Antiretroviral Guidelines

US DHHS Guidelines with Australian commentary

What’s New in the Guidelines?

The ASHM Sub-Committee for Guidance on HIV Management in Australia notes that COVID-19 and its implications for people with HIV is a rapidly changing field. Guidelines making recommendations in this field have the potential to become outdated quickly, therefore guidance should always be considered in the context of Australian-based resources that are rapidly updated.

View the ARV Guidelines COVID-19 web-page for access to AU commentary in addition to the US DHHS guidance written below.

Interim Guidance for COVID-19 and Persons with HIV

Last Updated: June 19, 2020; Last Reviewed: June 19, 2020

This interim guidance reviews special considerations for persons with HIV and their health care providers in the United States regarding COVID-19. Information and data on COVID-19 are rapidly evolving. This guidance includes general information to consider. People with HIV who have COVID-19 have an excellent prognosis, and they should be clinically managed the same as persons in the general population with COVID-19, including when making medical care triage determinations.

Clinicians should refer to updated sources for more specific recommendations regarding COVID-19.

Guidance for all Persons with HIV

In current reports, individuals aged >60 years and those with diabetes, hypertension, cardiovascular disease, pulmonary disease, or obesity are at highest risk of life-threatening COVID-19, the illness caused by the virus known as SARS-CoV-2.
The limited data currently available do not indicate that the disease course of COVID-19 in persons with HIV differs from that in persons without HIV. Before the advent of effective combination antiretroviral therapy (ART), advanced HIV infection (i.e., CD4 cell count <200/mm³) was a risk factor for complications of other respiratory infections. Whether this is also true for COVID-19 is yet unknown.
Some people with HIV have other comorbidities (e.g., cardiovascular disease, lung disease) that increase the risk for a more severe course of COVID-19 illness. Chronic smokers are also at risk of more severe disease.
Thus, until more is known, additional caution for all persons with HIV, especially those with advanced HIV or poorly controlled HIV, is warranted.
Every effort should be made to help persons with HIV maintain an adequate supply of ART and all other concomitant medications.
Influenza and pneumococcal vaccinations should be kept up to date.
Persons with HIV should follow all applicable recommendations of the U.S. Centers for Disease Control and Prevention (CDC) to prevent COVID-19, such as social distancing and proper hand hygiene. These recommendations are regularly updated.
Information on COVID-19 prevention in children with HIV for pediatric health care providers and the general public is available from CDC.
CDC also provides information about COVID-19 prevention during pregnancy.

Antiretroviral Therapy

Persons with HIV Should:

Maintain on-hand at least a 30-day supply—and ideally a 90-day supply—of antiretroviral (ARV) drugs and other medications.
Talk to their pharmacists and/or health care providers about changing to mail order delivery of medications when possible.
Persons for whom a regimen switch is planned should consider delaying the switch until close follow-up and monitoring are possible.
To date, no drug has been proven to be safe and effective for treating COVID-19. Many drugs, including some ARV agents (e.g., lopinavir/ritonavir, boosted darunavir, tenofovir disoproxil fumarate/emtricitabine), are being evaluated in clinical trials or are prescribed for off label use for the treatment or prevention of COVID-19. Persons with HIV should not switch their ARV regimens or add ARV drugs to their regimens for the purpose of preventing or treating SARS-CoV-2 infection.

Clinic or Laboratory Monitoring Visits Related to HIV Care:

Together with their health care providers, persons with HIV and their providers should weigh the risks and benefits of attending, versus not attending in-person, HIV-related clinic appointments at this time. Factors to consider include the extent of local COVID-19 transmission, the health needs that will be addressed during the appointment, and the person’s HIV status (e.g., CD4 cell count, HIV viral load) and overall health.
Telephone or virtual visits for routine or non-urgent care and adherence counseling may replace face-to-face encounters.
For persons who have a suppressed HIV viral load and are in stable health, routine medical and laboratory visits should be postponed to the extent possible.

