Four‐drug induction regimen for patients with high baseline viral load

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Early virologic changes after treatment have been associated with long‐term virologic success. The objective of this pilot, randomised, prospective study is to evaluate the effect of an induction, 4‐drug HAART regimen in patients with high baseline viral load. Twenty‐one naïve patients with HIV‐RNA>100,000 copies/ml were randomised to TDF+FTC+EFV (1); TDF+FTC+EFV+RAL (2), TDF+FTC+RAL (3). Viral load, CD4 and immune activation markers were evaluated at days 7, 14, 30, 60, 120 from the start of therapy. Mean age was 38.2 years, 19 (90.5%) were male, and the main risk factor for HIV infection was heterosexual contacts in 52.4% of patients. The mean baseline viral load was 265,266 copies/ml and the mean CD4 cell count was 314 cell/mm3. CD8+CD38+HLA‐DR+ cells mean was 38%. No difference was observed among the three groups. Early HIV‐RNA reduction was significantly higher in group 2 at day 7 (P=0.007), 14 (P=0.018), 30 (P=0.046) after HAART start, thereafter HIV‐RNA values were comparable among the groups. No significant differences were observed at any time‐point between group 1 and group 3. The viral decay (delta VL), evaluated as reduction of viral load, was faster and higher in group 2 at any time‐point; the reduction was statistically significant (compared to group 1 and 3) after 7 days (P=0.006), but not thereafter. No differences were observed between group 1 and 3 (Figure, panel A). At the end of follow‐up (120 days) only patients in group 2 reduced HIV‐RNA below<3 copies/ml in 30% of cases. Although not statistically significant (probably because of the small sample) immune recovery, as measured by the increment of CD4 cells, was greater in the two groups receiving RAL (Figure, panel B). At the end of the follow up the mean increment was 142 cells/mm3 in group 1; 258 cells/mm3 in group 2 and 360 cells/mm3 in group 3. No difference was observed as far as the reduction of immune activation is concerned. A 4‐drug regimen in naïve patients with high pre‐therapy viral load improves early virologic response, that has been proved to be a prognostic marker for sustained virologic response. CD4 cell recovery is much higher in patients receiving RAL compared to those treated with EFV. This study highlights the importance of a personalised therapy especially in high‐risk patients. Further studies are necessary to define the best therapeutic regimen in patients with high baseline viral load.image