Safety and efficacy of reduced doses of ritonavir (RTV) plus saquinavir (SQV) in the treatment of AIDS patients in Brazil

The use of reduced doses of Ritonavir (RIT) and Saquinavir (SQV) is considered a potent alternative in treating patients infected by HIV-1. We tested a combination of 300mg of RIT plus 600mg of SQV, twice daily, in association with two reverse transcriptase inhibitors to treat AIDS patients for a period of 6 monts. Evaluation of HIV-1 RNA plasma levels, CD4+/CD8+ cell count and biochemical/hematological parameters (liver enzymes, serum electrolytes, creatinin, blood glucose, uric acid, white blood cell count, platelet count, and hemoglobin level) were performed after 30, 90 and 180 days of therapy. Clinical failure and adverse reactions were also recorded in order to assess safety and efficacy of the treatment. A total of 30 AIDS patients (25 male; 5 female) were enrolled in the study. Eight patients discontinuede the therapy due to intolerance, 2 patients presented clinical failure (onset of AIDS defining events during the study period), 2 patients were excluded due to protocol violation. Five patients tolerated only a lower dose of RIT (400mg/day). Patients who completed 6 months of therapy had a drop in viral load from 4.8ñ.7log10median4.9log) to 3.4ñ1.0log10(median 2.6log), and an increase in CD4+ count from 109ñ86 cells/ml(median 84 cells/ml) to 249ñ114 cells/ml(median 265cells/ml), compared to baseline values. However, patients who used a lower dose of RIT (400mg/day) had a less impressive drop in viral load values(mean0.6log10RNA copies/ml) when compared with those using the 600mg/day of the drug(mean 2.4log10). The percentage of patients presenting undetectable levels of HIV-1 RNA in plasma was quite different for the 2 groups: 92 percent of patients with a viral load <400 RNA copies/ml were using 600mg of RIT. The combination of reduced doses of RIT and SQV reduced viral load >1.0log10 after 6 months in 83 percent of study patients. The dose of 600mg/day of RIT was more effective in reducing viral load than 400mg/day, but was less well-tolerated. CD4+ cell counts increased in all patients regardless of the RIT dose used.

Safety and Efficacy of Reduced Doses of Ritonavir (RTV) Plus Saquinavir (SQV) in the Treatment of AIDS Patients in Brazil.

The use of reduced doses of Ritonavir (RIT) and Saquinavir (SQV) is considered a potent alternative in treating patients infected by HIV-1. We tested a combination of 300mg of RIT plus 600mg of SQV, twice daily, in association with two reverse transcriptase inhibitors to treat AIDS patients for a period of 6 months. Evaluation of HIV-1 RNA plasma levels, CD4+/CD8+ cell count and biochemical/hematological parameters (liver enzymes, serum electrolytes, creatinin, blood glucose, uric acid, white blood cell count, platelet count, and hemoglobin level) were performed after 30, 90 and 180 days of therapy. Clinical failure and adverse reactions were also recorded in order to assess safety and efficacy of the treatment. A total of 30 AIDS patients (25 male; 5 female) were enrolled in the study. Eight patients discontinued the therapy due to intolerance, 2 patients presented clinical failure (onset of AIDS-defining events during the study period), 2 patients werc excluded due to protocol violation. Five patients tolerated only a lower dose of RIT (400mg/day). Patients who completed 6 months of therapy had a drop in viral load from 4.8+/-.7 log(10) median 4.9 log) to 3.4 +/- 1.0 log(10) (median 2.6 log), and an increase in CD4+ count from 109 +/- 86cells/ml (median 84cells/ml) to 249+/- 114 cells/ml (median 265 cells/ml), compared to baseline values. However, patients who used a lower dose of RIT (400mg/day) had a less impressive drop in viral load values (mean 0.6 log(10) NA copies/ml) when compared with those using the 600mg/day of the drug (mean 2.4 log(10)). The percentage of patients presenting undetectable levels of HIV-1 RNA in plasma was quite different for the 2 groups: 92% of patients with a viral load <400 RNA copies/ ml were using 600mg of RIT. The combination of reduced doses of RIT and SQV reduced viral load >1.0 log(10) after 6 months in 83% of study patients. The dose of 600mg/day of RIT was morc effective in reducing viral load than 400mg/day, but was less well-tolerated. CD4+ cell counts increased in all patients regardless of the RIT dose used.

Use of Standard Therapy for Tuberculosis is Associated with Increased Adverse Reactions in Patients with HIV.

Hepatitis due to anti-tuberculosis therapy is an infrequent, but potentially devastating event. In HIV positive patients with tuberculosis (TB), the consequences are likely to be even greater, as they frequently require other hepatotoxic medications. The object of our study was to determine the frequency of toxic hepatitis during therapy for TB. Included were 198 patients with a presumed or confirmed diagnosis of tuberculosis; of whom, 69 were HIV positive (35%), 75 were negative (38%) and 54 had unknown HIV status (27%). Toxic hepatitis occurred in 15/198 (8%) patients. The incidence of hepatitis in HIV patients was much greater than in HIV negative/unknown [RR=7.5 (2.2-25.6); p=0.0001] and the onset of hepatitis was short (median 7 days in HIV patients). During TB therapy, 1 in S (12.5%) patients taking ketoconazole developed hepatitis; 9/53 (17%) taking sulfamethoxazole-trimethoprim [RR=3.4 (1.1-9.3); p=0.03]. Among the 15 patients who developed hepatitis 11 required hospitalization (mean 19 days), 5 died (33.3%), 2/15 (13%) due to hepatitis. HIV positive patients had a significantly higher rate of toxic hepatitis during anti-tuberculosis therapy than those without HIV infection. Hepatitis occurred just after initiation of TB treatment. Clinical findings were non-specific and hepatic enzyme elevations were moderate, yet hospitalization and mortality rates were high. This suggests that in settings where careful monitoring of patients early in their course of TB treatment is routine, morbidity and mortality may be low, but poor monitoring would have potentially serious consequences. There is a need for new drug treatments (schedules or regimens) for TB in an effort to reduce these adverse events.

Once Daily Fleroxacin and Twice Daily Ciprofloxacin are Both Effective in the Treatment of Complicated Urinary Tract Infections.

In a multicenter randomized double-blind, trial, 90 patients received either fleroxacin 400mg pa once/day or ciprofloxacin 500mg po twice/day for treatment of complicated urinary tract infections (UTI). Treatment was administered orally and presumptively. Bacteriological efficacy was assessed 7 days post-treatment. In total, 78 patients were available for efficacy testing: 40 in the fleroxacin group and 38 in the ciprofloxacin group. The bacteriological cure rate was 92.5% and 94.7% in the fleroxacin and ciprofloxacin groups, respectively. The most commonly isolated pathogen (E.coli) was erradicated in 94.1% and 95.8% of the cases in fleroxacin and ciprofloxacin groups, respectively. Eight patients in the fleroxacin group had some adverse events, two of them severe (insomnia and photodermatitis). In the ciprofloxacin group, 11 patients had adverse events of mild to moderate intensity, mainly affecting the digestive system. ln conclusion, fleroxacin 400mg po once/day and ciprofloxacin 500mg po twice/day were both effective in the treatment of complicated urinary tract infections.