ABSTRACT
OBJECTIVES: Several single-tablet regimens (STRs) are now available and are recommended for first-line antiretroviral therapy (ART); however, STR use for youth with HIV (YHIV) has not been systematically studied. We examined the characteristics associated with initiation of STRs versus multi-tablet regimens (MTRs) and the virological outcomes for youth with nonperinatally acquired HIV (nPHIV). METHODS: A retrospective cohort study of nPHIV youth aged 13-24 years initiating ART between 2006 and 2014 at 18 US HIV clinical sites in the HIV Research Network was performed. The outcomes measured were initiation of STRs versus MTRs, virological suppression (VS) at 12 months, and time to VS. Demographic and clinical factors associated with initiation of STR versus MTR ART and VS (< 400 HIV-1 RNA copies/mL) at 12 months after initiation were assessed using multivariable logistic regression. Cox proportional hazards regression was used to assess VS within the first year. RESULTS: Of 987 youth, 67% initiated STRs. Of the 589 who had viral load data at 1 year, 84% of those on STRs versus 67% of those on MTRs achieved VS (P < 0.01). VS was associated with STR use [adjusted odds ratio (AOR) 1.61; 95% confidence interval (CI) 1.01-2.58], white (AOR 2.41; 95% CI 1.13-5.13) or Hispanic (AOR 2.38; 95% CI 1.32-4.27) race/ethnicity, and baseline CD4 count 351-500 cells/µL (AOR 1.94; 95% CI 1.18-3.19) and > 500 cells/µL (AOR 1.76; 95% CI 1.0-3.10). STR use was not associated with a shorter time to VS compared with MTR use [hazard ratio (HR) 1.07; 95% CI 0.90-1.28]. CONCLUSIONS: Use of STR was associated with a greater likelihood of sustained VS 12 months after ART initiation in YHIV.
Subject(s)
Anti-Retroviral Agents/administration & dosage , HIV Infections/drug therapy , HIV-1/drug effects , Adolescent , Anti-Retroviral Agents/pharmacology , Female , HIV Infections/virology , HIV-1/genetics , Humans , Logistic Models , Male , Retrospective Studies , Tablets , Treatment Adherence and Compliance , Viral Load/drug effects , Young AdultABSTRACT
Calcium phosphate cements (CPC) are used as bone void filler in various orthopedic indications; however, there are some major drawbacks regarding mixing, transfer, and injection of traditional CPC. By using glycerol as mixing liquid, a premixed calcium phosphate cement (pCPC), some of these difficulties can be overcome. In the treatment of vertebral fractures the handling characteristics need to be excellent including a high radio-opacity for optimal control during injection. The aim of this study is to evaluate a radiopaque pCPC regarding its resorption behavior and biocompatibility in vivo. pCPC and a water-based CPC were injected into a Ø 4-mm drilled femur defect in rabbits. The rabbits were sacrificed after 2 and 12 weeks. Cross sections of the defects were evaluated using histology, electron microscopy, and immunohistochemical analysis. Signs of inflammation were evaluated both locally and systemically. The results showed a higher bone formation in the pCPC compared to the water-based CPC after 2 weeks by expression of RUNX-2. After 12 weeks most of the cement had been resorbed in both groups. Both materials were considered to have a high biocompatibility since no marked immunological response was induced and extensive bone ingrowth was observed. The conclusion from the study was that pCPC with ZrO(2) radiopacifier is a promising alternative regarding bone replacement material and may be suggested for treatment of, for example, vertebral fractures based on its high biocompatibility, fast bone ingrowth, and good handling properties.
