HIV Treatment Regimens CDC Guidelines, Adult/Adolescent

The Centers for Disease Control (CDC) and other federal government agencies have issued several guidelines and recommendations regarding the prevention, screening, diagnosis, treatment, and management of HIV infection. ^[1] The CDC references the most current Department of Health and Human Services (DHHS) guidelines for the use of antiretroviral agents in HIV-1–infected adults and adolescents, as summarized below. ^[2]

Initial Combination Regimens for Antiretroviral-Naive Patients with HIV Infection

An initial antiretroviral regimen generally consists of two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in combination with a third active drug from one of the following classes: non-nucleoside reverse transcriptase inhibitor (NNRTI), protease inhibitor (PI) with a booster (ritonavir or cobicistat), or an integrase strand transfer inhibitor (INSTI).

Selection of a regimen should be individualized based on virologic efficacy, potential adverse effects, pill burden, dosing frequency, drug-drug interaction potential, the patient's resistance test results, co-morbid conditions, drug availability, and cost. Clinicians also should discuss the patient's intentions toward pregnancy and perform a pregnancy test before initiating therapy.

Recommended Initial Antiretroviral Therapy (ART) Regimen Options for Most Patients with HIV Infection

Recommended ART regimens for treatment-naive patients with HIV infection are INSTI-based, and are as follows:

• Bictegravir/tenofovir alafenamide/emtricitabine
• Dolutegravir/abacavir/lamivudine (only for patients who are HLA-B*5701 negative and do not have chronic hepatitis B (HBV) co-infection)
• Dolutegravir plus  either  emtricitabine or  lamivudine, plus either  tenofovir disoproxil fumarate or tenofovir alafenamide
• Dolutegravir/lamivudine ^[3]  (only if HIV RNA < 500,000 copies/mL, there is no HBV co-infection, or in cases where ART is started prior to known HIV genotype resistance testing and HBV testing) 

Long active intra-muscular cabotegravir plus rilpivirine is not currently approved as an initial ART regimen. Patients must first achieve viral suppression on another regimen before switching.

For patients with HIV who have used long acting cabotegravir as PrEP, INSTI resistance testing should be done before starting ART. If ART is started before the genotype test results are known, then the following regimen is recommended:

• Boosted darunivir plus   either  tenofovir alafenamide or  tenofovir disoproxil fumarate, plus either  emtricitabine  or lamivudine

Considerations in Pregnant People and Nonpregnant People Who are Trying to Conceive

Prior to starting dolutegravir in patients with childbearing potential, clinicians should discuss the risk and benefits with the patient. Data from a study in Botswana raised concerns about a slightly higher risk for neural tube defects in infants born to patients who were receiving dolutegravir at the time of conception compared to those who were not. ^[4]  In a Brazilian cohort, increased risk for neural tube defects was not seen with dolutegravir use prior to conception. ^[5]  Dolutegravir is otherwise a preferred agent recommended for treatment of acute HIV infection during pregnancy. ^[6]  

Bictegravir should not be used in patients who are pregnant, as there is insufficient data in this population.

Oral cabotegravir and long acting intra-muscular cabotegravir plus rilpivirine are not recommended in pregnancy, as there is insufficient data for use. 

Cobicistat should be avoided in pregnancy due to the risk for lower concentrations of the drug and its boosted drugs - darunavir, atazanavir and elvitegravir - that can be seen in the second and third trimesters. If a patient is virally suppressed while on a cobicistat containing regimen and becomes pregnant, they should be counseled on the risk for reduced drug concentration and their viral load should be monitored frequently. 

In all cases of patients with childbearing potential, clinicians should refer to the Perinatal HIV guidelines to help determine appropriate ART regimens prior to conception and during pregnancy. ^[7]  

Recommended Initial ART Regimens in Certain Clinical Situations

The following regimens are effective and tolerable alternatives to the ART regimens listed above, but they differ in that they have some potential disadvantages. These may include but are not limited to: contraindications in certain patient populations with co-morbid conditions or in patients who are pregnant; drug toxicity; cost; variable pill burden; or when there is less supporting data from randomized clinical trials. 

INSTI plus 2 NRTIs regimens include:

• Elvitegravir/cobicistat/tenofovir alafenamide/emtricitabine
• Elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine
• Raltegravir plus either  tenofovir alafenamide or  tenofovir disoproxil fumarate plus either  emtricitabine or lamivudine

Boosted PI plus 2 NRTIs regimens include: (Note: boosted darunavir generally is preferred over boosted atazanavir) 

• Darunavir/cobicistat or  darunavir/ritonavir plus either  tenofovir disoproxil fumarate or  tenofovir alafenamide plus either  emtricibatine or lamivudine
• Atazanavir/cobicistat or  atazanavir/ritonavir plus either  tenofovir disoproxil fumarate or  tenofovir alafenamide plus either  emtricitabine or lamivudine
• Darunavir/cobicistat or  darunavir/ritonavir plus abacavir/lamivudine (if HLA-B*5701 negative)

NNRTI plus 2 NRTIs regimens include:

• Doravirine/tenofovir disoproxil fumarate/lamivudine  or  doravirine  plus tenofovir alafenamide/emtricitabine
• Efavirenz  plus either  tenofovir disoproxil fumarate  or  tenovofir alafenamide  plus either  emtricitabine  or lamivudine
• Rilpivirine  plus either  tenofovir disoproxil fumarate  or  tenofovir alafenamide  plus  emtricitabine (if HIV RNA < 100,000 copies/mL and CD4 count >200 cells/mm ³⁾

If abacavir, tenofovir alafenamide, and/or tenofovir disoproxil fumarate cannot be used or are suboptimal, consider one of the following regimens:

• Dolutegravir/lamivudine (only if HIV RNA < 500,000 copies/mL, there is no HBV co-infection, or in cases where ART is started prior to known HIV genotype resistance and HBV test results)
• Darunavir/ritonavir plus  raltegravir twice a day (if HIV RNA < 100,000 copies/mL and CD4 count >200 cells/mm ³)
• Darunavir/ritonavir once daily plus lamivudine