ABSTRACT
BACKGROUND: The effects of ezetimibe on cholesterol metabolism in HIV-infected patients receiving boosted protease inhibitors have not been thoroughly assessed. The aim of this study was to assess cholesterol homeostasis in patients with PI associated dyslipidemia and its relationship with the response to treatment with the cholesterol-absorption inhibitor ezetimibe. METHODS: Fifteen patients with ritonavir-boosted PI-containig therapy and LDL-cholesterol > 3.36 mmol/L (>130 mg/dL) were assessed at baseline and after an 8-week course of ezetimibe 10 mg/d. Serum non-cholesterol sterols were measured at each visit as markers of cholesterol synthesis and absorption. Total-, LDL-, and HDL-cholesterol triglycerides, apolipoproteins A1 and B, high sensitivity C-reactive protein, CD4 cells and HIV-1 RNA were also measured. RESULTS: Ezetimibe treatment was well tolerated in all patients and resulted in significant reductions in total cholesterol (-11.4%, p = .002), LDL-cholesterol (-20.4%, p = .003), non-HDL-cholesterol (-13.4%, p = .002) and apolipoprotein B (-9.1%, p = .021). Treatment with ezetimibe was associated with decreased cholesterol absorption markers (campesterol-to-cholesterol ratio -43.0%, p = .001; sitosterol-to-cholesterol ratio -41.9%, p = .001) and increased synthesis markers (lathosterol-to-cholesterol ratio 53.2%, p = .005). Baseline absorption or synthesis markers were unrelated to the response to treatment. CD4 cell count and plasma HIV-1 RNA remained unchanged. CONCLUSIONS: The level of cholesterol absorption or synthesis does not appear to be a major determinant of the responsiveness to ezetimibe in patients on ritonavir-boosted PI-containing therapy. TRIAL REGISTRATION: EudraCT: 2006-006156-36.
Subject(s)
Azetidines/therapeutic use , Cholesterol, LDL/metabolism , Dyslipidemias/drug therapy , HIV Infections/complications , Protease Inhibitors/therapeutic use , Adult , Aged , Anticholesteremic Agents/therapeutic use , C-Reactive Protein/chemistry , Cholesterol/analogs & derivatives , Cholesterol/therapeutic use , Ezetimibe , Female , HIV Infections/drug therapy , Humans , Lipid Metabolism , Male , Middle Aged , Phytosterols/therapeutic use , Protease Inhibitors/adverse effectsABSTRACT
We aimed to evaluate markers of vascular dysfunction in patients with resistant hypertension (RH). A group of 144 patients (61 years, 42% women) with essential RH were divided in two groups based on ambulatory blood pressure monitoring (ABPM). True RH (72%) was considered when 24-h blood pressure (BP) was ≥ 130 and/or 80 mmHg. Otherwise, patients were classified as white coat RH (28%). Hyperemia-induced forearm vasodilation (HIFV), serum inflammatory biomarkers (hs-CRP, s-ICAM-1, s-VCAM-1, e-selectin, p-selectin and MCP-1) and large (C1) and small arterial (C2) compliance (HDI/Pulse Wave CR 2000) were determined in all individuals. In comparison with patients with white coat RH, and after adjustment for age, office systolic BP and diabetes status, those with true RH had a more impaired HIFV (201 ± 159 vs 436 ± 157%; p < 0.001), increased e-selectin (53.1 ± 29.8 vs 40.7 ± 23.5 ng/ml; p = 0.035), and MCP-1 (445 ± 120 vs 386 ± 126 ng/ml; p = 0.027). No significant differences were observed in arterial compliance. Maximal HIFV inversely correlated with urinary albumin excretion (Rho: - 0.278; p = 0.004) and with some inflammatory biomarkers (MCP-1: - 0.441; p < 0.001, e-selectin: - 0.468; p < 0.001 and p-selectin: - 0.329; p = 0.001). We conclude that true RH, diagnosed by ABPM, is associated with a more severe degree of vascular dysfunction, as measured by HIFV and serum biomarkers, whereas other types of vascular alterations, such as compliance, are not directly linked with the level of BP.
