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Background Adolescent girls and young women aged 15‒24 years in sub-Saharan Africa are at disproportionate risk of human immunodeficiency virus (HIV) infection. Given the known association between vaginal microbial dysbiosis and HIV susceptibility, we performed an age-stratified analysis of the vaginal microbiome in South African women and compared this to their risk of HIV acquisition. Methods Vaginal microbiome data were generated by mass spectrometry–based proteomic analysis of cervicovaginal lavages collected from participants (n = 688) in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial. Participants were grouped by age (18–19 years, n = 93; 20–24 years, n = 326; 25–41 years, n = 269). Results Four microbiome types were identified based on predominant taxa, including Lactobacillus crispatus (CST-LC, 12.2%), Lactobacillus iners (CST-LI, 43.6%), Gardnerella vaginalis (CST-GV, 26.6%), or polymicrobial (CST-PM, 15.1%). Women aged 18–19 and 20–24 years had increased CST-PM and a non-Lactobacillus-dominant microbiome compared to those 25–41 years (odds ratio [OR], 3.14 [95% confidence interval {CI}, 1.12–7.87], P = .017; OR, 2.81 [95% CI, 1.07–7.09], P = .038, respectively; and OR, 1.65 [95% CI, 1.02–2.65], P = .028; OR, 1.40 [95% CI, 1.01–1.95], P = .030, respectively). The HIV incidence rate of women with CST-PM microbiome was 7.19-fold higher compared to women with CST-LC (hazard ratio [HR], 7.19 [95% CI, 2.11–24.5], P = .00162), which was also consistent in women aged 20–24 years (HR, 4.90 [95% CI, 1.10–21.9], P = .0375). Conclusions Younger women were more likely to have a higher-risk polymicrobial microbiome suggesting that vaginal microbiota are contributing to increased HIV-1 susceptibility in this group. Clinical Trials Registration NCT00441298.

BackgroundEvidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) by risk groups is limited in Africa. We assessed prevalence, trends, and transmission dynamics of pre-treatment HIVDR within-and-between men who have sex with men (MSM), people who inject drugs (PWID), female sex workers (FSW), heterosexuals (HET), and children infected perinatally in Kenya.MethodsHIV-1 partialpolsequences from antiretroviral-naïve samples collected between 1986-2020 were used. Pre-treatment RTI, PI and INSTI mutations were assessed using the Stanford HIVDR database. Phylogenetics methods were used to determine and date transmission clusters.ResultsOf 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2-16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSW (15.1%) and HET (13.9%). No INSTI resistance mutations were detected. Among HET, pre-treatment HIVDR increased from 6.6% in 1986-2005 to 20.2% in 2011-2015 but dropped to 6.5% in 2016-2020. Overall, 22 clusters with shared pre-treatment HIVDR mutations were identified. The largest was a K103N mutation cluster involving 16 MSM sequences sampled between 2010-2017, with an estimated tMRCA of 2005 (HPD, 2000-2008). This lineage had a growth rate=0.1/year and R0=1.1, indicating propagation over 12 years among ART-naïve MSM in Kenya.ConclusionsCompared to HET, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2016 may have reversed the increase in pre-treatment RTI mutations in Kenya. Continued surveillance of HIVDR, with a particular focus on children and key populations, is warranted to inform treatment strategies in Kenya.SummaryCompared to the heterosexual population, key populations had higher levels of pre-treatment HIV-1 drug resistance (HIVDR). Propagation of HIVDR was risk-group exclusive. Introduction of integrase inhibitors abrogated propagation of reverse transcriptase inhibitors mutations among the heterosexual, but not key populations.

Purpose of Review To review the impact of the COVID-19 pandemic and its public health response on key populations at risk of HIV infection, with a focus on sex workers. Recent Findings Since last year several groups have documented how the COVID-19 pandemic has impacted the livelihoods and health of sex workers. We focus on case studies from Kenya, Ukraine, and India and place these in the broader global context of sex worker communities, drawing on common themes that span geographies. Summary COVID-19-associated lockdowns have significantly disrupted sex work, leading to economic and health challenges for sex workers, ranging from HIV-related services to mental health and exposure to violence. Several adaptations have been undertaken by sex workers and frontline workers, including migration, a move to mobile services, and struggling to find economic supports. Strengthening community-based responses for future pandemics and other shocks is critical to safeguard the health of marginalized populations.

