Asda Vibhagool

Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV

Background:Atazanavir, an azapeptide protease inhibitor (PI), has pharmacokinetics that allow once-daily dosing, and it is not associated with significant PI-associated dyslipidemia. Methods:A randomized, double-blind, double-dummy, active-controlled, 2-arm study comparing the antiviral efficacy and safety of atazanavir 400 mg administered once daily with efavirenz 600 mg administered once daily in combination with open-label fixed-dose zidovudine plus lamivudine twice daily. The 810 treatment-naive patients were stratified by HIV RNA level. The primary efficacy end point was the proportion of treated patients with HIV RNA levels <400 copies/mL through week 48. Results:At week 48, HIV RNA levels were <400 copies/mL in 70% of patients receiving atazanavir and 64% of patients receiving efavirenz (intent-to-treat, difference; 95% confidence interval: 5.2%; −1.2%, 11.7%). Median CD4+ cell counts increased at comparable magnitudes and rates in the 2 treatment arms (mean change at week 48: 176 cells/mm3 with atazanavir, 160 cells/mm3 with efavirenz). Atazanavir-treated patients relative to comparator-treated patients did not demonstrate significant increases in total cholesterol, fasting low-density lipoprotein cholesterol, or fasting triglycerides over 48 weeks of therapy. Atazanavir-linked bilirubin elevations infrequently resulted in treatment discontinuation (<1%). Atazanavir treatment did not increase fasting glucose or insulin levels. Conclusions:For initial HIV treatment, a highly active antiretroviral therapy regimen of atazanavir/zidovudine/lamivudine is as efficacious and well tolerated as the combination of efavirenz/zidovudine/lamivudine.

Ceftriaxone Compared with Sodium Penicillin G for Treatment of Severe Leptospirosis

A prospective, open-label, randomized trial at Khon Kaen Hospital (Thailand) was conducted from July 2000 through December 2001 to compare the clinical efficacies of ceftriaxone and sodium penicillin G for the treatment of severe leptospirosis. A total of 173 patients with severe leptospirosis were randomly assigned to be treated with either intravenous ceftriaxone (1 g daily for 7 days; n=87) or intravenous sodium penicillin G (1.5 million U every 6 h for 7 days; n=86). The primary outcome was time to fever resolution. Survival analysis demonstrated that the median duration of fever was 3 days for both groups. Ten patients (5 in each group) died of leptospirosis infection. There were no statistically significant differences in the duration of organ dysfunction. Ceftriaxone and sodium penicillin G were equally effective for the treatment of severe leptospirosis. Once-daily administration and the extended spectrum of ceftriaxone against bacteria provide additional benefits over intravenous penicillin.

The TREAT Asia HIV Observational Database: baseline and retrospective data.

Background:Relatively little is known regarding HIV disease natural history and response to antiretroviral treatments among Asian people infected with HIV. The Therapeutics Research, Education, and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) is a recently established collaborative observational cohort study that aims to assess HIV disease natural history in treated and untreated patients in the Asia-Pacific region. Methods:Observational data are collected on HIV-infected patients from 11 sites in the Asia-Pacific region. Data are centrally aggregated for analyses, with the first baseline and retrospective data transferred in September 2003. Retrospective data were analyzed to assess the response to highly active antiretroviral treatment (HAART) over a 6-month period in terms of changes in CD4 count and proportions of patients achieving an undetectable HIV viral load (<400 copies/mL). Results:By the end of May 2004, 1887 patients had been recruited to the TAHOD. Seventy-two percent of patients were male, with median age 36 years. Seventy-eight percent of patients reported HIV infection through heterosexual contact. Forty-three percent of patients had a previous AIDS diagnosis, of whom 55% had tuberculosis. The mean 6-month CD4 count increase was 115 cells/μL (SD = 127) after starting triple-combination therapy. Smaller CD4 count increases were associated with a higher CD4 count before starting treatment, prior treatment with monotherapy or double therapy, and treatment with a HAART regimen containing a nucleoside reverse transcriptase inhibitor (NRTI) and/or protease inhibitor (PI) but without a nonnucleoside reverse transcriptase inhibitor (NNRTI). Five hundred and ninety-eight patients started HAART and had a viral load assessment at 6 months, with 69% attaining an undetectable viral load. Older patients, patients not exposed to HIV through heterosexual contact, and patients treated with HAART containing NRTIs and NNRTIs but without PIs were found to be more likely to achieve an undetectable level. Conclusion:Analyses of retrospective data in the TAHOD suggest that the overall response to HAART in Asian populations is similar to that seen in Western countries.

