Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
1.
AIDS ; 30(3): 435-44, 2016 Jan 28.
Article in English | MEDLINE | ID: mdl-26765937

ABSTRACT

OBJECTIVES: To evaluate the impact of liver and kidney transplantation on survival in HIV-positive transplant candidates and compare outcomes between HIV-positive and negative recipients. DESIGN: Observational cohort of HIV-positive transplant candidates and recipients and secondary analysis comparing study recipients to HIV-negative national registry controls. METHODS: We fit proportional hazards models to assess transplantation impact on mortality among recipients and candidates. We compared time to graft failure and death with HIV-negative controls in unmatched, demographic-matched, and risk-adjusted models. RESULTS: There were 17 (11.3%) and 46 (36.8%) deaths among kidney and liver recipients during a median follow-up of 4.0 and 3.5 years, respectively. Transplantation was associated with survival benefit for HIV-infected liver recipients with model for end-stage liver disease (MELD) greater than or equal 15 [hazard ratio (HR) 0.1; 95% confidence interval (CI) 0.05, 0.01; P < 0.0001], but not for MELD less than 15 (HR 0.7; 95% CI 0.3, 1.8; P = 0.43) or for kidney recipients (HR 0.6; 95% CI 0.3, 1.4; P = 0.23). In HIV-positive kidney recipients, unmatched and risk-matched analyses indicated a marginally significant HR for graft loss [1.3 (P = 0.07) and HR 1.4 (P = 0.052)]; no significant increase in risk of death was observed. All models demonstrated a higher relative hazard of graft loss or death in HIV-positive liver recipients; the absolute difference in the proportion of deaths was 6.7% in the risk-matched analysis. CONCLUSION: Kidney transplantation should be standard of care for well managed HIV-positive patients. Liver transplant in candidates with high MELD confers survival benefit; transplant is a viable option in selected candidates. The increased mortality risk compared with HIV-negative recipients was modest. TRIAL REGISTRATION: ClinicalTrials.Gov; NCT00074386; http://clinicaltrials.gov/.


Subject(s)
HIV Infections/mortality , Transplant Recipients , Adult , Cohort Studies , Female , Humans , Kidney Transplantation , Liver Transplantation , Male , Middle Aged , Survival Analysis , Treatment Failure
2.
Am J Addict ; 23(2): 137-44, 2014.
Article in English | MEDLINE | ID: mdl-24118434

ABSTRACT

BACKGROUND AND OBJECTIVES: Alcohol abuse complicates treatment of HIV disease and is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders possibly related to concerns about drug interactions between antiretroviral (ARV) medications and DIS. METHOD: This pharmacokinetics study (n=40) examined the effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase (ALDH) activity which mediates the DIS-alcohol reaction. RESULTS: EFV administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate (DIS carbamate), a metabolite of DIS (p=.001) and a precursor to the metabolite responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO). EFV was associated with increased DIS inhibition of ALDH activity relative to DIS alone administration possibly as a result of EFV-associated induction of CYP 3A4 which metabolizes the carbamate to DETC-MeSO (which inhibits ALDH). Conversely, ATV co-administration reduced the effect of DIS on ALDH activity possibly as a result of ATV inhibition of CYP 3A4. DIS administration had no significant effect on any ARV studied. DISCUSSION/CONCLUSIONS: ATV may render DIS ineffective in treatment of alcoholism. FUTURE DIRECTIONS: DIS is infrequently utilized in HIV-infected individuals due to concerns about adverse interactions and side effects. Findings from this study indicate that, with ongoing clinical monitoring, DIS should be reconsidered given its potential efficacy for alcohol and potentially, cocaine use disorders, that may occur in this population.


