Viral load response at 4 weeks predicts treatment success

To prevent the development of drug resistance, it is useful to be able to predict at an early stage whether or not a treatment-naïve patient’s viral load will become undetectable (VL <50) after 24 weeks.

The possibility that results taken at week 4 of a given new treatment regimen could predict the outcome after 24 weeks was discussed by British and German researchers in the September 2004 issue of AIDS.

Previous studies have pointed toward a correlation between results at week 4, and those of week 24 – but the viral load lower limit was measured at 500 copies/mL, not using the ultra-sensitive assay.

This study looked at 656 anti-retroviral naïve patients attending three centres – Chelsea & Westminster and Royal Free hospitals in London, and the JW Goethe University Hospital in Frankfurt – who had had baseline viral loads measured before starting treatment and had subsequent viral load measurements recorded at close to 4 (range 2-6) and 24 (range 16-32) weeks. The majority (73%) of patients showed viral load suppressed to below 50 copies/mL and 51 patients (8%) had undetectable loads after just 4 weeks.

The association between viral load at week 4 and week 24 was statistically significant – with those patients who had the lowest viral load after 4 weeks being more likely to attain undetectable levels at week 24 (P<0.0001).

Indeed, for every 1-log higher viral load at week 4, the odds of having a viral load of <50 copies at week 24 decreased about 3-fold (odds ratio 0.35; 95% CI, 0.27 – 0.45). The researchers also found that patients with the lowest baseline viral loads were most likely to achieve virologic suppression at 24 weeks (P=0.0001).

Three hundred and sixty (84%) patients with viral load <1000 copies/mL at 4 weeks went on to experience viral suppression <50 copies/mL by week 24 – but only 61% of those with viral loads between 1001 and 10,000 copies/ml at 4 weeks did so.

Explanations for why the viral loads of some did not fall to below 1000 copies at week 4 include: inadequate adherence, poor absorption, pre-existing drug resistance, or a very high initial viral load.

In their discussion, the authors write: “Although we have shown that the week 4 viral load is associated with subsequent virologic outcome, it is unclear whether acting on this information will improve outcome. If there is suboptimal adherence, simplification of the regimen or some other intervention to improve adherence may be appropriate, although awareness of the possible implications of a high viral load at week 4 for future virologic response may in itself act as an intervention to improve adherence.”

They point out that they did not consider clinical outcomes or immune response to HAART, although viral response has been shown to be a good predictor of long-term clinical outcome.