• Impact of Treatment Interruption on Plasma Viral Load, CD4 Count and Virtual Phenotypes (Virco) in HIV Patients Who Failed Multiple Courses of Antiretroviral Therapy (Abstract 111)
  Speaker: A. Tesiorowski
  Authored by Tesiorowski, A.; Harris, M.; Harrigan, R.; O'Shaughnessy, M.; Montaner, J.; British Columbia Centre for Excellence in HIV/AIDS, Canadian HIV Trials Network, St. Paul's Hospital, University of British Columbia, Vancouver, Canada

The purpose of this observational study was to assess changes during treatment interruption in plasma viral load, absolute CD4 count, genotypic resistance and virological and immunological response to subsequent antiretroviral therapy.

The study examined HIV-infected, treatment-experienced patients, who had stopped treatment due to virological failure and who had documented genotypic resistance to >2 classes of ARV therapy.

Thirty-one male patients were studied; they had a mean age of 38 years and a mean duration of treatment interruption (TI) of 24 weeks (5-111).

Some researchers, most notably Veronica Miller, have maintained that patients who revert to wild-type virus may do better after treatment interruption. The current investigators examined various factors to see if there was some way to predict who would switch to wild type.

Patients were restarted on therapy. There was not statistically significant difference between those who had wild-type virus and those who did not. Both groups achieved undetectability on ultrasensitive testing.

Nor was there any significant difference in CD4 response in the two groups.

The authors concluded that treatment interruption of 5-111 weeks caused significant increases in pVL and a loss of CD4 cells. Genotypic resistance profiles analyzed by virtual phenotype change considerably after treatment interruption. Once again, while most viral isolates lost their resistance to D drugs, 3TC, abacavir and PIs, there was a tendency to retain resistance to NNRTIs and AZT. Patients with lower nadir CD4 counts were more likely to retain resistant virus and reversion to wild type was not associated with any better response to ARV therapy.

Not much in this study is really surprising. Most data over the last two years has tended to support the notion that the reversion to wild-type virus does not give any better outcome to salvage therapy. The greater decreases in pVL seen in early studies were most likely due to the higher levels seen in patients who were off therapy (if you've got further to drop you can get a bigger log decrease). This study should help lay to rest the need for treatment interruption before real salvage therapy. It may be nice to give patients a "break" before resuming therapy, but it is not necessary, and, as other studies have shown, the large decrease in CD4 levels seen puts some patients at risk of developing opportunistic infections.

The most interesting information was the continued presence of detectable phenotypic resistance to NNRTIs after treatment interruption. Fully 75% of patients who showed NNRTI resistance prior to treatment interruption still showed it after treatment interruption. This should be reassuring for those who are just beginning to use phenotyping, since it alleviates some of the worry that we will miss archived mutations if we don't have prior phenotypes. That worry is clearly still valid, though, for most of the drugs.

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