community consultant for the section on suboptimal CD4 recovery.
A two-week period for public comment is also included in the review process. Feedback on the latest revisions should be emailed to HIVinfo@NIH.gov by 9 October using the subject line “Adult and Adolescent Antiretroviral Guidelines”.
Reference
US DHHS. Updates to the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. (26 September 2025).
https://www.hiv.gov/blog/updates-to-the-guidelines-for-the-use-of-antiretroviral-agents-in-adults-and-adolescents-with-hiv (webpage)
https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/guidelines-adult-adolescent-arv.pdf (PDF)