Subject(s)
Biocompatible Materials/pharmacology , Bone Cements/pharmacology , Calcium Phosphates/pharmacology , Contrast Media/pharmacology , Materials Testing , Animals , Biomarkers/metabolism , Core Binding Factor Alpha 1 Subunit/metabolism , Female , Femur/drug effects , Femur/pathology , Femur/ultrastructure , Gene Expression Regulation/drug effects , Immunohistochemistry , Inflammation/pathology , RabbitsABSTRACT
OBJECTIVE: Combination treatment with candesartan and hydrochlorothiazide (HCT) has been shown to provide the full additive antihypertensive effect of the components. A clinical program has been undertaken to study the efficacy and safety of the fixed dose combinations of candesartan 32 mg and HCT 12.5 or 25 mg in patients with mild to moderate hypertension. This study evaluated the drug-drug interaction potential of the highest dose combination of candesartan 32 mg and HCT 25 mg. SUBJECTS AND METHODS: 53 healthy male and female subjects were randomized to sequential treatment with single doses of one candesartan/ HCT 32/25 mg tablet, two 16/12.5 mg tablets, one candesartan 32 mg tablet and one HCT 25 mg tablet using an open 4-way cross-over design. RESULTS: There was no pharmacokinetic interaction between candesartan 32 mg and HCT 25 mg during concomitant administration. AUC and Cmax were within the accepted confidence limits of 0.8 - 1.25 compared to the monocomponents, and tmax and t1/2 were similar to those of the monocomponents. There were no unexpected safety findings, and no subject discontinued study treatment due to an adverse event. CONCLUSION: There was no pharmacokinetic interaction found between the high doses of candesartan 32 mg and HCT 25 mg.
Subject(s)
Angiotensin II Type 1 Receptor Blockers/pharmacokinetics , Benzimidazoles/pharmacokinetics , Biphenyl Compounds/pharmacokinetics , Diuretics/pharmacokinetics , Hydrochlorothiazide/pharmacokinetics , Tetrazoles/pharmacokinetics , Adolescent , Adult , Benzimidazoles/administration & dosage , Biphenyl Compounds/administration & dosage , Cross-Over Studies , Drug Interactions , Drug Therapy, Combination , Female , Humans , Hydrochlorothiazide/administration & dosage , Male , Middle Aged , Tetrazoles/administration & dosageABSTRACT
PURPOSE: We investigated the effects of maraviroc, the first approved CC-chemokine receptor 5 (CCR5) antagonist, on blood lipids in a post hoc analysis of the phase 3 MERIT study in treatment-naïve patients. METHODS: Patients received maraviroc 300 mg twice daily (n = 360) or efavirenz 600 mg once daily (n = 361), both in combination with zidovudine/lamivudine, for up to 96 weeks. Baseline and on- treatment lipid profiles were analyzed according to National Cholesterol Education Program (NCEP) thresholds. RESULTS: Baseline characteristics and lipid profiles were comparable between groups. Among patients with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) below NCEP treatment thresholds at baseline, significantly more efavirenz- than maraviroc-treated patients exceeded those thresholds at 96 weeks (TC: 35% [74/209] vs 11% [20/188], P < .0001; LDL-c: 23% [47/197] vs 8% [15/183], P < .0001). Among patients exceeding NCEP thresholds at baseline, significantly more efavirenz- than maraviroc-treated patients exceeded the thresholds at 96 weeks (TC: 83% [24/29] vs 50% [17/34], P = .0084; LDL-c: 86% [19/22] vs 55% [16/29], P = .0314). Of those with baseline high- density lipoprotein cholesterol (HDL-c) < 40 mg/dL, 43% (56/130) of maravirocand 62% (86/139) of efavirenz-treated patients achieved HDL-c≥40 mg/dL at 96 weeks (P = .0020). CONCLUSIONS: Maraviroc was not associated with elevations in TC, LDL-c, or triglycerides and showed beneficial effects on lipid profiles of dyslipidemic patients.
