Early ART is not associated with a higher risk of HIV drug resistance
Simon Collins, HIV i-Base
A paper using observational data from the HIV CAUSAL collaboration, published ahead-of-print in the journal AIDS, is helpful in allaying the concern of developing drug resistance with early ART. 
This question is important because viral load does not always become undetectable in a small percentage of people on first-line ART – commonly due to pre-existing drug resistance or intermittent adherence. This, together with a concern for side effects at a time when people were asymptomatic, was a reason for running the large randomised START trial. 
While START clearly showed that clinical benefits of early ART at high CD4 count outweighed the risk of side effects, leading to recommendations in 2015 for universal access to treatment, START hasn’t yet reported on drug resistance.
The current paper, from Sara Lodi and colleagues, used a retrospective analysis of samples from more than 50,000 people with baseline CD4 counts >500 cells/mm3 before ART.
The results showed no significant differences in the development of resistance by CD4 count in 794/2,672 with resistance test results. The estimated 7-year risk (95% CI) of acquired drug resistance was 3.2% (2.8 to 3.5), 3.1% (2.7 to 3.3) and 2.8% (2.5 to 3.0) for starting ART with CD4 counts >500, 350 to 500 and < 350 cells/mm3 respectively. When the analysis was restricted to people with baseline in 2005–2015, the corresponding estimates were 1.9% (1.8 to 2.5), 1.9% (1.7 to 2.4) and 1.8% (1.7 to 2.2).
Although these data were not protected by randomisation, the results are reassuring from a real world setting that there is no signal that accumulation of drug resistance is a risk from earlier ART.
It is important to note that this data was from countries with good access to viral load and genotype testing.
- Lodi S et al. Effect of immediate initiation of antiretroviral treatment on the risk of acquired HIV drug resistance. AIDS: Post Acceptance: November 10, 2017 doi: 10.1097/QAD.0000000000001692,
- Initiation of antiretroviral therapy in early asymptomatic HIV infection. Lundgren JD, Babiker AG, Gordin F, Emery S, Grund B, Sharma S, Avihingsanon A, Cooper DA, Fätkenheuer G, Llibre JM, Molina J-M, Munderi P, Schechter M, Wood R, Klingman KL, Collins S, Lane HC, Phillips AN, Neaton JD. NEJM 2015; 373(9):795-802. (27 August 2015).