Study suggests WHO should reconsider guidance on second-line HIV therapy
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Study findings reported this week at the Conference on Retroviruses and Opportunistic Infections suggest that WHO should reconsider part of its guidance on second-line therapy for HIV, researchers said.
Specifically, the findings indicated that tenofovir is superior to zidovudine, although WHO continues to recommend a switch to zidovudine, according to Nicholas Paton, MD, FRCP, a professor of medicine at the National University of Singapore, and colleagues.
Paton presented 96-week data from the Nucleosides and Darunavir/Dolutegravir (NADIA) trial.
“The study was prompted by the weakness of the evidence base for WHO's 2018 recommendation to use dolutegravir combined with two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line therapy in the public health approach, given the known high rates of resistance in the NRTI drugs in program settings,” Paton told Healio.
Last year at the conference, Paton and colleagues reported 48-week results from the trial, which demonstrated that the regimen offered highly effective viral suppression in people with HIV who failed a first-line regimen.
“There was a risk of a public health catastrophe if the WHO recommendation turned out to be incorrect,” Paton said.
The trial enrolled 464 patients at seven sub-Saharan African sites who were failing a first-line, nonnucleoside reverse transcriptase inhibitor-based regimen. The researchers randomly assigned participants to receive dolutegravir or ritonavir-boosted darunavir, plus tenofovir or zidovudine. All participants also received lamivudine. More than half of participants had intermediate-to-high level resistance to tenofovir at baseline, and more than 90% had resistance to lamivudine.
According to the 96-week data presented this year, dolutegravir was noninferior — but not superior — to darunavir, with rates of viral suppression calculated to be 89.9% and 86.9% in the two treatment arms, respectively.
Six participants to date had intermediate- to high-level dolutegravir resistance and none had darunavir resistance. Five of the cases of resistance were in the zidovudine group, Paton and colleagues reported.
“Darunavir looks good ⎼⎼ better than the other protease inhibitor tested against dolutegravir in second line and probably deserves to be bumped up the hierarchy to be the preferred protease inhibitor in WHO guidelines [although] it currently languishes behind lopinavir and atazanavir as an ‘alternative,’” Paton said. “Switching to zidovudine in second line belongs in the dustbin of history. WHO need to revise their guidelines, pronto.”
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