Impact of Newly Available Drugs on Clinical Progression in Patients with Virological Failure after Exposure to Three Classes of Antiretrovirals

Objective To study the prognosis of HIV-infected patients with virological failure after exposure to three classes of antiretroviral drugs (ARVs).Design Cohort study. Setting: French Hospital Database on HIV.Patients Patients previously exposed to at least two nucleoside reverse transcriptase inhibitors (NRTIs), two protease inhibitors and one non-NRTI, with viral load (VL) values of >5000 copies/ml after the exposure criteria were met and a new treatment initiated between 1998 and 2001 with VL >5000 copies/ml.Main outcome measures Risk of new AIDS-defining-events (ADEs) or death from first introduction of a drug never used before occurring between 1998 and 2001 defined as baseline.Results The main baseline characteristics of the 1092 patients were: previous ADE in 49% of cases, median CD4 cell count 181 µl, median VL 4.9 log10copies/ml, median duration of ARV therapy 5.0 years and previous exposure to a median of nine ARVs. The crude progression rates were 20.1/100 patient-years among patients included in 1998, 15.1 in 1999, 11.1 in 2000 and 8.6 in 2001. After adjustment for baseline characteristics, the calendar year of inclusion was associated with the risk of clinical progression (P<0.001). When the types of newly available drugs used at baseline or during follow-up were introduced into the model, year of inclusion was no longer associated with the risk of clinical progression (P=0.42), while exposure to amprenavir/r, lopinavir/r, abacavir or tenofovir was associated with a lower risk.Conclusions The clinical prognosis of heavily pretreated patients experiencing virological failure improved between 1998 and 2001, mainly thanks to the use of newly available drugs with more favourable resistance profiles.