Subject(s)
Blood Vessels/physiopathology , Hypertension/physiopathology , Adult , Aged , Blood Pressure Monitoring, Ambulatory , Compliance , Female , Forearm/blood supply , Humans , Male , Middle Aged , VasodilationABSTRACT
Antiretroviral therapy during pregnancy is critical to preventing human immunodeficiency virus vertical transmission. Physiological changes during pregnancy can alter drug kinetics. The aim of this study was to assess the pharmacokinetics (PK) of saquinavir (SQV) boosted with ritonavir during pregnancy and postpartum. Fourteen human immunodeficiency virus-positive pregnant women started SQV 500 mg new tablet formulation plus ritonavir at a dose of 1000/100 mg twice a day + 2 nucleoside retrotranscriptase inhibitors during pregnancy. At weeks 24 and 34 of pregnancy and 6 weeks postpartum, a 12-hour PK study was conducted. PK parameters were calculated using Win Nolin software version 4.1. At week 24, the geometric mean values for SQV area under the plasma concentration-time curve from 0-12 hours (AUC0â12), the maximum observed plasma concentration (C(max)), trough plasma concentration (C(min)), and the elimination half-life (t(1/2)) were 24.80 mg·h⻹·mL⻹, 4.66 mg/mL, 0.93 mg/mL, and 4.31 hours, respectively. At week 34, AUC0â12, C(max), C(min), and t(1/2) were 12.71 mg·h⻹·mL⻹, 3.23 mg/mL, 0.26 mg/mL, and 4.06 hours, respectively. Finally, at 6 weeks postpartum, mean values for SQV AUC0â12, C(max), C(min), and t(1/2) were 28.94 mg·h⻹·mL⻹, 3.92 mg/mL, 0.86 mg/mL, and 3.60 hours, respectively. Although PK parameters in week 24 and postpartum were very similar, those for week 34 showed an important reduction: -71.20%, -30.61%, -48.73%, and -5.81% in C(min), C(max), AUC0â12, and t(1/2), respectively, compared with week 24, but no statistically significant differences were shown between patients. No vertical transmissions were reported. Therapeutic drug monitoring of SQV during pregnancy should be considered, mainly during the third trimester, to ensure adequate drug exposure throughout the entire pregnancy.
Subject(s)
HIV Protease Inhibitors/pharmacokinetics , HIV Seropositivity/blood , HIV Seropositivity/drug therapy , Pregnancy Complications, Infectious/blood , Pregnancy Complications, Infectious/drug therapy , Ritonavir/pharmacokinetics , Saquinavir/pharmacokinetics , Adult , Antiretroviral Therapy, Highly Active/adverse effects , Body Mass Index , Cohort Studies , Female , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/blood , HIV Protease Inhibitors/therapeutic use , HIV Seropositivity/complications , HIV Seropositivity/metabolism , Half-Life , Humans , Infectious Disease Transmission, Vertical/prevention & control , Overweight/complications , Pilot Projects , Postpartum Period , Pregnancy , Pregnancy Complications, Infectious/metabolism , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Prospective Studies , Ritonavir/adverse effects , Ritonavir/blood , Ritonavir/therapeutic use , Saquinavir/adverse effects , Saquinavir/blood , Saquinavir/therapeutic useABSTRACT
Acute hepatitis C (AHC) is an increasing health issue. Despite the decline of blood-to-blood transmission of hepatitis C virus (HCV) through donor screening programs and a decline in intravenous drug use, the incidence of sexual transmission has now increased, particularly in HIV-infected homosexual patients. The presentation is almost always asymptomatic, which complicates diagnosis. Spontaneous clearance of the virus occurs in 25% of cases and usually, within the first three months after onset of symptoms and in symptomatic patients. If serum HCV-RNA remains detectable after this period, antiviral treatment should be started without delay, since sustained viral response rate in the acute phase is higher than that achieved with chronic liver disease. The optimal treatment regimen (interferon alone or combined with ribavirin) and its duration are not clearly established at the present time.
Subject(s)
Hepatitis C/epidemiology , Acute Disease , Antiviral Agents/therapeutic use , Asymptomatic Diseases , Comorbidity , Female , HIV Infections/epidemiology , Hepacivirus/genetics , Hepacivirus/isolation & purification , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/prevention & control , Hepatitis C/transmission , Humans , Interferon-alpha/therapeutic use , Male , RNA, Viral/blood , Ribavirin/therapeutic use , Risk Factors , Sexual Behavior , Spain/epidemiology , Substance Abuse, Intravenous/epidemiology , Viremia/diagnosis , Viremia/epidemiologyABSTRACT
UNLABELLED: Although two pegylated interferons (Peg-IFN) are available to treat chronic hepatitis C virus (HCV) infection, no head-to-head comparative studies have been published. We aim to compare the efficacy and safety of PEG IFN alfa-2b (PEG 2b) versus PEG IFN alfa-2a (PEG 2a), plus ribavirin (RBV). A prospective, randomized, multi-center, open-label clinical trial including 182 human immunodeficiency virus (HIV)-hepatitis C virus (HCV) patients naïve for HCV therapy was performed. Patients were assigned to PEG 2b (80-150 mug/week; n = 96) or PEG 2a (180 mug/week; n = 86), plus RBV (800-1200 mg/day) for 48 weeks. The primary endpoint was sustained virological response (SVR: negative HCV-RNA 24 weeks after completion of treatment). At baseline, both groups were well balanced: 73% male; 63% HCV genotype 1 or [corrected] 4; 29% had fibrosis index of 3 or greater. The overall SVR was 44% (42% PEG 2b versus 46% PEG 2a, P = 0.65). Among genotypes 1 or [corrected] 4, SVRs were 28% versus 32% (P = 0.67) and 62% versus 71% (P = 0.6) in genotypes 2 or [corrected] 3 for PEG 2b and PEG 2a, respectively. Early virological response (EVR; >or=2 log reduction from baseline or negative HCV-RNA at week 12) was 70% in the PEG 2b group and 80% in the PEG 2a group (P = 0.13), reaching a positive predictive value of SVR of 64% and a negative predictive value of 100% in both arms. Side effects were present in 96% of patients but led to treatment discontinuation in 10% of patients (8% on PEG 2b and 13% on PEG 2a, P = 0.47). CONCLUSION: In patients with HIV, HCV therapy with PEG 2b or PEG 2a plus RBV had no significant differences in efficacy and safety.
