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"Medical Journeys" is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

Antiretroviral therapy (ART) is the backbone of HIV treatment, and advances in ART have been tied to increased survival and a better prognosis for people living with HIV.

While ART regimens have diversified over the years in terms of number of medicines and delivery systems, the core therapeutic elements have remained the same.

"Given the many excellent options for initial therapy, selection of a regimen for a particular patient should be guided by factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug–drug interaction potential, resistance-test results, comorbid conditions, access, and cost," the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents wrote in the group's

Start as Early as Possible

Once a person is diagnosed with HIV, it is critical to start ART "at the time of diagnosis (when possible)" or "soon afterwards," the panel members noted. They cited data from observational studies examining when ART was initiated on the day of diagnosis, such as the HIV . Data from this program, first presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in 2018, found that of the 225 patients started on RAPID from 2013 to 2017, after intake (96%). Moreover, viral suppression rates were 92% at "last recorded viral load."

However, the panel pointed out that whether this rapid initiation of therapy "improves long-term care engagement and virologic suppression is not yet known."

"While the infrastructure and resources necessary to implement an immediate ART program may not be available in all health care settings, removing structural barriers in order to facilitate rapid ART initiation may improve outcomes in the United States," the panel wrote.

The document detailed the advantages to early ART initiation including, "to increase the uptake of ART, decrease the time required to achieve linkage to care and virologic suppression, and improve the rate of virologic suppression among individuals who have recently received HIV diagnoses."

Options for Patients

Examining specific therapies, adults and adolescents (defined as ages 13 and up) diagnosed with HIV on two nucleoside reverse transcriptase inhibitors and either an integrase strand transfer inhibitor, a non-nucleoside reverse transcriptase inhibitor, or a "booster" such as cobicistat or ritonavir (defined as a protease inhibitor with a pharmacokinetic enhancer).

Despite containing three drugs, most ART regimens are now combined into one tablet, and most recommended drugs continue to be daily oral treatment. As of March 2022, the panel recommended that most adults and adolescents diagnosed with HIV should be started on one of the following ART regimens:

• Bictegravir/tenofovir alafenamide (TAF)/emtricitabine (FTC) (Biktarvy)

• Dolutegravir (DTG)/TAF or tenofovir disoproxil fumarate (TDF)/FTC or lamivudine (3TC)

• DTG/abacavir (ABC)/3TC (Triumeq) for patients who are HLA-B*5701 negative and without chronic hepatitis B virus (HBV)

Patients with the ability to become pregnant should receive a pregnancy test prior to ART initiation, the panel noted.

Two Drugs Equal to Three?

The panel added that data also support use of a two-drug regimen, DTG/3TC (Dovato). The combination was for treatment-naïve patients, with an for virologically suppressed patients (defined as HIV RNA <50 copies/mL) without a history of treatment failure and no history of resistance to the drug's individual components.

Approval was granted based on the non-inferiority GEMINI-1 and GEMINI-2 trials published in . The studies randomized treatment-naïve patients to daily regimens of DTG/3TC or DTG/TDF/3TC. Both found virological suppression was comparable for the two-drug regimen when non-inferiority was defined as a -10% margin (pooled analysis adjusted treatment difference -1.7%, 95% CI -4.4 to 1.1).

According to the panel, DTG/3TC may be an ART option for treatment-naïve patients, except for patients with a high viral load at diagnosis (defined as HIV RNA over 500,000 copies/mL), individuals with HBV co-infection, or if ART must be started prior to the results of "genotypic resistance testing for reverse transcriptase" or testing for HBV.

Accounting for Injectable PrEP Use

Certain forms of pre-exposure prophylaxis (PrEP), or "treatment as prevention," to protect high-risk individuals from contracting HIV infection added a new wrinkle to the treatment guidelines. Specifically, the panel cited injectable long-acting cabotegravir (CAB-LA, or Apretude), which was approved .

For adults and adolescents using CAB-LA as PrEP, the panel recommended "INSTI [integrase strand transfer inhibitors] genotypic resistance testing." However, if testing results are unavailable prior to treatment initiation, those patients should be started on boosted darunavir plus (TAF or TDF) plus (FTC or 3TC), pending the results of genotypic testing.

A Long-Acting Injectable Option

In January 2021, the FDA approved for adults with HIV. Rather than a daily pill, cabotegravir and rilpivirine (Cabenuva) are injections of ART therapy.

However, patients cannot simply be started on this treatment at diagnosis. FDA outlined a lead-in period of oral treatment with oral cabotegravir (Vocabria) and oral rilpivirine (Edurant), both of which patients should take daily prior to initiating the injectable formula "to ensure the medications are well-tolerated," the agency wrote.

The panel members were more stringent. As of September 2022, they wrote that patients should be and should be "engaged with their healthcare," enough to make the regular clinic visits needed to receive treatment. The panel also said that the injectable treatment could be given "every 1-2 months."

Results of the SOLAR trial presented at CROI in February 2023 also found that long-acting injectable therapy was non-inferior to daily oral treatment (bictegravir/TAF/FTC) for maintaining virologic suppression.

Read Part 1 of this series: The Evolution of HIV: From Death Sentence to Chronic Condition

Up next: The role of viral load and the importance of virologic suppression