Morphologic and metabolic changes associated with protease inhibitor (PI) therapy have been reported since the introduction of PIs for treatment of human immunodeficiency virus infection. These changes were measured 12-20 months after initiation of PI therapy in a cross-sectional study involving 614 patients from the Antiprotéases Cohorte (APROCO) Study (Agence Nationale de Recherches sur le Sida-EP11). The prevalence was 21% for isolated peripheral atrophy, 17% for isolated fat accumulation, 24% for mixed syndrome, 23% for glucose metabolism alterations, 28% for hypertriglyceridemia (triglyceride level, > or =2.2 mM), and 57% for hypercholesterolemia (cholesterol level, > or =5.5 mM). Age was significantly associated with different phenotypes of lipodystrophy and metabolic alterations, but body-mass index, CD4(+) cell count, and type of nucleoside reverse-transcriptase inhibitor or PI received were not constantly associated with these changes. Furthermore, in all models tested, exposure to stavudine was associated with lipoatrophy and exposure of ritonavir was associated with hypertriglyceridemia. Detection and management of these disorders should be implemented to prevent further complications.

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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...

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