A low rebound in viral load in patients taking a protease inhibitor does not have significant clinical or immunological consequences – in the mid-term at least, according to a French study published in the December 1st edition of Clinical Infectious Diseases, which is available now online.
Investigators analysed the records of 3736 HIV-positive individuals who started a protease inhibitor-containing HAART regimen between January 1997 and December 1998 at 68 treatment centres across France. All the patients initially achieved an undetectable viral load on HAART (below 500 copies/mL). Investigators wished to establish which factors were associated with three levels of effectiveness of HAART during the year after an initial undetectable viral load was achieved. These were a sustained undetectable viral load; a low rebound in viral load (between 500 copies/mL and 5000 copies/mL), and a high rebound in viral load (above 5000 copies/mL). The investigators also wished to see what impact each of these three levels of efficacy had on HIV disease progression and changes in CD4 cell count.
In the year after inclusion in the study, 2636 patients (70.6%) had a persistently undetectable viral load, with 387 individuals (10.4%) experiencing a low rebound in their viral load, and 713 patients (19%) a high rebound.
Patients with a previous AIDS diagnosis (p=0.006), a high HIV viral load at the time of starting HAART (p
Compared to patients who had never taken anti-HIV drugs before starting the PI-containing HAART regimen, those who had received prior therapy with one or two drugs were 50% less likely to achieve a sustained undetectable viral load, and individuals who had received treatment with more than two antiretroviral drugs were 66% less likely to achieve this outcome.
Individuals taking indinavir or saquinavir boosted by ritonavir were more likely to maintain an undetectable viral load than those taking ritonavir (OR 0.74, 95% CI 0.57 – 0.95, p=0.016) saquinavir hard gel (OR 0.50, 95% CI 0.41 – 0.61, p
Taking a long time (six months or more) to achieve an initial viral load below 500 copies/mL (OR 0.63, 95% CI 0.51 – 0.77, p
Unsurprisingly, the investigators found that the patients with the most sustained viral suppression had the largest median increase in CD4 cell count (163 cells/mm3 and that patients with high viral load rebounds, the lowest median CD4 cell gains (59 cells/mm3). The median increase in CD4 cell counts for patients with a low viral load rebound was 120 cells/mm3.
In the 12 months after first achieving an initial undetectable viral load, a total of 1041 patients experienced either a decrease in their CD4 cell count or a clinical event. Investigators calculated that the 15-month probability of clinical failure was 2.4% (95% CI, 1.7% – 3.4%) amongst patients with a persistently undetectable viral load, 2.2% (95% CI 0.9% - 5.3%) for individuals whose viral load rebounded to up to 5000 copies/mL, and 5.8% (95% CI, 3.6% - 9.2%) in patients with higher sustained rebound in viral load.
The corresponding 15-month probabilities if immunological failure were 37.2% (95% CI, 34.5% - 40%) for those with a sustained undetectable viral load, 39.7% (95% CI, 33.2% - 46.6%) for patients with a persistently low viral load, and 51.9% (95% CI, 46.5% - 57.3%) for individuals with a persistently high viral load.
”Hazard ratios for clinical and immunological failure were similar among patients with persistent undetectability and patients with low viral rebound, and they were significantly higher among patients with high viral rebound”, note the investigators.
This leads the investigators to conclude “among patients with low level rebound who are receiving PI-containing HAART, who have difficulties with treatment adherence, and who have previously been exposed to multiple antiretroviral regimens, delays in treatment switches may spare some therapeutic options for future use” They recommend that this strategy should be evaluated with regard to long-term outcome and the occurrence of drug resistance.
Further information on this website
CD4 and viral load tests - overview
Combination of indinavir/AZT/3TC still effective for majority of patients at 6 years, says US study - news story
Abgrall S et al. Clinical and immunological outcome in patients with human immunodeficiency virus infection, according to virologic efficacy in the year after virus undetectability, during antiretroviral therapy. Clinical Infectious Diseases 37 (on-line edition), 2003.