Endpoints
Few patients may achieve undetectability: change in HIV RNA may be more relevant than % undetectable
The classic clinical composite endpoint “progression or death” may not be as relevant in persons taking many drugs. It may be worth considering composites that also incorporate major toxicities, like cardiovascular disease
A secondary endpoint should be rates of genotypic and phenotypic resistance, to both the study agent(s) and the BG Tx
Since we are (in general) defining salvage populations based on virologic response (or rather, lack thereof) it may be less productive to even use HIV RNA as a primary endpoint - there are clearly people who remain healthy despite elevated HIV RNA - theories about “crippled virus” abound. It is worth considering CD4 as the primary surrogate outcome. After all it is clearly the best predictor of short to mid term risk