In September, the Department of Health and Human Services updated its Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Several revisions were made and new sections were added related to HIV treatment, associated comorbidities and considerations for specific populations.

Antiretroviral Therapy

One key change to the guidelines relates to starting antiretroviral therapy. Recommended first-line regimens have demonstrated clinical efficacy and a high barrier to resistance, are well tolerated and can be given once daily.

  • Dolutegravir/abacavir/lamivudine (the drugs in the Triumeq coformulation) has been moved from the list of “recommended initial regimens for most people with HIV” to “other initial antiretroviral regimens for certain clinical scenarios.” The change was made because abacavir requires HLA-B*5701 hypersensitivity testing and has been linked to increased cardiovascular risk.
  • Regimens containing boosted elvitegravir, raltegravir or boosted atazanavir and the rilpivirine/tenofovir disoproxil fumarate/emtricitabine combination (the drugs in Complera)—are no longer recommended for initial treatment due to a higher pill burden, more side effects or a lower barrier to resistance compared with other recommended antiretrovirals.

Two changes address man agement of virological failure, meaning a regimen never suppresses HIV or no longer does so.

  • For people who experience virological failure on their first regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs), a salvage regimen of dolutegravir plus boosted darunavir (Prezista or Prezcobix) may be used.
  • For people who are unable to achieve or maintain viral suppression on a daily oral regimen, Cabenuva (long-acting cabotegravir and rilpivirine injections) may be a feasible option. The Food and Drug Administration has approved Cabenuva only for people switching from another regimen with an undetectable viral load, but pilot studies and clinical experience have shown that it can also work well for some people without viral suppression. The guidelines panel says providers can consider Cabenuva on a case-by-case basis for select individuals with persistent virological failure on oral antiretrovirals despite intensive adherence support who have no evidence of resistance to cabotegravir or rilpivirine, with shared decision-making between providers and people with HIV. They caution, however, that resistance to NNRTIs and integrase inhibitors may develop if virological failure occurs on Cabenuva, which could limit future treatment options and lead to HIV transmission.

In addition, the guidelines offer recommendations for optimizing treatment for people with viral suppression, including an expanded discussion of clinical trial data on switch strategies for those with drug resistance or challenges with adherence.

Comorbidities

The guidelines include several updated recommendations for people with HIV and hepatitis B virus (HBV) coinfection.

  • As more people switch to antiretroviral regimens that don’t include NRTIs or only include lamivudine, it’s important to keep drugs that are dually active against both HIV and HBV, such as tenofovir disoproxil fumarate or tenofovir alafenamide, or to add drugs specifically for hepatitis B, such as entecavir (Baraclude).
  • The panel recommends HBV screening before starting NRTI-sparing or NRTI-limited regimens for people whose hepatitis B status is unknown and urges HBV vaccination for those who test negative.
  • The guidelines no longer recommend treatment with pegylated interferon, except for rare cases in consultation with a hepatitis B expert.
  • The panel notes that around 4% of people with HBV/HIV coinfection also have hepatitis D virus (HDV)—which can lead to more serious liver complications—and recommends HDV screening.

The guidelines also feature updated recommendations for people with HIV and tuberculosis (TB), including a dolutegravir dose adjustment for those taking isoniazid plus rifapentine to treat latent TB and a recommendation against the use of rifamycin drugs with long-acting injectable cabotegravir, rilpivirine or lenacapavir (Sunlenca). 

Special Populations

The section on “HIV and the Older Person” includes a new subsection on HIV and immunologic aging, an expanded discussion of non-AIDS complications among older people living with HIV and a recommendation for using statins to reduce the risk of cardiovascular disease based on results from the REPRIEVE trial.

The section on transgender people with HIV features an update on the epidemiology of HIV in this population, based on recent data from national surveys and surveillance reports. It also includes an update on interactions between antiretrovirals and gender-affirming hormone therapy, a discussion of cardiovascular risk for HIV-positive trans people using hormone therapy and an expanded discussion of barriers transgender adults and adolescents may face in accessing care and maintaining HIV suppression.

The section on people with substance use disorders includes a new subsection on unstable housing and its impact on HIV care and adherence to antiretroviral treatment and an expanded discussion of Cabenuva for people with substance use issues. It also adds information on xylazine—an adulterant that may be added to opioids such as fentanyl—which can interact with CYP3A4 inhibitors such as ritonavir or cobicistat and further increase the risk of overdose.

A new section has been added to provide guidance on management of antiretroviral therapy for people with HIV who are candidates for or recipients of solid organ or stem cell transplants. The panel emphasizes the importance of maintaining viral suppression before and after a transplant. The addition of immunosuppressive therapy to prevent organ rejection and prophylaxis against opportunistic infections increases pill burden and the potential for drug interactions and adverse effects. Because of these complexities, the panel recommends that HIV-position people who require a transplant should be managed by a multidisciplinary team before, during and after the procedure.

Other Updates

Turning to adherence, the guidelines panel emphasizes that addressing social determinants of health is essential for enhancing adherence throughout the HIV continuum of care. A new section has been added on the importance of guiding people with HIV through transitions between different health care systems to ensure continuity of care.

The guidelines also feature updated data on interactions between antiretrovirals and new medications that were approved over the past three years. The panel has removed sections on antiretroviral drugs that are not recommended. Finally, the latest version has minor updates to several sections, including drug-resistance testing, acute and recent HIV infection, women with HIV and cost considerations.

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