Persons with HIV and in Opioid Treatment Programs:

Clinicians caring for persons with HIV who are enrolled in opioid treatment programs (OTPs) should refer to the Substance Abuse and Mental Health Service Administration (SAMHSA) website for updated guidance on avoiding treatment interruptions. State methadone agencies are also responsible for regulating OTPs in their jurisdictions and may provide additional guidance.

Guidance for Specific Populations

Pregnant Individuals with HIV:

Currently, there is limited information about pregnancy and maternal outcomes in individuals who have COVID-19.
Immunologic and physiologic changes during pregnancy generally increase a pregnant individual’s susceptibility to viral respiratory infections, possibly including COVID-19. As observed with other coronavirus infections, the risk for severe illness, morbidity, or mortality with COVID-19 may be greater among pregnant individuals than among the general population.¹
Although limited, currently available data do not indicate that pregnant individuals are more susceptible to COVID-19 infection or that pregnant individuals with COVID-19 have more severe illness.^2,3 Adverse pregnancy outcomes, such as fetal distress and preterm delivery, were noted in a small series of pregnant women with COVID-19 infection and have been reported with SARS and MERS infections during pregnancy.^4-6
Findings from a small group of pregnant women with COVID-19 did not find evidence for vertical transmission of COVID-19, although at least one case of neonatal COVID-19 has been described.^3,7,8
Information on pregnancy and COVID-19 is available from CDC, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists.

Children with HIV:

From the limited available data, children appear less likely to become severely ill with COVID-19 than older adults.^9-11 However, there may be subpopulations of children at increased risk of more severe COVID-19 illness; in studies of infection with non-SARS-CoV-2 coronaviruses in children, younger age, underlying pulmonary pathology, and immunocompromising conditions were associated with more severe outcomes.¹²
Infants and children with HIV should be up to date on all immunizations, including influenza and pneumococcal vaccines. Refer to the Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Exposed and HIV-Infected Children information on immunizations, including a vaccine schedule for children with HIV.

Guidance for Persons with HIV in Self-Isolation or Quarantine Due to SARS-CoV-2 Exposure

Health Care Workers Should:

Verify that patients have adequate supplies of all medications and expedite additional drug refills as needed.
Devise a plan to evaluate patients if they develop COVID-19-related symptoms, including for possible transfer to a health care facility for COVID-19-related care.

Persons with HIV Should:

Contact their health care provider to report that they are self-isolating or in quarantine.
Specifically, inform their health care provider how much ARV medications and other essential medications they have on hand.

Guidance for Persons with HIV who have Fever or Respiratory Symptoms and are Seeking Evaluation and Care

Health Care Workers Should:

Follow CDC recommendations, as well as state and local health department guidance on infection control, triage, diagnosis, and management.

Persons with HIV Should:

Follow CDC recommendations regarding symptoms.
If they develop a fever and symptoms (e.g., cough, difficulty breathing), they should call their health care provider for medical advice.
Call the clinic in advance before presenting to the care providers.
Use respiratory and hand hygiene and cough etiquette when presenting to the health care facility and request a face mask as soon as they arrive.
If they present to a clinic or an emergency facility without calling in advance, they should alert registration staff immediately upon arrival of their symptoms so that measures can be taken to prevent COVID-19 transmission in the health care setting. Specific actions include placing a mask on the patient and rapidly putting the patient in a room or other space separated from other people.

Guidance for Managing Persons with HIV who Develop COVID-19

When Hospitalization is Not Necessary, the Person with HIV Should:

Manage symptoms at home with supportive care for symptomatic relief.
Maintain close communication with their health care provider and report if symptoms progress (e.g., sustained fever for >2 days, new shortness of breath).
Continue their ARV therapy and other medications, as prescribed.

