glycogen and HIV-Infections

While resistance to HIV transmission is due to multiple mechanisms such as the epithelium, a lower genital tract microbiota dominated by Lactobacillus appears to play an important role. This article reviews selected recent research on genital tract microbiota in women including how microbiota impacts HIV resistance and factors affecting Lactobacillus colonization.

Topics: Cervix Uteri; Epithelium; Female; Glycogen; HIV Infections; Humans; Hydrogen Peroxide; Immunity, Innate; Lactobacillus; Microbiota; Vagina

Measurements of HIV exposure could help identify subpopulations at highest risk of acquisition and improve the design of HIV prevention efficacy trials and public health interventions. The HVTN 915 study evaluated the feasibility of self-administered vaginal swabs for detection of HIV virions to assess exposure.. Fifty 18- to 25-year-old sexually active HIV-seronegative women using contraception were enrolled in Soweto, South Africa. Participants self-administered daily vaginal swabs and answered sexual behavior questions through mobile phone for 90 days. Clinician-administered vaginal swabs, behavioral questionnaires, HIV diagnostic testing, and counseling were performed at 8 clinic visits. Glycogen concentrations assessed adherence to swabbing. Y-chromosome DNA (Yc-DNA) assessed the accuracy of reported condom use. HIV exposure was measured by virion polymerase chain reaction in swabs from 41 women who reported unprotected vaginal sex during follow-up.. Glycogen was detected in 315/336 (93.8%) participant-collected and in all clinician-collected swabs. Approximately 20/39 daily swabs (51.3%) linked to mobile reports of unprotected sex tested positive for Yc-DNA, whereas 10/187 swabs collected after 3 days of abstinence or protected sex (5.3%) had detectable Yc-DNA. No participant became HIV infected during the study; yet, exposure to HIV was detected by nucleic acids in 2 vaginal swabs from 1 participant, collected less than 1 hour after coitus.. There was high adherence to daily vaginal swabbing. Daily mobile surveys had accurate reporting of unprotected sex. Detection of HIV in self-collected vaginal swabs from an uninfected participant demonstrated it was possible to measure HIV exposure, but the detection rate was lower than expected.

Topics: Adolescent; Adult; Cell Phone; Cohort Studies; Coitus; Condoms; Female; Glycogen; HIV Infections; Humans; Risk-Taking; Safe Sex; Self Report; Sexual Behavior; South Africa; Surveys and Questionnaires; Unsafe Sex; Vagina; Vaginal Smears; Virion; Young Adult

Topics: Administration, Intravaginal; Animals; Anti-HIV Agents; Anti-Infective Agents, Local; Biological Assay; Calcium Carbonate; Chemical Engineering; Chemistry, Pharmaceutical; Concanavalin A; Cross-Linking Reagents; Drug Delivery Systems; Drug Liberation; Female; Glycogen; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Keratinocytes; Lactobacillus crispatus; Methylmannosides; Mice; Nanoparticles; RAW 264.7 Cells; Swine; Tenofovir; Vagina

Previous studies have suggested that glycogen expression in the vaginal epithelium decreases during menopause, resulting in reduced levels of lactobacilli. However, free glycogen in genital fluids and its relationship with Lactobacillus levels have not been compared in premenopausal and postmenopausal women.. Eighty-two cervicovaginal lavage samples were collected at different phases of the menstrual cycle from 11 premenopausal (4 HIV-uninfected and 7 HIV-infected) and 12 postmenopausal (7 HIV-uninfected and 5 HIV-infected) women during a 1- to 3-month period. Free glycogen was quantified in genital fluids. Lactobacillus levels were quantified by real-time polymerase chain reaction. Estrogen and progesterone levels in blood were determined by enzyme-linked immunosorbent assay.. Free glycogen was detected in both premenopausal and postmenopausal women. Across all samples, those from postmenopausal women had significantly lower levels of free glycogen than those from premenopausal women (median, 0.002 vs 0.065 μg/μL, respectively; P = 0.03). Lactobacillus levels correlated positively with free glycogen in both premenopausal (Spearman r = 0.68, P < 0.0001) and postmenopausal (r = 0.60, P < 0.002) women. Samples from premenopausal women had higher Lactobacillus levels and lower vaginal pH (median log, 8.1; median pH, 4) than those from postmenopausal women (median log, 7.1; median pH, 4.6), although these differences were not significant. HIV status had no significant effect on these relationships.. Free glycogen is detected in both premenopausal and postmenopausal women and correlates with Lactobacillus in both groups. These results point to the complexity of the relationship between menopause and vaginal microbiota and indicate that more careful studies of the role of glycogen are warranted.