Subject(s)
Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Adult , Drug Therapy, Combination , Female , HIV Infections/complications , Hepatitis C, Chronic/etiology , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Leukopenia/chemically induced , Male , Middle Aged , Polyethylene Glycols/adverse effects , Recombinant ProteinsABSTRACT
PURPOSE OF REVIEW: With effective antiretroviral therapy, cardiovascular disease has gained importance as a cause of morbidity and mortality in HIV-infected persons. We review the risk of cardiovascular disease in HIV-infected persons compared with that in uninfected persons and discuss the relative contributions of host, HIV, and antiretroviral therapy in the light of current knowledge. RECENT FINDINGS: The incidence of cardiovascular disease in HIV-infected patients receiving antiretroviral therapy is low. However, the risk of cardiovascular disease increased compared with that in uninfected persons. This fact is substantially due to a higher prevalence of underlying traditional cardiovascular risk factors that are mostly host dependent. HIV may additionally contribute both directly through immune activation and inflammation, and indirectly through immunodeficiency. In a more modest way than that of HIV infection, the type of antiretroviral therapy may also contribute through its impact on metabolic and body fat parameters, and possibly through other factors that are currently unclear. SUMMARY: Prevention of cardiovascular disease in HIV-infected patients should be standard of care. Traditional risk factors should be investigated and aggressively treated when possible. Antiretroviral therapy should be initiated earlier in patients with high cardiovascular risk. From a purely cardiovascular perspective, the benefits of antiretroviral therapy clearly outweigh any potential risk.
Subject(s)
Antiretroviral Therapy, Highly Active , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , HIV Infections/complications , HIV Infections/drug therapy , Risk Factors , Case Management , HumansABSTRACT
BACKGROUND: CD4+ T cell recovery dynamics were analysed during the 'on treatment' periods in structured therapy interruption (STI) as well as the long-term immune reconstitution with highly active antiretroviral therapy (HAART) after finishing STI. METHODS: One hundred and twenty HIV-1-infected patients on successful HAART were randomized to receive for 2 years continuous HAART (n=37) or two different strategies of STI (n=83). After this period, most patients received continuous HAART for 2 years. RESULTS: During the STI period, the rate of recovery of CD4+ T cells decreased progressively from the first to the last resumption of HAART {median change of increase: +232 [interquartile range (IQR): +126, +318], +116 (IQR: +10, +471), +87 (IQR: -54, +252) and -26 (IQR: -352, +211) cells/mm3 after the first, second, third and fourth resumption, respectively}. After the STI period and 2 years of continuous HAART, the median CD4+ count remained significantly lower than at baseline in STI arms, both in the virological arm [559 (IQR: 383, 727) versus 771 (IQR: 625, 913) cells/mm3, P<0.0001] and the immunological arm [619 (IQR: 501, 789) versus 787 (IQR: 657, 954) cells/mm3, P<0.0001], but not in the control arm [886 (IQR: 564, 1122) versus 780 (IQR: 539, 945) cells/mm3, P=0.68]. In a multivariate analysis, the nadir of CD4+ T cells and the baseline value of CD4+ before the STI period independently predicted the level of CD4+ T cells 2 years after resumption of HAART (in both cases, P<0.0001). CONCLUSION: The drop in CD4+ cell count after a first and a second period of 3 months of interruption of HAART was completely recovered after resuming HAART; conversely, interruptions longer than 6 months were deleterious for the recovery of CD4+. CD4+ cell count did not rebound completely in patients who received 2 years of HAART after 2 years of STIs.
Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , HIV Infections/immunology , Withholding Treatment , Adult , CD4 Lymphocyte Count , Female , HIV Infections/virology , HIV-1/isolation & purification , Humans , Male , Middle Aged , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
BACKGROUND: Hypertension has been related to endothelial dysfunction. Patients with refractory hypertension (RH) have a reduced number of endothelial progenitor cells (EPCs). AIM: To evaluate if blood EPC levels relate to endothelium-dependent vasodilation (ED-VD) in RH. METHODS: We analyzed 29 RH confirmed by 24-h ambulatory blood pressure monitoring and assessed complete clinical and laboratory evaluation. EPCs were isolated from peripheral mononuclear cells (MNC) by flow cytometry. ED-VD was determined measuring flow-mediated dilation (FMD) by venous occlusion plethysmography. Results. Circulating EPCs/10(5) MNC (median [Q1-Q3]): 23.0 [4.5-53.8]. FMD (median [Q1-Q3]): 211.7 [79.5-365.8]%. Significant correlations with log-FMD: EPCs (r = 0.469; p = 0.018) and homocysteine (r = -0.414; p = 0.045). There was no collinearity between EPCs and homocysteine. FMD did not correlate with age, gender, office BP, 24-h systolic blood pressure or 24-h diastolic blood pressure, laboratory parameters, C-reactive-protein, left ventricular-mass index, dyslipidaemia, smoking habit and statin or angiotensin system blockers treatment. Multiple linear regression analysis showed that after age-adjustment, EPC (p = 0.027) and homocysteine (p = 0.004) were the only variables that predicted FMD (R = 0.740). After dividing patients according to EPC number, patients in the lower tertile showed a significantly reduced FMD compared with those in the group of the two upper tertiles of EPC: log-FMD (mean+/-SD): 4.7+/-0.9 vs 5.6+/-0.8, respectively (p = 0.031). CONCLUSIONS: ED-VD independently correlates with circulating EPCs in RH. Homocysteine is also an independent predictor of lower FMD in such patients.
Subject(s)
Dilatation, Pathologic/diagnosis , Endothelial Cells/pathology , Hypertension/pathology , Stem Cells/pathology , Adult , Cell Count , Cell Separation , Dilatation, Pathologic/pathology , Flow Cytometry , Homocysteine/blood , Humans , Middle Aged , Predictive Value of Tests , Regression Analysis , VasodilationABSTRACT
BACKGROUND: Stavudine (d4T)-containing regimens are associated with a potential for lipoatrophy and dyslipidaemia. We assessed the safety and efficacy of reducing the dose of stavudine compared with switching to tenofovir or maintaining the standard dose of d4T. METHODS: Clinically stable HIV-infected patients receiving antiretroviral therapy containing stavudine 40 mg twice daily with a plasma HIV RNA < 200 copies/ml for at least 6 months were randomized to maintain stavudine 40 mg twice daily (d4T40 arm), to reduce to 30 mg twice daily (d4T30 arm), or to switch from d4T to tenofovir (TDF arm). RESULTS: Fifty-eight (93% male) patients were included: 22 in the d4T40 arm, 19 in the d4T30 arm and 17 in TDF arm. At baseline, median time on d4T was 6 years (interquartile range [IQR] 2.6-7.1), median age 43 years (IQR 36-51) and median CD4+ T-cell count was 587/mm3 (IQR 329-892). At week 24, median limb fat changes (g) were as follows: d4T40 = -182 (95% CI: -469- -5); d4T30 = 527 (95% CI: -343-694); and TDF = 402 (95% CI: 130-835; d4T40 versus TDF, P = 0.0003). Significant differences between median values of laboratory parameters were detected: triglycerides (mg/dl): d4T40 = 19; d4T30 = -23 and TDF = -79 (d4T40 versus TDF, P = 0.03); and total cholesterol (mg/dl): d4t40 = 22, d4T30 = -4, and TDF = -28 (d4T40 versus TDF, P = 0.04). No significant difference was observed in mitochondrial function assessed in peripheral blood mononuclear cells. CONCLUSIONS: Although both strategies were associated with a trend toward a decrease in plasma lipids and an increase in body fat, the only significant changes were observed among those who switched to tenofovir.
Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV , Organophosphonates/therapeutic use , Stavudine/therapeutic use , Adenine/therapeutic use , Adult , Anti-HIV Agents/adverse effects , Body Composition , Cholesterol/blood , Drug Administration Schedule , Female , HIV Infections/blood , Humans , Leukocytes, Mononuclear/metabolism , Lipodystrophy/chemically induced , Male , Middle Aged , Mitochondria/metabolism , Oxygen Consumption , Stavudine/adverse effects , Tenofovir , Treatment Outcome , Triglycerides/bloodABSTRACT
Patterns of mutations associated with didanosine (ddI) resistance are still a controversial issue. The correlation between different clusters of reverse transcriptase mutations with the short-term virological activity of ddI when added to a failing regimen was examined in 40 patients. The median fall in plasma viral load at week 4 was 0.67 log10 copies/ml. There was good correlation between the median fall in plasma HIV RNA levels and the number of nucleoside-associated (P = 0.0152) or thymidine-associated (P = 0.0142) mutations. In conclusion, ddI retained substantial antiretroviral activity when the number of nucleoside-associated or thymidine-associated mutations was less than four.
Subject(s)
Didanosine/therapeutic use , HIV Infections/drug therapy , Reverse Transcriptase Inhibitors/therapeutic use , HIV Infections/genetics , HIV Reverse Transcriptase/genetics , Humans , Mutation , Nucleosides/genetics , Prospective Studies , RNA, Viral/analysis , Thymidine/genetics , Treatment Outcome , Viral LoadABSTRACT
BACKGROUND: Pre-eclampsia and/or fetal death have increased sharply in HIV-infected pregnant women receiving HAART. METHODS: The occurrence of pre-eclampsia or fetal death was analysed in women who delivered after at least 22 weeks of gestation for all women (January 2001 until July 2003) and for HIV-infected women (November 1985 until July 2003). RESULTS: In 2001, 2002 and 2003, the rates per 1000 deliveries of pre-eclampsia and fetal death, respectively, remained stable in all pregnant women at 25.4, 31.9 and 27.7 (P = 0.48) and 4.8, 5.8, and 5.0 (P = 0.89) (n = 8768). In 1985-2000 (n = 390) to 2001-2003 (n = 82), rates per 1000 deliveries in HIV-infected women rose from 0.0 to 109.8 (P < 0.001) for pre-eclampsia and from 7.7 to 61.0 (P < 0.001) for fetal death. In all pregnant women, factors associated with pre-eclampsia or fetal death were multiple gestation [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI), 2.3-5.6; P < 0.001], HIV infection (adjusted OR, 4.9; 95% CI, 2.4-10.1; P < 0.001), multiparity (adjusted OR, 0.76; 95% CI, 0.58-0.98; P = 0.040) and tobacco smoking (adjusted OR, 0.65; 95% CI, 0.46-0.90; P = 0.010). The use of HAART prior to pregnancy (adjusted OR, 5.6; 95% CI, 1.7-18.1; P = 0.004) and tobacco smoking (adjusted OR, 0.183; 95% CI, 0.054-0.627; P = 0.007) were risk factors in HIV-infected women. CONCLUSIONS: HIV infection treated with HAART prior to pregnancy was associated with a significantly higher risk for pre-eclampsia and fetal death.
Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , Fetal Death/etiology , HIV Infections/drug therapy , Pre-Eclampsia/etiology , Pregnancy Complications, Infectious/drug therapy , Adult , E-Selectin/blood , Female , Fetal Death/chemically induced , HIV Infections/complications , Humans , Insulin/blood , P-Selectin/blood , Parity , Pre-Eclampsia/chemically induced , Pregnancy , Pregnancy Outcome , Prospective Studies , Risk Factors , Smoking/adverse effectsABSTRACT
BACKGROUND: Salt sensitivity in essential hypertension is associated with both endothelial dysfunction and increased cardiovascular risk. We evaluated several serum markers of atherosclerosis and endothelial function in a group of essential hypertensive patients classified on the basis of their salt sensitivity. METHODS: Forty-three patients were classified as having salt-sensitive (20 subjects) or salt-resistant (23 subjects) hypertension on the basis of their 24-h blood pressure (BP) response from low salt (50 mmol/d) to high salt (250 mmol/d) intake. Endothelium-dependent and independent responses were measured in the forearm previously to salt manipulation. High-sensitivity C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), e-selectin, p-selectin, interleukin-6 (IL-6), monocyte chemotactic protein type 1 (MCP-1), matrix metalloproteinases types 1, 2, and 9 (MMP-1, MMP-2, and MMP-9), and the tissue inhibitor of metalloproteinases type 1 (TIMP-1) were measured in serum on the last day of both low salt and high salt intakes. RESULTS: Compared to salt-resistant patients, salt-sensitive hypertensives showed age-adjusted increased levels of p-selectin (P = .006), e-selectin (P = .042), and MCP-1 (P = .036), although differences in e-selectin were not maintained after adjustment for BP values. Moreover, salt-sensitive subjects exhibited decreased serum levels of MMP-9 (P = .007) and increased levels of TIMP-1 (P = .045). No differences in serum CRP, sICAM-1, sVCAM-1, or IL-6 were observed between salt-sensitive and salt-resistant patients. Finally, maximal acetylcholine-induced vasodilation (319% +/- 153% v 414% +/- 178% increase in forearm blood flow; P = .022 age-adjusted) was significantly impaired in salt-sensitive hypertensives. CONCLUSIONS: Serum markers of inflammation, especially selectins and chemokines, as well as markers of vascular remodeling, and endothelium-dependent vasodilation are altered in salt-sensitive hypertension. These alterations could help to explain the greater target organ damage and cardiovascular risk observed in salt-sensitive subjects.
