Choosing a first combination

With more than 20 antiretroviral drugs now on the market or available through expanded access programmes, there are more options than ever for constructing an effective first-line ART regimen. But with this larger array of choices comes added complexity .

Many factors are involved when considering what drugs to start with, including readiness to start treatment and ability to achieve good adherence, current state of disease progression (HIV viral load, CD4 cell count, and disease symptoms), any existing drug resistance, drug dosing requirements and convenience, side-effects, long-term toxicities, and co-existing conditions such as cardiovascular disease or hepatitis.

Presently, first-line therapy is chosen from three classes of drugs: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). There are multiple choices available in each class, with varying dosing requirements and potential side-effects.

Most people starting treatment today use a three-drug regimen that includes two NRTIs/NtRTIs plus either an NNRTI or a protease inhibitor. One common NNRTI-based regimen, consisting of tenofovir, emtricitabine and efavirenz, is now available as a single once-daily pill (Atripla). Using multiple drugs that attack HIV by different mechanisms can help minimise the risk of drug resistance.

BHIVA recommends beginning treatment with the NNRTI efavirenz plus an NRTI backbone consisting either of tenofovir/emtricitabine (Truvada) or 3TC/abacavir (Kivexa, Epzicom).

US guidelines give equal weight to starting treatment with a regimen based on an NNRTI, a protease inhibitor, or an integrase strand transfer inhibitor (INSTI) - all accompanied with 2 NRTIs. The preferred regimens are:

  • NNRTI + 2 NRTIs (efavirenz/tenofovir/emtricitabine, coformulated as Atripla)
  • PI  +  2 NRTIs (boosted atazanavir or boosted darunavir + tenofovir/emtricitabine, coformulated as Truvada)
  • INSTI + 2 NRTIs (raltegravir + Truvada)

The preferred regimen for pregnant women would be boosted lopinavir twice daily + AZT/3TC (Combivir).

World Health Organization guidelines recommend starting therapy with an NNRTI (either efavirenz or nevirapine) plus two NRTIs, one of which should be zidovudine (AZT) or tenofovir. Developing countries are encouraged to progressively reduce the use of stavudine (d4T) in first-line regimens.

Further information concerning alternate regimens can be found in the Treatment guidelines section.

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.