New second-line antiretroviral combinations are best for children living with HIV, according to CHAPAS-4 trial
15 May 2025
Newer antiretroviral drug combinations including tenofovir alafenamide and dolutegravir are superior to older second-line options for children living with HIV. This is according to new results from the CHAPAS-4 trial, published this week in the New England Journal of Medicine.
The trial also found that combinations including darunavir or atazanavir are excellent alternative options.
The CHAPAS-4 trial included 919 children aged 3-15 years from Uganda, Zambia and Zimbabwe. It aimed to improve treatment options for children living with HIV who require 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, as the virus can develop resistance to first-line drugs. This means they need to change to a different combination 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 study tested a new mini-tablet drug combination for children weighing under 25kg, which is made up of tenofovir-alafenamide (TAF) plus emtricitabine (FTC) and taken once daily. Children weighing over 25kg could use the adult formulation of TAF. This was compared to the current standard of abacavir (ABC) or zidovudine (ZDV) plus lamivudine (3TC).
The study found that TAF successfully suppressed HIV in 6% more children than ABC or ZDV plus 3TC. Side-effects were similar between the groups.
TAF plus FTC was less costly than the current standard-of-care by $37.68, meaning that TAF plus FTC is likely to be cost-saving.
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.
DRV/r fully suppressed HIV in around 6% more children than LPV/r and ATV/r, but this did not meet the pre-defined threshold for a statistically significant difference between these groups.
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.
DTG was the least costly anchor drug, saving $190.77 compared with ATV/r.DRV/r was the most expensive.
These results reinforce the current WHO recommendation of DTG-based regimens being the preferred second-line regimen for children. They also provide new evidence for the use of TAF in second-line combinations for children.
Results from sub-studies looking at drug levels in blood samples from CHAPAS-4 are also contributing to the evidence for simplified weight-band dosing of these drugs for children. This will 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 it easier for children to take this medication.
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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