Adolescent girls and young women aged 15-24 in sub-Saharan Africa are at disproportionate risk of HIV infection. Given the known association between vaginal microbial dysbiosis and HIV susceptibility, we performed an age-stratified analysis of the vaginal microbiome in South African women and compared this to their risk of HIV acquisition.Vaginal microbiome data were generated by mass spectrometry-based proteomic analysis of cervicovaginal lavages collected from participants (n = 688) in the CAPRISA 004 trial. Participants were grouped by age (18-19 years old (y), n = 93; 20-24y, n = 326; 25-41y, n = 269).Four microbiome types were identified based on predominant taxa including: L. crispatus (CST-LC, 12.2%), L. iners (CST-LI, 43.6%), G. vaginalis (CST-GV, 26.6%) or polymicrobial (CST-PM, 15.1%). Compared to the 25-41y group, 18-19y and 20-24y women increased CST-PM and a non-Lactobacillus-dominant (nLD) microbiome (OR = 3.14, 95% CI: 1.12-7.87, P = 0.017; OR = 2.81, 95% CI: 1.07-7.09, P = 0.038, respectively; and OR = 1.65, 95% CI: 1.02-2.65, P = 0.028; OR = 1.40, 95% CI: 1.01-1.95, P = 0.030, respectively). Compared to 25-41y women, 18-19y women were more likely to have increased abundance of Megasphaera (L2FD = 1.72, P = 0.0023, adj. P = 0.0498). HIV incidence rate of women with CST-PM microbiome was 7.19-fold higher compared to women with CST-LC in all study participants (HR = 7.19, 95% CI: 2.11-24.5, P = 0.00162), which was also consistent in 20-24y women (HR = 4.90, 95% CI: 1.10-21.9, P = 0.0375).Younger women were more likely to have a higher risk polymicrobial microbiome that associated with substantial increased risk of HIV acquisition. These data suggest that the vaginal microbiota is a contributing factor to increased HIV-1 susceptibility in younger women.

ObjectivesSTIs cause inflammation that is detrimental for both HIV risk and reproductive health. We assessed the impact of point-of-care (POC) STI testing, immediate treatment and expedited partner therapy (EPT) on genital tract cytokines among a cohort of young South African women.MethodsHIV-negative women underwent POC testing for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV) by Xpert CT/NG and OSOM TV, and for bacterial vaginosis (BV) by microscopy. Women with STIs and/or BV received immediate treatment, EPT for STIs and retested after 6 and 12 weeks. Concentrations of 48 cytokines were measured in cervicovaginal fluid at each visit using multiplex ELISA technology. The impact of STI treatment on cytokine concentrations was assessed by multivariable linear mixed models and principal component analysis.ResultsThe study enrolled 251 women with median age of 23 years (IQR 21–27). The prevalence of CT, NG and TV were 14.3%, 4.4% and 4.0%, and 34.3% had BV. Women with STIs or BV at baseline (n=94) had significantly higher concentrations of pro-inflammatory cytokines (interleukin (IL)-1α, IL-1β, IL-6, tumour necrosis factor (TNF)-α, TNF-β, IL-18 and macrophage inflammatory factor (MIF)) and chemokines (IL-8, IL-16, macrophage inflammatory protein (MIP)-1α, IFN-α2, monokine induced by gamma interferon (MIG), monocyte chemoattractant protein (MCP)-3, regulated on activation normal T cell expressed and secreted and eotaxin) compared with women without (n=157). STI treatment was strongly associated with reduced concentrations of pro-inflammatory cytokines IL-6 (p=0.004), IL-1β (p=0.013), TNF-α (p=0.018) and chemokines MIG (p=0.008) and growth-related oncogene (GRO)-α (p=0.025). A lower Nugent score was associated with a reduction in pro-inflammatory cytokines IL-1α (p=0.003), TNF-related apoptosis-inducing ligand (p=0.004), MIF (p=0.010) and IL-18 (pConclusionsA comprehensive STI intervention effectively reduced genital inflammation among young women, thereby improving vaginal health and potentially reducing HIV risk.

