Determinants of response to first HAART regimen in antiretroviral-naïve patients with an estimated time since HIV seroconversion

To study the determinants of immunological and virological response to highly active antiretroviral therapy (HAART) in naïve patients, adjusting for time since HIV-1 seroconversion.

Data from HIV-cohort studies where dates of seroconversion have been reliably estimated. Methods In previously untreated patients, short- and long-term marker responses from HAART initiation (three or more antiretroviral drugs) to the end of follow-up or any treatment modification were considered using mixed effects models accounting for undetectable HIV viral load and informative dropout.

In total, 943 patients were treated with a first HAART regimen for a median of 29 months. In adjusted analyses, compared with a reference group of homosexual men without AIDS initiating treatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 and HIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log(10) HIV-1 RNA copies/mL at 1.5 months, P=0.03) and poorer long-term immunological response (522 vs 631 cells/microL at 24 months, P<0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/microL, P<0.0001), their immunological responses were similar to those of individuals without AIDS. Similarly, individuals further from seroconversion started HAART at lower CD4 counts (e.g. 311 vs 382 cells/microL at vs before 9 years from seroconversion, P<0.0001), but had similar CD4 responses. However, they experienced poorer long-term virological response (0.67 log(10) copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion.

Taking into account the time elapsed since seroconversion, this study suggests that careful choices of initial treatment should be made and intensive follow-up carried out in high-risk subgroups such as IDUs who have poorer responses.