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      Low-level genital HIV shedding in Thai HIV-infected women with suppressed plasma viral load after menopause: a longitudinal study

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          Abstract

          Objectives

          First, to evaluate the longitudinal changes of HIV RNA in genital secretions in HIV-positive women with plasma HIV RNA <50 copies/mL before and after the onset of menopause. Second, to assess inflammatory markers and prevalence of comorbidities after the onset of menopause.

          Methods

          This was a prospective observational study with two time points. HIV RNA in genital secretions (GVL) was measured in 15 HIV-positive menopausal women (second time point). Results were compared to earlier available data for GVL from the same participant before the onset of menopause (first time point).

          Results

          Median age at the first time point was 42 years, and 52 years at the second time point. Median time since the onset of menopause was 2 years and 33% of women were sexually active. Eighty per cent had at least one comorbidity. The GVL before menopause was >50 copies/mL in 27% of the participants, and in 40% after menopause. The GVL was <1000 copies/mL in all but one measurement. There was no significant difference between the two time points ( P=0.687). Intermediate vaginal flora or bacterial vaginosis was found in 73% of participants during the second time point.

          Conclusions

          There was a high prevalence of low-level GVL shedding before and after menopause. This needs further investigation, especially in relation to the vaginal microbiome and the complex interactions between micro-organisms. HIV-infected women in menopause do not seem to present a major public health risk for HIV transmission. Nevertheless, safe sex should be discussed with all, regardless of age. The high prevalence of non-communicable diseases after menopause requires special attention and comprehensive care.

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          Most cited references24

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          Menopause and the vaginal microbiome.

          For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis.
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            Sex steroid hormones, hormonal contraception, and the immunobiology of human immunodeficiency virus-1 infection.

            Worldwide, an increasing number of women use oral or injectable hormonal contraceptives. However, inadequate information is available to aid women and health care professionals in weighing the potential risks of hormonal contraceptive use in individuals living with HIV-1 or at high risk of infection. Numerous epidemiological studies and challenge studies in a rhesus macaque model suggest that progesterone-based contraceptives increase the risk of HIV-1 infection in humans and simian immunodeficiency virus (SIV) infection in macaques, accelerate disease progression, and increase viral shedding in the genital tract. However, because several other studies in humans have not observed any effect of exogenously administered progesterone on HIV-1 acquisition and disease progression, the issue continues to be a topic of intense research and ongoing discussion. In contrast to progesterone, systemic or intravaginal treatment with estrogen efficiently protects female rhesus macaques against the transmission of SIV, likely by enhancing the natural protective properties of the lower genital tract mucosal tissue. Although the molecular and cellular mechanisms underlying the effect of sex steroid hormones on HIV-1 and SIV acquisition and disease progression are not well understood, progesterone and estrogen are known to regulate a number of immune mechanisms that may exert an effect on retroviral infection. This review summarizes current knowledge of the effects of various types of sex steroid hormones on immune processes involved in the biology of HIV-1 infection.
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              Estradiol Reduces Susceptibility of CD4+ T Cells and Macrophages to HIV-Infection

              The magnitude of the HIV epidemic in women requires urgent efforts to find effective preventive methods. Even though sex hormones have been described to influence HIV infection in epidemiological studies and regulate different immune responses that may affect HIV infection, the direct role that female sex hormones play in altering the susceptibility of target cells to HIV-infection is largely unknown. Here we evaluated the direct effect of 17-β-estradiol (E2) and ethinyl estradiol (EE) in HIV-infection of CD4+ T-cells and macrophages. Purified CD4+ T-cells and monocyte-derived macrophages were generated in vitro from peripheral blood and infected with R5 and X4 viruses. Treatment of CD4+ T-cells and macrophages with E2 prior to viral challenge reduced their susceptibility to HIV infection in a dose-dependent manner. Addition of E2 2 h after viral challenge however did not result in reduced infection. In contrast, EE reduced infection in macrophages to a lesser extent than E2 and had no effect on CD4+ T-cell infection. Reduction of HIV-infection induced by E2 in CD4+ T-cells was not due to CCR5 down-regulation, but was an entry-mediated mechanism since infection with VSV-G pseudotyped HIV was not modified by E2. In macrophages, despite the lack of an effect of E2 on CCR5 expression, E2–treatment reduced viral entry 2 h after challenge and increased MIP-1β secretion. These results demonstrate the direct effect of E2 on susceptibility of HIV-target cells to infection and indicate that inhibition of target cell infection involves cell-entry related mechanisms.
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                Author and article information

                Journal
                J Virus Erad
                J Virus Erad
                JOURNAL OF VIRUS ERADICATION
                Journal of Virus Eradication
                Mediscript Ltd
                2055-6640
                2055-6659
                October 2017
                1 October 2017
                : 3
                : 4
                : 204-207
                Affiliations
                [ 1 ] HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT) , Bangkok, Thailand
                [ 2 ] Thai Red Cross AIDS Research Centre , Bangkok, Thailand
                [ 3 ] SEARCH , Bangkok, Thailand
                [ 4 ] University of Amsterdam , the Netherlands
                [ 5 ] US Military HIV Research Program, Walter Reed Army Institute of Research , Silver Spring, MD, USA
                [ 6 ] Faculty of Medicine, Chulalongkorn University , Bangkok, Thailand
                Author notes
                [* ]Corresponding author: Nadia Kancheva Landolt, HIV-NAT, Thai Red Cross AIDS Research Centre , 104 Rajdamri Road, Pathumwan, Bangkok, Thailand10330Email:  nadia.kl@ 123456hivnat.org
                Article
                5632546
                89d02802-226c-46b6-9f6f-9efc2038a3b1
                © 2017 The Authors.  Journal of Virus Eradication published by Mediscript Ltd

                This is an open access article published under the terms of a Creative Commons License.

                History
                Categories
                Original Research

                hiv and women, menopause, genital viral shedding, metabolic syndrome

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