High-dose saquinavir plus ritonavir: long-term efficacy in HIV-positive protease inhibitor-experienced patients and predictors of virologic response.

The year-long antiviral efficacy of a high-dose salvage regimen consisting of saquinavir (800 mg twice daily) plus ritonavir (400 mg twice daily) was evaluated in 58 HIV-positive patients who had seen no improvement under first-line protease inhibitor-containing regimens, nor in baseline predictors of virologic response. The efficacy of therapy was determined by CD4+/CD8+ and HIV-1 RNA values. The primary endpoint of our study was the percentage of patients with HIV-1 RNA levels <200 copies/ml (virologic success) at 6 and 12 months of of follow-up. Secondary endpoints were log10 reduction in HIV-1 RNA levels and CD4+ increases through follow-up. Surrogate markers related with a lower HIV-1 RNA area under the curve were identified at baseline. Kaplan-Meier analysis and Cox proportional hazards models were applied to identify baseline predictors of achieving viral suppression at <200 copies/ml. All analyses were intention to treat-last observation carried forward. Patients achieved a median HIV-1 RNA level reduction of >0.5 log through 1 year (-0.59 log10 at 12 months), as well as CD4+ counts increased significantly (89 cells/mm3 at 12 months). Overall, 53% of patients were likely to achieve HIV-1 RNA levels <200 copies/ml at 6 months. Seventy-six percent of patients who started therapy at HIV-1 RNA levels <5000 copies/ml but only 42% with baseline viral load of 5000 to 30,000 copies/ml and 18.7% with baseline viral load >30,000 copies/ml were likely to achieve viral suppression at 6 months (p < .001, log-rank test). Patients with baseline HIV-1 RNA levels between 5000 and 30,000 copies/ml (relative hazard [RH], 0.39; 95% confidence interval [CI], 0.01 to 0.98; p = .0396) and patients with baseline HIV-1 RNA levels >30,000 copies/ml (RH, 0.20; 95% CI, 0.07-0.61; p = .0040) were less likely to reach undetectable HIV-1 RNA levels than those with baseline HIV-1 RNA levels <5000 copies/ml. Salvage highly active antiretroviral therapy (HAART) strategies including saquinavir (SQV) at high doses plus ritonavir (RTV) exert a significant long-term efficacy in more than half of PI-experienced patients without significant additional toxicity. This therapeutic efficacy is strongly implemented by a switch at the lower HIV-1 RNA levels.

[Value of HIV-1 viral load and CD4 lymphocyte count as determinants of progression to AIDS and survival]. / Valor de la carga viral del VIH-1 y de los linfocitos CD4+ como determinantes de la progresión a sida y de la supervivencia.

BACKGROUND: HIV-1 viral load is regarded as a better surrogate marker for progression and death than CD4+ cell counts. Both markers are analysed in a cohort of patients with unknown seroconversion date and advanced HIV infection. PATIENTS AND METHODS: Retrospective cohort analysis of 421 patients, most on antiretroviral therapy, with a median initial CD4+ cell count of 209 x 10(6)/l and a median initial viral load of 4.7 log copies/ml. One thousand two hundred and eighty-six samples were analysed. Univariate and bivariate analysis were performed with initial and sequential CD4+ cell counts and viral load values to estimate the risk of progression and death by Cox regression models. RESULTS: After a median follow up of 763 days, 124 patients developed AIDS and 117 died. Relative risks of progression related to the group that maintained viral load values always < 35,000 copies/ml were: 5-fold (95% CI: 1.4-17.0; p < 0.05) for patients with any viral load value > 35,000 copies/ml but always < 200,000 copies/ml; and 13.6 fold (95% CI: 5.4-34.2; p < 0.0001) for patients who could not maintain viral load < 200.000 copies/ml. CD4+ counts = 100 x 10(6)/l and viral load = 220,000 copies/ml were the threshold values that best fitted to estimate the probability of survival by a bivariate analysis. CONCLUSIONS: The maintenance of sequential viral load values < 35.000 copies/ml is associated with a lower risk of progression. The maintenance of sequential viral load values < 150,000 copies/ml is associated with higher short-term survival rates.

[Acute pancreatitis in patients infected with the human immunodeficiency virus]. / Pancreatitis aguda en pacientes infectados por el virus de la inmunodeficiencia humana.

This study was designed to define the etiological spectrum of acute pancreatitis in patients infected with HIV in our environment and to evaluate the relevance of cytomegalovirus as etiological agent. A retrospective analysis was first made of clinical, analytical, radiological and pathological findings of patients infected with HIV clinically diagnosed of acute pancreatitis (period 1984-1993). Then, clinical records of patients with necropsy proven CMV pancreatic involvement were retrospectively analyzed (period 1985-1992) to evaluate whether they had been diagnosed of acute pancreatitis when alive. Nine cases were diagnosed of acute pancreatitis. A presumptive etiology (didanosine) was considered in seven cases and idiopathic in two. Five patients died, two from causes directly related to acute pancreatitis. Necropsy was performed in two cases. Mortality was associated with the development of renal insufficiency or the appearance of three or more complications (p = 0.039). With regard to the second phase of the study CMV pancreatic involvement was demonstrated in 4 necropsies out of a total of 22 with evidence of CMV infection in one or more organs. None of these patients was diagnosed of acute pancreatitis when alive. Acute pancreatitis is an uncommon entity in patients infected with HIV. Presumptively, it could be attributed to didanosine therapy in most of our cases. The mortality rate was high, particularly when renal failure developed. In no case was CMV involved as etiologic agent when the patient was alive, although necropsy showed that pancreas can be subclinically involved in the context of a CMV disseminated infection.