Topics: Adult; Cervix Mucus; Enzyme-Linked Immunosorbent Assay; Estrogens; Female; Glycogen; HIV Infections; Humans; Lactobacillus; Menstrual Cycle; Microbiota; Middle Aged; Postmenopause; Premenopause; Progesterone; Real-Time Polymerase Chain Reaction; Vagina

Understanding factors that affect heterosexual transmission of HIV in women is of great importance. Lactobacilli in the lower genital tract of women utilize glycogen in vaginal epithelial cells as an energy source and produce lactic acid. The resultant vaginal acidity is believed to provide protection against HIV infection. Conversely, bacterial vaginosis (BV) is characterized by less lactic acid and a higher pH, and is associated with increased susceptibility to HIV infection. Because vaginal infection of macaques with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) is used as a model to study HIV sexual transmission, and because previous studies have shown a paucity of lactobacilli in rhesus macaques' lower genital tract, we compared lactic acid and glycogen levels in the genital fluid of rhesus and pigtail macaques with levels found in humans. The levels of lactic acid were lower in both rhesus (median=1.2 mol lactate/mg protein) and pigtail macaques (median=0.7 mol/mg) compared to women with healthy genital microbiota (median=4.2 mol/mg). Glycogen levels were significantly lower in both rhesus (median=0.004 μg glycogen/μg protein) and pigtail macaques (median=0 μg/μg) than in women (median=0.2 μg/μg). No significant differences in glycogen or lactate levels were observed comparing longitudinally collected samples from cycling pigtail macaques. These data show that the previously reported scarcity of lactobacilli in macaques correlates with low glycogen and lactic acid levels. These findings have important implications for studies of vaginal infection of macaques with SIV or SHIV and further our understanding of how the bacterial microbiota influences HIV infection.

Topics: Animals; Disease Susceptibility; Female; Glycogen; HIV Antibodies; HIV Infections; HIV-1; Humans; Lactic Acid; Macaca mulatta; Macaca nemestrina; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Vagina; Vaginosis, Bacterial; Women

We recently reported that treatment with a pharmacologic dose of recombinant human growth hormone (GH) resulted in a significant loss of body fat and gain in lean tissue in HIV-infected patients with syndromes of fat accumulation. However, insulin-mediated glucose disposal decreased transiently after one month of GH therapy. The present paper focuses on the changes of hepatic carbohydrate and fat metabolism associated with GH treatment in the same subjects. We assessed hepatic insulin sensitivity under both fasting and hyperinsulinemic-euglycemic clamp conditions prior to and after one and six months of GH treatment (3 mg/day) in five patients using stable isotope tracer techniques. Indirect calorimetry, and measurements of lipid concentrations. Fasting endogenous glucose production (EGP) increased significantly at one month (12.0 +/- 0.7 to 14.9 +/- 0.9 micromol/kg/min, P < 0.03), and the increase was sustained at six months of GH treatment (14.0 +/- 1.1 micromol/kg/min, NS). This increase in EGP was driven in part by increased glucogenesis (GNG) (3.5 +/- 0.9 to 5.2 +/- 0.9 and 5.8 +/-1.2 micromol/kg/min, n = 4, P < 0.01 and P < 0.01 at one and six months, respectively); small changes in hepatic glycogenolysis also contributed. Sustained increases in lipolysis and progressive decreases in hepatic fractional de novo lipogenesis (DNL) and triglyceride concentrations occurred with GH treatment. These changes were accompanied by an improved lipid profile with a significant increase in HDL cholesterol and significant decreases in total and LDL cholesterol and triglyceride levels, the latter consistent with the decrease in hepatic DNL. During a hyperinsulinemic-euglycemic glucose clamp, EGP and GNG were markedly suppressed compared to the corresponding time points under fasting conditions, albeit less so when measured after one month of GH treatment. Thus, in HIV-infected patients with abnormal fat distribution, pharmacologic doses of GH improved the overall lipid profile, but worsened glucose homeostasis under both fasting and hyperinsulinemic conditions. The combined implications of these positive and negative metabolic effects for cardiovascular disease risk remain unknown.