Subject(s)
Anti-HIV Agents/administration & dosage , Benzoxazines/administration & dosage , Cyclohexanes/administration & dosage , Dyslipidemias/drug therapy , Dyslipidemias/virology , HIV Infections/blood , HIV-1/isolation & purification , Triazoles/administration & dosage , Adult , Alkynes , CCR5 Receptor Antagonists , Chi-Square Distribution , Cholesterol/blood , Cyclopropanes , Dyslipidemias/blood , Female , HIV Infections/drug therapy , HIV Infections/virology , Humans , Lipid Metabolism/drug effects , Male , Maraviroc , Receptors, CCR5/metabolism , Triglycerides/bloodABSTRACT
We evaluated immunologic predictors of response to HBV vaccine administered in the presence or absence of GM-CSF in HIV infected individuals. We measured peripheral blood hematopoietic progenitor, monocyte and myeloid-derived suppressor cell (MDSC) frequencies, and expression of GMCSF receptor on monocytes and MDSCs, at baseline and 4weeks after immunization in relation to antibody response. We observed higher baseline progenitor and lower monocyte frequencies among week 16 antibody responders. Week 4 decline in MDSC frequency was associated with week 16 antibody response, while administration of GM-CSF was associated with preservation of these cells. No significant differences in GM-CSF receptor expression were observed in the presence vs. absence of GM-CSF. These findings are consistent with a positive role of progenitor cells and a potential negative role of monocytes in vaccine response. Additionally, GM-CSF augmented the preservation of peripheral blood MDSC, which may contribute to the lack of improved vaccine responses.
Subject(s)
HIV Infections/immunology , Hematopoietic Stem Cells/immunology , Hepatitis B Vaccines/immunology , Monocytes/immunology , Antibody Formation , Antigen-Presenting Cells/immunology , Antigens, CD34/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes , Female , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , HIV/immunology , Hepatitis B Antibodies/blood , Hepatitis B Vaccines/adverse effects , Humans , Lipopolysaccharide Receptors/immunology , Male , Middle Aged , Pilot Projects , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/immunologyABSTRACT
HIV-infected persons are at risk for HBV co-infection which is associated with increased morbidity and mortality. Unfortunately, protective immunity following HBV vaccination in HIV-infected persons is poor. This randomized, phase II, open-label study aimed to evaluate efficacy and safety of 40 mcg HBV vaccine with or without 250 mcg GM-CSF administered at day 0, weeks 4 and 12. HIV-infected individuals >or=18 years of age, CD4 count >or=200 cells/mm(3), seronegative for HBV and HCV, and naïve to HBV vaccination were eligible. Primary endpoints were quantitative HBsAb titers and adverse events. The study enrolled 48 subjects. Median age and baseline CD4 were 41 years and 446 cells/mm(3), 37 were on ART, and 26 subjects had undetectable VL. Vaccination was well tolerated. Seven subjects in the GM-CSF arm reported transient grade >or=2 signs/symptoms (six grade 2, one grade 3), mostly aches and nausea. GM-CSF had no significant effect on VL or CD4. Four weeks after vaccination, 26 subjects (59%) developed a protective antibody response (HBsAb >or=10 mIU/mL; 52% in the GM-CSF arm and 65% in the control arm) without improved Ab titer in the GM-CSF vs. control arm (median 11 mIU/mL vs. 92 mIU/mL, respectively). Response was more frequent in those with CD4 >or=350 cells/mm(3) (64%) than with CD4 <350 cells/mm(3) (50%), though not statistically significant. GM-CSF as an adjuvant did not improve the Ab titer or the development of protective immunity to HBV vaccination in those receiving an accelerated vaccine schedule. Given the common routes of transmission for HIV and HBV, additional HBV vaccine research is warranted.
Subject(s)
Adjuvants, Immunologic/administration & dosage , Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage , HIV Infections/immunology , Hepatitis B Vaccines/immunology , Adult , Antibody Formation , Female , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Hepatitis B/immunology , Hepatitis B/prevention & control , Hepatitis B Antibodies/blood , Hepatitis B Vaccines/adverse effects , Humans , Male , Middle Aged , Pilot ProjectsABSTRACT
By using a premixed calcium phosphate cement (CPC), the handling properties of the cement are drastically improved, which is a challenge for traditional injectable CPCs. Previously premixed cements have been based on apatitic cements. In this article, acidic cement has been developed and evaluated. Monocalcium phosphate monohydrate and beta-tricalcium phosphate were mixed with glycerol to form a paste. As the paste does not contain water, no setting reaction starts and thus the working time is indefinite. Powder/liquid ratios (P/L) of 2.25, 3.5 and 4.75 were evaluated. Setting time (ST) and compressive strength (CS) were measured after 1 day, 1 week and 4 weeks in phosphate buffered saline (PBS) solution, and the corresponding microstructure was evaluated using electron microscopy and X-ray diffraction. The ST started when the cements were placed in PBS and ranged from 28 to 75 min, higher P/L gave a lower ST. Higher P/L also gave a higher CS, which ranged from 2 to 16 MPa. The microstructure mainly consisted of monetite, 1-5 microm in grain size. After 4 weeks in PBS, the strength increased. As acidic cements are resorbed faster in vivo, this cement should allow faster bone regeneration than apatitic cements. Premixed cements show a great handling benefit when compared with normal CPCs and can be formulated with similar ST and mechanical properties.
