The majority of individuals in the EuroSIDA cohort experiencing virologic failure of their anti-HIV treatment do not experience large increases in viral load over a 12 month period, according to findings published in the latest edition of Antiviral Therapy.
The EuroSIDA cohort is an observational cohort that has recruited patients at 64 centres throughout Europe. This study looked at 488 patients who still had viral load between 1,000 copies/ml and 10,000 copies/ml more than six months after starting their first HAART regimen. The majority of patients had already received nucleoside analogues before commencing a triple drug regimen. Individuals who subsequently experienced a viral load decline below 500 copies/ml were excluded from the analysis, as were individuals whose viral load was already above the level recorded before starting any antiretroviral therapy.
After 12 months follow-up, 62.5% of the group remained on the failing regimen, and after 24 months 35.6% remained on the failing regimen (95% CI 30.7%-40.5%). When observation of treatment failure began, the median viral load was 3,162 copies/ml.
The median viral load increase was +0.024 log10 copies/ml per month (P=0.0001), the equivalent of a viral load increase from 1,000 copies/ml to 2,000 copies/ml, or from 10,000 to 20,000 copies/ml, in the course of a year. The median CD4 cell count fell by 0.53 cells per month (range –25, +5) (p=0.0001). In one third of patients the CD4 cell count increased by at least 1 cell per month, and in a further third it increased by at least 2 cells per month, suggesting that immune reconstitution continued, or was not compromised, in the majority of patients despite ongoing viral replication above the limits of detection.
Surprisingly, the researchers found that people receiving NNRTI-containing triple combinations were significantly less likely to have switched treatment within tweleve months of treatment failure compared to people taking protease inhibitor-containing regimens. People taking regimens containing more than three agents were significantly more likely to switch within twelve months than people taking a protease inhibitor with two NRTIs.
The researchers suggest that the main reason for this observation is likely to be the greater tolerability of NNRTI-containing regimen rather than any effect of such regimens on the replicative capacity of the virus. Researchers in San Francisco have previously suggested that a lack of viral rebound and preservation of CD4 cell gains may be attributed to a reduced ability of HIV to replicate after the development of certain drug resistance mutations.
The authors paln to look at the evolution of resistance in relation to viral rebound in this patient group in the future.
Cozzi-Lepri A et al. Changes in viral load in people with virological failure who remain on the same HAART regimen. Antiviral Therapy 8: 127-136, 2003.