Subject(s)
Alcohol Deterrents/pharmacology , Aldehyde Dehydrogenase/antagonists & inhibitors , Anti-HIV Agents/pharmacology , Benzoxazines/pharmacology , Disulfiram/metabolism , Disulfiram/pharmacology , Ethanol/metabolism , Oligopeptides/pharmacology , Pyridines/pharmacology , Adult , Alcohol Deterrents/administration & dosage , Alcohol Deterrents/metabolism , Alcohol Deterrents/therapeutic use , Alcoholism/drug therapy , Aldehyde Dehydrogenase/metabolism , Alkynes , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/pharmacokinetics , Atazanavir Sulfate , Benzoxazines/administration & dosage , Benzoxazines/pharmacokinetics , Biotransformation/drug effects , Cyclopropanes , Disulfiram/agonists , Disulfiram/antagonists & inhibitors , Disulfiram/therapeutic use , Ditiocarb/analogs & derivatives , Ditiocarb/metabolism , Drug Interactions , Drug Therapy, Combination , Female , Half-Life , Healthy Volunteers , Humans , Male , Middle Aged , Oligopeptides/administration & dosage , Oligopeptides/pharmacokinetics , Pyridines/administration & dosage , Pyridines/pharmacokinetics , Ritonavir/administration & dosage , Ritonavir/pharmacokinetics , Ritonavir/pharmacology , Thiocarbamates/metabolism
3.
J Int Assoc Provid AIDS Care ; 12(6): 375-7, 2013.
Article in English | MEDLINE | ID: mdl-23881910

ABSTRACT

BACKGROUND: Alcohol use is common among people with HIV, and beliefs about alcohol interactions with medications predict decreased medication adherence, risking drug-resistant mutations. Maraviroc is an HIV entry inhibitor approved for treatment of both drug-sensitive and drug-resistant HIV strains. The present study evaluated the effects of alcohol on maraviroc pharmacokinetics and the effects of maraviroc on alcohol pharmacokinetics. METHODS: Ten healthy adults completed alcohol (1 g/kg) and placebo alcohol pharmacokinetics sessions before and after 7 days of maraviroc administration. RESULTS: Alcohol concentrations increased 12% following maraviroc. Maraviroc pharmacokinetics were unaffected by alcohol. CONCLUSIONS: Maraviroc treatment should not be interrupted if alcohol is consumed.


Subject(s)
Alcohol Drinking/metabolism , Cyclohexanes/pharmacokinetics , Ethanol/pharmacokinetics , HIV Fusion Inhibitors/pharmacokinetics , HIV Infections/drug therapy , HIV Infections/metabolism , Triazoles/pharmacokinetics , Adult , Area Under Curve , Cyclohexanes/administration & dosage , Cyclohexanes/blood , Double-Blind Method , Drug Interactions , Ethanol/administration & dosage , Female , HIV Fusion Inhibitors/administration & dosage , HIV Fusion Inhibitors/blood , Humans , Male , Maraviroc , Triazoles/administration & dosage , Triazoles/blood
4.
Infect Dis Clin North Am ; 27(2): 459-71, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23714349

ABSTRACT

Human immunodeficiency virus (HIV) infection is no longer an absolute contraindication for transplantation for patients with advanced kidney and liver failure. This article reviews the outcome data in the solid organ transplantation of HIV-infected patients that led to a change in thinking by the transplant community. Several emerging issues are also reviewed, such as eligibility criteria, selection of optimal immunosuppression agents and antiretroviral therapy in this population, and management of coinfection with hepatitis B and hepatitis C after transplant.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , Kidney Transplantation , Liver Transplantation , Graft Rejection/epidemiology , Hepatitis B, Chronic/therapy , Hepatitis C, Chronic/therapy , Humans , Treatment Outcome
5.
J Addict Med ; 7(4): 264-70, 2013.
Article in English | MEDLINE | ID: mdl-23666322

