'Important' New Data on Second-Line HIV Treatment Regimens: The NADIA Study

By Reuters Staff

June 30, 2022

NEW YORK (Reuters Health) - For second-line HIV therapy, both dolutegravir and ritonavir-boosted darunavir regimens, plus two nucleoside reverse-transcriptase inhibitors (NRTIs), maintained good viral suppression during 96 weeks follow-up in the NADIA trial.

Dolutegravir was non-inferior to darunavir but had a greater risk of resistance in second-line therapy, according to the results published in The Lancet HIV.

The 96-week follow up data confirm the 48-week follow up data published in July 2021 in The New England Journal of Medicine (https://bit.ly/3ytiHn4).

"However, these longer-term follow-up data provide essential reassurance that even when dolutegravir is combined with NRTIs to which the virus has acquired resistance, and where treatment is delivered under conditions typical of the public health approach, including sparse (usually annual) viral load monitoring, viral suppression can be sustained in a high proportion of patients, compatible with targets considered necessary for achieving overall reduction in incident HIV infections at a population level," the study team writes.

The NADIA trial of second-line HIV treatment included 465 people living with HIV from seven sites in Kenya, Uganda, and Zimbabwe.

The observation that darunavir produced durable viral suppression without risk of resistance suggests that it "merits consideration for an expanded role in the public health approach," write Dr. Nicholas Paton with National University of Singapore and colleagues.

The 96-week results also show that maintaining tenofovir in second-line therapy is superior to switching to zidovudine.

Current World Health Organization (WHO) treatment guidelines for the public health approach to HIV treatment continue to recommend a switch from tenofovir to zidovudine at transition to second-line therapy, the investigators note.

"Our findings of superior viral suppression, less frequent viral rebound, greater CD4 cell count increase, and possible reduced risk of developing high-level dolutegravir drug resistance with maintaining tenofovir versus switching to zidovudine indicate that this recommendation should be revised to one of maintaining tenofovir," they say.

The author of a linked comment agrees.

"WHO's recommendation of switching to zidovudine if tenofovir is used in first- line ART no longer makes sense when considering the 96-week data of the NADIA study," writes Dr. Josep Llibre, with the Fight AIDS and Infectious Diseases Foundation and University Hospital Germans Trias, Badalona, Spain.

Dr. Llibre notes that "growing resistance to HIV drugs in Africa is threatening progress made in the global fight against the virus, and integrase resistance in particular must be tackled. Therefore, further studies are needed to fine-tune the activity of second-line regimens and mitigate integrase resistance selection in low-income countries. Meanwhile, ritonavir-boosted darunavir merits consideration for an expanded role in second-line ART in the public health approach in Africa."

The study was funded by Janssen. Several authors have financial relationships with the company.

SOURCE: https://bit.ly/3HX0uld and https://bit.ly/3Nr5UWv The Lancet HIV, June 1, 2022.