Subject(s)
Bone Cements , Calcium Phosphates , Materials Testing , Compressive Strength , Stress, Mechanical , Time FactorsABSTRACT
Chronic hepatitis B virus infections are a major cause of morbidity and mortality in HIV co-infected patients. The standard of care for treating HCV co-infection has been guided by major clinical trials, but the treatment of HBV co-infection has not been as thoroughly studied and the standard of care remains largely untested. The single pill formulation of tenofovir with emtricitabine has become a standard treatment approach in HBV co-infected patients. WU114 was a phase 1 clinical trial that examined the safety and tolerability of sequential treatment of HBV with pegylated interferon-alpha2a plus delayed-initiation tenofovir in HIV co-infected individuals. We postulated that initial HBV viral load reduction with pegylated interferon prior to initiation of nucleoside/nucleotide therapy would increase seroconversion events and durability of HBV virologic suppression. No severe pegylated IFN-alpha2a drug toxicities were seen in either the monotherapy or delayed tenofovir arms. Sequential pegylated interferon and tenofovir-based therapy was tolerable and should be compared with dual nucleoside/nucleotide suppression to determine relative frequencies of seroconversion and durability of HBV suppression in co-infected patients.
Subject(s)
Adenine/analogs & derivatives , HIV Infections/complications , Hepatitis B, Chronic/drug therapy , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Organophosphonates/adverse effects , Organophosphonates/therapeutic use , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use , Adenine/adverse effects , Adenine/therapeutic use , Adult , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Female , Hepatitis B, Chronic/complications , Humans , Interferon alpha-2 , Male , Middle Aged , Recombinant Proteins , TenofovirABSTRACT
Clarithromycin 500 mg po bid or azithromycin 1200 mg po weekly is recommended as first line prophylaxis for Mycobacterium avium complex (MAC) in patients with HIV infection whose CD4 counts are <50 cells/microL. HIV-infected patients with CD4+ T-cell counts <200 cells/microL were randomized to receive either clarithromycin 500 mg po bid or azithromycin 1200 mg po weekly for 12 weeks. Nasopharyngeal swabs for Streptococcus pneumoniae and Haemophilus influenzae plus an anterior nare culture for Staphylococcus aureus were obtained at pretreatment, at 6 weeks, and at 12 weeks. A throat culture for oral flora was obtained for susceptibility testing against erythromycin. Minimum inhibitory concentrations (MICs) for clarithromycin and azithromycin were performed on all S. pneumoniae, H. influenzae, and S. aureus isolates. The study was terminated after respiratory flora, from all participants, revealed macrolide resistance. Because results of recent randomized trials indicate minimal efficacy of continuing MAC prophylaxis in patients who respond to potent combination antiretroviral therapy, the observed high incidence of macrolide-resistant bacterial colonization of the respiratory tract in this trial supports the discontinuation of macrolide prophylaxis in all AIDS patients whose CD4 counts have risen above 100 cells/microL.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis , Azithromycin/therapeutic use , Clarithromycin/therapeutic use , Drug Resistance, Bacterial , Mycobacterium avium-intracellulare Infection/prevention & control , AIDS-Related Opportunistic Infections/prevention & control , Adult , Anti-Bacterial Agents/pharmacology , Anti-HIV Agents/therapeutic use , Azithromycin/pharmacology , Bacteria/drug effects , Bacteria/isolation & purification , Clarithromycin/pharmacology , HIV Infections/drug therapy , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Mycobacterium avium Complex/drug effects , Respiratory System/microbiologyABSTRACT