Young heterosexual men have low uptake of HIV prevention and treatment services and represent an important key population that may require novel strategies. We recruited 1271 heterosexual men, 12 years and older from socializing venues such as “shebeens”, transport hubs, “spaza” shops, and community centers in rural KwaZulu-Natal, South Africa. Participants completed a questionnaire and were tested for HIV serostatus. Generalized estimating equations (GEE) with exchangeable covariance structure estimated factors independently associated with prevalent HIV infection. Median age was 25 years [Interquartile range (IQR) 21–29]. HIV prevalence was 15.5% [95% confidence interval (CI) 11.0–21.9] and increased significantly by age. Factors associated with higher odds of HIV infection were being 25 years and older [adjusted odds ratio (aOR) 4.82, 95% CI 3.47–6.69; p

OBJECTIVES Empirical time trends in HIV prevalence in female sex workers (FSWs) are helpful to understand the evolving HIV epidemic, and to monitor the scale-up, coverage, and impact of ongoing HIV prevention and treatment programmes. DESIGN Serial HIV prevalence study. METHODS We analyzed time trends in HIV prevalence in FSWs accessing services at seven Sex Worker Outreach Programme (SWOP) clinics in Nairobi from 2008 to 2017 (N = 33 560). The Mantel--Haenszel test for trend and independent samples Kruskal--Wallis test were used to analyze categorical and continuous variables, respectively. Multivariable binomial regression was used to estimate prevalence ratios/year, adjusting for several covariates. RESULTS HIV prevalence decreased over time in all age groups. This was particularly evident among FSWs less than 25 years of age; HIV was 17.5% in 2008-2009, decreasing to 12.2% in 2010-2011, 8.3% in 2012-2013, 7.3% in 2014-2015, and 4.8% in 2016-2017 (P

In Kenya, HIV-1 key populations including men having sex with men (MSM), people who inject drugs (PWID) and female sex workers (FSW) are thought to significantly contribute to HIV-1 transmission in the wider, mostly heterosexual (HET) HIV-1 transmission network. However, clear data on HIV-1 transmission dynamics within and between these groups are limited. We aimed to empirically quantify rates of HIV-1 flow between key populations and the HET population, as well as between different geographic regions to determine HIV-1 'hotspots' and their contribution to HIV-1 transmission in Kenya. We used maximum-likelihood phylogenetic and Bayesian inference to analyse 4058 HIV-1 pol sequences (representing 0.3 per cent of the epidemic in Kenya) sampled 1986-2019 from individuals of different risk groups and regions in Kenya. We found 89 per cent within-risk group transmission and 11 per cent mixing between risk groups, cyclic HIV-1 exchange between adjoining geographic provinces and strong evidence of HIV-1 dissemination from (i) West-to-East (i.e. higher-to-lower HIV-1 prevalence regions), and (ii) heterosexual-to-key populations. Low HIV-1 prevalence regions and key populations are sinks rather than major sources of HIV-1 transmission in Kenya. Targeting key populations in Kenya needs to occur concurrently with strengthening interventions in the general epidemic. ispartof: VIRUS EVOLUTION vol:8 issue:1 ispartof: location:England status: published

Background Sexually transmitted infections (STIs) and Human immunodeficiency virus (HIV) share a complex bidirectional relationship, however, population prevalence and the association between the presence of STIs and HIV in a high HIV burden district in KwaZulu-Natal, South Africa is not known. Methods A total of 9812 participants aged 15–49 years were enrolled in a cross-sectional population-based household survey. Participants completed a structured questionnaire and provided first-pass urine (males) or self-collected vulvo-vaginal swabs (females) for the detection of STIs. Results Prevalence of herpes simplex virus type-2 (HSV-2) was 57.8%, syphilis was 1.6%, Neisseria gonorrhoeae was 2.8%, Chlamydia trachomatis was 7.1%, Trichomonas vaginalis was 9.0%, Mycoplasma genitalium was 5.5% and HIV was 36.3%. HIV positive status was associated with an increased probability of having M. genitalium (aPR = 1.49, 95% CI 1.02–2.19) among males and syphilis (aPR = 2.54, 95% CI 1.32–4.86), N. gonorrhoeae (aPR = 2.39, 95% CI 1.62–3.52), T. vaginalis (aPR = 1.70, 95% CI 1.43–2.01) and M. genitalium (aPR = 1.60, 95% CI 1.15–2.22) among females. HIV viral load ≥400 copies per mL was associated with an increased probability of N. gonorrhoeae (aPR = 1.91, 95% CI 1.36–2.70), C. trachomatis (aPR = 1.52, 95% CI 1.12–2.05) and M. genitalium (aPR = 1.83, 95% CI 1.27–2.63). Conclusions The high prevalence of STIs and the association between STIs and HIV, and HIV viral load underscores the public health implications of sustained transmission risk of STIs and HIV. These findings highlight the urgent need for expanding STI surveillance and implementing interventions to monitor and reduce the STI burden.

