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HIV risk associated with serum medroxyprogesterone acetate levels among women in East and southern Africa.

ABSTRACT: BACKGROUND:Some observational studies have found increased HIV risk associated with self-reported use of injectable depot medroxyprogesterone acetate. Testing blood samples for medroxyprogesterone acetate (MPA), the progestin in depot medroxyprogesterone acetate, permits validation of self-reported data, and exploration of whether potential HIV risk is correlated with MPA levels, which are highest soon after injection. METHODS:We conducted a case-control study testing archived serum from women who participated in three longitudinal studies of HIV prevention in East and southern Africa. Case samples, from women who acquired HIV, were from visits that occurred at or immediately prior to the first evidence of HIV infection. Secondary analyses restricted to case samples collected within 15 and 30 days of the estimated date of HIV infection. Matched control samples were from women who remained HIV uninfected. We used multivariable conditional logistic regression to compare exogenous hormone levels, quantified through mass spectrometry, among cases and controls. RESULTS:When restricted to cases with samples collected within 15 days or less of estimated date of HIV infection, MPA detection was more frequent among women who acquired HIV (adjusted odds ratio?=?2.75, 95% confidence interval 1.22-6.19). In this subset, the increase in HIV risk was only among samples with MPA detected at a low level of 0.02-0.50?ng/ml: 36.7% of cases and 9.4% of controls, adjusted odds ratio?=?6.03, 95% confidence interval 2.50-14.54. CONCLUSION:Detection of MPA at low levels close to the estimated time of HIV acquisition was significantly more frequent among women who acquired HIV. Studies are needed that explore biological mechanisms elicited by any MPA level and HIV risk.

SUBMITTER: Heffron R

PROVIDER: S-EPMC6399047 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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HIV risk associated with serum medroxyprogesterone acetate levels among women in East and southern Africa.

Heffron Renee R Stalter Randy R Pyra Maria M Nanda Kavita K Erikson David W DW Hladik Florian F Blue Steven W SW Davis Nicole L NL Mugo Nelly N Kourtis Athena P AP Lingappa Jairam R JR Baeten Jared M JM

AIDS (London, England) 20190301 4

<h4>Background</h4>Some observational studies have found increased HIV risk associated with self-reported use of injectable depot medroxyprogesterone acetate. Testing blood samples for medroxyprogesterone acetate (MPA), the progestin in depot medroxyprogesterone acetate, permits validation of self-reported data, and exploration of whether potential HIV risk is correlated with MPA levels, which are highest soon after injection.<h4>Methods</h4>We conducted a case-control study testing archived ser ...[more]

PMID: 30585845

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Project description:BackgroundInjectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead.ObjectiveThe objective of our study was to investigate the association between current DMPA use and blood lead concentrations.MethodsWe conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women who were 23-35 years of age. Data on DMPA use were collected by computer-assisted telephone interview. Blood lead concentrations were measured in whole blood samples among 1,548 participants (91% of cohort). We estimated the adjusted percent difference in blood lead concentrations and 95% confidence intervals (CI) between current DMPA users and nonusers using multivariable linear regression.ResultsGeometric mean blood lead concentration was 0.69μg/dL (95% CI: 0.67, 0.71). After adjustment, current DMPA users (7% of cohort) had blood lead concentrations that were 18% higher than those of nonusers (95% CI: 8%, 29%). Similar associations were observed with additional analyses to assess for potential bias from smoking, DMPA-induced amenorrhea, use of estrogen-containing contraceptives, having given birth in the prior year, and history of medical conditions or current medication use associated with bone loss.DiscussionOur results indicate that current DMPA use is associated with increased blood lead concentrations. Further research, particularly in populations highly exposed to lead, is warranted to consider tradeoffs between the adverse effects of lead on human health and the importance of DMPA as a contraceptive option to prevent unintended pregnancy. https://doi.org/10.1289/EHP7017.

Project description:IntroductionSocial protection programmes are considered HIV-sensitive when addressing risk, vulnerability or impact of HIV infection. Socio-economic interventions, like livelihood and employability programmes, address HIV vulnerabilities like poverty and gender inequality. We explored the HIV-sensitivity of socio-economic interventions for unemployed and out-of-school young women aged 15 to 30 years, in East and Southern Africa, a key population for HIV infection.MethodsWe conducted a systematic review using a narrative synthesis method and the Mixed Methods Appraisal Tool for quality appraisal. Interventions of interest were work skills training, microfinance, and employment support. Outcomes of interest were socio-economic outcomes (income, assets, savings, skills, (self-) employment) and HIV-related outcomes (behavioural and biological). We searched published and grey literature (January 2005 to November 2019; English/French) in MEDLINE, Scopus, Web of Science and websites of relevant international organizations.ResultsWe screened 3870 titles and abstracts and 188 full-text papers to retain 18 papers, representing 12 projects. Projects offered different combinations of HIV-sensitive social protection programmes, complemented with mentors, safe space and training (HIV, reproductive health and gender training). All 12 projects offered work skills training to improve life and business skills. Six offered formal (n = 2) or informal (n = 5) livelihood training. Eleven projects offered microfinance, including microgrants (n = 7), microcredit (n = 6) and savings (n = 4). One project offered employment support in the form of apprenticeships. In general, microgrants, savings, business and life skills contributed improved socio-economic and HIV-related outcomes. Most livelihood training contributed positive socio-economic outcomes, but only two projects showed improved HIV-related outcomes. Microcredit contributed little to either outcome. Programmes were effective when (i) sensitive to beneficiaries' age, needs, interests and economic vulnerability; (ii) adapted to local implementation contexts; and (iii) included life skills. Programme delivery through mentorship and safe space increased social capital and may be critical to improve the HIV-sensitivity of socio-economic programmes.ConclusionsA wide variety of livelihood and employability programmes were leveraged to achieve improved socio-economic and HIV-related outcomes among unemployed and out-of-school young women. To be HIV-sensitive, programmes should be designed around their interests, needs and vulnerability, adapted to local implementation contexts, and include life skills. Employment support received little attention in this literature.