UNLABELLED: The effect of ritonavir 400 mg/saquinavir 400 mg twice daily on the stereoselective pharmacokinetics of methadone was examined in 12 HIV-infected, methadone-using study subjects. DESIGN: A 24-hour methadone pharmacokinetic study was performed before antiretroviral therapy was begun and after 15 days of therapy. Methadone concentration was measured by a chiral plasma assay because the drug is administered as a racemic mixture of R- and S-methadone, but only the R-isomer is active. Both changes in plasma protein binding and changes in objective and subjective opioid effect were monitored. RESULTS: Ritonavir/saquinavir administration was associated with 40% decrease in total S-methadone AUC0-24hr and 32% decrease in R-methadone area under the curve (AUC)0-24hr, and both changes were statistically significant (p =.001 for both). When AUC was corrected for the changes in protein binding induced by ritonavir/saquinavir, R-methadone free AUC0-24hr decreased 19.6% whereas the S-methadone decreased 24.6%, neither of these changes was statistically significant (p =.129 and p =.0537, respectively). This change in methadone exposure was not associated with any evidence of withdrawal from narcotics and no modification of methadone dose was required. CONCLUSIONS: Our data indicate that ritonavir/saquinavir administration is associated with induction of metabolism of methadone but this is greater for the inactive S-methadone. However, approximately 37% of the decrease in the total R-methadone exposure can be explained by protein binding displacement. Ritonavir/saquinavir can be used in HIV-infected people taking methadone without routine dose adjustments.
Subject(s)
HIV Protease Inhibitors/administration & dosage , Methadone/pharmacokinetics , Narcotics/pharmacokinetics , Ritonavir/administration & dosage , Saquinavir/administration & dosage , Adult , Drug Interactions , Female , HIV Infections/drug therapy , HIV-1/physiology , Humans , Male , Methadone/therapeutic use , Middle Aged , Narcotics/therapeutic use , Ritonavir/blood , Saquinavir/blood , Stereoisomerism , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/rehabilitationABSTRACT
There is growing concern that the metabolic complications associated with HIV and antiretroviral therapy may lead to accelerated coronary artery disease (CAD). Traditional cardiovascular risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, and visceral fat accumulation, are increasingly seen in HIV patients receiving HAART. These factors are in addition to nonreversible risk factors, such as male sex, age greater than 40 years, and family history of premature CAD. Patients may also be smokers and may have a sedentary lifestyle, both of which predispose to significant CAD. In older patients and those with other risk factors, there may be an accentuation of these risk factors by HAART, although these factors also occur in young patients with no other risk factors. It is still unknown whether the factors predispose HIV patients to accelerated cardiovascular disease. Short-term studies, including 2 large cross-sectional studies, do not show an increased risk of cardiovascular complications or cardiac death, but longer follow-up is needed to answer such questions effectively. Even if patients are not at increased risk for cardiovascular disease, they are at least at the same risk as HIV-negative, age-matched persons with similar risk factors. It is, therefore, pertinent to identify and effectively manage those risk factors that can be modified.
Subject(s)
Antiretroviral Therapy, Highly Active/adverse effects , Cardiovascular Diseases/chemically induced , HIV Infections/drug therapy , Hyperlipidemias/chemically induced , Cross-Sectional Studies , Humans , Risk FactorsABSTRACT
We report the first described case of Arthrographis kalrae pansinusitis and meningitis in a patient with AIDS. The patient was initially diagnosed with Arthrographis kalrae pansinusitis by endoscopic biopsy and culture. The patient was treated with itraconazole for approximately 5 months and then died secondary to Pneumocytis carinii pneumonia. Postmortem examination revealed invasive fungal sinusitis that involved the sphenoid sinus and that extended through the cribiform plate into the inferior surfaces of the bilateral frontal lobes. There was also an associated fungal meningitis and vasculitis with fungal thrombosis and multiple recent infarcts that involved the frontal lobes, right caudate nucleus, and putamen. Post mortem cultures were positive for A. kalrae.