When the Person with HIV is Hospitalized:

ART should be continued. If the ARV drugs are not on the hospital’s formulary, administer medications from the patients’ home supplies.
ARV drug substitutions should be avoided. If necessary, clinicians may refer to recommendations on ARV drugs that can be switched in the U.S. Department of Health and Human Services (HHS) guidelines for caring for persons with HIV in disaster areas.
For patients who receive ibalizumab (IBA) intravenous (IV) infusion every 2 weeks as part of their ARV regimen, clinicians should arrange with the patient’s hospital provider to continue administer of this medication without interruption.
For patients who are taking an investigational ARV medication as part of their regimen, arrangements should be made with the investigational study team to continue the medication if possible.
For critically ill patients who require tube feeding, some ARV medications are available in liquid formulations and some, but not all, pills may be crushed. Clinicians should consult an HIV specialist and/or pharmacist to assess the best way for a patient with a feeding tube to continue an effective ARV regimen. Information may be available in the drug product label or from this document from the Toronto General Hospital Immunodeficiency Clinic.

When Receiving Investigational or Off-Label Treatment for COVID-19:

There is currently no approved treatment for COVID-19. Several investigational and marketed drugs are being evaluated in clinical trials to treat COVID-19 or may also be available via compassionate use or off-label use.
For patients receiving COVID-19 treatment, clinicians must assess the potential for drug interactions between the COVID-19 treatment and the patient’s ARV therapy and other medications. Information on potential drug interactions may be found in product labels, drug interaction resources, clinical trial protocols, or investigator brochures.
When available, clinicians may consider enrolling patients in a clinical trial evaluating the safety and efficacy of experimental treatment for COVID-19. Persons with HIV should not be excluded from these trials. ClinicalTrials.gov is a useful resource to find studies investigating potential treatments for COVID-19.

Additional Guidance for HIV Clinicians

More information regarding ARV management in adult, pregnant, and pediatric patients, as well as recommendations for prophylaxis and treatment of specific opportunistic infections, can be found in the medical practice guidelines for HIV/AIDS.

The CDC website provides information about COVID-19 for people with HIV.

This interim guidance was prepared by the following working groups of the Office of AIDS Research Advisory Council:

HHS Panel on Antiretroviral Guidelines for Adults and Adolescents
HHS Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV
HHS Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission
HHS Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV
HHS Panel on Opportunistic Infections in HIV-Exposed and HIV-Infected Children

References

Clinical trials have shown that using effective antiretroviral therapy (ART) to consistently suppress plasma HIV RNA levels to <200 copies/mL prevents transmission of HIV to sexual partners. When ART is used to prevent HIV transmission, this strategy is called treatment as prevention (TasP), commonly known as Undetectable = Untransmittable or U=U.

The Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) has added a new section to help providers integrate TasP into their clinical practice. The key recommendations include:

Providers should inform persons with HIV that maintaining HIV RNA levels <200 copies/mL with ART prevents HIV transmission to sexual partners (AII).
Persons starting ART should use another form of prevention with sexual partners for at least the first 6 months of treatment and until an HIV RNA level of <200 copies/mL has been documented (AII). Many experts recommend confirming sustained suppression before assuming that there is no risk of sexual HIV transmission (AIII).
Persons with HIV who rely on ART for prevention need to maintain high levels of ART adherence (AIII). They should be informed that transmission is possible during periods of poor adherence or treatment interruption (AIII).
Providers should inform patients that maintaining an HIV RNA level of <200 copies/mL does not prevent acquisition or transmission of other sexually transmitted infections (AII).

The latest data on neural tube defects (NTDs) in infants born to women who received dolutegravir (DTG) around the time of conception have shown that the prevalence of NTDs is lower than initially reported (the rate has been reduced from 0.9% to 0.3%). However, this rate is still higher than the rate reported for infants born to individuals who received ART that did not contain DTG (0.1%).

In the previous version of the guidelines, the Panel did not recommend the use of DTG in persons who are pregnant and within 12 weeks post-conception or persons of childbearing potential who are planning to become pregnant or who are sexually active and not using effective contraception. Based on the new data, the Panel has revised these recommendations:

Providers should discuss the benefits of using DTG and the risk of NTDs with the person of childbearing potential, to allow the person to make informed decisions about care.
DTG may be used as an alternative antiretroviral (ARV) drug for individuals who are of childbearing potential and trying to conceive (BII) and those who are sexually active and not using contraception (BII).
For individuals who are using effective contraception, DTG may be used as a recommended option (AII).
Providers should refer to the Perinatal Guidelines for recommendations on the use of DTG during pregnancy.

