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Individualizing ART at Initiation
The Art of Starting ART: Individualizing HIV Care From the Beginning

Released: August 30, 2023

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Key Takeaways
  • Several fixed-dose, single-tablet oral HIV regimens consisting of 2-3 drugs are recommended for people living with HIV who are treatment naive.
  • Several factors should be considered when individualizing ART at treatment initiation, such as baseline HIV-1 RNA, resistance mutations, pregnancy status, coinfections, comorbidities, drug‒drug interactions, and individual preferences.

The START study provides strong evidence that all people living with HIV should start antiretroviral therapy (ART) as soon as possible after diagnosis—regardless of their CD4 cell count—to protect their health and reduce the risk of transmission to their partners. Although knowing when to initiate ART is more straightforward, selecting the right ART treatment for a patient can be complicated. 

An ideal ART regimen should be simple for an individual to take and provide durable HIV suppression. Luckily, people living with HIV who are treatment naive have many proven ART regimens to choose from, depending on availability, cost, and a few other patient-specific factors. 

Selecting Between 2- and 3-Drug Regimens

Current guidelines recommend several single-tablet oral regimens consisting of 2-3 drugs. Most of these are integrase strand transfer inhibitor‒based regimens that are combined with 1 or 2 nucleos(t)ide reverse-transcriptase inhibitors. A doravirine-based regimen is another preferred regimen recommended by the European AIDS Clinical Society guidelines.

Two-drug regimens may be a great option for individuals who want to limit the number of agents in their single-tablet regimen or who want to avoid abacavir and tenofovir (TFV). However, there are a few instances where 2-drug regimens—such as dolutegravir with lamivudine—are not recommended. Two-drug regimens should not be used in individuals living with HIV who have transmitted resistance to either agent, have an HIV-1 RNA >500,000 copies/mL, and/or have hepatitis B virus (HBV).

Of importance, 2-drug regimens are not recommended during pregnancy, as there is not enough evidence to support efficacy during pregnancy for the mother or prevention of vertical transmission to the infant. 

HBV Coinfection

Coinfections and comorbidities also play an important role in individualizing ART. Individuals living with HIV and HBV should always receive a regimen that contains 2 agents with HBV activity—typically TFV plus emtricitabine or lamivudine. Screening for HBV before starting or changing therapies is essential to avoid the possibility of fulminant liver failure in the setting of immune reconstitution or if HBV therapy is unintentionally removed.

Findings from ALLIANCE, a randomized phase III study that compared bictegravir/emtricitabine/tenofovir alafenamide with bictegravir/emtricitabine/tenofovir disoproxil fumarate, provide reassuring data that either formulation of TFV can be used in individuals living with HIV and HBV. 

Other Comorbidities

The presence of noninfectious comorbidities should factor into choosing an initial regimen. For instance, people with significant renal impairment should consider avoiding TFV and may require dose reduction of other agents. Often for these patients, regimens with a fixed-dose combination tablet are inappropriate. Another example includes the need to be cautious when using abacavir in those at risk or with a prior history of cardiovascular disease.

Drug‒Drug Interactions

Individuals with comorbidities likely are prescribed other medications. As such, healthcare professionals should cautiously consider drug‒drug interactions. Several resources to assess for potential drug‒drug interactions exist, including the US Department of Health and Human Services guidelines, the University of Liverpool HIV Drug Interactions website, and the HIV-ASSIST tool.

Individual Preferences

Of most importance, healthcare professionals should address the individual’s personal preferences when selecting any ART regimen. The balance of risk from potential adverse events and which adverse events they most wish to avoid should be considered. Injectable ART regimens are not currently recommended for treatment initiation but may be part of a future plan to transition individuals when these regimens will best suit their lifestyles.

Your Thoughts?

How do you individualize regimens when initiating ART in your patients living with HIV? Join the discussion by posting a comment.