Subject(s)
AIDS-Related Opportunistic Infections/microbiology , Meningitis, Fungal/microbiology , Mitosporic Fungi , Mycoses/complications , Sphenoid Sinusitis/microbiology , AIDS-Related Opportunistic Infections/complications , Adult , Fatal Outcome , Humans , Male , Meningitis, Fungal/pathology , Mitosporic Fungi/classification , Mitosporic Fungi/isolation & purification , Mycoses/pathology , Pneumonia, Pneumocystis/complications , Pneumonia, Pneumocystis/pathology , Sphenoid Sinusitis/pathologyABSTRACT
Nevirapine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) that has the most common treatment limiting side effect of rash. Severe rash has been observed in 3% of patients taking nevirapine in clinical trials, 85% of whom were men. In a multicenter, retrospective cohort study of all patients who received nevirapine over a 5-year period, severe rash was noted in 9 of 95 women and 3 of 263 men (risk ratio [RR], 8.31; 95% confidence interval [CI], 2.3-30.0; P=.005). Women were more likely to discontinue nevirapine therapy because of rash (RR, 4.5; 95% CI, 1. 9-10.5; P=.0005). After adjusting for age and baseline CD4 cell count in multivariate analysis, women had a 7-fold increase in risk for severe rash and were 3.5 times more likely to discontinue nevirapine therapy. In women of reproductive age for whom contraception may occur, nevirapine remains the NNRTI of choice. Recognition of sex differences in this severe adverse event will be important in prescribing nevirapine.
Subject(s)
Anti-HIV Agents/adverse effects , Drug Eruptions , Exanthema/chemically induced , HIV Infections/complications , Nevirapine/adverse effects , Reverse Transcriptase Inhibitors/adverse effects , Sex Characteristics , Adult , Anti-HIV Agents/therapeutic use , Cohort Studies , Female , HIV Infections/drug therapy , Humans , Male , Multivariate Analysis , Nevirapine/therapeutic use , Retrospective Studies , Reverse Transcriptase Inhibitors/therapeutic useABSTRACT
BACKGROUND: The pharmacokinetics and pharmacodynamics of immediate-release (IR) metoprolol, 50 mg 3 times daily, were compared with those of different doses of controlled-release/extended-release metoprolol (CR/XL) given once daily. METHODS AND RESULTS: Fifteen patients with chronic heart failure were randomized to a 3-way crossover study to receive metoprolol IR 50 mg 3 times daily, CR/XL 100 mg once daily, and CR/XL 200 mg once daily for 7 days. On the seventh day of each treatment, serial plasma samples were drawn and standardized exercise tests and a 24-hour Holter recording were performed. Metoprolol IR 50 mg produced peak plasma levels comparable to those observed for CR/XL 200 mg (285 v 263 nmol/L). The difference in mean 24-hour heart rate between CR/XL 100 mg and IR 50 mg was 1.0 bpm (95% confidence interval [CI]), -2.9 to 4.9; NS) compared with -3.8 bpm (95% CI, -7.6 to -0.04; P = .048) between CR/XL 200 mg and IR 50 mg. Submaximal exercise heart rate was lower for patients receiving CR/XL 200 mg than those receiving IR 50 mg. No difference in tolerance or exercise performance was observed between treatment regimens. CONCLUSIONS: Peak plasma levels produced by metoprolol 200 mg CR/XL were similar to those of 50 mg IR. Metoprolol CR/XL 200 mg was associated with a more pronounced suppression of heart rate than metoprolol IR 50 mg. It is suggested that patients can safely be switched from multiple dosing of metoprolol IR 50 mg to a once-daily dose of metoprolol CR/XL.