Subject(s)
Atherosclerosis/blood , Atherosclerosis/diagnosis , Hypertension/blood , Sodium, Dietary/pharmacology , Adult , Atherosclerosis/etiology , Biomarkers/blood , Blood Pressure/drug effects , Blood Pressure/physiology , C-Reactive Protein/analysis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/physiopathology , Cell Adhesion Molecules/blood , Chemokine CCL2/blood , Collagenases/blood , Endothelium, Vascular/physiopathology , Female , Humans , Hypertension/complications , Hypertension/physiopathology , Interleukin-6/blood , Male , Middle Aged , Risk Factors , Tissue Inhibitor of Metalloproteinase-1/bloodABSTRACT
Several reports have shown that left ventricular hypertrophy (LVH) is an independent predictor of acute cerebrovascular events. The aim of the present study was to investigate the relationship between LVH and cerebral blood flow in middle-aged patients with essential hypertension. Forty never-treated hypertensive patients (24 men, 16 women, aged 50-60 years) without clinical evidence of target organ damage were studied. Regional cerebral blood flow was measured by means of single photon emission computed tomography of the brain. Twenty-nine patients showed echocardiographic criteria of LVH; 11 patients did not show this feature. No differences were found in regional cerebral blood flow ratio of all brain areas studied between hypertensives with or without LVH except for the striatum area. The regional cerebral blood flow ratio was significantly reduced in the striatum region of hypertensive patients with LVH, compared with patients without LVH (91.5+/-7.4 vs 98.1+/-8.3; P=.023). This relationship remained significant after adjusting for blood pressure. The authors conclude that the presence of LVH in middle-aged patients with essential hypertension is associated with a reduction of regional cerebral blood flow in the striatum area.
Subject(s)
Cerebrovascular Circulation , Hypertension/diagnostic imaging , Hypertension/physiopathology , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/physiopathology , Tomography, Emission-Computed, Single-Photon , Blood Pressure , Blood Pressure Monitoring, Ambulatory , Brain/blood supply , Brain/diagnostic imaging , Circadian Rhythm , Echocardiography , Female , Humans , Male , Middle Aged , Regional Blood FlowABSTRACT
We evaluated the virological outcome of tenofovir plus didanosine-based regimens in 67 HIV-suppressed patients. After a median follow-up of 26 months (IQR 10.5-40.5), 12 (18%) discontinued the therapy because of virological failure. At virological failure 'de novo' selected mutations were identified in 11 of the 12 failing patients, including the K65R mutation in seven patients. These results argue against the use of tenofovir-didanosine not only in naive patients, but also in previously suppressed patients.
Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/therapeutic use , Didanosine/therapeutic use , HIV Infections/drug therapy , HIV-1/drug effects , Organophosphonates/therapeutic use , Adenine/therapeutic use , Antiretroviral Therapy, Highly Active , Drug Resistance, Multiple, Viral , HIV Infections/virology , HIV-1/genetics , Humans , Mutation , Tenofovir , Treatment FailureABSTRACT
Intensification therapy adding a boosted protease inhibitor (PI) to a failing regimen has the potential to worsen the resistance profile. Sixty-six patients included in four different boosted PI intensification studies were assessed and resistance mutations in the reverse transcriptase and protease genes were evaluated at baseline and 4 weeks after the initiation of the intensification strategy. Only one of the 66 patients developed changes in their pattern of mutations able to generate or increase resistance to new drugs.
Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV Protease/genetics , HIV Reverse Transcriptase/genetics , HIV-1/genetics , Mutation , Antiretroviral Therapy, Highly Active , Carbamates , Drug Resistance, Multiple, Viral , Follow-Up Studies , Furans , HIV Infections/virology , Humans , Indinavir/therapeutic use , Lopinavir , Pyrimidinones/therapeutic use , Ritonavir/therapeutic use , Saquinavir/therapeutic use , Sulfonamides/therapeutic use , Treatment Failure , Viral LoadABSTRACT
BACKGROUND: Coinfection with hepatitis C virus (HCV) and HIV is not uncommon and therapies for both infections are currently available. A major drawback, however, could be a potentially higher risk for mitochondrial toxicity (MT), defined as the elevation of pancreatic enzymes or lactate levels due to the nucleoside analogue reverse transcriptase inhibitors contained in both therapies. METHODS: Prospective analyses of clinical and laboratory data, including plasma lactate levels and pancreatic enzymes, of 113 consecutive HIV/HCV-coinfected patients were assigned to receive ribavirin (RBV) plus interferon (IFN)-alpha. RESULTS: Fourteen patients (12%) showed increased levels of amylase/lipase and/or hyperlactataemia. No patient developed clinical pancreatitis. Four patients with hyperlactataemia had clinical symptoms of lactic acidosis and recovered uneventfully by 2 weeks after treatment withdrawal. The variables significantly associated with MT in the univariate analysis were: therapy with didanosine (ddl), ddl plus stavudine (d4T), previous history of diabetes and the baseline lactate level. However, ddl use was the only independent risk factor for MT identified in the multivariate analysis. MT was not associated with gender, age, alcohol consumption, type of IFN, degree of steatosis and fibrosis in liver biopsy, presence of lipodystrophy, CD4+ cell count, HCV or HIV viral load, mitochondrial DNA and COXII-expression in liver tissue, or antiretroviral therapy containing d4T or protease inhibitors. CONCLUSIONS: 12% of HIV/HCV-coinfected patients receiving IFN plus RBV concomitantly with highly active antiretroviral therapy developed laboratory markers of MT. Although most of cases were asymptomatic, our study suggests that concomitant use of RBV plus ddl should be avoided, and that routine monitoring of lactate and pancreatic enzymes may be recommended.
Subject(s)
Antiviral Agents/adverse effects , HIV Infections/physiopathology , Hepatitis C/physiopathology , Mitochondrial Diseases/epidemiology , Adult , Antiretroviral Therapy, Highly Active/adverse effects , Antiviral Agents/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis C/complications , Hepatitis C/drug therapy , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Male , Mitochondrial Diseases/chemically induced , Mitochondrial Diseases/etiology , Prospective Studies , Recombinant Proteins , Ribavirin/adverse effects , Ribavirin/therapeutic use , Risk FactorsABSTRACT
The rise in didanosine concentrations in plasma when given with tenofovir raises concern for a high risk of toxic effects. Recommendations to reduce didanosine dose have been issued, but only for adults weighing more than 60 kg. We reviewed cases of pancreatitis in patients receiving didanosine plus tenofovir, didanosine alone, and tenofovir alone to assess the incidence of and risk factors for pancreatitis. Between Aug 1, 2001, and Nov 30, 2003, five of 185 (2.7%) patients receiving didanosine plus tenofovir, one of 182 (0.5%) on didanosine without tenofovir, and none of 208 on tenofovir without didanosine developed pancreatitis (p=0.016). Co-administration of both drugs versus each of them individually was an independent risk factor for pancreatitis (crude hazard ratio 10.666, 95% CI 1.246-91.294, p=0.031). These results suggest that the risk of pancreatitis is heightened when didanosine and tenofovir are given together.
Subject(s)
Adenine/analogs & derivatives , Adenine/adverse effects , Anti-HIV Agents/adverse effects , Didanosine/adverse effects , Organophosphonates , Organophosphorus Compounds/adverse effects , Pancreatitis/chemically induced , Reverse Transcriptase Inhibitors/adverse effects , Adenine/administration & dosage , Adult , Anti-HIV Agents/administration & dosage , Body Weight , Didanosine/administration & dosage , Drug Interactions , Drug Therapy, Combination , Female , HIV Infections/drug therapy , Humans , Male , Organophosphorus Compounds/administration & dosage , Reverse Transcriptase Inhibitors/administration & dosage , TenofovirABSTRACT
BACKGROUND: Current therapies for chronic hepatitis C virus (HCV) in HIV co-infected patients have a low success rate and are poorly tolerated. We have evaluated the efficacy and safety of interferon alfa-2b (IFN) + ribavirin (RBV) versus pegylated interferon alfa-2b (PEG-INF) + RBV. METHODS: Randomized, single-centre, open-label clinical trial including patients with: detectable HCV-RNA, alanine aminotransferase > 1.5-fold upper limit of normal, abnormal liver histology, CD4 cell count > 250 x 10/l and HIV RNA < 10 000 copies/ml. Patients were assigned to INF (3 x 10 units three times/week) or PEG-IFN (100-150 microg/week) plus RBV (800-1200 mg/day). Duration of treatment was 48 weeks (only 24 weeks for HCV genotypes 2 or 3 and baseline HCV RNA < 800 000 IU/ml). The primary endpoint was a sustained virological response (SVR). RESULTS: Ninety-five patients were randomized (43 INF + RBV, 52 PEG-INF + RBV), 68% males, 82% injecting drug users; 63% genotypes 1 or 4 and 36% genotypes 2 or 3; 62% fibrosis index grade >/=2 and 30% bridging fibrosis/cirrhosis. SVR was significantly higher in the PEG-INF + RBV arm, 44% versus 21% (intent to treat; P = 0.017). Among patients with genotypes 1 or 4, SVR were 38% versus 7% (P = 0.007) and 53% versus 47% (P = 0.730) for genotypes 2 or 3. CD4 cell count but not its percentage dropped in both arms and HIV RNA viral load did not change from baseline. Side effects were very frequent in both arms leading to treatment discontinuation in 14 patients without statistical differences between arms (P = 0.565). CONCLUSION: PEG-INF + RBV was significantly more effective than INF + RBV for the treatment of chronic hepatitis C in HIV co-infected patients, mainly of genotype 1 or 4.
