Buongiorno from Florence, Italy, Doctor ! I have been on Structured interruption therapy for over 1,5 years and now it is time to start again (CD4 200). So Would like to ask which are my options considering my worst side effect so far has been fat loss. Started meds in 1999 zerit-viramune-videx cd4 500-600 viral load zero. in 2003 changed zerit in favor of tenofovir (and reduced videx to 250 mg). same results cd4 500-600 viral load zero. November 2004 interrupted treatment today cd4 200 and viral load 40.000. a Resistance test done in 2003 shows: MODEST: DDI TDF CONSISTENT:ABC D4T DDC HIGH: 3TC AZT DLV EFV NVP NO RESISTANCE TO PI AT ALL. I believe we have most of the meds you use in the States so based on the above which options can you suggest ? Grazie !!! Giancarlo

Hello and thanks for posting.

The resistance test results from 2003 are very interesting. The test showed high level resistance to Viramune, and partial resistance to the other 2 agents in that you were subsequently treated with. Based on these results, the last regimen would have been expected to fail, yet it was successful since you had an undetectable viral load and good CD4+ lymphocyte counts.

So if you tolerated the last regimen well, it might be possible to simply restart it and see if you again have the same positive response (in spite of the old resistance test which would predict failure of this strategy). But Videx (ddI) is associated with mitochondrial toxicity and may contribute to fat loss.

If your "case" was presented at a case conference, a mainstream recommendation would be that you be offered a boosted protease inhibitor regimen plus tenofovir plus ddI. This would fulfill the mandate for 3 active agents after taking into consideration the prior resistance test. But again, this resistance test did was not terribly helpful last time around, so relying on it to direct your next regimen may be problematic.

A number of studies have shown the potential efficacy of boosted PI monotherapy for HIV infection, and although this approach is not ready for prime time, it suggests that the 3 active agents are not always needed to control viral replication. But if boosted PI monotherapy is too new and risky, what about a regimen based on 2 active agents? The HIV treatment literature is replete with examples of sustainable virologic control with only 2 active agents in the combination. Our team has many patients with situations similar to yours, who have successful control on a boosted PI (mostly Reyataz/Norvir) plus one other active agent like tenofovir (Viread).

So there you have it utter confusion: Choice one recycle your last regimen which should not have worked last time, but did anyway. Choice 2 conventional triple therapy with boosted PI and 2 NRTIs (they like this in Boston). Choice 3 boosted PI monotherapy. Choice 4 boosted PI plus one NRTI to make a dual therapy regimen. The good news is that there are many good options; the bad news is that we do not have the studies to precisely inform treatment decisions in situations like yours. Let us know what you decide to do and how things turn out. Best of luck!