Dolutegravir in combination with an NRTI proves effective even in face of resistance

Data presented at CROI 2021 this week has shown that dolutegravir, when used in combination with two NRTI agents, provides effective viral suppression – even in NRTI-resistant patients.

The World Health Organisation (WHO) recommends dolutegravir (DTG) with two NRTIs as a second-line treatment for HIV, if NNRTI regimens such as those containing efavirenz and rilpivirine have not been effective.

However, the effectiveness of this regimen had not been sufficiently studied in cases where the activity of NRTI agents cannot be guaranteed due to drug resistance, or in the case of switching from tenofovir (TDF) to zidovudine (ZDV).

The NADIA study compared the efficacy of DTG and ritonavir boosted darunavir (DRV/r) versus TDF / lamivudine (3TC) and ZDV / 3TC for second line HIV treatment.

In total 464 people participated in the trial covering Uganda, Kenya and Zimbabwe between July and December 2019. Participants were assigned to receive DTG or DRV/r in combination with either TDF/3TC or ZDV/3TC. Analysis of viral load and immune health was to be performed at week 24 and 48.

Of the those participating 61% were women, 28% had a HIV viral load above 100,000 copies and 58.5% were resistant to TDF whilst 92% were resistant to 3TC.

At week 48: 90.2% of the DTG group had a viral load below 400 copies and 91.7% in the DRV/r group. In the subgroup without predicted NRTI activity 92.4% of those on DTG and 93.7% on DRV/r achieved <400 copies.

When comparing TDF to 3TC a viral load of <400 copies was found in 92.3% of the TDF group and 89.6% of the ZDV group.

Conclusion

Dolutegravir used in conjunction with two NRTI agents provides highly effective viral suppression at 48 weeks, even in patients with severe resistance and in the absence of predicted NRTI activity. Dolutegravir is non-inferior to boosted darunavir, which is in line with the WHO’s recommendations for the use of this regimen as a second-line HIV treatment. This study also demonstrates the safety of transition of stable patients from efavirenz to dolutegravir regimens without additions tests for viral load and resistance. Darunavir, however, when used with two NRTI agents remains a reliable alternative to dolutegravir

Lead investigator, Professor Nicholas Paton, confirmed that the study data may warrant changes to the WHO guidelines for switching from tenofovir to zidovudine. Indeed, as the results have shown, the TDF / 3TC regimen is equally effective both in combination with darunavir and with dolutegravir, even in patients with K65R / M184V resistance variants. Moreover, the tenofovir regimen is more attractive to patients and programs because it can be available in a combined single tablet form.