Treatment training manual

3.10 Treatment choices: WHO guidelines

Globally, more than 30 drugs and formulations are approved. However, only a few main combinations are recommended in treatment guidelines.

WHO guidelines are mainly developed for low- and middle-income countries (LMICs). The drugs are just as good as in high-income countries, but there is less choice.

WHO guidelines are for population-based care. This is for countries with high numbers of people that need ART but where there are limited resources. This is a slightly different approach to high-income guidelines that emphasise individualised care.

Population-based care involves the most cost-effective way to to provide the best overall responses to HIV on a country level. For example, how to get the highest numbers of people on treatment and to get the highest percentage of people to have an undetectable viral load.

In practice, this is based on using one main combination for each stage of treatment, with one or two alternatives. This makes it easier to negotiate lower prices for each combination.

Most high-income countries are organised based on individualised care. This is because drug prices are much higher which allows for many more different drug choices.

WHO guidelines: first-line ART

WHO guidelines strongly recommend ART for all people living with HIV. This is even at high CD4 counts. This includes offering same-day or rapid ART for people that are ready to start when they are first diagnosed.

People with active TB should treat TB first and start HIV treatment two weeks later. People with HIV and TB-meningitis or cryptococcal meningitis should delay ART for 4-6 weeks.

Most guidelines recommend that first-line treatment is a combination of an integrase inhibitor (dolutegravir) plus two nukes (NRTIs). The NRTIs are likely to be tenofovir (TD) plus either lamivudine or emtricitabine.

WHO consolidated HIV guidelines are posted and updated online.
https://www.who.int/publications/i/item/9789240052390 (July 2022 edition)
https://www.who.int/publications/i?publishingoffices=c09761c0-ab8e-4cfa-9744-99509c4d306b (guidelines page)

The main changes in each edition are included in the introduction.

The preferred first-line therapy for adults is a fixed-dose combination of::

This is often called TLD.

Emtricitabine is sometimes used instead of lamivudine as they are very similar drugs,

If this combination is not available or cannot be used, the alternative is:

  • tenofovir (DF) + 3TC + low dose efavirenz 400 mg

This is often called TLE (but check the efavirenz dose).

Sometimes other combinations are used For example, using a boosted protease inhibitor called darunavir.

Fixed dose combinations (FDCs) are where all three drugs in these combinations are supplied in one pill. FTC can be used instead of 3TC.

People already on a different first combination can switch to TLD. This will depend on guidelines in each country.

WHO guidelines: second-line ART

Most guidelines recommend changing to a new main drug for second-line therapy. The background NRTIs will usually change to tenofovir DF and either lamivudine or emtricitabine, even if you were taking these in your current combination,

  • People failing on an NNRTI-based ART can switch to dolutegravir + two nukes.
  • People failing on an integrase inhibitor-based combination will change to  a boosted PI-based combination with two nukes. are recommended This should be darunavir/b although atazanavir/b or lopinavir/r are alternatives.

The two nukes will depend on the individual treatment history. Recent studies showed that if someone is already using tenofovir DF and lamivudine or emtricitabine, these might not need to be changed.

WHO guidelines: third-line ART

Darunavir/r is recommended for third-line therapy. The choice of nukes will depend on the individual ART history – and likely drug resistance.

Third-line treatment might also need dolutegravir, especially if there is extensive resistance to NRTIs.

The UK, US, European and other high-income countries have a wider choice of drugs and drug classes.

New drugs have been recently approved from different classes to treat multidrug resistance. These include lenacapavir, fostemsavir and ibalizumab,

Last updated: 1 January 2023.