Subject(s)
Adrenergic beta-Antagonists/pharmacokinetics , Adrenergic beta-Antagonists/therapeutic use , Heart Failure/drug therapy , Heart Rate/drug effects , Metoprolol/pharmacokinetics , Metoprolol/therapeutic use , Adrenergic beta-Antagonists/blood , Aged , Blood Pressure/drug effects , Circadian Rhythm/drug effects , Dose-Response Relationship, Drug , Electrocardiography, Ambulatory , Exercise Test , Female , Heart Failure/blood , Humans , Male , Metoprolol/blood , Middle AgedABSTRACT
BACKGROUND: Nontraditional manifestations of primary hyperparathyroidism (HPT) are controversial and may include morbidity, mortality, and risk factors for cardiovascular diseases. This study evaluates cardiovascular functions at rest and during exercise in HPT. METHOD: Thirty patients with HPT (mean serum calcium, 2.97 +/- 0.24 mmol/L) and 30 control people with normocalcemia, matched for age and sex, underwent symptom-limited exercise testing and echocardiography before and 13 months (mean) after having a parathyroidectomy. RESULTS: Despite similar maximal workload and blood pressures at rest in patients and healthy controls, HPT associated with higher systolic blood pressure during exercise (P =.03) and increased number of ventricular extrasystolic beats (P =.04). There was also an operatively reversible increase in ST-segment depression during exercise. Echocardiography showed an increased left ventricular (LV) isovolemic relaxation time (P =.02) and mitral deceleration time (P =.08), which indicate an LV diastolic dysfunction that could be partially reversed by operation. LV systolic function (ejection fraction and shortening fraction) tended to be elevated in HPT (P =.07 and.06, respectively) and diminished after parathyroidectomy. There was a trend toward higher LV mass, especially among the men with HPT (P =.06), which was unchanged postoperatively. CONCLUSIONS: HPT couples to reversible signs of myocardial ischemia and LV dysfunctions with a possible increased risk of life-threatening arrhythmia.
Subject(s)
Diastole , Exercise Test , Hyperparathyroidism/surgery , Parathyroidectomy , Systole , Ventricular Function, Left , Adult , Aged , Aged, 80 and over , Echocardiography , Female , Humans , Hyperparathyroidism/complications , Hyperparathyroidism/physiopathology , Hypertrophy, Left Ventricular/etiology , Male , Middle AgedABSTRACT
Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy. These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the management of dyslipidemia in the general population formed the general basis for our recommendations. Data on the prevalence and treatment of dyslipidemia of HIV-infected patients, implications of treatment-related dyslipidemia in other chronically ill populations, and pharmacokinetic profiles for the available hypolipidemic agents in non-HIV populations were considered. Although the implications of dyslipidemia in this population are not fully known, the frequency, type, and magnitude of lipid alterations in HIV-infected people are expected to result in increased cardiovascular morbidity. We propose that these patients undergo evaluation and treatment on the basis of existing guidelines for dyslipidemia, with the caveat that avoidance of interactions with antiretroviral agents is paramount.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/complications , Hyperlipidemias/drug therapy , Acquired Immunodeficiency Syndrome/prevention & control , Acquired Immunodeficiency Syndrome/virology , Adult , Cardiovascular Diseases/drug therapy , HIV Infections/drug therapy , Humans , Hyperlipidemias/complications , Hypolipidemic Agents/therapeutic useABSTRACT
BACKGROUND: Patients infected with HIV who experience increases in CD4(+) cell counts are at reduced risk for opportunistic infections. However, the safety of discontinuing prophylaxis against Mycobacterium avium complex has been uncertain. OBJECTIVE: To compare the rate of M. avium complex infection in patients with increased CD4(+) cell counts who receive azithromycin and those receiving placebo. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 29 university-based clinical centers in the United States. PARTICIPANTS: 643 HIV-1-infected patients with a previous CD4(+) cell count less than 0.05 x 10(9) cells/L and a sustained increase to greater than 0.10 x 10(9) cells/L during antiretroviral therapy. INTERVENTION: Azithromycin, 1200 mg once weekly (n = 321), or matching placebo (n = 322). MEASUREMENTS: Mycobacterium avium complex cultures, CD4(+) cell counts, and clinical evaluations for AIDS-defining illnesses and bacterial infections were done every 8 weeks. Plasma HIV-1 RNA levels were measured at 16-week intervals. RESULTS: During follow-up (median, 16 months), 2 cases of M. avium complex infection were reported among the 321 patients assigned to placebo (incidence rate, 0.5 event per 100 person-years [95% CI, 0.06 to 1.83 events per 100 person-years]) compared with no cases among the 322 patients assigned to azithromycin (CI, 0 to 0.92 events per 100 person-years), resulting in a treatment difference of 0.5 event per 100 person-years (CI, -0.20 to 1.21 events per 100 person-years) for placebo versus azithromycin. Both cases were atypical in that M. avium complex was localized to the vertebral spine. Patients receiving azithromycin were more likely than those receiving placebo to discontinue treatment with the study drug permanently because of adverse events (8% vs. 2%; hazard ratio, 0.24 [CI, 0.10 to 0.57]). CONCLUSIONS: Prophylaxis against Mycobacterium avium complex can safely be withdrawn or withheld in adults with HIV infection who experience increases in CD4(+) cell count while receiving antiretroviral therapy.
Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , CD4 Lymphocyte Count , HIV Infections/drug therapy , HIV Infections/immunology , Mycobacterium avium-intracellulare Infection/prevention & control , Adult , Anti-Bacterial Agents/adverse effects , Anti-HIV Agents/therapeutic use , Azithromycin/adverse effects , Disease Progression , Double-Blind Method , Female , HIV Infections/virology , HIV-1/genetics , Humans , Immunocompromised Host , Male , Mycobacterium avium Complex , Placebos , Proportional Hazards Models , RNA, Viral/blood , Viral LoadABSTRACT
Critical questions remain unanswered regarding the safety and efficacy of withdrawing primary and secondary prophylaxis in the context of HAART-associated immune reconstitution. What are the mediators of first phase cellular increases? Will continued HIV suppression result in continued immune restoration? And what are the immunological consequences of viral rebound despite HAART in patients whose CD4 counts remain elevated? Can immunity, once lost, be restored by reintroduction of antigens such as by tetanus or pneumococcal vaccination? Can immunoassays predict who will relapse or reactivate an OI? Is it possible to eradicate infections such as MAC, cryptococcosis, and histoplasmosis? Certainly, one can never eradicate CMV infection but can immunoassays predict who will have disease-reactivate? Unfortunately, various studies have reported contradicting results regarding the immunological response in vitro to specific antigens. Until these immunoassays become standardized and validated, it is unclear if immunoassays will be predictive of who would be at risk of development of disease or relapse. Therefore, until such time, clinicians may want to initiate and maintain primary prophylaxis in HIV-infected individuals as recommended by the USPHS/IDSA guidelines based on the nadir CD4+ T-cell count at least until studies have clearly demonstrated whether the increased CD4+ T-cell response attributed to HAART does in fact confer protection against these pathogens. Although for some OIs it does appear safe to withdraw primary prophylaxis and probably secondary prophylaxis, the decision to stop prophylaxis or maintenance therapy should be a joint decision by the patient and clinician based on the risks and benefits of stopping the therapy and the availability of close clinical monitoring for evidence of disease.
Subject(s)
AIDS-Related Opportunistic Infections/prevention & control , Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/immunology , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/immunology , Antiretroviral Therapy, Highly Active , Drug Therapy, Combination , HIV Infections/complications , Humans , Viral LoadABSTRACT
PURPOSE: The purpose of our study was to define the time course and clinical role of monitoring serum cryptococcal antigen titers (sCRAG) in patients with AIDS-related cryptococcal disease. METHOD: A retrospective chart review was conducted. The medical records for all HIV-infected patients with positive cryptococcal antigen (CRAG) tests from January 1993 to May 1998 at San Francisco General Hospital (SFGH) were reviewed for sCRAG titer levels and clinical outcomes. RESULTS: Out of the 314 patients found to have positive antigen tests, 136 met the inclusion criteria. Twelve (8.8%) had no change in titer from baseline, 6 (4.4%) had an increase, and 118 (86.8%) had a decrease. Examining the association of sCRAG with time to relapse using a variety of Cox models produced largely null results. Rate of change in sCRAG over time (slope) was not significantly predictive of time to relapse nor of time to definite relapse/probable relapse/persistent disease. CONCLUSION: Although in the majority of patients, the sCRAG titers appeared to decrease over time, we could not detect a significant correlation between sCRAG titer results of patients who had a clinical response to treatment and sCRAG titers in patients who experienced persistent disease, probable relapse, or definitive relapse of cryptococcal disease. We conclude that follow-up monitoring of the sCRAG titer is not useful in the management of patients with AIDS-related cryptococcal disease on treatment.