Topics: Adipose Tissue; Carbohydrate Metabolism; Gluconeogenesis; Glucose; Glycogen; Growth Hormone; HIV Infections; Human Growth Hormone; Humans; Lipid Metabolism; Lipids; Lipolysis; Liver

Changes in glucose and fat metabolism associated with human immunodeficiency virus (HIV) infection have received attention because of the development of glucose intolerance, dyslipidemia, and lipodystrophy associated with protease inhibitor (PI) therapy. The response to ingested [13C]glucose (1.4 g/kg) was determined in 9 asymptomatic male HIV patients before and after 4.8 months of PI therapy (nelfinavir, 2,250 mg/d) compared with 9 matched seronegative HIV controls. No significant difference was observed for basal plasma glucose, insulin, and C-peptide concentrations between controls and patients before PI therapy. After 4.8 months of PI therapy, basal plasma glucose concentration was slightly, but significantly, increased (approximately 15%) compared with controls or HIV patients prior to receiving PI therapy. Over the first hour following ingestion of the glucose load, plasma glucose and insulin concentrations were higher in HIV patients than in controls, both before (approximately 15% and approximately 29%, respectively) and after (approximately 32% and approximately 43%, respectively) PI therapy. In addition, plasma C-peptide concentration was approximately 61% higher after PI therapy. The oxidation rate of fat, endogenous, and exogenous glucose was computed from the VO2 and respiratory exchange ratio corrected for protein oxidation and from 13C/12C in expired CO2. The only difference between controls and patients both before and after PI therapy was observed over the first 120 minutes following ingestion of the glucose load, when HIV patients oxidized approximately 18% more glucose and approximately 19% less fat than controls. This was not due to a larger oxidation rate of exogenous glucose, but to a larger oxidation rate of endogenous glucose (approximately 50%) in patients compared with controls. These data indicate that HIV infection is associated with minor changes in glucose metabolism, and that PI therapy with nelfinavir for 4.8 months only slightly further impairs glucose metabolism as assessed in response to a large oral glucose load. However, the larger stimulation of total and endogenous glucose oxidation and the larger reduction in fat oxidation, observed in the metabolic response to the glucose load in HIV patients, over time, could result in the accumulation of body fat and could contribute to lipodystrophy.

Topics: Adult; Blood Glucose; C-Peptide; Calorimetry, Indirect; Carbon Isotopes; Fats; Fatty Acids, Nonesterified; Glucose; Glycogen; HIV Infections; HIV Protease Inhibitors; HIV Seronegativity; Humans; Insulin; Longitudinal Studies; Male; Nelfinavir; Oxidation-Reduction; Time Factors; Urea