Discontinuation of Secondary Prophylaxis for Cryptococcal Meningitis in Human Immunodeficiency Virus-Infected Patients Treated with Highly Active Antiretroviral Therapy: A Prospective, Multicenter, Randomized Study

A prospective, multicenter, randomized study was conducted with human immunodeficiency virus (HIV)-infected patients who were successfully treated for acute cryptococcal meningitis, were receiving secondary prophylaxis, and were naive for antiretroviral therapy. Patients were randomized to continue or discontinue secondary prophylaxis when the CD4 cell count had increased to >100 cells/microL and an undetectable HIV RNA level had been sustained for 3 months. At a median of 48 weeks after randomization, there were no episodes of cryptococcal meningitis in either group.

Efavirenz 600 mg/day versus efavirenz 800 mg/day in HIV-infected patients with tuberculosis receiving rifampicin: 48 weeks results.

The potential of drug–drug interaction between efavirenz and rifampicin is a major concern in the treatment of HIV and tuberculosis. The optimal efavirenz dosage is still unclear. Our randomized control trial study recently reported the similar efavirenz level between efavirenz 600 and 800 mg/day in HIV-infected patients receiving rifampicin. We report the similar virological and immunological outcomes at 48 weeks between the two groups. Efavirenz 600 mg/day should be sufficient for concurrent use with rifamipicin.

Efavirenz levels and 24-week efficacy in HIV-infected patients with tuberculosis receiving highly active antiretroviral therapy and rifampicin

Background:Concomitant use of efavirenz and rifampicin is common for treatment of HIV and tuberculosis. Plasma efavirenz levels can be reduced by rifampicin, but the appropriate daily dosage of efavirenz is unclear. Methods:HIV-infected patients with active tuberculosis, receiving rifampicin > 1 month, were randomized to receive stavudine and lamivudine plus efavirenz 600 or 800 mg daily. Plasma efavirenz levels were measured (at 12 h after dosing and on day 14) by high-performance liquid chromatography. Plasma HIV RNA was assessed at 16 and 24 weeks after antiretroviral therapy. Results:Baseline characteristics were comparable in the 84 patients (two groups of 42). Median plasma efavirenz levels were 3.02 mg/l (range, 0.07–12.21) in the 600 mg group and 3.39 mg/l (range, 1.03–21.31) in the 800 mg group (P = 0.632). Plasma efavirenz levels were < 1 mg/l in 3 of 38 (7.9%) patients in the 600 mg group and in none of the 800 mg group (P = 0.274). Approximately 40 and 45% of patients had efavirenz levels > 4 mg/l, respectively. There was no significant difference in time to HIV RNA < 50 copies/ml (P = 0.848). Conclusions:Median plasma efavirenz levels were comparable among both groups. Efavirenz 600 mg/day should be sufficient for most Thai HIV-infected patients receiving rifampicin with body weight approximately 50 kg. These results may not be applicable to other ethic populations who have higher body weights. However, the study of long-term virological and immunological outcomes is needed and under further investigation.

Experience with the use of a first-line regimen of stavudine, lamivudine and nevirapine in patients in the TREAT Asia HIV observational Database

The antiretroviral treatment (ART) combination of stavudine, lamivudine and nevirapine (d4T/3TC/NVP) is the most frequently used initial regimen in many Asian countries. There are few data on the outcome of this treatment in clinic cohorts in this region.

Nevirapine- versus efavirenz-based highly active antiretroviral therapy regimens in antiretroviral-naïve patients with advanced HIV infection.

To compare virological and immunological responses to nevirapine (NVP)‐based and efavirenz (EFV)‐based highly active antiretroviral therapy (HAART) regimens in antiretroviral‐naïve patients with advanced HIV infection.

Initiation of highly active antiretroviral therapy in advanced AIDS with CD4 < 50 cells/mm3 in a resource-limited setting: efficacy and tolerability

In developing countries, patients often present late with advanced AIDS and a very low CD4 cell count. A retrospective cohort study was conducted in HIV-infected patients who had been initiated into highly active antiretroviral therapy (HAART) with CD4 cell count <50 cells/mm3. There were 159 patients of mean age 36.6 years and 60.4% had previous major opportunistic infections. Mean CD4 was 22 cells/mm3 and 80% had HIV RNA>100,000 copies/mL. The majority of HAART regimens is non-nucleoside reverse transcriptase inhibitor-based (81.8%). In as-treated analysis, 50, 71.2, 79.7, 79.4, and 80.1% of patients achieved undetectable HIV RNA (<50 copies/mL) at 12, 24, 36, 48, and 60 weeks, respectively. The corresponding mean CD4 counts were 95, 125, 166, 201, and 225 cells/mm3. Twenty two patients (13.8%) had adverse drug events and half of these had to discontinue HAART. Initiation of HAART in advanced AIDS with CD4 cell count <50 cells/mm3 is effective, safe, and well tolerated and should not be delayed.