ABSTRACT

OBJECTIVE: Alcohol abuse occurs frequently in those with human immunodeficiency virus (HIV) infection. Alcohol has been linked to poor response to HIV treatment and more rapid progression of HIV. One possible contributor to such observations is drug interactions between alcohol and antiretroviral (ARV) medications. This study examined drug interactions between antiretroviral therapies (ARTs) containing either efavirenz or ritonavir with alcohol. METHODS: Human immunodeficiency virus-infected individuals not currently receiving ARTs participated in a randomized, double-blind, placebo-controlled study in which alcohol (or placebo) was administered and followed by blood sampling for pharmacokinetics, subjective, cardiovascular, and neuropsychological responses obtained at predetermined times. Antiretroviral therapy was then initiated and alcohol (or placebo) sessions were repeated after at least 2 weeks of observed ART. RESULTS: Blood alcohol concentrations (BAC) were lower after ART in a pattern consistent with decreased bioavailability. No effect of alcohol on ritonavir or efavirenz pharmacokinetics was observed. A pharmacodynamic interaction between alcohol and efavirenz was observed as evidenced by no change in intoxication or drowsiness before and after efavirenz ART despite lower BAC. CONCLUSIONS: These results show the effectiveness of implementing ART and its role in diminution of BAC, which could be associated with decreased risk of physiological toxicities related to alcohol consumption relative to those with untreated HIV infection. A potential pharmacodynamic interaction between alcohol and efavirenz was observed as demonstrated by a lack of decline in ratings of intoxication and drowsiness despite decreased BAC. Alcohol consumption did not alter the pharmacokinetics of ritonavir or efavirenz.


Subject(s)
Alcohol Drinking/metabolism , Anti-Retroviral Agents/pharmacokinetics , Benzoxazines/pharmacokinetics , Ethanol/pharmacokinetics , HIV Infections/drug therapy , HIV Infections/metabolism , Ritonavir/pharmacokinetics , Adult , Alcohol Drinking/blood , Alkynes , Anti-Retroviral Agents/administration & dosage , Anti-Retroviral Agents/blood , Anti-Retroviral Agents/therapeutic use , Benzoxazines/administration & dosage , Benzoxazines/blood , Cyclopropanes , Drug Interactions , Ethanol/administration & dosage , Ethanol/blood , Female , Humans , Male , Middle Aged , Ritonavir/administration & dosage , Ritonavir/blood , Statistics, Nonparametric
6.
J Acquir Immune Defic Syndr ; 60(3): 282-8, 2012 Jul 01.
Article in English | MEDLINE | ID: mdl-22495786

ABSTRACT

BACKGROUND: Alcohol abuse has been associated with HIV/AIDS progression, but the effects of HIV infection and treatment on alcohol exposure have not been explored to date. This pilot study examines the relationship of untreated HIV infection to blood alcohol concentrations (BAC) relative to BAC after initiation of antiretroviral therapy (ART). METHODS: Fifteen volunteers with untreated HIV/AIDS participated in 2 sets of alcohol or alcohol placebo administration studies before and after initiation of ART. Oral alcohol (1 g/kg) or alcohol placebo was administered, participants were followed for pharmacokinetics, subjective responses, and cognitive effects over 8 hours. After initial alcohol studies, the ART regimen selected by participant clinicians was instituted. Observed ART dosing took place for at least 2 weeks. Participants then returned for a second set of alcohol/placebo administration studies while on ART. RESULTS: Participants had significantly higher BAC (P < 0.001) before ART than after ART administration. Alcohol area under the curve was significantly higher in untreated HIV disease (P = 0.011) with significantly higher C(max) (P = 0.015) and C(min) (P = 0.05). The elimination rate was not different between pre-ART and post-ART conditions. Despite declines in BAC after ART initiation, no differences in subjective responses were observed with alcohol administration. CONCLUSIONS: Untreated HIV infection is associated with risk for higher BAC than that observed after ART. These findings indicate that patients with untreated HIV disease who ingest alcohol are at greater risk for alcohol associated adverse events and toxicities and underscores the need for simultaneous treatment of alcohol use disorders and HIV in patients with co-occurring conditions.


Subject(s)
Alcoholism/blood , Alcoholism/complications , Ethanol/blood , HIV Infections/blood , HIV Infections/complications , Adult , Alcoholism/psychology , Alkynes , Anti-HIV Agents/therapeutic use , Benzoxazines/therapeutic use , Cognition/drug effects , Cyclopropanes , Disease Progression , Double-Blind Method , Ethanol/administration & dosage , Ethanol/pharmacokinetics , Female , HIV Infections/drug therapy , HIV Infections/psychology , Humans , Intestinal Absorption , Male , Middle Aged , Pilot Projects , Ritonavir/therapeutic use
7.
Emerg Med Clin North Am ; 28(2): 299-310, Table of Contents, 2010 May.
Article in English | MEDLINE | ID: mdl-20413013