To investigate the skeletal muscle mitochondrial function in HIV-infected patients with lipodystrophy or elevated p-lactate levels.. Eight HIV patients treated with highly active antiretroviral therapy, with lipodystrophy or elevated p-lactate, and eight healthy controls were exposed to incremental exercise until exhaustion.. Blood samples and gas analysis were performed at rest, during exercise and in recovery. Oxygen consumption, workload and blood lactate were assessed. Before and immediately after exercise muscle biopsies were obtained, in which citrate synthase (CS), hydroxyacyl-coenzyme A dehydrogenase (HD), glycogen and nucleotides were measured.. Maximal workload was significantly lower in patients compared with controls [171 Watt (88-206) versus 235 Watt (118-294) P = 0.05]. A trend towards lower maximal oxygen consumption (VO(2max)) was detected in patients [2136 ml/min (1221-2598) versus 2985 ml/min (1506-3959) P = 0.11]. Patients had significantly elevated levels of blood lactate at rest [1.55 mmol/l (1-2.5) versus 0.8 mmo/l (0.37-1.1) P < 0.01), but no significant difference in maximal blood-lactate values was found. The decline in blood lactate in the recovery period was similar between groups. There was no significant difference in CS, HD, glycogen or nucleotides.. The significantly lower working capacity and the trend towards reduced VO(2max) in patients could be caused by mitochondrial dysfunction, but may also be caused by impaired physical fitness. The similar levels of nucleotides, CS, HD, and glycogen and the normal increase in blood lactate during exercise indicates a normal oxidative phosphorylation. No evidence of serious damage to skeletal muscle mitochondrial function was found.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Acidosis, Lactic; Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Biopsy; Body Composition; Citrate (si)-Synthase; Exercise Test; Exercise Tolerance; Female; Glycogen; HIV Infections; Humans; Lactates; Lipodystrophy; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Nucleotides; Oxygen Consumption; Pyruvates; Reverse Transcriptase Inhibitors

Topics: Adenocarcinoma; Female; Glycogen; HIV Infections; Humans; Hydrogen Bonding; Phosphorus; Precancerous Conditions; Spectroscopy, Fourier Transform Infrared; Uterine Cervical Neoplasms

Patients with HIV have an increased incidence of cervical cancer, necessitating increased surveillance. Infrared spectroscopy (IRS) has the potential of aiding the diagnosis of cervical neoplasia and also of providing clues into its pathogenesis. We studied by IRS cervical scrapings from 22 HIV-infected and 23 control women; 8 of the former and none of the latter had dysplasia. The infrared spectra followed three patterns, designated pattern I (similar to that previously associated with normal cervical samples), pattern II (intermediate between patterns I and III), and pattern III (associated with cervical neoplasia). Compared with HIV-negative controls, HIV-infected women had a higher prevalence of pattern III and a lower prevalence of pattern II; these differences were statistically significant (P = .015 by chi2 analysis). Similar spectroscopic changes were present even when only the cytologically normal samples from HIV-positive and HIV-negative women were analyzed. We speculate that these changes may reflect early structural changes associated with cervical neoplasia that are not detectable cytologically. The infrared spectra in the region 950 to 1,300 cm(-1) could not differentiate cervical samples from HIV-infected and uninfected patients. The potential practical applications of IRS in HIV cervical disease are discussed.

Topics: Adenocarcinoma; Adolescent; Adult; Female; Glycogen; HIV Infections; Humans; Hydrogen Bonding; Middle Aged; Phosphorus; Precancerous Conditions; Spectroscopy, Fourier Transform Infrared; Uterine Cervical Neoplasms; Vaginal Smears

In 34 patients with human immunodeficiency virus (HIV) infection at the asymptomatic stage and 29 patients with chronic viral hepatitis B at the period of exacerbation (of these 14 patients had chronic persistent hepatitis and 15 patients had chronic active hepatitis) the complex study of the functional activity of lymphocytes and neutrophils was carried out by cytochemical methods with the simultaneous determination of the content of immunoregulating lymphocyte subpopulations. In patients with chronic active hepatitis a decrease in the percentage and the absolute number of helper T-lymphocytes and the ratio of CD4/8 in comparison with those in patients with HIV infection were revealed. At the same time patients with HIV infection exhibited more pronounced decrease in the activity of all lymphocytic enzymes under study (neutrophil esterase, acidic phosphatase and succinate dehydrogenase in lymphocytes), as well as in the activity of myeloperoxidase and the content of cation proteins and glycogen in neutrophils in comparison with patients having chronic active hepatitis.

Topics: Adult; CD4-Positive T-Lymphocytes; Cell Separation; Female; Glycogen; Hepatitis B; Hepatitis, Chronic; HIV Infections; HIV-1; Humans; Leukocyte Count; Lymphocytes; Male; Neutrophils