Project description:Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive used by millions of women worldwide. However, experimental studies have associated DMPA use with genital epithelial barrier disruption and mucosal influx of human immunodeficiency virus (HIV) target cells. We explored the underlying molecular mechanisms of these findings. Ectocervical biopsies and cervicovaginal lavage (CVL) specimens were collected from HIV-seronegative Kenyan sex workers using DMPA (n=32) or regularly cycling controls (n=64). Tissue samples were assessed by RNA-sequencing and quantitative imaging analysis, whereas protein levels were measured in CVL samples. The results suggested a DMPA-associated upregulation of genes involved in immune regulation, including genes associated with cytokine-mediated signaling and neutrophil-mediated immunity. A transcription factor analysis further revealed DMPA-associated upregulation of RELA and NFKB1 which are involved in several immune activation pathways. Several genes significantly downregulated in the DMPA versus the control group were involved in epithelial structure and function, including genes encoding keratins, small proline-rich proteins, and cell-cell adhesion proteins. Pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development, including keratinization and cornification processes. The cervicovaginal microbiome composition (Lactobacillus dominant and non-Lactobacillus dominant) had no overall interactional impact on the DMPA associated tissue gene expression. Imaging analysis verified that DMPA use was associated with an impaired epithelial layer as illustrated by staining for the selected epithelial junction proteins E-cadherin, desmoglein-1 and claudin-1. Additional staining for CD4+ cells revealed a more superficial location of these cells in the ectocervical epithelium of DMPA users versus controls. Altered protein levels of SERPINB1 and ITIH2 were further observed in the DMPA group. Identification of specific impaired epithelial barrier structures at the gene expression level, which were verified at the functional level by tissue imaging analysis, illustrates mechanisms by which DMPA adversely may affect the integrity of the genital mucosa.

Project description:BackgroundHunter-gatherer lifestyles dominated the southern African landscape up to ~ 2000 years ago, when herding and farming groups started to arrive in the area. First, herding and livestock, likely of East African origin, appeared in southern Africa, preceding the arrival of the large-scale Bantu-speaking agro-pastoralist expansion that introduced West African-related genetic ancestry into the area. Present-day Khoekhoe-speaking Namaqua (or Nama in short) pastoralists show high proportions of East African admixture, linking the East African ancestry with Khoekhoe herders. Most other historical Khoekhoe populations have, however, disappeared over the last few centuries and their contribution to the genetic structure of present-day populations is not well understood. In our study, we analyzed genome-wide autosomal and full mitochondrial data from a population who trace their ancestry to the Khoekhoe-speaking Hessequa herders from the southern Cape region of what is now South Africa.ResultsWe generated genome-wide data from 162 individuals and mitochondrial DNA data of a subset of 87 individuals, sampled in the Western Cape Province, South Africa, where the Hessequa population once lived. Using available comparative data from Khoe-speaking and related groups, we aligned genetic date estimates and admixture proportions to the archaeological proposed dates and routes for the arrival of the East African pastoralists in southern Africa. We identified several Afro-Asiatic-speaking pastoralist groups from Ethiopia and Tanzania who share high affinities with the East African ancestry present in southern Africa. We also found that the East African pastoralist expansion was heavily male-biased, akin to a pastoralist migration previously observed on the genetic level in ancient Europe, by which Pontic-Caspian Steppe pastoralist groups represented by the Yamnaya culture spread across the Eurasian continent during the late Neolithic/Bronze Age.ConclusionWe propose that pastoralism in southern Africa arrived through male-biased migration of an East African Afro-Asiatic-related group(s) who introduced new subsistence and livestock practices to local southern African hunter-gatherers. Our results add to the understanding of historical human migration and mobility in Africa, connected to the spread of food-producing and livestock practices.

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HIV risk associated with serum medroxyprogesterone acetate levels among women in East and southern Africa.

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HIV risk associated with serum medroxyprogesterone acetate levels among women in East and southern Africa.

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