It was concluded that only conventional cardiovascular risk factors are independently associated with increased IMT in HIV-infected patients.

The response to regimens including lopinavir-ritonavir (LPV/r) in patients who have received multiple protease (PR) inhibitors (PI) can be analyzed in terms of human immunodeficiency virus type 1 (HIV-1) genotypic and pharmacokinetic (pK) determinants. We studied these factors and the evolution of HIV-1 resistance in response to LPV/r in a prospective study of patients receiving LPV/r under a temporary authorization in Bordeaux, France. HIV-1 PR and reverse transcriptase sequences were determined at baseline LPV/r for all the patients and at month 3 (M3) and M6 in the absence of response to treatment. pK measurements were determined at M1 and M3. Virological failure (VF) was defined as a plasma viral load >400 copies/ml at M3. , and the individual exposure to LPV were also included covariates. Sixty-eight patients were enrolled. Thirty-four percent had a virological response at M3. An LPV mutation score of >5 mutations, the presence of the PR I54V mutation at baseline, a high number of previous PIs, prior therapy with ritonavir or indinavir, absence of coprescription of efavirenz, and a lower exposure to LPV or lower LPV trough concentrations were independently associated with VF on LPV/r. Additional PI resistance mutations, including primary mutation I50V, could be selected in patients failing on LPV/r. Genotypic and pK parameters should be used to optimize the virological response to LPV/r in PI-experienced patients and to avoid further viral evolution. Treatment of human immunodeficiency virus (HIV)-in-fected individuals with combination therapy including protease inhibitors (PI) results in a significant suppression of HIV replication (1, 2, 3, 11) and in improvement in clinical outcomes, with marked reductions in HIV-associated morbidity and mortality (5, 9). However, the efficacy of antiretroviral (ARV) treatment can be impaired by several factors, including poor compliance with treatment regimens, suboptimal antiviral potency and drug concentrations, and selection of ARV-resistant HIV quasispecies (6). Resistance to PI is driven by the selection of primary mutations located close to the active site of the HIV type 1 (HIV-1) protease, producing significant changes in the affinity of the binding of the inhibitor to the mutant active site (4) and often occurs early during virological rebound. Secondary resistance mutations may be selected later and may compensate for the initial decrease of viral fitness related to the appearance of primary mutations. These secondary mutations tend to be common to all PI, facilitating the emergence of resistance to the whole PI class.Lopinavir (LPV)-ritonavir (LPV/r) is a coformulation of lopinavir, an HIV PI, and low-dose ritonavir, which inhibits LPV metabolism and which enhances plasma LPV levels (12). LPV/r has shown significant potency in treatment-naive and in PI-experienced patients. Few data concerning the determinants and the emergence of drug resistance in LPV/r-treated patients are available. In the LPV/r arm of a first-line ARV therapy protocol, all virological fa...

Background-The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear.Methods-We analyzed data on 20,379 treatment-naive HIV-1-infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of followup, 1844 AIDS events, and 1005 deaths).Results-Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART).Conclusions-Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART.

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