ABSTRACT

Diarrhea is an exceedingly common complaint in patients with human immunodeficiency virus (HIV) infection, and the severity of symptoms ranges from mild, self-limiting diarrhea to debilitating disease that can result in malnutrition, volume loss, and shock. Up to 40% of patients with HIV infection report at least 1 episode of diarrhea in a given month, and approximately 1 quarter of patients experience chronic diarrhea at some point. The prevalence of diarrhea increases with decreasing CD4 counts. The clinical features, diagnosis, and management of diarrhea in patients with HIV are reviewed.


Subject(s)
Diarrhea/diagnosis , Diarrhea/etiology , Diarrhea/therapy , Emergency Treatment/methods , HIV Infections/complications , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/etiology , AIDS-Related Opportunistic Infections/therapy , Acute Disease , Anti-HIV Agents/adverse effects , CD4 Lymphocyte Count , Chronic Disease , Diagnosis, Differential , Diarrhea/epidemiology , Emergency Medicine/methods , Emergency Service, Hospital , HIV Infections/drug therapy , HIV Infections/immunology , Humans , Medical History Taking , Physical Examination , Prevalence , Risk Factors
8.
Emerg Med Clin North Am ; 28(2): 393-407, Table of Contents, 2010 May.
Article in English | MEDLINE | ID: mdl-20413021

ABSTRACT

Immune reconstitution inflammatory syndrome (IRIS) must be considered in the differential diagnosis for any patient infected with HIV who has begun ART in the preceding months. Distinguishing between manifestations of IRIS and active infection is of paramount importance and poses a diagnostic challenge to the provider in the acute care setting. Presentations of IRIS are often atypical for the precipitating pathogen, and novel presentations are likely. Of the diseases associated with IRIS, mycobacteria and cryptococcal infections are commonly encountered, as are dermatologic symptoms in general. The most clinically significant complications of IRIS are those involving the central nervous system, lungs, and eye, and in many of these scenarios systemic steroids may be of benefit. Management should rarely include interruption of ART, except possibly in severe, life-threatening complications.


Subject(s)
AIDS-Related Opportunistic Infections/complications , Emergency Treatment/methods , HIV Infections/complications , Immune Reconstitution Inflammatory Syndrome , Abdominal Pain/etiology , Anti-Inflammatory Agents/therapeutic use , Antiretroviral Therapy, Highly Active/adverse effects , Diagnosis, Differential , Emergency Medicine/methods , Fever/etiology , Graves Disease/complications , HIV Infections/drug therapy , HIV Infections/immunology , Headache/etiology , Hepatitis/etiology , Humans , Immune Reconstitution Inflammatory Syndrome/diagnosis , Immune Reconstitution Inflammatory Syndrome/epidemiology , Immune Reconstitution Inflammatory Syndrome/etiology , Immune Reconstitution Inflammatory Syndrome/therapy , Incidence , Lung Diseases/etiology , Risk Factors , Sarcoidosis/complications , Skin Diseases/etiology
9.
AIDS Res Hum Retroviruses ; 24(10): 1275-80, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18844462

ABSTRACT

Data from two Phase IIb trials, POWER 1 and 2 (TMC114-C213 and C202), were pooled to examine the effect of baseline viral susceptibility on response to control protease inhibitors [CPI(s)] compared with response to darunavir (TMC114) given with low-dose ritonavir (darunavir/r) in treatment-experienced HIV patients. POWER 1 and 2 were randomized, controlled Phase IIb trials with a similar design. Patients with one or more primary PI mutations and HIV-1 RNA >1000 copies/ml were randomized to receive an optimized background regimen plus darunavir/r or CPI(s). POWER 1 and 2 week 24 efficacy (intent-to-treat using time-to-loss of virologic response algorithm) data were pooled and analyzed according to baseline subgroups of susceptibility to the CPI regimen, fold-change (FC) in EC(50) to darunavir, and number of darunavir resistance-associated mutations (RAMs). In total, 131 patients received darunavir/r 600/100 mg twice daily; 124 received CPI(s) [lopinavir/r, 20%; saquinavir/r, 19%; (fos)-amprenavir/r, 24%; atazanavir/r, 11%; and 23% used dual-boosted CPI(s)]. At baseline, 72% of patients were resistant (defined as FC) to their investigator-selected CPIs. At week 24, darunavir/r 600/100 mg twice daily provided greater efficacy benefits over CPI(s), even when the virus was predicted to be fully susceptible to the CPI. The response to darunavir decreased when FC to darunavir at baseline was >40 or when three or more darunavir RAMs (in addition to other PI mutations) were present at baseline. Darunavir/r 600/100 mg twice daily showed efficacy benefits over CPI use regardless of viral susceptibility at baseline, FC to darunavir or boosting type in a population of treatment-experienced HIV-infected patients.


