CHAPAS-4 trial shows benefit of new antiretroviral combinations for second-line treatment of children living with HIV

25 Jul 2023

The CHAPAS-4 trial has found that newer antiretroviral combinations including tenofovir alafenamide and dolutegravir are superior to older second-line options for children living with HIV. These results were presented today at the International AIDS Society Conference in Australia.

In addition, CHAPAS-4 found that combinations including the drugs darunavir or atazanavir are excellent alternative options.

CHAPAS-4 was a large randomised controlled trial, with 919 children aged 3-15 years from Uganda, Zambia and Zimbabwe taking part. It aimed to improve treatment options for children living with HIV requiring second-line treatment after first-line treatment with efavirenz or nevirapine. Children were followed-up for at least two years after starting second line treatment.

Overall, children in the CHAPAS-4 trial did very well. Very few children experienced their disease getting worse, or were hospitalised. One child died for reasons unrelated to trial treatment.

HIV treatment regimens are usually made up of a backbone of two drugs, with a third drug from a different class of antiviral medicines (called an anchor drug). For some people, initial treatment regimens can stop working with HIV developing resistance to first-line drugs, meaning they need to change to a different combinations of drugs (second-line treatment). Children living with HIV whose first-line treatment is no longer working well have few options for second-line antiretroviral therapy.

CHAPAS-4 compared a treatment backbone of tenofovir-alafenamide (TAF) plus emtricitabine (FTC) to the current standard of abacavir (ABC) or zidovudine (ZDV) plus lamivudine (3TC). TAF successfully suppressed HIV in 6% more children than ABC or ZDV plus 3TC. Side-effects were similar between the groups.

CHAPAS-4 also compared four different options as anchor drugs:

  • Once-daily atazanavir/ritonavir (ATV/r), or
  • Once-daily darunavir/ritonavir (DRV/r), or
  • Once-daily dolutegravir (DTG), or
  • Twice daily lopinavir/ritonavir (LPV/r)

The trial showed that DTG-based regimens were superior to LPV/r and ATV/r-based regimens. Dolutegravir fully suppressed HIV in 10% more children than LPV/r and ATV/r.

There was also a trend towards DRV/r being superior to LPV/r and ATV/r, with HIV being fully suppressed in around 6% more children in the DRV/r group. However, for this comparison the pre-defined statistical significance threshold of p=0.03 was not quite met.

ATV/r-based regimens were as good as LPV/r-based regimens at keeping HIV suppressed.

Compared to children on LPV/r-based regimens, children on DRV/r-, ATV/r- or DTG-based regimens had better growth, bone health and cholesterol levels.

These results reinforce the current WHO recommendation of DTG-based regimens being preferred second-line regimen for children. They also provide new evidence for use of TAF in second-line combinations for children.

Results from sub-studies looking at drug levels in blood samples from CHAPAS-4 will contribute to the evidence for simplified weight-band dosing of these drugs for children. It will also help with the development of new formulations such as dispersible fixed-dose drug combination minipills of TAF+FTC, with or without DTG, which will make taking medication easier for children.

CHAPAS-4 was funded by the EDCTP2 programme, supported by the European Union [TRIA2015-1078]. Additional funding support was provided by Janssen Pharmaceutical and Gilead Sciences Inc.

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