Objective: This report identifies the profound effects that the COVID-19 pandemic and the resultant government lockdown have had on sexual health services delivery to a community of marginalised male sex workers in Nairobi, Kenya. Methods: Based on the experiences shared during ongoing virtual conversations with peer health workers, a case study was developed to identify the challenges encountered by peer health workers. Findings: Peer health workers confronted the new health crisis surrounding COVID-19 while also persisting in their efforts to deliver HIV services to male sex workers. Unable to receive status as ‘essential workers’, their actions often fell short in efforts to maintain male sex workers’ access to vital HIV prevention, treatment and care resources. Conclusion: The struggles encountered, amid dwindling resources, underscore the vital work needed to meet the health needs of a marginalised group that remains largely excluded from the government health system.

Human papillomavirus (HPV) infection correlates with higher rates of HIV acquisition, but the underlying biological mechanisms are unclear. Here we study associations between HPV and HIV acquisition and relate these to vaginal cytokine profiles in an observational cohort of women at high risk of HIV infection (CAPRISA 004, n = 779) and with 74% HPV prevalence. We report here that HPV infection associates with a 2.5-fold increase in HIV acquisition risk in this population (95% CI: 1.2–5.3). Among 48 vaginal cytokines profiled, cytokines associated with HPV infection overlap substantially with cytokines associated with HIV risk, but are distinct from those observed in HPV negative women. Although our data do not establish a causative link between HPV status and the risk of HIV, we suggest that increasing HPV vaccination coverage may carry an additional benefit of reducing the risk of contracting HIV infection, particularly in regions with high HPV prevalence., Cervicovaginal inflammation and human papillomavirus (HPV) are separately associated with increased risk of HIV acquisition. Here the authors longitudinally profile 48 cervicovaginal cytokines and HPV status in a large observational HIV high-risk cohort, and show the same cytokines associate with HPV infection and HIV risk.

HIV-1 transmission dynamics involving men who have sex with men (MSM) in Africa are not well understood. We investigated the rates of HIV-1 transmission between MSM across three regions in Kenya: Coast, Nairobi, and Nyanza. We analyzed 372 HIV-1 partial

Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127lowTregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8vs2.0%, pvs6.0%, pLactobacillusdominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10CD4+ T cells per log10Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.

Genital inflammation (GI) undermines topical human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4 + T-cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficacy of antiretroviral-based PrEP in women with GI.

Inflammatory cytokines augment humoral responses by stimulating antibody production and inducing class-switching. In women, genital inflammation (GI) significantly modifies HIV risk. However, the impact of GI on mucosal antibodies remains undefined. We investigated the impact of GI, pre-HIV infection, on antibody isotypes and IgG subclasses in the female genital tract. Immunoglobulin (Ig) isotypes, IgG subclasses and 48 cytokines were measured prior to HIV infection in cervicovaginal lavages (CVL) from 66 HIV seroconverters (cases) and 66 matched HIV-uninfected women (controls) enrolled in the CAPRISA 004 and 008 1% tenofovir gel trials. Pre-HIV infection, cases had significantly higher genital IgM (4.13; IQR, 4.04–4.19) compared to controls (4.06; IQR, 3.90–4.20;p = 0.042). More than one-quarter of cases (27%) had GI compared to just over one-tenth (12%) in controls. Significantly higher IgG1, IgG3, IgG4 and IgM (allp p