Subject(s)
HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Interferon-alpha/therapeutic use , Ribavirin/administration & dosage , Adult , CD4 Lymphocyte Count , Drug Therapy, Combination , Female , Hepatitis C, Chronic/complications , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Polyethylene Glycols , Prospective Studies , Recombinant Proteins , Ribavirin/adverse effects , Treatment OutcomeABSTRACT
The evolution of fasting glucose, triglyceride, and total and high-density lipoprotein (HDL) cholesterol level and the factors associated with development of clinically significant abnormalities in these metabolic parameters at 6 months were assessed in 353 consecutive human immunodeficiency virus (HIV)-infected patients who were receiving antiretroviral therapy containing lopinavir-ritonavir. Although glucose and HDL cholesterol levels did not change, triglyceride and total cholesterol levels significantly increased (P<.0001 for each), as did the proportion of patients with a triglyceride level of >400 mg/dL and a total cholesterol level of >240 mg/dL (P=.002). A baseline triglyceride level of >400 mg/dL and a baseline total cholesterol level of >240 mg/dL were identified as independent factors predicting clinically significant hypertriglyceridemia and hypercholesterolemia, respectively, at 6 months. These findings may have clinical implications when the therapeutic option of lopinavir-ritonavir is considered.
Subject(s)
HIV Infections/complications , HIV Protease Inhibitors/adverse effects , Metabolic Diseases/chemically induced , Pyrimidinones/adverse effects , Ritonavir/adverse effects , Adult , Antiretroviral Therapy, Highly Active , Cholesterol/metabolism , Cholesterol, HDL/metabolism , Female , HIV , HIV Infections/drug therapy , Humans , Lopinavir , Male , Metabolic Diseases/epidemiology , Risk Factors , Triglycerides/metabolismABSTRACT
BACKGROUND: The prevalence, risk factors, and potential hormonal abnormalities associated with gynecomastia in a cohort of HIV-infected men are poorly understood. METHODS: Breast enlargement was assessed in consecutively evaluated HIV-infected men, and gynecomastia was subsequently confirmed with sonography. For each patient with breast enlargement, a randomly selected control subject without breast enlargement was studied. Clinical data were obtained, including age, body mass index, clinically evident lipodystrophy, prior symptomatic hyperlactatemia, current antiretroviral therapy and duration of exposure to each antiretroviral drug, history of injection drug use, and serological status regarding hepatitis B and hepatitis C. Laboratory parameters, including plasma HIV-1 RNA load, CD4 cell count, free testosterone index, and levels of fasting triglycerides, cholesterol, prolactin, total testosterone, sex hormone-binding globulin, 17-beta-estradiol, follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone, were measured. RESULTS: There were 44 of 2275 patients with breast enlargement, of whom 40 (1.8%) had gynecomastia. The mean free testosterone index (+/-SD) was significantly lower among the 40 patients with gynecomastia (42.6%+/-24.0%) than among the 44 control subjects (58.0%+/-25.3%) (P=.006). Although the proportion of patients who were receiving treatment with zidovudine, stavudine, and/or efavirenz at the time of the present study was significantly different between case patients and control subjects, the duration of exposure to each individual antiretroviral drug was not. Lipoatrophy (adjusted odds ratio [OR], 5.6; 95% confidence interval [CI], 1.7-18.6; P=.005), hepatitis C (adjusted OR, 6.1; 95% CI, 1.8-20.6; P=.003), and hypogonadism (adjusted OR, 7.6; 95% CI, 1.8-32.2; P=.003) were independent factors associated with gynecomastia. CONCLUSIONS: The data suggest that gynecomastia among HIV-infected patients is related to hypogonadism, rather than to an adverse effect of antiretroviral drugs.