CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception.
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ABSTRACT:
SUBMITTER: Sciaranghella G
PROVIDER: S-EPMC4601918 | biostudies-literature | 2015 Nov
REPOSITORIES: biostudies-literature
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CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal Contraception.
Sciaranghella Gaia G Wang Cuiwei C Hu Haihong H Anastos Kathryn K Merhi Zaher Z Nowicki Marek M Stanczyk Frank Z FZ Greenblatt Ruth M RM Cohen Mardge M Golub Elizabeth T ET Watts D Heather DH Alter Galit G Young Mary A MA Tsibris Athe M N AM
The Journal of infectious diseases 20150420 9
Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases ...[more]
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Project description:ObjectivesTo evaluate whether hormonal contraceptive use among cisgender women is associated with differences in pharmacokinetic (PK) parameters of a long-acting injectable formulation of the integrase strand transfer inhibitor, cabotegravir (CAB-LA).SettingThis is a secondary analysis of 85 cisgender women enrolled in HPTN 077, a phase 2a multicenter study that enrolled HIV-uninfected, low-risk individuals in Malawi, Brazil, South Africa, and the United States.MethodsParticipants received 4-week daily oral cabotegravir lead-in, followed by CAB-LA 800 mg injection every 12 weeks (cohort 1) or 600 mg every 8 weeks (after 4-week initial interval between injections, cohort 2), over 41 weeks. Participants were followed 52-76 weeks subsequent to final injection. Generalized estimating equations and linear regression were used to evaluate differences in CAB-LA PK parameters (peak concentration, trough concentration, area under the curve, apparent terminal half-life, and time to lower limit of quantification) and self-reported hormonal contraceptive stratified by type (oral, injectable, implants, and other), controlling for body mass index and cohort.ResultsCompared to women reporting no hormonal contraception (n = 6), oral contraceptive use (n = 18) was associated with lower CAB-LA peak concentration but was not associated with differences in other PK parameters. No other hormonal contraceptive type (injectable, implants, and other) was associated with significant differences in CAB-LA PK parameters.ConclusionAlthough oral contraceptive use was associated with differences in CAB-LA peak concentration, no differences were observed in other PK parameters, suggesting that this association is not likely to be clinically significant. However, these data highlight the need for further research exploring potential drug-drug interactions between CAB-LA and hormonal contraceptives.
| S-EPMC7549535 | biostudies-literature
Project description:BackgroundHormonal contraception use is common among human immunodeficiency virus (HIV)-infected women. Risk of psychiatric and other noninfectious complications of hormonal contraception use has not been described in this population.MethodsWe performed a retrospective cohort study of HIV-infected women receiving care in Tennessee from 1998 to 2008 to examine the risks of incident psychiatric and other noncommunicable diseases (NCDs), including cardiovascular, hepatic, renal, and malignant diseases, and hormonal contraception use, including depot medroxyprogesterone acetate (DMPA) and combined estrogen- and progestin-containing hormonal contraceptives. We used marginal structural models with inverse probability weights to account for time-varying confounders associated with hormonal contraception use.ResultsOf the 392 women included, 94 (24%) used hormonal contraception during the study period. Baseline psychiatric disease was similar between women who received and did not receive hormonal contraception. There were 69 incident psychiatric diagnoses and 72 NCDs. Only time-varying DMPA use was associated with increased risk of psychiatric disease (adjusted odds ratio [aOR] 3.70; 95% confidence interval [95% CI] 1.32-10.4) and mood disorders, specifically (aOR 4.70 [1.87-11.8]). Time-varying and cumulative combined hormonal contraception use were not statistically associated with other NCDs (aOR 1.64, 95% CI 0.64-4.12 and aOR 1.16, 95% CI 0.86-1.56, respectively). However, risk of incident NCDs was increased with cumulative DMPA exposure (per year exposure aOR 1.45, 95% CI 1.01-2.08).ConclusionsAmong HIV-infected women, DMPA was associated with risk of incident psychiatric diseases, particularly mood disorders, during periods of use. Cumulative DMPA exposure was also associated with risk of other NCDs. However, combined estrogen and progestin-containing hormonal contraception use was not statistically associated with risk of any NCDs.
