Differential CD4+ cell count increase and CD4+ : CD8+ ratio normalization with maraviroc compared with tenofovir

Studies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence it remains unclear whether MVC has unique immunologic effects in comparison to other antiretroviral drugs. We sought to determine whether MVC has differential effects compared to tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy

A Comparison of Lower Genital Tract Glycogen and Lactic Acid Levels in Women and Macaques: Implications for HIV and SIV Susceptibility

Understanding factors that affect eterosexual 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 = 1.2mol lactate/mg protein) and pigtail macaques (median = 0.7mol/mg) compared to women with healthy genital microbiota (median = 4.2mol/mg). Glycogen levels were significantly lower in both rhesus (median = 0.004 lg glycogen/lg protein) and pigtail macaques (median = 0 lg/lg) than in women (median = 0.2 lg/lg). 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

A Comparison of Lower Genital Tract Glycogen and Lactic Acid Levels in Women and Macaques: Implications for HIV and SIV Susceptibility

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

A Summary of the First HIV Microbiome Workshop 2015

The role of microbiota in the pathogenesis of HIV infection has become the subject of intense research in recent years. A rapidly growing amount of data suggest that microbial dysbiosis-in the gut or the genital tract-can influence HIV transmission and/or disease progression; however, a deeper understanding of the mechanisms involved is lacking. To better understand the relationship between the microbiome and HIV infection, investigators from a wide variety of disciplines, including those working in basic and clinical HIV studies, cardiovascular disease, reproductive health, and bioinformatics, gathered at the first International Workshop on Microbiome in HIV Pathogenesis, Prevention and Treatment, at NIH on 7 and 8 April, 2015

Glycogen Levels in Undiluted Genital Fluid and Their Relationship to Vaginal pH, Estrogen, and Progesterone

<div><p>Background</p><p>Colonization of the female lower genital tract with <i>Lactobacillus</i> provides protection against STIs and adverse pregnancy outcomes. Growth of genital <i>Lactobacillus</i> is postulated to depend on epithelial cell-produced glycogen. However, the amount of cell-free glycogen in genital fluid available for utilization by <i>Lactobacillus</i> is not known.</p><p>Methods</p><p>Eighty-five genital fluid samples from 7 pre-menopausal women taken over 4–6 weeks were obtained using the Instead SoftCup^® (EvoFem, Inc., San Diego, CA, USA) by consented donors. Cell-free glycogen and glucose in genital fluids and estrogen and progesterone in blood were quantified.</p><p>Findings</p><p>Glycogen ranged from 0.1–32 μg/μl. There were significant differences between women in glycogen over the observation period. There was a strong negative correlation between glycogen and vaginal pH (r = -0.542, p<0.0001). In multivariable analysis, free glycogen levels were significantly negatively associated with both vaginal pH and progesterone (p < 0.001 and p = 0.004, respectively). Estrogen, glucose, age, sexual intercourse 24 hours prior to visit, and days after the initial visit were not significantly associated with free glycogen levels.</p><p>Conclusion</p><p>Cell-free glycogen concentrations can be very high, up to 3% of genital fluid, and are strongly associated with acidic vaginal pH. However, the fluctuations in glycogen levels in individuals and differences between individuals do not appear to be associated with estrogen.</p></div