Immune gains can persist for three years after viral rebound
A study of 483 patients who began receiving protease inhibitor therapy before 1998 shows that in those who experienced failure of the regimen, immune system improvements on therapy persisted for a median of three years.
The findings add further weight to the view that for patients who have experienced failure of multiple regimens, treatment continues to provide benefit even when it is not possible to assemble a new regimen that can control viral load below 50 copies/ml.
The study, conducted at San Francisco General Hospital by Dr Steven Deeks, also found that the viral load reduction that occurred after starting PI therapy was a significant predictor of immunologic failure (defined as a CD4 cell decline to pre-treatment levels). Those who experienced a viral load reduction of less than 1.13 log after starting the PI-containing regimen were significantly more likely to experience immunologic failure when compared to those who had experienced a viral load reduction of at least 1.68 log.
Two hundred and ninety one patients experienced treatment failure after starting a pI-containing regimen. Treatment failure was defined as two consecutive viral load measurements above 500 copies.
Those with viral load above 31,000 copies/ml after treatment failure were at significantly higher risk of immunologic failure than those with viral load below 1,000 copies/ml.
Factors which may have created bias in the results
People who discontinued treatment were twice as likely to experience immunologic failure, regardless of their pre-treatment viral load (typically the level at which viral load stablises after rebound on treatment interruption). If those who discontinued therapy were excluded from the analysis, the delay between viral rebound and immunologic failure became longer.
The authors admit that the study may have underestimated the true rate of immunologic failure, since some individuals switched therapy after treatment failure. Twenty nine per cent of those who experienced treatment failure were able to switch to a successful salvage regimen, and were censored from the analysis at this point.
Implications
The authors suggest that “our data provide support for a more conservative strategy, particularly for those patients with limited therapeutic options. For patients achieving some degree of viral suppression below pre-therapy levels, continuing a well-tolerated regimen despite ongoing viral replication may be beneficial.”
They suggest that where limited treatment options are available, it may be better to stick with an existing treatment that is well tolerated rather than trying to assemble a more complex salvage regimen that is poorly tolerated.
The findings also lend further weight to the observation that people from the same cohort had lower rates of T-cell destruction at any given level of viral load than untreated people with wild type virus.
Deeks S et al. Duration and predictors of CD4 T-cell gain in patients who continue combination therapy despite detectable plasma viremia. AIDS 16: 201-207, 2002.
Deeks S et al. CD4+ T cell kinetics and activation in human immunodeficiency virus-infected patients who remain viremic despite long-term treatment with protease inhibitor-based therapy. Journal of Infectious Diseaeses 185: 315-23, 2002.