| S-EPMC4490777 | biostudies-literature
Project description:We carried out a global whole blood genome wide expression profiling of HIV exposed and uninfected women from Nairobi to identify host factors which may be a key contribution to HIV resistance phenomenon. To identify novel biomarkers for HIV resistance including pathways that may be critical in anti-HIV vaccine design, we carried out a gene expression analysis on blood samples obtained from HIV Exposed and uninfected volunteers from a commercial sex worker cohort in Nairobi and compared their profiles to HIV susceptible negative controls. Whole blood samples were collected from 43 HIV resistant and a similar number of HIV negative antenatal clinic attendees and total RNA extracted and hybridized to the affymetrix HUG 133 Plus 2.0 micro arrays (Affymetrix, Santa Clara CA). More than 2,274 probe sets were differentially expressed in the HIV resistant women as compared to the control group (fold change ≥1.3; p value ≤ 0.0001, FDR <0.05) . Unsupervised hierarchical clustering of the differentially expressed genes readily distinguished EUs from susceptible controls. Pathway analysis of the differentially expressed genes through the KEGG signaling revealed a majority of the impacted pathways (13 of 15, 87%) were significantly down expressed. The most down expressed pathways were glycolysis/gluconeogenesis, pentose phosphate, Phosphatidyl inositol, Natural Killer cell cytotoxicity and T-cell receptor signaling. Ribosomal protein synthesis and tight junction genes were up expressed. We infer that the hallmark of HIV resistance is down regulation of genes in key signaling pathways that HIV depends on for infection and suggest that an anti-HIV vaccine design may need to incorporate components that switch down specific immune activating factors.
2012-11-11 | GSE33580 | GEO
Project description:While hormonal contraceptives are efficacious and available in several forms for women, perception of safety and concern over side effects are a deterrent for many. Existing non-hormonal contraceptives include permanent sterilization, copper intrauterine devices (IUDs), chemical/physical barriers such as spermicides and condoms, as well as traditional family planning methods including withdrawal and the rhythm method. Individuals who wish to retain their fertility in the future can achieve highest adherence and efficacy with long-acting, reversible contraceptives (LARCs), though there is only one, the copper IUD, that is non-hormonal. As rates of unintended pregnancies remain high with existing contraceptive options, it is becoming increasingly attractive to develop novel pregnancy prevention methods for both women and men. Non-hormonal contraceptives can target a variety of critical reproductive processes discussed here. This review focuses on identified non-hormonal contraceptive targets and subsequent drug candidates in development.
| S-EPMC10381146 | biostudies-literature
Project description:Hormonal contraceptives are used widely worldwide; their effect on HIV acquisition remains unresolved. We reanalyzed data from the Hormonal Contraception and HIV Study using marginal structural modeling to reduce selection bias due to time-dependent confounding. Replicating our original analysis closely, we found that depo-medroxyprogesterone acetate (DMPA) but not combined oral contraceptive (COC) was associated with increased HIV acquisition. Also, young (18-24 years) but not older women who used DMPA and COCs were at increased HIV risk.
| S-EPMC3148067 | biostudies-literature
Project description:OBJECTIVE:Combined oral contraceptives induce a reversible hypercoagulable state with an enhanced risk of venous thromboembolism, but the underlying mechanism(s) remain unclear. Subjects on combined oral contraceptives also demonstrate a characteristic resistance to APC (activated protein C) in the thrombin generation assay. Here, we report the potential role of plasma factor IXa (FIXa) as a mechanism for hormone-induced systemic hypercoagulability. APPROACH AND RESULTS:A novel assay was used to determine FIXa activity in plasma samples from volunteer blood donors. Plasma from 36 premenopausal females on hormonal contraception and 35 not on hormonal contraception, 35 postmenopausal females, and 10 males were analyzed for FIXa activity, total PS (protein S), total tissue factor pathway inhibitor (TFPI), and TFPI-? antigen. Premenopausal females on hormonal contraception demonstrated significantly increased FIXa activity and decreased TFPI-? compared with the other groups. Remarkably, FIXa values were not normally distributed in the hormonal contraception group, but skewed toward the high end. Plasma FIXa activity inversely correlated with both TFPI-? and total PS antigen. Ex vivo determination of TF-dependent FIX activation in FV-deficient plasma demonstrated that inhibitory anti-TFPI antibodies enhanced FIXa generation by 2- to 3-fold, whereas addition of 75 nmol/L PS reduced FIXa generation by ?2-fold. Further, increasing FIXa concentration enhanced APC resistance during TF-triggered plasma thrombin generation. CONCLUSIONS:Elevation of plasma FIXa activity in association with reductions in TFPI-? and PS is a potential mechanism for systemic hypercoagulability and resistance to APC in premenopausal females on hormonal contraception.
