International Panel updates guidelines for Treatment and Prevention of HIV in Adults

The International Antiviral Society–USA Panel has updated its 2018 guidance on use of antiretroviral drugs to prevent and treat HIV infection to include recommendations on long-acting injections. The guidelines appear in JAMA.

The group recommends use of new long-acting injectable antiretroviral regimens (cabotegravir/rilpivirine) given every 4 or 8 weeks. These regimens are awaiting FDA approval. Cabotegravir injected every 8 weeks is also recommended for preexposure prophylaxis for high-risk cisgender men and transgender women who have sex with men, again, pending regulatory approval.

With the aim to evaluate new data and incorporate them into current recommendations for initiating HIV therapy, monitoring individuals starting on therapy, changing regimens, preventing HIV infection for those at risk, and special considerations for older people with HIV,the expert panel laid down the following guidelines.

Key Recommendations for When to Start Antiretroviral Therapy (ART)

• Initiation of ART is recommended as soon as possible after HIV diagnosis, including immediately after diagnosis if the patient is ready to commit to treatment .

• Structural barriers that delay receipt of ART should be removed to allow newly diagnosed persons to receive ART at the first clinic visit after diagnosis if they and their clinicians determine that this approach is appropriate.

• Initiation of ART is recommended within 2 weeks of initiation of treatment for most opportunistic infections , except: • For individuals with tuberculosis and CD4 cell counts of 50/μL or above, ART should be initiated within 2 to 8 weeks of initiation of tuberculosis treatment (evidence rating: AIa) • For individuals with cryptococcal meningitis, ART should be initiated within 4 to 6 weeks after starting antifungal therapy .

• Initiation of ART is recommended immediately in the setting of a new diagnosis of cancer with attention to drug-drug interaction.

Recommended Initial Antiretroviral Therapy (ART) Regimens Recommended for Most People With HIVa

• Bictegravir/tenofovir alafenamide/emtricitabine

• Dolutegravir plus • Tenofovir alafenamide/emtricitabine • Tenofovir disoproxil fumarate/emtricitabine • Tenofovir disoproxil fumarate/lamivudine .

• Dolutegravir/lamivudine with caveats

Recommended in the Setting of Opportunistic Infection Treatment

• Dolutegravir (50 mg twice daily), efavirenz (600 mg/d), or raltegravir (800 mg twice daily) plus 2 nucleoside reverse transcription inhibitors is recommended for initial ART in people with HIV who have active tuberculosis and are receiving a rifamycin-based tuberculosis treatment regimen .

• Bictegravir with rifampin is not recommended due to drug-drug interactions (evidence rating: AIIa) • Boosted protease inhibitors are recommended only if an integrase strand transfer inhibitor–based or efavirenz-based regimen is not an option; if possible, rifabutin (150 mg/d) should be substituted for rifampin in the tuberculosis treatment regimen if a protease inhibitor–based regimen must be used .

Recommended During Pregnancy

• Atazanavir/ritonavir

• Darunavir/ritonavir

• Dolutegravir

Key Recommendations for When and How to Switch Antiretroviral Therapy (ART) Regimens

• Review of the patient's ART regimen history, regimen tolerability, co-medications, food requirements, cost, and results from prior resistance tests is recommended before any treatment changes are made .

• HIV viral load assessment is recommended 1 month after switching regimens.

Switching When the Patient Has Achieved Viral Suppression

• Patients with HIV and hepatitis B virus (HBV) co-infection who are switching therapy should continue taking tenofovir alafenamide or tenofovir disoproxil fumarate unless these drugs are contraindicated. Switching to a regimen including lamivudine or emtricitabine and excluding tenofovir alafenamide or tenofovir disoproxil fumarate will not maintain suppression of chronic HBV and is not recommended; alternative HBV suppressive therapy is recommended .

• In patients with nucleoside reverse transcriptase inhibitor (nRTI) resistance mutations, switching from a boosted protease inhibitor (PI) to a regimen containing a drug with a low genetic barrier to resistance (eg, nonnucleoside reverse transcriptase inhibitor [NNRTI] or raltegravir) is not recommended (evidence rating: AIa).

• In the setting of viral suppression, switching from a 3-drug regimen to an oral 2-drug regimen is an appropriate strategy to manage toxic effects, intolerance, adherence, or patient preference provided both agents are fully active . Recommended regimens include dolutegravir/rilpivirine (evidence rating: AIa), a boosted PI with lamivudine , dolutegravir/lamivudine or a long-acting injectable 2-drug regimen of cabotegravir and rilpivirine dosed every 4 weeks (evidence rating: AIa) or every 8 weeks pending approval by regulatory bodies and availability.

• Monotherapy with boosted PIs or dolutegravir is not recommended.

• Review of co-medications is recommended to ensure no change in tenofovir alafenamide dosing is needed .

Switching for Virological Failure

• Resistance testing is recommended while the patient is taking the failing ART regimen (evidence rating: AIa) or within 4 weeks of stopping ART .

• Adding a single active agent to a failing regimen is not recommended

• Dolutegravir plus 2 nRTIs (with 1 active drug determined by genotypic testing) is recommended after initial treatment failure with an NNRTI.

• A boosted PI plus 2 nRTIs (with 1 active nRTI) is recommended for initial treatment failure of an integrase strand transfer inhibitor– containing regimen .

• Dolutegravir (dosed twice daily) plus at least 1 fully active other agent is recommended in the setting of raltegravir or elvitegravir resistance .

• Virological failure due to resistance mutations is rare with PIs (evidence rating: AIa). Support for adherence or an alternative regimen that improves adherence, tolerability, or both is recommended .

• In the setting of multiclass resistance (3-class resistance), the next regimen should be constructed using drugs from new classes if available ; eg, fostemsavir or ibalizumab with at least 1 additional active drug in an optimized ART regimen.

Key Recommendations for the Use of Preexposure Prophylaxis (PrEP) and Postexposure Prophylaxis

• PrEP is recommended for individuals at risk for HIV infection (evidence rating: AIa)

• Initiation of PrEP is recommended as soon as feasible for individuals who have chosen to use it (evidence rating: AIII)

• Tenofovir disoproxil fumerate/emtricitabine once daily is recommended for oral PrEP (evidence rating: AIa).

• For men who have sex with men (MSM), a double dose (2 pills) of tenofovir disoproxil fumerate/emtricitabine is recommended on the first day (evidence rating: AIIa) • For MSM with or at risk for kidney dysfunction, osteopenia, or osteoporosis, daily tenofovir alafenamide/emtricitabine is recommended (evidence rating: BIa)

• Oral PrEP dosing using the 2-1-1 (or on-demand) method is recommended only for MSM (evidence rating: AIa)

• Injectable cabotegravir every 8 weeks (see text for details) is recommended (pending approval by regulatory agencies and availability) as PrEP for cisgender men and transgender women who have sex with men.

Besides the above some other guidelines have also been proposed. Among the other updates:

Dolutegravir/lamivudine is an effective initial and subsequent treatment, but the recommendation comes with caveats. For instance, it's unknown whether the combination is effective in patients with high HIV RNA loads. In addition, it should not be given to patients with hepatitis B coinfection.

The guidance now includes a section on aging to help manage older adults with HIV.

During the COVID-19 pandemic, clinicians should ensure that patients' access to antiretroviral therapies is not interrupted. As such, the group recommends 90-day over 30-day refills.

For the full article,follow the link: doi:10.1001/jama.2020.17025

Primary source:JAMA