US HIV treatment guidelines updated (June 2021)

Simon Collins, HIV i-Base

On 3 June 2021, the main US HIV treatment were updated.

The main changes to this 450-page document, many already integrated into clinical practice, are summarised below.

  • The guidelines strongly recommend routinely starting ART soon after diagnosis. They include a new discussion on same-day ART and on the importance of removing structural barriers that might limit this.
  • Dolutegravir can now be routinely used by women during pregnancy. This is because longer follow-up failed to confirm any significant risks of neural tube defects (NTD).
  • Raltegravir is no longer recommended as preferred choice for starting ART. This is based on having a higher pill count and lower protection against drug resistance, compared to other first-line options. It is now only recommended as an alternative in certain situations.
  • Changing treatment for viral failure can now be to a combination with two fully active drugs, so long as one of these has a high barrier to drug resistance (ie dolutegravir or boosted darunavir. The previous guidelines recommended “at least two, and preferably three, fully active drugs”.
  • The dual combination of long-acting cabotegravir/rilpivirine injections is recommended as a switch option for people on stable ART. It is not recommended for first-line ART. Practical issues related to are discussed, including dosing recommendation and continued use where adherence is suboptimal.
  • The dual combination of dolutegravir plus rilpivirine is also recommended as a switch option for people with undetectable viral load.
  • Fostemsavir has been added as a recommended treatment for multidrug HIV resistance.
  • People with extensive drug resistance and who still have detectable viral load are also recommended to consider pipeline drugs that are currently only available in research studies. These investigational compounds include islatravir and lenacapavir (and, more surprisingly, leronlimab).
  • The discussion on CD4 non-responders and role of ART to reduce inflammation is expanded to include recent research, even though there are no new options for clinical treatment.
  • The section on ART for adolescents and young adults has a major revision with a focus on transition to adult services and complications due to low adherence.
  • The section on women and ART includes significant additions on weight gain, drug interactions with hormone treatment and considerations related to the menopause.
  • Considerations about choice of ART when isoniazid and rifapentine is prescribed for three months to treat latent TB.
  • The guidelines retain and update the section on drug pricing and cost effectiveness of treatment.
  • Tables on drug interactions and side effects have been updated to include latest treatments.


As always, this update is an important summary of the most significant research.

Although many changes are already established practice, updates are essential as a reference for minimum standard of care.

As with all treatment information, guidelines are dependent on being routinely updated.


US Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. (3 June 2021). (html web pages) (PDF)

Links to other websites are current at date of posting but not maintained.