The Department of Health and Human Services (DHHS) is the U.S. federal government agency responsible for protecting the health of the American public.

The DHHS HIV guidelines help inform healthcare professionals of the best ways to treat HIV based on the latest clinical evidence and expert opinions.

In this article, we break down some of the key points of the DHHS guidelines and what to know about the most recent changes.

The main goal of the DHHS guidelines is to offer recommendations to healthcare professionals on the best treatment options for people with HIV. The guidelines are written and updated based on the most recent scientific evidence.

Doctors can consult these guidelines to determine the right treatment at various stages of HIV. For example, the guidelines provide recommendations on when to start antiretroviral therapy (ART), which drugs should be used, and what to do if initial treatment isn’t working.

The full guidelines provide a long list of recommendations you can read here. We’ve summarized some key points below so you can get an idea of the type of information these guidelines include.

Drugs when starting treatment

  • ART is recommended for all people with HIV to reduce the chances of severe illness, death, and transmission.
  • People with a new diagnosis of HIV should start ART as soon as possible.
  • Genetic testing is recommended at the beginning of treatment to screen for potential drug resistance.
  • Medical professionals should discuss future pregnancy plans with patients who are able to become pregnant. A pregnancy test may be performed before starting HIV treatment.

Preventing sexual transmission

  • People with HIV should be informed that keeping their plasma HIV viral load under 200 copies per milliliter prevents sexual transmission of HIV.
  • To avoid transmission to a sexual partner, people starting ART should use a barrier method, such as a condom, for at least the first 6 months of treatment and until they have a viral load under 200 copies per milliliter.
  • If a person’s viral load rises over 200 copies per milliliter, a barrier method should be used until the virus is resuppressed.
  • People should be informed that maintaining a viral load under 200 copies per milliliter doesn’t stop the transmission of other sexually transmitted infections (STIs).

Types of drugs

Initial HIV treatment generally consists of two medications called nucleoside reverse transcriptase inhibitors in combination with a third active antiretroviral (ARV) drug from one of three drug classes:

  1. integrase strand transfer inhibitors
  2. non-nucleoside reverse transcriptase inhibitors
  3. protease inhibitors with a pharmacokinetic enhancer

The following drug regimens are classified as “recommended initial regimens for most people with HIV.” A slash (/) between medications means they’re available as a combination drug within the same pill:

  • bictegravir/tenofovir alafenamide/emtricitabine
  • dolutegravir/abacavir/lamivudine in people without the HLA-B*5701 gene and without chronic hepatitis B infection
  • dolutegravir and either emtricitabine or lamivudine, and tenofovir alafenamide or tenofovir disoproxil fumarate
  • dolutegravir/lamivudine except for people with a viral load greater than 500,000 copies per milliliter or with chronic hepatitis B infection; also not suitable if ART is started before receiving genetic testing results

Treatment failure

When ART isn’t working, several factors should be considered, including:

  • drug-drug interactions
  • drug-food interactions
  • drug tolerability
  • HIV viral count
  • CD4 cell count
  • ART history
  • results of drug-resistance tests
  • treatment plan adherence

Specific patient groups

  • ART is recommended for all adolescents and young adults to reduce the chances of severe symptoms, early death, and transmission.
  • ART is recommended for all transgender people.
  • ART is especially important for older adults because they have a greater risk of non-AIDS complications and don’t generally respond as well to ART as younger people.
  • Substance use disorders are common among people with HIV and can contribute to poor outcomes. Screening should be a regular part of care. The most common substances to screen for include:
    • alcohol
    • benzodiazepines
    • cannabis
    • opioids
    • cocaine
    • methamphetamines
    • tobacco


  • When prescribing ARV drugs to women, healthcare professionals should consider that some ARV drugs interact with hormonal birth control.
  • Healthcare professionals should consider that weight gain is possible for this group. If obesity is a concern, healthcare professionals should factor that into the treatment choice.

At the time this article was written, the DHHS guidelines were most recently updated on June 3, 2021.

Researchers are continuing to improve their understanding of how to best treat and manage HIV. The guidelines are updated periodically to include the latest research and expert opinions.

Here’s an overview of the most recent changes included in the 2021 update.

Drugs when starting treatment

New evidence from the Botswana Tsepamo Study, an ongoing observational study that started in 2014, suggests that the rate of neural tube defects (a type of structural change in a developing fetus) is lower than expected in women taking dolutegravir at the time of conception.

Dolutegravir is now recommended as an initial treatment option for people who may get pregnant.

The medication raltegravir was moved from “recommended initial regimens for most people with HIV” to “recommended initial regimen in certain clinical situations.”

The change was partially made due to the results of the Botswana Tsepamo Study. Since dolutegravir is now a viable treatment for people who can get pregnant, it’s no longer necessary to choose raltegravir over dolutegravir.

Treatment failure

It was initially recommended that if ART treatment doesn’t work, it should be followed by two and preferably three fully active ARV drugs.

It’s now recommended that the new treatment can include two fully active drugs if at least one has a high resistance barrier. Examples of such drugs include boosted darunavir or dolutegravir. The change was made based on the results of ongoing clinical trials.

Poor CD4 recovery and inflammation

Updates include the mechanism behind declining CD4 counts despite suppressive ART.

CD4 cells are a type of white blood that fights infections. Knowing a person’s CD4 count helps determine their risk of developing opportunistic infections.

The new guidelines also include updated strategies to reduce persistent inflammation.

Optimizing ART

Updates include the role of long-acting injectable regimens cabotegravir plus rilpivirine. Long-acting injectables are a new form of ART that involve infrequent injections instead of daily oral medication.

The Food and Drug Administration (FDA) approved the first long-acting injectable for treating HIV in January 2021.

Adolescents and young adults

The adolescent and young adults section has been updated to include current data on the rate of HIV among youth in the United States.

The guidelines now also have more details on the unique challenges that youth with HIV face compared to adults.


This section now includes data from a 2020 review of eight studies that found that women are more likely to gain weight than men after starting ART.

There’s also now more information regarding the effects of menopause and hormone replacement therapy while on HIV treatment.

Substance use disorder

This section now includes information about when to consider the long-acting injectable cabotegravir plus rilpivirine in people with a substance use disorder.

Current research is limited to people with good medication adherence.

Drug-drug interaction tables

Newly discovered drug interactions have been included in the guidelines, including interactions between the drugs cabotegravir plus rilpivirine and fostemsavir.

Cost considerations

A section was added discussing the cost effectiveness of new drugs, such as ibalizumab, in HIV that’s resistant to multiple ARV drugs.

Monthly prices of commonly prescribed ARV drugs have been updated with 2021 prices.

Tuberculosis coinfection

Updates describe current recommendations for ARV drugs that can be used if 3 months of isoniazid and rifapentine are prescribed for tuberculosis.

The DDHS HIV guidelines were developed to help healthcare professionals stay up to date with the latest HIV research so they can provide the best possible treatment. The guidelines are updated regularly as new research or evidence becomes available.

The guidelines are available online for free to anybody who wants to read them.