Subject(s)
Drug Resistance, Viral , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , HIV-1/drug effects , Ritonavir/therapeutic use , Sulfonamides/therapeutic use , Adult , Darunavir , Female , HIV Protease/genetics , HIV Protease Inhibitors/pharmacology , HIV-1/genetics , Humans , Male , Mutation, Missense , RNA, Viral/blood , RNA, Viral/genetics , Ritonavir/pharmacology , Sulfonamides/pharmacology , Treatment Outcome , Viral Load
10.
J Infect Dis ; 195(3): 387-91, 2007 Feb 01.
Article in English | MEDLINE | ID: mdl-17205477

ABSTRACT

Many antiretroviral drugs continue to exert an anti-human immunodeficiency virus (HIV) benefit in the presence of drug resistance mutations. The degree to which enfuvirtide exerts continued antiviral activity in the presence of incomplete viral suppression has not been defined. To address this question, 25 subjects interrupted enfuvirtide while remaining on a stable background regimen. Enfuvirtide interruption was associated with an immediate but limited increase in plasma HIV-1 RNA levels. Enfuvirtide resistance waned rapidly in the absence of drug pressure and was no longer detectable by week 16 in most individuals. These data indicate that enfuvirtide has measurable antiviral activity in the setting of incomplete viral suppression. Although enfuvirtide resistance mutations are associated with significant fitness defects in vivo, the clinical significance of these mutations remains undefined.


Subject(s)
HIV Envelope Protein gp41/therapeutic use , HIV Fusion Inhibitors/therapeutic use , HIV Infections/drug therapy , HIV-1 , Peptide Fragments/therapeutic use , Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Drug Resistance, Viral , Drug Therapy, Combination , Enfuvirtide , HIV Envelope Protein gp41/pharmacology , HIV Fusion Inhibitors/pharmacology , HIV Infections/immunology , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Humans , Mutation , Peptide Fragments/pharmacology , RNA, Viral/blood , Treatment Outcome , Withholding Treatment
11.
J Acquir Immune Defic Syndr ; 43(1): 60-4, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16885776

ABSTRACT

OBJECTIVES: To study the dynamics of enfuvirtide (T-20) resistance development in HIV-1-infected subjects. PATIENTS AND METHODS: Clonal analysis of gp41 sequences was performed on serial samples obtained from HIV-1-infected subjects with early virologic failure of T-20-based regimens. RESULTS: Enfuvirtide resistance mutations at codons 36 to 45 in the first heptad repeat of gp41 emerged within 2 weeks in most subjects and were associated with the return of plasma HIV-1 RNA level toward baseline by weeks 4 to 8. Mutations at codons 36 (G36E, G36D, or G36S) and 38 (V38A, V38G, or V38M) were the most commonly detected resistance mutations at week 2. Mutations at codons 40 (Q40H) and 43 (N43D) were more prevalent at week 4 than at week 2 and seemed to emerge more slowly than mutations at codons 36 and 38. CONCLUSIONS: The rapid emergence of mutations associated with T-20 resistance in the absence of a fully suppressive antiretroviral regimen demonstrates a low genetic barrier to resistance and underscores the importance of combining T-20 with other active drugs when constructing regimens for highly treatment-experienced patients.


