t data from the U.K. CHIC Study showed that the risk of HIV rebound, or virological breakthrough, decreases with longer duration of viral suppression, regardless of the number of previous failed antiretroviral regimens.

At the 8th Congress on Drug Therapy in HIV Infection this month in Glasgow, researchers from London presented data from an expanded analysis designed to determine whether previous treatment interruptions are associated with an increased risk of virological rebound after restarting therapy.

All patients who achieved undetectable viral load (50 copies/mL or less) for the first time while receiving HAART were followed until rebound occurred (defined as 2 consecutive viral load measurements > 400 copies/mL or one such measurement followed by a change of regimen). Treatment interruptions were defined as discontinuation of all treatment for at least 2 weeks at any time after starting HAART.

Results

17.3% of subjects (2246 out of 12,997) had at least 1 treatment interruption before their first episode of virological suppression; 15.8 had 2 interruptions, and 1.5% had 3 or more interruptions.

Of these, about one-third interrupted non-nucleoside reverse transcriptase inhibitor (NNRTI) regimens, nearly half interrupted protease inhibitor (PI) regimens, and about 15% interrupted regimens consisting of only nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs).

The median number of treatment interruptions per patient was 1, and the median length per interruption was about 150 days.

The following rates of virological rebound were observed:

- 2202 instances in 31,060 person-years (PY) among patients with no treatment interruptions (7.1 per 100 PY);
- 704 instances in 5799 PY among patients with 1-2 interruptions (12.1 per 100 PY);
- 106 instances in 472 PY among patients with 3 or more interruptions (22.5 per 100 PY);

Adjusting for viral load at the time of treatment interruption, patients with undetectable HIV RNA when they interrupted therapy were not at greater risk of subsequent virological rebound after restarting therapy, compared with those who had no interruptions.

However, having 1-2 interruptions of therapy with viral loads above 400 copies/mL was associated with a 34% greater risk of later virological rebound.

Having 3-4 interruptions with detectable viral load was associated with a 89% greater risk of later rebound.

Conclusion

The researchers suggested that virological rebound may occur after treatment interruptions with detectable viral load because even low-level viral replication facilitates the emergence of resistance mutations. They urged that patients should be made aware of the potential risks of treatment interruption, even if they are able to regain virological suppression after a treatment break.

11/28/06

Reference
L K Bansi, A A Benzie, C A Sabin, and others. Are treatment interruptions associated with higher viral rebound rates in patients with viral suppression? 8th Congress on Drug Therapy in HIV Infection (HIV8). Glasgow. November 12-16, 2006. Abstract PL8.3.