March 08, 2021
3 min read
Source / information
Published by:
Source:
Paton N et al. Abstract 94. Presented at: Conference on Retroviruses and Opportunistic Infections; 6-10 March 2021 (virtual meeting).
Disclosure:
Paton reports that the study was funded by Janssen. He also reports that he has received honoraria for lectures and advisory board membership from AbbVie, as well as a Janssen research grant for a tuberculosis trial.
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Newly reported study results provided support for a guideline recently passed by WHO recommending dolutegravir plus two nucleoside reverse transcriptase inhibitors as the preferred second-line therapy for HIV, a researcher said.
The randomized controlled trial of nucleosides and darunavir / dolutegravir (NADIA) showed that therapy with dolutegravir (DTG) plus two nucleoside reverse transcriptase inhibitors (NRTIs) provided highly effective virus suppression in people with HIV who were first-line -Nonnucleoside Reverse Transcriptase Inhibitor Failed (NNRTI) -based regimen.
“We can now be sure that with DTG plus two NRTIs in second-line therapy after NNRTI failure, good virological responses are achieved – as good as a protease inhibitor (PI) and two NRTIs, even if the NRTIs in the spine are predicted to be inactive , ” Nicholas Paton, MD, FRCP, Healio said, a professor in the medical school at the National University of Singapore.
Paton presented the results of the study during the conference on retroviruses and opportunistic infections.
The results also indicated that the regimen was effective in a patient population with no predicted activity for prescribed NRTIs. This can have important implications for patients who switch from an NRTI-only regimen to an NRTI with DTG after treatment failure.
“This is particularly good news for resource constrained environments where resistance testing is not widely available. As a result, it is often not possible to ensure the prescription of DTG with fully active NRTIs,” said Paton.
“Full reservations” guidelines
Speaking at a press conference on the results, Paton said that the WHO 2018 guidelines recommending DTG with two NRTIs as the preferred second-line therapy in a public health approach to resource-constrained environments were based on a randomized controlled trial that identified “many gaps left behind in the evidence. “
“The guidelines were full of reservations about this group with no predicted active NRTIs,” he told Healio. “The guidelines effectively bounced off a long-proven effective second-line regimen – one PI plus two NRTIs – for one with a potentially massive problem when implemented in a public health approach, but luckily it turned out to be as well call. NADIA has proven that this is safe, at least in the short term, for up to 48 weeks. I would expect the guidelines in the next issue to be much more confident about this recommendation. “
“Reassuring” results
For the study, Paton and colleagues enrolled 464 HIV patients from sub-Saharan Africa in an open, non-inferiority study that experienced treatment failure with NNRTI, tenofovir (TDF), and lamivudine (3TC). They randomly selected patients who received either DTG or ritonavir-enhanced darunavir (DRV / r) and TDF or zidovudine. All patients also received 3TC.
The researchers rated the patients’ viral loads at 24 and 48 weeks and set the percentage of patients with weekly viral loads less than 400 copies / ml at week 48 as the primary outcome of the study.
The results showed that 58.5% of the patients had moderate to high resistance to TDF and 92% had resistance to 3TG at the start of the study. At week 48, the percentage of patients with a viral load less than 400 copies / ml was 90.2% in the DTG group and 91.7% in the DRV / r group. In patients not predicted to have active NRTIs, the percentage of patients with viral loads below 400 copies / ml was 92.4% in patients receiving DTG and 93.7% in patients in the DRV / r arm.
Paton said dolutegravir was “not inferior, but not superior to darunavir”.
“Our results are reassuring even for large-scale programs that are currently switching patients [efavirenz (EFV) to DTG (+TDF/ 3TC)] Regimen, often without a viral load test, therefore again concerns about patients with occult viral load recovering with accumulated NRTI resistance; Our results allay those fears, ”said Paton. “These patients should be doing well.”
Paton said the main limitation of the analysis was that researchers could only access 48 weeks of follow-up data so far. However, there are plans to follow up all patients after 96 weeks – which may allow “more robust conclusions” to be painted.
“It looks like we don’t fully understand how NRTI resistance works when these drugs are combined with very potent drugs like DTG and DRV / r, and that the combination of TDF / 3TC in particular creates a solid backbone Even if the theory and the resistance tests suggest that it should be affected by mutations from previous use, ”he said.
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