Subject(s)
Drug Resistance, Viral , HIV Envelope Protein gp41/genetics , HIV Fusion Inhibitors/therapeutic use , HIV-1/genetics , Peptide Fragments/therapeutic use , Amino Acid Sequence , Cloning, Molecular , DNA Primers , Enfuvirtide , HIV Envelope Protein gp41/drug effects , HIV Envelope Protein gp41/therapeutic use , HIV-1/drug effects , Humans , Molecular Sequence Data , Mutation , Reverse Transcriptase Polymerase Chain Reaction
12.
Antivir Ther ; 11(3): 315-9, 2006.
Article in English | MEDLINE | ID: mdl-16759047

ABSTRACT

Most individuals with multidrug-resistant HIV who switch to a new therapeutic regimen containing a single fully effective agent experience incomplete viral suppression. We postulated that interruption of antiretroviral therapy prior to the introduction of such a regimen would improve long-term virological outcomes. Thirty, three-class experienced, enfuvirtide-naive individuals with detectable drug-resistant viraemia were randomized to an immediate enfuvirtide/optimized-background treatment regimen or a 16-week treatment interruption followed by enfuvirtide/optimized-background treatment regimen. The median CD4+ T-cell count and viral load at study entry were 39 cells/mm and 4.72 log10 copies RNA/ml, respectively. There was no evidence of any virological or immunological benefit associated with the interruption. In multivariate analysis, only the baseline phenotypic susceptibility score was predictive of treatment response at week 48 (P=0.009). Only 40% of individuals had evidence of a shift in drug-resistance genotype during the interruption. In summary, interrupting therapy prior to initiating salvage therapy in patients with advanced disease did not result in an improved virological response to enfuvirtide. The collective predictive activity of an enfuvirtide-containing regimen was important in predicting treatment response.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Envelope Protein gp41/administration & dosage , HIV Fusion Inhibitors/administration & dosage , HIV Infections/drug therapy , Peptide Fragments/administration & dosage , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Drug Administration Schedule , Drug Resistance, Multiple, Viral , Drug Therapy, Combination , Enfuvirtide , HIV Envelope Protein gp41/therapeutic use , HIV Fusion Inhibitors/therapeutic use , HIV Infections/immunology , HIV Infections/virology , Humans , Microbial Sensitivity Tests , Peptide Fragments/therapeutic use , Pilot Projects , RNA, Viral/blood , Treatment Outcome
13.
HIV Clin Trials ; 5(6): 383-91, 2004.
Article in English | MEDLINE | ID: mdl-15682351

ABSTRACT

BACKGROUND: The relationship between insulin resistance, dyslipidemia, HIV infection, and antiretroviral therapy remains unclear, and the atherogenic nature of lipid and lipoprotein profiles in HIV-infected patients has not been fully characterized. METHOD: We measured plasma lipid and lipoprotein subfractions using Vertical Auto Profile-II methodology and directly measured insulin-mediated glucose disposal in 45 protease inhibitor (PI)-treated and non-PI-treated HIV-infected patients. RESULTS: PI-treated patients had higher total, LDL, and narrow-density LDL cholesterol (p <.05) and a trend toward higher triglycerides, whereas HDL cholesterol and LDL particle characteristics were unrelated to PI use or history of lipodystrophy. Insulin sensitivity did not differ on the basis of PI therapy, but decreased insulin sensitivity was associated with lower HDL and HDL-3 cholesterol (p <.01); elevated triglyceride (p <.01), VLDL 1+2, and VLDL 3a+3b lipoproteins (p <.01); and smaller, denser (more atherogenic) LDL particle characteristics (p <.01). Thus, the lipoprotein abnormality associated with PI use was increased LDL cholesterol, whereas changes in TG and HDL metabolism were associated with insulin resistance, independent of PI use. CONCLUSION: The variables of PI-treatment, dyslipidemia, lipodsytrophy, and insulin resistance do not always cluster together in HIV-infected patients, which suggests that the metabolic phenotype emerging in treated patients results from a complex interplay of drug effects, immune restoration, and baseline insulin sensitivity.


