As long as your HAART regimen isn't based on abacavir or nevirapine as the third drug to go with your nucleoside reverse transcriptase inhibitor (NRTI) backbone, there appears to be no difference in CD4 counts after two years if you start HAART when your CD4 count is above 200 cells/mm3, according to the calculations of a Dutch-British team who presented their data at the first full day of the Ninth European AIDS Conference in Warsaw. This difference did not appear to relate to early response to treatment.
Using a mathematical model, they calculated that the predicted difference in absolute CD4 counts after two years was about 150 CD4 cells/mm3 between those taking what they found was the least potent regimen (abacavir-based HAART with an AZT+3TC backbone) and the most potent regimen (nelfinavir-based HAART with a d4T+3TC backbone).
The team analysed data from 1349 drug-naive members of the observational ATHENA cohort who started their first-line HAART containing a 3TC+AZT (n=1076) or 3TC+d4T (n=273) backbone combined with either abacavir, or one NNRTI (efavirenz or nevirapine) or a single or boosted PI (not including atazanavir), the most common being indinavir (n=264), nelfinavir (n=228), full dose ritonavir (n=129) and lopinavir/r (n=118).
They calculated the average slope of the CD4 count rise during the first 18 weeks on HAART and then modelled results based on 96 weeks on the same regimen (assuming optimal adherence) adjusting for the duration of regimen, CD4 count and plasma viral load, at baseline and at 18 weeks, age, gender, risk group (i.e. heterosexual, gay or IDU transmission) and year of initiating HAART.
They found that there was no significant difference in predicted CD4 rise at 96 weeks in those who had less than 200 CD4 cells/mm3 at 18 weeks, for either the NRTI backbone used, or the third drug.
However, for those who had a CD4 count above 200 cells/mm3 at 18 weeks, there was a statistically significant difference between those who were on nevirapine-based and abacavir-based HAART after 96 weeks (p=0.002 and p=0.005, respectively). Surprisingly, those on lopinavir/r-based HAART had a predicted worse CD4 increase than nevirapine, but due to the small number of people on Kaletra who had a CD4 count above 200, this was not found to be statistically significant (p=0.07). The reason for this discrepancy appears to be that Kaletra was the newest drug at the time of the study, and was reserved for those with the lowest CD4 counts.
Whilst this is interesting data, it is based on mathematical modelling and not on real world results. It also does not take into account more recent advances in therapeutic drug monitoring, PI-boosting and the availability of new drugs. So, although their predictions for abacavir and ring true based on recent trial results, their predictions for nevirapine and lopinavir/r do not correlate with the latest data.
Still, perhaps this presentation serves as a reminder that most currently used HAART regimens are able to increase CD4 counts substantially, and that it is the clinically important differences - e.g. short and long-term toxicity and emergence of resistance - which should have priority when deciding on a first-line HAART combination.
Gras L et al. Predicting the long term slope Of CD4+T-cell counts for different Highly Active Antiretroviral Therapies in therapy naïve patients Ninth European AIDS Conference, Warsaw, abstract F4/1, 2003.