More detailed recommendations on the use of DTG and other integrase strand transfer inhibitors (INSTIs) in persons of childbearing potential can be found in the table Considerations Before Initiating Dolutegravir and Other Integrase Strand Transfer Inhibitors as Therapy for Persons of Childbering Potential, as well as in different sections of the guidelines where DTG is discussed.

The Panel emphasizes the importance of screening and early diagnosis of HIV. In order for persons with HIV to benefit from early diagnosis, the Panel recommends that ART be started immediately or as soon as possible after diagnosis to increase the uptake of ART, decrease the time required to achieve linkage to care and virologic suppression for individual patients, reduce the risk of HIV transmission, and improve the rate of virologic suppression among persons with HIV (AII).

Based on the results of two large, randomized controlled trials that showed that a two-drug regimen of DTG plus lamivudine (DTG/3TC) was noninferior to DTG plus tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), the Panel has added DTG/3TC to the list of Recommended Initial Regimens for Most People with HIV, except for individuals:

With pre-treatment HIV RNA >500,000 copies/mL;
Who are known to have active hepatitis B virus (HBV) coinfection; or
Who will initiate ART before results of HIV genotype testing for reverse transcriptase or HBV testing are available.

The table Considerations Before Initiating Dolutegravir and Other Integrase Strand Transfer Inhibitors as Therapy for Persons of Childbearing Potential has been updated with revised recommendations on the use of DTG in individuals of childbearing potential.

Current data on the possible association between weight gain and the use of INSTIs and tenofovir alafenamide (TAF) are reviewed in the sections on INSTIs and nucleoside reverse transcriptase inhibitors.

This section has been updated with new clinical trial data from switch studies that were published or presented since the last revision.

The Panel emphasizes the importance of reviewing a patient’s ART history and recognizing any past instances of treatment failure and drug resistance when selecting a new ART regimen. The Panel also emphasizes that using two-drug ART regimens is not recommended for persons with active HBV coinfection.

This section has been updated with new data related to older persons with HIV. These updates focus on:

The need to identify individuals who are at risk of HIV and the need for early diagnosis;
The impact of age on HIV disease progression and the increase in age-related comorbidities; and
The importance of initiating ART while being aware of the complexities of management in older persons with HIV due to polypharmacy and the potential for drug-drug interactions.

The Panel emphasizes the importance of recognizing and managing HIV-associated neurocognitive disorder (HAND), which may be associated with reduced ART adherence and poorer overall health outcomes. The Panel also recognizes that mental health disorders in older persons with HIV is a growing concern; screening for depression and management of depression are critical components of care for these patients.

Key updates to this section include:

An overview of the individual and societal costs of HIV care in the United States.
A new sub-section on cost sharing that describes how varying cost-containment practices may impact the out-of-pocket payments for patients with Medicaid, Medicare, and Ryan White (AIDS Drug Assistance Program) coverage. To help clinicians to better understand the different ART-related pricing systems in the United States, a new table entitled Table 19a. Insurance and Health Program Prescription Drug Pricing and Access was created.
A revised discussion of ARV drug costs that highlights the increased cost of brand-name drugs and the impact that anticipated commercialization of additional generic-based regimens will have on the cost of ART.
An updated discussion of the economic value of several HIV-specific laboratory tests.

The following tables have been updated using data that has become available since the last revision:
- Adverse Effects of Antiretroviral Agents: Common and/or Severe Adverse Effects Associated with Antiretroviral Therapy and Antiretroviral Therapy-Associated Adverse Events that can be Managed with Substitution of Alternative Antiretroviral Agent
- Drug-Drug Interactions Tables:
- Drug Characteristics Tables

Last Updated: June 8, 2021; Last Reviewed: June 8, 2021