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

Objective: 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. Design: 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. Results: In total, 943 patients were treated with a first HAART regimen for a median of 29 months. Inadjusted analyses, compared with a reference group of homosexual men without AIDS initiatingtreatment 4 years after seroconversion, injecting drug users (IDUs) were treated at similar CD4 andHIV RNA levels but had poorer short-term virological response (2.54 vs 2.13 log₁₀ HIV-1 RNAcopies/mL at 1.5 months, P=0.03) and poorer long-term immunological response (522 vs 631 cells/mL at 24 months, P <0.0001). Although individuals with AIDS at HAART initiation had lower CD4 counts (206 vs 382 cells/mL, 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/ μL 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 log₁₀ copies/mL/year smaller decline, P<0.0001) compared to those treated before 9 years from seroconversion. Conclusion: 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.