Risk factors for mortality in symptomatic hyperlactatemia among HIV-infected patients receiving antiretroviral therapy in a resource-limited setting.

OBJECTIVES: To determine the mortality rate and risk factors after experiencing symptomatic hyperlactatemia in HIV-infected patients receiving antiretroviral therapy (ART). METHODS: A retrospective cohort study was conducted among patients who were diagnosed with symptomatic hyperlactatemia (lactate >2.5mmol/l) between January 2004 and April 2006. All patients were followed until 3 months after the diagnosis. RESULTS: One hundred and twenty-five patients were included in the study. The mean+/-standard deviation (SD) age was 39.9+/-10.1 years and body weight was 58.2+/-16.9kg; 60.8% were male. Symptomatic hyperlactatemia in 114 (91.2%) was associated with receiving d4T, in five (4.0%) with d4T+ddI, in four (3.2%) with ZDV+ddI, and in two (1.6%) with ddI (d4T, stavudine; ddI, didanosine; ZDV, zidovudine). The median duration of ART was 13 months. Nine (7.2%) patients died. Patients who died had a higher mean lactate level (8.0 vs. 5.1mmol/l) and mean alanine aminotransferase (ALT; 164 vs. 48U/l) at the time of diagnosis when compared to those who survived (p<0.05). Patients who died had a lower mean weight than those who survived (48 vs. 59kg, p=0.008). By logistic regression, mortality was associated with patients whose body weight was <45kg (p=0.014, odds ratio (OR) 9.090, 95% confidence interval (CI) 1.575-52.632) and whose serum lactate was >10mmol/l (p=0.004, OR 20.372, 95% CI 2.610-159.001). CONCLUSIONS: The mortality rate of symptomatic hyperlactatemia among HIV-infected patients receiving ART is substantial. Almost all patients received d4T. Patients who have a low body weight and high serum lactate level are at a higher risk of mortality.

Effectiveness and metabolic complications after 96 weeks of a generic fixed-dose combination of stavudine, lamivudine, and nevirapine among antiretroviral-naive advanced HIV-infected patients in Thailand: A prospective study.

BACKGROUND: Generic fixed-dose combination (FDC) antiretroviral therapy (ART) has been widely used in resource-limited settings. Treatment based on these combinations provide low pill burden and are less expensive. OBJECTIVE: The aim of this study was to determine the long-term effectiveness and metabolic complications of a generic FDC of stavudine (d4T)/lamivudine (3TC)/ nevirapine (NVP), among ART-naive HIV-infected patients. METHODS: A prospective study was conducted among patients who were initiated on d4T/3TC/NVP between November 2004 and March 2005. Plasma HIV-1 RNA, CD4 and alanine transaminase were assessed every 12 weeks. Fasting plasma glucose (FPG) and lipid profile were determined at 96 weeks. Adverse events and genotypic drug resistance were recorded. The primary outcome of interest was the proportion of patients who achieved plasma HIV-1 RNA <50 copies/mL after 96 weeks of ART and analyzed by intent-to-treat (ITT) and on-treatment (OT) populations. RESULTS: There were 140 patients (mean [SD] age, 35.7 [7.6] years; male, 67.9%) enrolled in the study. Median (interquartile range [IQR]) baseline CD4 was 31 (14-79) cells/mm(3) and HIV-1 RNA count was 433,500 (169,000-750,000) copies/mL. At week 96, 87 patients (ITT, 62.1%; OT, 87.0%) achieved HIV-1 RNA -50 copies/mL. Median (IQR) CD4 at 96 weeks was 328 (229-450) cells/mm(3). The reasons for drug discontinuation were as follows: drug resistance (9.3%), lost to follow-up (9.3%), NVP- related rashes (7.9%), death (5.0%), d4T-related adverse events (3.6%), and transferred to another hospital (2.1%). At 96 weeks, 25 patients (28.7%) had low-density lipoprotein cholesterol (LDL-C) >130 mg/dL, 7 (8.0%) had LDL-C >160 mg/dL, 6 (6.9%) had triglycerides >400 mg/dL, and 2 (2.3%) had FPG >126 mg/dL. Eleven patients (12.6%) had a lactic acid level >2.5 mmol/L. Eight patients (9.2%) needed to take antihypertensive agents. Of 13 patients who developed virologic failure, 76.9% and 61.5% had M184V/I and Y181C/I mutations, respectively. CONCLUSIONS: Initiation of this FDC ofd4T/3TC/NVP in these ART-naive patients with advanced HIV infection and low baseline CD4 cell count was effective at 96 weeks of follow-up with regard to virologic and immunologic responses. However, long-term metabolic complications, particularly dyslipidemia, were common and should be closely monitored.

Plasma nevirapine levels, adverse events and efficacy of antiretroviral therapy among HIV-infected patients concurrently receiving nevirapine-based antiretroviral therapy and fluconazole.

BACKGROUND: The clinical data of plasma NVP level, safety and efficacy of antiretroviral therapy (ART) for the concurrent use of nevirapine (NVP)-based ART and fluconazole (FLU) is scanty. METHODS: A retrospective study was conducted in patients who were initiated NVP-based ART between October 2004 and November 2005. The objectives were to compare NVP levels, adverse events, and 36-week efficacy of NVP-based ART between patients who did not receive FLU (group A) and those who received FLU 200 mg/day or 400 mg/day (group B). RESULTS: There were 122 patients with mean +/- SD age of 36 +/- 9 years; 81 in group A and 41 in group B. Median (IQR) baseline CD4 cell count was 29 (8-79) cell/mm3 in group A and 19 (8-33) cell/mm3 in group B (P = 0.102). Baseline characteristics between the two groups were similar. Mean +/- SD NVP levels were 6.5 +/- 3.0 mg/L in group A and 11.4 +/- 6.1 mg/L in group B(P < 0.001). One (2.4%) patient in group B developed clinical hepatitis (P = 0.336). Six (7.4%) patients in group A developed NVP-related skin rashes (P = 0.096). There were no differences in term of 36-week antiviral efficacy between the two groups (P > 0.05). CONCLUSION: Co-administration of NVP and daily dosage of FLU (200 mg/day and 400 mg/day) results in markedly increased trough plasma NVP level when compared to the administration of NVP alone. The concurrent use of NVP and FLU in very advanced HIV-infected patients is well-tolerated. The immunological and virological responses are favorable.