Nucleoside Analogue Use Before and During Highly Active Antiretroviral Therapy and Virus Load Rebound

Patients who use nucleoside reverse-transcriptase inhibitors (NRTIs) before highly active antiretroviral therapy (HAART) have an increased rate of virus rebound. Study of rebound according to specific NRTIs used might inform which NRTIs retain activity once others have failed. We focused on 2280 patients who had received zidovudine and either didanosine or lamivudine before starting HAART, started HAART that included zidovudine with didanosine or lamivudine or stavudine with didanosine or lamivudine, and had virus loads <500 copies/mL within 24 weeks. In a Cox model, the relative hazard (RH) of virus rebound for having switched from zidovudine to stavudine (vs. retaining zidovudine) was 0.94 (95% confidence interval [CI], 0.77-1.15), which suggests little or no benefit in terms of reduced rebound rate. Having switched from didanosine to lamivudine, or vice versa, was associated with a reduced rebound rate (RH, 0.59 [95% CI, 0.48-0.73]), which suggests that these drugs retain appreciable activity after use of the other and of zidovudine.