| S-EPMC5746428 | biostudies-literature
Project description:The use of the hormonal contraceptive DMPA has been associated with a moderate increase in sexually transmitted infections, including HIV-1. To better understand the biological mechanisms behind this phenomenon, we report here the use of mRNA-sequencing on the Illumina HiSeq2000 of vaginal epithelial cells from women using DMPA or controls. We found that women using DMPA demonstrate over 330-fold decrease in the anti-microbial peptide human beta defensin 3 (HBD3) and massive downregulation of genes involved in structural integrity, barrier function, and wound healing. CXCL6, CXCL1, and IL-1B among other inflammatory genes were up-regulated in the tissue of DMPA users compared to controls. Overall, these results demonstrate significant differences in basic epithelial functions following DMPA use.
2016-04-23 | GSE68229 | GEO
Project description:ObjectiveIn 2017, New Mexico approved an amendment allowing pharmacists to prescribe and dispense hormonal contraception. We interviewed rural New Mexico women to determine their perceptions of pharmacy access to hormonal contraception.Study designWe conducted semi-structured telephone interviews with women recruited from rural New Mexico communities. The interview guide explained the amendment followed by questions about the advantages and disadvantages of pharmacy access to hormonal contraception within rural communities.ResultsBetween November 2017 and May 2018, we recruited 32 women to participate. Participants were young (26/32 18-29 years old), gravid (27/31), employed (30/32), white (22/32) and Hispanic (26/31). The majority used Medicaid as their primary insurance (16/28). Most participants were supportive of pharmacy access to hormonal contraception. Participants saw their rural communities as facing health care barriers, some of which could be alleviated by pharmacy access. Perceived benefits of pharmacy access included convenience of pharmacy hours, shorter wait times, and no need for an appointment. Participants expressed concerns about lack of privacy in their pharmacies. Many expressed trust in their pharmacist to review side effects and explain usage of contraception- a role that was considered separate from that of a primary care provider who offers regular medical visits for routine screening and nuanced or complex discussions about contraception. Some participants expressed that pharmacy access could be especially beneficial for teens.ConclusionsRural New Mexico women were supportive of pharmacy access to contraception and accept pharmacists as trusted members of the health care team.ImplicationsRural New Mexico women find benefit in pharmacy access to hormonal contraception, citing improved access to contraceptives in their communities.
| S-EPMC8367852 | biostudies-literature
Project description:OBJECTIVES:A recent study of HIV serodiscordant couples found that depot medroxyprogesterone acetate (DMPA) and oral contraceptive pills (OCPs) were associated with increased HIV risk in the presence, but not in the absence, of bacterial vaginosis. We assessed whether bacterial vaginosis is an effect modifier of the association between hormonal contraception and HIV seroconversion in female sex workers (FSWs) in Mombasa, Kenya. DESIGN:Prospective cohort study. METHODS:Data collected from HIV-negative FSWs from 1993 to 2017 were analyzed. Cox proportional hazards models were used to assess the relationship between HIV seroconversion and use of DMPA, OCPs, or hormonal contraceptive implants (Norplant, Jadelle). RESULTS:A total of 1985 women contributed 7127 person-years of follow-up; 307 women seroconverted to HIV (4.32/100 person-years). DMPA was significantly associated with elevated risk of HIV seroconversion in women with [aHR 1.56, 95% confidence interval (CI) 1.08-2.25; P?=?0.02] and without (aHR 2.08, 95% CI 1.46-2.97; P?<?0.001) bacterial vaginosis (interaction P?=?0.4). Similarly, OCP use was associated with increased HIV risk both in the presence (aHR 1.50, 95% CI 0.94-2.39; P?=?0.09) and absence (aHR 1.61, 95% CI 0.99-2.64; P?=?0.06) of bacterial vaginosis (interaction P?=?0.9), though neither stratum reached statistical significance. Implants were not associated with HIV seroconversion overall (aHR 0.99, 95% CI 0.40-2.45; P?=?0.9), or in women with (aHR 0.65, 95% CI 0.16-2.72; P?=?0.6) and without (aHR 1.39, 95% CI 0.43-4.46; P?=?0.6) bacterial vaginosis (interaction P?=?0.5). CONCLUSION:Bacterial vaginosis had no effect on the associations between hormonal contraceptives and HIV seroconversion in this cohort. Contraceptive implants were not associated with increased HIV risk compared with no contraception.
| S-EPMC6501800 | biostudies-literature
Project description:Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.
| S-EPMC7365466 | biostudies-literature