New drugs for tuberculosis treatment.

Available data on anti-tuberculosis drug research reveal different properties of the agents and provoke speculation about future directions. Higher doses of the rifamycins are promising and are currently being evaluated in regimens of shorter duration that the isoniazid plus rifampin-based, six-to-nine month-course therapy. Moxifloxacin and gatifloxacin might shorten tuberculosis treatment as well, possibly in combination with rifapentine, while SQ109 could enhance the activity of rifampin-containing regimens. On the other hand, co-administration of moxifloxacin and PA-824 could be active against latent tuberculosis, whereas linezolid, PA-824 and TMC207 are candidates for a rifampin-free regimen in multidrug-resistant and extensively-resistant tuberculosis. Unfortunately, shorter than existent treatment regimens based on the new agents discussed here are likely to take at least another decade to be fully developed and implemented in clinical practice.

Subclinical carotid atherosclerosis in HIV-infected patients: role of combination antiretroviral therapy.

BACKGROUND AND PURPOSE: Whether or not combination antiretroviral therapy (CART) alone directly contributes to accelerating atherosclerosis in HIV-infected patients has not been studied in depth. This study aimed to ascertain the relationship between this therapy and subclinical carotid atherosclerosis according to cardiovascular risk. METHODS: Sixty-eight HIV-infected patients with < or =1 cardiovascular risk factors and 64 with > or =2 risk factors completed the study protocol consisting of clinical, laboratory, and vascular evaluation by carotid high-resolution B-mode ultrasonography. Univariate and multivariate logistic regression analyses were performed with the presence of subclinical carotid atherosclerosis, defined by carotid intima-media thickness >0.8 mm or the presence of plaque being the dependent variable. RESULTS: Among the 132 enrolled patients, 93 (70.5%) were on CART and 39 (29.5%) had never been on antiretroviral therapy. In accordance with cardiovascular risk stratification, subclinical carotid atherosclerosis was found in 26.6% (17 of 64 patients) of the very low-risk group (10-year coronary risk <5%), 35.3% (12 of 34 patients) of the low-risk group (10-year coronary risk between 5% and 9%) and 76.5% (26 of 34 patients) of the moderate/high-risk group (10-year coronary risk > or =10%). Thus, 55 (41.7%) of the 132 HIV-infected patients had subclinical carotid atherosclerosis, and independent variables associated with carotid atherosclerosis (odds ratio; 95% CI) were: CART exposure (10.5; 2.8 to 39) and 10-year coronary risk > or =10% (4.2; 1.5 to 12). In very low coronary risk patients (<5%), age (per 10-year increment: 4.01; 1.12 to 14.38), systolic blood pressure (per unit mm Hg 1.07; 1.01 to 1.14), and CART exposure (8.65; 1.54 to 48.54) were independently associated with subclinical carotid atherosclerosis. CONCLUSIONS: CART should be considered a strong, independent predictor for the development of subclinical atherosclerosis in HIV-infected patients, regardless of known major cardiovascular risk factors and atherogenic metabolic abnormalities induced by this therapy.

Hypertension in HIV-infected patients: prevalence and related factors.

BACKGROUND: Little is known about hypertension in the HIV-infected population. This study aimed to assess the prevalence of hypertension and related factors in HIV-infected patients. METHODS: In this prospective cross-sectional study, 710 HIV-infected patients (626 on combination antiretroviral therapy and 84 naive) managed at the outpatient clinic of a tertiary hospital during 2003 and 802 controls completed the study protocol consisting of medical examination and a 6-month follow-up period including three control visits. RESULTS: Hypertension prevalence was 13.1% in HIV-infected patients and 13.5% in the control group. Age (per 10-year increment) (odds ratio [OR]: 1.92; 95% confidence interval [CI]: 1.48-2.48), body mass index (OR: 1.18; 95% CI: 1.10-1.27), and lipoaccumulation pattern of fat redistribution (OR: 2.26; 95% CI: 1.20-4.24) were independently and significantly associated with the presence of hypertension in HIV-infected patients at logistic regression analysis. CONCLUSIONS: The present results suggest no meaningful difference in prevalence of hypertension between subjects with and without HIV infection. Thus, the influence of combination antiretroviral therapy appears to have little impact on the prevalence of hypertension.

Metabolic syndrome among HIV-infected patients: prevalence, characteristics, and related factors.

OBJECTIVE: To assess the prevalence in HIV-infected patients of the metabolic syndrome as defined by the National Cholesterol Education Program, i.e., three or more of the following components: abdominal obesity, hypertriglyceridemia, low HDL cholesterol, high blood pressure, and high fasting glucose. RESEARCH DESIGN AND METHODS: In this cross-sectional study, 710 HIV-infected patients managed at the outpatient clinic of a tertiary hospital during 2003 completed the study protocol consisting of a medical examination and laboratory analysis after a 12-h overnight fast. RESULTS: Metabolic syndrome prevalence was 17% and increased from 5.1% among HIV-infected patients under age 30 years to 27.0% for those aged 50-59 years. Age (per 10-year increment) (odds ratio [OR] 1.41 [95% CI 1.12-1.77]), BMI (1.27 [1.19-1.36]), past and present protease inhibitor exposure (2.96 [1.03-3.55] and 4.18 [1.4-12.5], respectively) were independently associated with the metabolic syndrome on logistic regression analysis. Furthermore, only stavudine (d4T) (1.74 [1.01-2.98]) and lopinavir/ritonavir (2.46 [1.28-4.71]) were associated with the metabolic syndrome after adjustment for age and BMI. CONCLUSIONS: The prevalence of metabolic syndrome among these HIV-infected patients is similar to that previously reported in uninfected individuals. Of specific concern is the association of protease inhibitor exposure with the metabolic syndrome and, more specifically, with exposure to stavudine and lopinavir/ritonavir when individual antiretroviral drugs were analyzed.

Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients.

OBJECTIVES: To assess the effect of antiretroviral therapy (ART) adherence on survival in HIV-infected patients. DESIGN: Cohort study at a single hospital in Barcelona, Spain. METHODS: Data on HIV-infected patients older than 18 years of age who began ART during the period 1990 to 1999 were analyzed. Patients were considered nonadherent if the total dose of antiretroviral drug was less than 90% of that prescribed. Adherence was assessed through self-report and hospital pharmacy appointments. Cox regression with time-dependent variables was used. RESULTS: A total of 1219 patients were included. The first ART was with monotherapy in 23.7% of cases, with two drugs in 30.5%, and with triple therapy in 45.8%. In multivariate analysis, the variables that presented significant differences with respect to mortality were clinical stage at the beginning of treatment (AIDS: relative hazard (RH) = 2.97; 95% confidence interval [CI]: 2.14-4.13), CD4 cell count (<200 cells/microL: RH = 5.89; CI: 3.44-10.10), type of treatment (monotherapy: RH = 9.76; CI: 4.56-20.90; bi-therapy: RH = 9.12; CI: 4.23-19.64), and adherence (nonadherence: RH = 3.87; CI: 1.77-8.46). CONCLUSIONS: The modifiable factors most strongly associated with survival were type of treatment and adherence. It would be desirable to accompany therapy with intervention strategies intended to improve adherence.