The Department of Health and Human Services has revised its Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, incorporating several significant updates regarding HIV treatment, associated comorbidities, and specific population considerations.
Antiretroviral Therapy
A major revision concerns the initiation of antiretroviral therapy (ART). The recommended first-line treatments have been shown to provide strong clinical efficacy, have a high barrier to resistance, and are generally well tolerated with once-daily dosing.
Notably, the combination of dolutegravir, abacavir, and lamivudine (known as Triumeq) has been reclassified from “recommended initial regimens for most people with HIV” to “other initial antiretroviral regimens for certain clinical scenarios.” This adjustment was made due to abacavir’s requirement for HLA-B*5701 hypersensitivity testing and its association with elevated cardiovascular risks. In addition, regimens that include boosted elvitegravir, raltegravir, or boosted atazanavir, as well as the combination of rilpivirine, tenofovir disoproxil fumarate, and emtricitabine (found in Complera), are no longer recommended for initial HIV treatment. This change is due to factors such as higher pill burden, increased side effects, or a lower resistance barrier compared to other available antiretrovirals.
Two updates pertain to the management of virological failure, defined as the inability of a regimen to suppress HIV or maintain suppression.
For individuals who experience virological failure on a regimen containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) along with two nucleoside reverse transcriptase inhibitors (NRTIs), a salvage regimen combining dolutegravir and boosted darunavir (Prezista or Prezcobix) may be utilized.
For those unable to maintain viral suppression on a daily oral regimen, Cabenuva (a long-acting injectable combination of cabotegravir and rilpivirine) offers an alternative. Though initially approved only for individuals switching from a regimen with an undetectable viral load, clinical experience has shown it can be effective in certain cases of persistent virological failure. The guidelines suggest that Cabenuva may be an option for individuals with no resistance to cabotegravir or rilpivirine, although careful decision-making is needed due to potential future resistance risks and the possibility of HIV transmission if virological failure occurs.
Additionally, the guidelines provide recommendations on optimizing ART for individuals who have achieved viral suppression, with expanded discussions on treatment strategies for patients facing drug resistance or adherence difficulties.
Comorbidities
The revised guidelines include several updates for people co-infected with HIV and hepatitis B virus (HBV).
As more individuals switch to NRTI-sparing regimens or those containing only lamivudine, the importance of retaining agents that are active against both HIV and HBV, such as tenofovir disoproxil fumarate or tenofovir alafenamide, is emphasized. Alternatively, specific hepatitis B drugs, such as entecavir, may be added.
Screening for HBV before initiating NRTI-sparing regimens is advised for those with unknown hepatitis B status. For those who test negative, HBV vaccination is recommended. The use of pegylated interferon is no longer recommended, except in rare cases, following consultation with a hepatitis B specialist.
The panel also highlights that around 4% of individuals with HIV/HBV coinfection may also have hepatitis D virus (HDV), which can cause more severe liver complications. Screening for HDV is recommended as part of routine care.
Further updates pertain to people with HIV and tuberculosis (TB). These include adjusting the dosage of dolutegravir for patients taking isoniazid and rifapentine for latent TB treatment and advising against the use of rifamycin drugs with long-acting injectable cabotegravir, rilpivirine, or lenacapavir (Sunlenca).
Special Populations
The guidelines also address special populations, with several key updates.
For older individuals living with HIV, the section on immunologic aging has been expanded, along with recommendations for managing non-AIDS-related complications. Additionally, statin use is recommended to reduce cardiovascular risk, supported by findings from the REPRIEVE trial.
In the section on transgender individuals with HIV, there is an update on HIV epidemiology based on recent data, as well as an expanded discussion on the interaction between antiretroviral therapy and gender-affirming hormone treatments. The guidelines also discuss cardiovascular risks for transgender individuals on hormone therapy and highlight barriers that transgender adults and adolescents may face in accessing and maintaining HIV care.
For individuals with substance use disorders, a new subsection addresses the impact of unstable housing on HIV care and treatment adherence. Additionally, the guidelines provide updated information on using Cabenuva for people dealing with substance use. Notably, the document now includes information on xylazine, an adulterant often found in opioids like fentanyl, which can increase the risk of overdose when combined with CYP3A4 inhibitors like ritonavir or cobicistat.
A new section has also been added to guide the management of antiretroviral therapy for individuals with HIV who are candidates for or recipients of solid organ or stem cell transplants. The guidelines stress the importance of viral suppression before and after transplants, as well as the need for multidisciplinary management to navigate the added complexities of immunosuppressive therapy and prophylaxis for opportunistic infections.
Additional Updates
The guidelines emphasize the significance of addressing social determinants of health to improve adherence to ART across the HIV care continuum. A new section focuses on ensuring continuity of care as patients transition between healthcare systems.
Furthermore, the document has been updated to reflect the latest data on drug interactions between antiretrovirals and newly approved medications. Several sections, such as those on drug resistance testing, women with HIV, and cost considerations, have also undergone minor revisions.