Impact Of Long-Acting Contraceptives On Female Genital Tract Cytokine Profiles In A Randomised Controlled Trial Nina Radzey (Rdznin001)

List of abbreviations ......................................................................................................................................... 5

List of figures ................................................................................................................................................... 7

List of tables .................................................................................................................................................... 7

Summary.......................................................................................................................................................... 8

Background ...................................................................................................................................................... 9

Introduction ................................................................................................................................................. 9

Immunity in the Female Genital Tract........................................................................................................... 9

Inflammation and HIV Risk ....................................................................................................................... 10

The Role of Bacterial Vaginosis and Sexually Transmitted Infections in Genital Inflammation and HIV Risk

.................................................................................................................................................................. 12

The Role of the Hormonal Cycle in Inflammation and HIV Risk ................................................................. 13

Contraceptives and HIV risk ....................................................................................................................... 15

Injectables.............................................................................................................................................. 15

Intrauterine devices ................................................................................................................................ 17

Implants ................................................................................................................................................. 17

Mechanisms underlying the possible relationship between contraceptives and HIV risk ............................... 17

Impact of long-acting contraceptives on FGT immunity .......................................................................... 17

Impact of contraceptives on cervicovaginal structure .............................................................................. 19

Impact of synthetic hormones on endogenous hormones ......................................................................... 20

HCs and the acquisition of STIs and BV ................................................................................................. 20

Rationale.................................................................................................................................................... 22

Aims ...................................................................................................................................................... 22

Methods and Materials ................................................................................................................................... 23

Study participants ....................................................................................................................................... 23

Specimen collection ................................................................................................................................... 23

STI diagnosis ............................................................................................................................................. 23

Lateral vaginal wall swab processing and aliquoting ................................................................................... 23

Cytokine, antimicrobial peptide and prostate specific antigen measurement ................................................. 24

Data analysis .............................................................................................................................................. 24

Results ........................................................................................................................................................... 25

Baseline Demographics .............................................................................................................................. 25

Immune mediator detection ........................................................................................................................ 32

Analysis of absolute immune mediator concentrations ................................................................................ 33

Analysis of fold change in immune mediator concentrations ....................................................................... 39

Principal component analysis ..................................................................................................................... 43

Unsupervised hierarchical clustering........................................................................................................... 49

Longitudinal changes in immune mediators ................................................................................................ 51

Changes in cytokine concentrations after adjustment for potential confounders ........................................... 54

Discussion ...................................................................................................................................................... 57

Quality of mediator data .............................................................................................................................