ART Resistance Spreads: A Top HIV Clinical Development of 2017
With expansion of the use of antimicrobial agents comes the inevitable expansion of microbial drug resistance -- and so it is with antiretrovirals. In a 2017 World Health Organization (WHO) report on surveillance for pre-treatment antiretroviral drug resistance conducted in 11 countries (Uganda, Namibia, Zimbabwe, Cameroon, Nicaragua, Guatemala, Argentina, Brazil, Mexico, Colombia, Myanmar), six had rates of resistance to efavirenz (Sustiva, Stocrin) or nevirapine (Viramune) above 10%. For people who were antiretroviral-experienced and initiating or re-initiating first-line therapy, over 20% had evidence of non-nucleoside resistant virus. Remarkably, two-thirds of infants diagnosed in a South African early diagnosis program had viral resistance to this class of medications.
The WHO report articulates several actions centered largely on improved monitoring for drug resistance, support for medication adherence and care engagement, and the building of greater laboratory capability to reliably measure plasma viral load, which is woefully unavailable for millions on HIV therapy.
The Bottom Line
In a perspective in the New England Journal of Medicine, Beyrer and Pozniak, thinkers known for their prescience, warn that core first-line drug resistance threatens hard-won gains in bringing HIV therapy to more people across the globe, as well as the effectiveness of pre-exposure prophylaxis (PrEP), and that the response must go beyond the measures called for in the WHO report. Primarily, they advocate for the use of agents with high barriers to resistance as initial and salvage therapy. Expanded rollout of newer generation integrase inhibitors such as dolutegavir and bictegravir, as well as modern boosted protease inhibitors, could make a huge dent in combatting the development and spread of resistant HIV. Harking back to my first top 2017 HIV clinical development, "The Cost of Cuts in HIV Spending", they too share their fear that funding cuts to essential programs, such as the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the Centers for Disease Control and Prevention, USAID, the State Department, and the Global Fund, will be a retreat that will hasten the obsolescence of our HIV medications and erase the startling progress that has saved millions and could save millions more.
David Alain Wohl, M.D., is a professor of medicine in the Division of Infectious Diseases at the University of North Carolina (UNC). He is site leader of the UNC AIDS Clinical Trials Unit at Chapel Hill, director of the North Carolina AIDS Education and Training Center (AETC), and co-directs HIV services for the North Carolina state prison system. In 2014, he became co-director of the UNC-Duke Clinical RM Ebola Response Consortium.