If you aren’t aware yet, the NADIA trial team (Nucleosides And Darunavir/Dolutegravir In Africa) published their data findings in one of the world’s most prestigious journals – the New England Journal of Medicine (NEJM). It is a feat worth celebrating for the Infectious Diseases Institute (IDI) at the gallant Makerere University, Uganda, and Africa at large.
The NADIA trial evaluated options for second-line antiretroviral therapy in people living with HIV, particularly those who were failing on efavirenz or nevirapine as their first-line treatment. Here they put dolutegravir against ritonavir-boosted darunavir to ascertain whether the former was non-inferior (at least as good as) to the latter. They also assessed whether, despite an assumed cross-resistance to medications like tenofovir, lamivudine, or zidovudine – continuing a tenofovir-lamivudine regimen was non-inferior to zidovudine-lamivudine switch.
The trial intended to treat. The researchers conducted the study in Uganda, Kenya, and Zimbabwe: recruited 464 participants and followed them up for 48 weeks, monitoring their viral load with a primary outcome of 400 viral copies per millilitre of blood. By week 48, 90.2% of the patients in the dolutegravir group and 91.7% in the Darunavir group had achieved the primary outcome. Also, 92.3% in the tenofovir group and 89.6% in the zidovudine group had attained the primary outcome. The findings showed that dolutegravir was at least as good as darunavir, and so was tenofovir when compared to zidovudine.
The results from this trial are commendable for several reasons. First, before the NADIA trial, the World Health Organisation recommended a dolutegravir-based regimen as second-line therapy for HIV-1 infection. But evidence that supported its efficacy was lacking in a setting when efavirenz and nevirapine were no longer efficacious due to drug resistance. Also, there was no evidence to back switching from tenofovir to zidovudine as the preferred drug amongst those taking the former.
Second, there had been a general roll-out to dolutegravir among people living with HIV previously taking efavirenz or nevirapine-based regimen. And the public health specialists, as well as clinicians, needed evidence to support the policy. The NADIA trial just provided it.
Third, both tenofovir and zidovudine can have serious adverse effects, but zidovudine side effects are more apparent than tenofovir. Zidovudine causes bone marrow suppression that culminates in anaemia that may warrant blood transfusions. Tenofovir can cause kidney damage in susceptible individuals. The ability to avoid the twice-daily dosing of zidovudine without compromising the new regimen efficacy is crucial to maintain drug adherence.
In a nutshell, we commend IDI for such a marvellous job they have done. One thing to pull off a policy changing clinical trial, and the other having your data published in the NEJM. To further elucidate this achievement, about 5% of the 16,000 manuscripts submitted to this journal achieve publication. NEJM has the highest journal impact factor among all medical journals. So, not celebrating with this prestigious institute for accomplishing such an achievement is an act of bad faith.