My most recent numbers were CD4 460 and undetectable. I take Truvavda and Isentress. I have not missed a dose; however, i have been late with some of my dosages, but never skipped. What are the chances of resistance and also, what does it mean to be undetectable? Essentially, can someone still get AIDS when they are undetectable? and can a regimen, although working well, eventually become ineffective?

To be undetectable means that the level of plasma HIV RNA is so low that our assays are unable to measure the level. This is usually reported as below the lower threshold of the assay, eg <50 or <75 copies/ml. Most people in this range have SOME detectable virus, between 3 and 48 copies.

Most people who are undetectable experience substantial immune reconstitution, with an average rise in their CD4 cells of around 100 cells/yr; in 15% of cases, this rise may be blunted, and this is more commonly seen in patients who start ART with very low CD4 cells below 1-200 cells/ml.

The vast majority of people who are well controlled on ART with undetectable viral loads do not progress to AIDS by developing CD4 cells below 200 cells/ml or by suffering an AIDS-defining illness, but that is not true of all patients. We still see some cases of HIV encephalopathy and HIV-related neoplasms, even in patients who are well-controlled, although such cases are increasingly uncommon.

We have long term studies of patients who are well controlled on ART who remain on the same regimen for up to 7 years with little change in the effectiveness of their regimen. Uncommonly, patients with full suppression and excellent experience will develop drug resistance, for unclear reasons, but this is also an increasingly uncommon event. The best opportunity for a patient to achieve durable success is to ensure optimal adherence, i.e. to take every dose within the prescribed interval.

It is always preferred for doses to be taken within the recommended dose interval. Once a person has achieved an undetectable viral load, as in your case, there is a little more flexibility in dose intervals, though I would caution you and other patients never to be lax about adherence. In one study in Boston, patients who are fully suppressed are taking their regimens during week days, and then taking the weekends off, and to date they are doing just as well as a group as a control group that takes their drugs every day. In another study, patients who are fully suppressed and taking their drugs every week were compared to a group who stopped the drug for 7 days, and then resumed for 7 days, and again, there was no difference in outcomes. It appears that the virus takes a few days to fully resume replication after a drug is stopped IN PATIENTS WHO HAVE AN UNDETECTABLE VIRUS. I caution you and other readers that these are research experiments that should not be generalized; I note the findings to explain the greater forgiveness of dosing intervals in patients who have achieved full viral suppression.

I urge you to talk to your doctor about your questions and these responses.