Switch of protease inhibitor-containing HAART in routine clinical practice: a four-year prospective observational study

An evaluation was made of the frequency of outcomes, the features, and one- year outcomes of the substitution, carried out because of failure or toxici ty, of protease inhibitor (PI)-containing highly active antiretroviral ther apy (HAART). Nine hundred and seventy-two HIV-infected patients were prospe ctively followed up since 1996, with the condition that they had a minimum 80% adherence to prescribed regimens. Four hundred and fifty-two changes oc curred in 397 of the 876 evaluable patients (45.3%). Virological and/or imm unological failure was of concern in 245 cases (54.2%). Interest in saquina vir had the greatest incidence and earliest occurrence (although the subseq uent switch had a significantly better outcome than that of patients failin g with other PIs); nelfinavir benefited from a shorter time to change and a worse long-term outcome (probably attributable to its predominant use in i ndinavir- and ritonavir-experienced patients); while indinavir showed the l owest overall frequency of substitution. Intolerance occurred in the remain ing 207 cases (45.8%); with saquinavir being better tolerated than other PI s. A favourable outcome was obtained more frequently when poor tolerability was of concern, compared with therapeutic failure (P<0.008), while no sign ificant differences were found according to prior antiretroviral experience and the subsequently selected HAART regimen. The overall one-year outcome per single substituted compound proved significantly better fur patients wh o stopped using saquinavir and ritonavir, by contrast with those who stoppe d using indinavir and nelfinavir (P<0.0008). A significantly shorter mean t ime to substitution was recognized for nelfinavir and saquinavir than with ritonavir and indinavir (P<0.0001). When analysing the subset of patients e xperiencing HAART failure, a highly significant reverse relationship was de monstrated between mean time to failure, and rate of subsequent response to a modified antiretroviral regimen (P<0.0001). When considering the differe nt patterns of efficacy, durability, resistance induction, expected adheren ce, and safety of each antiretroviral drug, initial and subsequent therapeu tic choices should be carefully balanced against expected benefits and risk s.