Strategies for first line HIV therapy

May 2008     View PDF     En español

What to start first: NNRTIs or PIs?

No large study has yet been done that definitively shows which drug class is the better to start. So far, we know that when a person’s HIV level remains under 50 for at least one year on therapy, it usually remains that way for at least another two years, assuming good adherence. This is true for almost any combination used.

Less clear is how much the choice of a first regimen impacts how well a second one will work. In most cases if a person starts therapy with a PI, he or she will likely be able to use Sustiva successfully as second line therapy. So far, there are less data on the other way around, but there’s no reason to think there would be a difference.

Perhaps the most limiting factor of all the drugs is cross resistance. When a person’s HIV develops a high level of resistance to one drug in a specific class, it will generally have at least some resistance to the other drugs in that class. When HIV develops even low levels of resistance, it causes the drug to be less potent.

Some people believe that the best first line strategy is to take whatever is the most potent. The most powerful and long-lasting effects come from a person’s first regimen. The longer a person stays on it without major side effects or resistance, the better. The longer it continues working, the more likely that new drugs may be approved in the meantime, giving more options for second and third line regimens. As a rule, boosted PIs like Kaletra are con­sidered the most potent and long-lasting.

Others feel that saving potent and longer lasting medications for second line therapy is the better strategy. They think that starting treatment with an NNRTI is better. This would likely work for most people for some time and it keeps PIs for later. Unlike the PIs, it’s also hoped that the NNRTIs and NRTIs will have fewer long-term effects on cholesterol and triglycerides or fat redistribution (lipodystrophy), though these data are mixed. Again, the theory has some merit, but no studies prove this is the better long-term strategy.