Virologic and immunologic response to a boosted double-protease inhibitor-based therapy in highly pretreated HIV-1-infected patients.

PURPOSE: To assess the virologic and immunologic response to a boosted double-protease inhibitor (PI) regimen of highly pretreated patients infected with HIV-1 and to examine the role of PI resistance and concentration of serum saquinavir. METHOD: In an open-label prospective study, lopinavir/ritonavir, saquinavir-sgc, lamivudine, and other nucleoside analogues were offered to highly pretreated patients who had advanced HIV-1 infection and who had failed at least 2 previous highly active antiretroviral therapy regimens including at least 1 nonnucleoside reverse transcriptase inhibitor. The relationship between baseline drug resistance and steady-state saquinavir serum levels and early (week 4) and sustained (week 48) virologic response was documented. RESULTS: 35 advanced HIV-1 patients were enrolled. The boosted double-PI regimen was well tolerated. Twenty-two (63%) of the 35 patients had a > 0.8 log(10) decrease in HIV viral load at week 4. After 48 weeks of follow-up, the 22 patients who remained on the study therapy had an average decrease in viral load of 1 log(10) and had a median increase in CD4 cells of 60 cell/microL. Multiple logistic regression analysis indicated that genotypic resistance to both PIs and the week-3 trough concentrations of saquinavir were associated with virologic outcome at week 4. The presence of > or = 6 lopinavir mutations [odds ratio (OR) 0.03; 95% CI 0.01 to 0.79] and the 48V mutation (OR 0.01; 95%CI <0.01 to 0.88) was independently associated with lower odds of achieving an early response, whereas a higher saquinavir concentration at week 3 (OR 8.36; 95% CI 1.28 to 54.70) was associated with greater odds of an early response. CONCLUSION: These findings suggest that baseline PI resistance and saquinavir concentration were associated with virologic response and should be considered when planning salvage therapy.

Significance of microalbuminuria in long-duration type 1 diabetes.

OBJECTIVE: The value of microalbuminuria (MA) in predicting renal disease and premature mortality in longer duration type 1 diabetes is unclear. RESEARCH DESIGN AND METHODS: We followed 135 patients with long-standing type 1 diabetes (>30 years' duration) over a 7-year period, recording albuminuria and other clinical variables. Vital status was ascertained and cause of death was recorded. RESULTS: A total of 27 of 135 patients (20%) died during the follow-up period. Patients with MA (10 of 30, 33.3%) or proteinuria (5 of 6, 83.3%) at initial examination were more likely to die during follow-up than patients who had normal albumin excretion at baseline (12 of 99, 12%; chi(2) for trend 21.9, P < 0.0001). The presence of abnormal albumin excretion and low BMI were independent risk factors of premature death. The causes of death were similar in patients with normal and abnormal urine albumin excretion. A total of 24.4% of initially normoalbuminuric survivors developed MA, and persistent proteinuria developed in 3.5%. Progressors had significantly higher albumin excretion rate at baseline compared with those who remained normoalbuminuric: 9.0 microg/min (3.8-18) vs. 4.0 microg/min (0.4-17.5); P < 0.001. A total of 21% of patients with MA at baseline reverted to normoalbuminuria, and persistent proteinuria developed in 32%. The likelihood of progression to persistent proteinuria was significantly greater in those with baseline MA compared with those with normal albumin excretion (P < 0.001). CONCLUSIONS: Even in long-standing type 1 diabetes of >30 years' duration, MA and proteinuria predict all-cause mortality. MA is a good predictor of persistent proteinuria.