Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina

Mostad, Sara B.; Overbaugh, Julie; DeVange, Dana M; Welch, M.J.; Chohan, Bhavna; Mandaliya, Kishorchandra; Nyange, Patrick M.; Martin, Harold L.; Ndinya‐Achola, Jeckoniah; Bwayo, Job J.; Kreiss, Joan K.

doi:10.1016/s0140-6736(97)04240-2

Cited by 287 publications

(140 citation statements)

References 27 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…[12][13][14][29][30][31] Conflicting study outcomes have triggered doubts regarding the role of injectable contraceptives and their use in developing countries. [12][13][14][15][16][17][18] It is critical to determine to what degree hormonal contraceptives increase the risk of HIV-1 infection.…”

Section: Researchmentioning

confidence: 99%

Population-level impact of hormonal contraception on incidence of HIV infection and pregnancy in women in Durban, South Africa

Ramjee¹,

Wand²

2012

Bull World Health Org

View full text Add to dashboard Cite

Section: Researchmentioning

confidence: 99%

Population-level impact of hormonal contraception on incidence of HIV infection and pregnancy in women in Durban, South Africa

Ramjee¹,

Wand²

2012

Bull World Health Org

View full text Add to dashboard Cite

“…12 However, establishing indisputable evidence from such studies is extremely difficult due to methodological challenges and multiple confounding factors, such as the degree of exposure to HIV-1, condom usage, HSV-2 exposure as well as varying ages of women that have been enrolled in these studies. 9 Furthermore increases in both HIV-1 and HSV shedding have been reported in women using contraception, [17][18][19] as well as the presence of more viral variants and higher viral loads in HIV-1-infected DMPA users than non-users. 20 These findings are consistent with an increase in HIV-1 transmission found for injectable DMPA users.…”

Section: Introductionmentioning

confidence: 98%

Differential Glucocorticoid Receptor‐Mediated Effects on Immunomodulatory Gene Expression by Progestin Contraceptives: Implications for HIV‐1 Pathogenesis

Hapgood

Ray

Govender

et al. 2014

American J Rep Immunol

View full text Add to dashboard Cite

Whether hormonal contraceptives increase HIV‐1 acquisition, transmission and disease progression are critical questions. Clinical research has been hampered by a lack of understanding that different progestins used in contraception exhibit differential off‐target effects via steroid receptors other than the progesterone receptor. Of particular, relevance is the relative effects of medroxyprogesterone acetate (MPA) and norethisterone enanthate (NET‐EN), widely used as injectable contraceptives in sub‐Saharan Africa. While most high‐quality clinical studies find no increased risk for HIV‐1 acquisition with oral contraception or injectable NET‐EN, most do find an increase with MPA, particularly in young women. Furthermore, mounting evidence from animal, ex vivo and biochemical studies are consistent with MPA acting to increase HIV‐1 acquisition and pathogenesis, via mechanisms involving glucocorticoid‐like effects on gene expression, in particular genes involved in immune function. We report that MPA, unlike NET and progesterone, represses inflammatory genes in human PBMCs in a dose‐dependent manner, via the glucocorticoid receptor (GR), at concentrations within the physiologically relevant range. These and published results collectively suggest that the differential GR activity of MPA versus NET may be a mechanism whereby MPA, unlike NET or progesterone, differentially modulates HIV‐1 acquisition and pathogenesis in target cells where the GR is the predominant steroid receptor expressed.

show abstract

“…In both cross-sectional and longitudinal studies, oral hormonal contraceptive use was associated with an increased frequency of HSV detection in the lower genital tract (7,23,24). During pregnancy, HSV-2 seropositive women denying any prior history of herpetic outbreaks were at increased risk for symptomatic episodes of HSV reactivation (12).…”

mentioning

confidence: 99%

17-β Estradiol Promotion of Herpes Simplex Virus Type 1 Reactivation Is Estrogen Receptor Dependent

Miguel

Sheridan

Harvey³

et al. 2010

J Virol

View full text Add to dashboard Cite

Correlations between estrogen and herpes simplex virus (HSV) reactivation from latency have been suggested by numerous clinical reports, but causal associations are not well delineated. In a murine HSV-1 corneal infection model, we establish 17-␤ estradiol (17-␤E) treatment of latently infected ovariectomized mice induces viral reactivation, as demonstrated by increased viral load and increased immediate-early viral gene expression in the latently infected trigeminal ganglia (TG). Interestingly, the increased HSV reactivation occurred in the absence of inhibition of viral specific CD8؉ T-cell effector function. 17-␤E administration increased HSV reactivation in CD45؉ cell-depleted TG explant cultures, providing further support that leukocyte-independent effects on latently infected neurons were responsible for the increased reactivation. The drug-induced increases in HSV copy number were not recapitulated upon in vivo treatment of latently infected estrogen receptor alpha-deficient mice, evidence that HSV reactivation promoted by 17-␤E was estrogen receptor dependent. These findings provide additional framework for the emerging conceptualization of HSV latency as a dynamic process maintained by complex interactions among multiple cooperative and competing host, viral, and environmental forces. Additional research is needed to confirm whether pregnancy or hormonal contraceptives containing 17-␤E also promote HSV reactivation from latency in an estrogen receptor-dependent manner.Herpes simplex viruses (HSV) are ubiquitous pathogens of humans characterized by their propensity to establish latency in sensory neurons of the peripheral nervous system. Intermittent reactivation of HSV from latency, followed by recurrent shedding onto body surfaces in close proximity to sites of primary infection, often produces epithelial and mucosal ulcerations, while less frequently causing keratitis, retinal necrosis, meningitis, and encephalitis (9,16,17,37). Although increased levels of emotional stress, UV radiation exposure, and immunosuppression have been identified as risk factors (15,28,30,32), delineation of the underlying mechanisms responsible for HSV reactivation from latency is incomplete.Data accumulated from clinical research suggests that elevated levels of estrogen may also be included among the risk factors that promote increased HSV reactivation from latency. In both cross-sectional and longitudinal studies, oral hormonal contraceptive use was associated with an increased frequency of HSV detection in the lower genital tract (7,23,24). During pregnancy, HSV-2 seropositive women denying any prior history of herpetic outbreaks were at increased risk for symptomatic episodes of HSV reactivation (12). More frequent asymptomatic genital tract shedding of HSV has also been correlated with the escalating serum estrogen concentrations found in each successive trimester of pregnancy (5). Taken together, these clinical data support a plausible role for estrogen as a risk factor for HSV reactivation from latency.Adequate expl...

show abstract

Hormonal contraception, vitamin A deficiency, and other risk factors for shedding of HIV-1 infected cells from the cervix and vagina

Cited by 287 publications

References 27 publications

Population-level impact of hormonal contraception on incidence of HIV infection and pregnancy in women in Durban, South Africa

Population-level impact of hormonal contraception on incidence of HIV infection and pregnancy in women in Durban, South Africa

Differential Glucocorticoid Receptor‐Mediated Effects on Immunomodulatory Gene Expression by Progestin Contraceptives: Implications for HIV‐1 Pathogenesis

17-β Estradiol Promotion of Herpes Simplex Virus Type 1 Reactivation Is Estrogen Receptor Dependent

Contact Info

Product

Resources

About