Subject(s)
HIV Protease Inhibitors/pharmacology , Adult , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, HDL/drug effects , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Dose-Response Relationship, Drug , Female , HIV Infections/drug therapy , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/therapeutic use , Humans , Hyperlipidemias/chemically induced , Insulin Resistance , Lipids/blood , Lipoproteins/blood , Lipoproteins/drug effects , Male , Middle Aged , Triglycerides/blood
14.
Metabolism ; 52(7): 858-61, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12870161

ABSTRACT

Various indirect indices have been used in human immunodeficiency virus (HIV)-infected individuals to assess insulin resistance, but the validity of these measures has not been rigorously assessed by comparison with physiologic methods of quantifying insulin-mediated glucose uptake (IMGU). We directly measured IMGU in 50 nondiabetic HIV-positive subjects by determining the steady-state plasma glucose (SSPG) concentration in response to a 3-hour continuous infusion of insulin, glucose, and somatostatin. Because steady-state plasma insulin concentrations were similar (approximately 60 microU/mL) in all subjects, the SSPG concentrations provided direct assessments of insulin action. Relationships between SSPG levels and various surrogate measures of IMGU derived from the 75-g oral glucose tolerance test (OGTT) were determined. The indirect measure of IMGU most closely related to SSPG concentrations was the total integrated insulin response to a 75-g glucose load (r=0.78, P<.01), accounting for approximately two thirds of the variability in SSPG (r2=0.61). Other indirect measures of IMGU, including the homeostasis assessment for insulin resistance (HOMA-IR), were also significantly related to SSPG values, but had lower magnitudes of correlation (r=0.43 to 0.61), thereby possessing limited ability to predict SSPG variability (r2=0.18 to 0.37). In conclusion, indirect measures of IMGU need to be applied with caution when evaluating insulin action in HIV-infected patients.


Subject(s)
HIV Infections/complications , Insulin Resistance , Adult , Blood Glucose/analysis , Blood Glucose/metabolism , Fasting , Fatty Acids, Nonesterified/blood , Female , Glucose Tolerance Test , HIV Infections/blood , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Humans , Insulin/pharmacology , Male , Middle Aged
15.
J Acquir Immune Defic Syndr ; 33(1): 34-40, 2003 May 01.
Article in English | MEDLINE | ID: mdl-12792353

ABSTRACT

To describe the distribution of insulin sensitivity and glucose tolerance in HIV-infected patients, the authors measured insulin-mediated glucose disposal (IMGD) in 51 subjects (24 protease inhibitor (PI)-treated subjects and 27 non-PI-treated subjects). IMGD was determined by measuring the steady-state plasma glucose (SSPG) concentration during the last 30 minutes of a 180-minute intravenous infusion of octreotide, glucose, and insulin. In addition, oral glucose tolerance testing was performed. SSPG concentrations varied six-fold in both groups, and the mean values +/- SEM did not differ between PI-treated and non-PI-treated groups (8.7 +/- 0.9 vs. 8.0 +/- 0.7 mmol/L, respectively). The mean fasting plasma glucose concentration +/- SEM was higher in the PI-treated subjects than in the non-PI-treated subjects (5.44 +/- 0.11 vs. 5.05 +/- 0.11 mmol/L, respectively; p =.01), whereas fasting plasma insulin concentrations did not differ. PI-treated patients also had significantly higher plasma glucose (p =.001) and insulin (p =.03) responses to the oral glucose challenge. However, whereas the incremental plasma glucose response during the first 30 minutes was significantly higher in PI-treated patients, the incremental insulin response in the two groups was identical. In conclusion, insulin sensitivity varies widely in HIV-infected patients irrespective of PI treatment, and the adverse effect of PIs on insulin sensitivity is likely to be of modest magnitude. Finally, PI treatment may have an inhibitory effect on insulin secretion.


Subject(s)
Blood Glucose/metabolism , HIV Infections/metabolism , Insulin/metabolism , Adult , Blood Glucose/analysis , Female , Glucose/administration & dosage , Glucose/pharmacology , Glucose Tolerance Test , HIV Infections/drug therapy , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/therapeutic use , HIV-Associated Lipodystrophy Syndrome/chemically induced , Humans , Male , Middle Aged
SELECTION OF CITATIONS
SEARCH DETAIL
...