Resting CD4

Previous studies have highlighted the role of pre-infection systemic inflammation on HIV acquisition risk, but the extent to which it predicts disease progression outcomes is less studied. Here we examined the relationship between pre-infection plasma cytokine expression and the rate of HIV disease progression in South African women who seroconverted during the CAPRISA 004 tenofovir gel trial. Bio-Plex 200 system was used to measure the expression of 47 cytokines/chemokines in 69 seroconvertors from the CAPRISA 004 trial. Cox proportional hazards regression analyses were used to measure associations between cytokine expression and CD4 decline prior to antiretroviral therapy initiation. Linear regression models were used to assess whether pre-infection cytokine expression were predictors of disease progression outcomes including peak and set-point viral load and CD4:CD8 ratio at less and greater than180 days post infection. Several cytokines were associated with increased peak HIV viral load (including IL-16, SCGFβ, MCP-3, IL-12p40, SCF, IFNα2 and IL-2). The strongest association with peak viral load was observed for SCGFβ, which was also inversely associated with lowest CD4:CD8 ratio p = 0.008) in multivariable analysis adjusting for age, study site, contraception, baseline HSV-2 status and trial arm allocation. Our results show that pre-infection systemic immune responses could play a role in HIV disease progression, especially in the early stages of infection.

This is the accepted manuscript version of the work published in its final form as Ismail, S. D., Riou, C., Joseph, S. B., Archin, N. M., Margolis, D. M., Perelson, A. S., Cassidy, T., Abrahams, M., Moeser, M., Council, O. D., McKinnon, L. R., Osman, F., Karim, Q. A., Karim, S. S. A., Swanstrom, R., Williamson, C., Garrett, N. J., & Wendy A Burgers. (2021). Immunological Correlates of the HIV-1 Replication-Competent Reservoir Size.Clinical Infectious Diseases,73(8), 1528-1531. https://doi.org/10.1093/cid/ciab587 Deposited byshareyourpaper.organdopenaccessbutton.org. We've taken reasonable steps to ensure this content doesn't violate copyright. However, if you think it does you can request a takedown by emailinghelp@openaccessbutton.org.

Background Access to safe, effective, and affordable contraception is important for women’s health and essential to mitigate maternal and fetal mortality rates. The progestin‐based contraceptive depot medroxyprogesterone acetate (DMPA) is a popular contraceptive choice with a low failure rate and convenient administration schedule. Aim In this review, we compiled observational data from human cohorts that examine how DMPA influences the mucosal biology of the female genital tract (FGT) that are essential in maintaining vaginal health, including resident immune cells, pro‐inflammatory cytokines, epithelial barrier function, and the vaginal microbiome Materials and Methods This review focused on the recent published literature published in 2019 and 2020. Results Recent longitudinal studies show that DMPA use associates with an immunosuppressive phenotype, increase in CD4+CCR5+ T cells, and alterations to growth factors. In agreement with previous meta‐analyses, DMPA use is associated with minimal effects of the composition of the vaginal microbiome. Cross‐sectional studies associate a more pro‐inflammatory relationship with DMPA, but these studies are confounded by inherent weaknesses of cross‐sectional studies, including differences in study group sizes, behaviors, and other variables that may affect genital inflammation. Discussion & Conclusion These recent results indicate that the interactions between DMPA and the vaginal mucosa are complex emphasizing the need for comprehensive longitudinal studies that take into consideration the measurement of multiple biological parameters.

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the upper respiratory tract, remains lacking. We enumerated and phenotyped T cells in nasal mucosa and blood before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n =21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ expanded ∼12 days following the first and second doses, by 0.31 and 0.43 log10cells per swab respectively (p=0.058 and p=0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decreased post-vaccination. Similar increases in nasal CD8+CD69+CD103-T cells were observed, particularly following the second dose. CD4+ Th17 cells were also increased in abundance following both doses. Following stimulation with SARS-CoV-2 spike peptides, CD8+ T cells increased expression of CD107a and CD154. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

Bacterial vaginosis (BV) is a common yet poorly understood vaginal condition that has become a major focus of HIV transmission and immunology research. Varied terminologies are used by clinicians and researchers to describe microbial communities that reside in the female reproductive tract (FRT), which is driven, in part, by microbial genetic and metabolic complexity, evolving diagnostic and molecular techniques, and multidisciplinary perspectives of clinicians, epidemiologists, microbiologists, and immunologists who all appreciate the scientific importance of understanding mechanisms that underlie BV. This Perspectives article aims to clarify the varied terms used to describe the cervicovaginal microbiota and its “nonoptimal” state, under the overarching term of BV. The ultimate goal is to move toward language standardization in future literature that facilitates a better understanding of the impact of BV on FRT immunology and risk of sexually transmitted infections, including HIV.

Young adolescents in Sub Saharan Africa (SSA) are at high risk of involvement in sexual risk behaviors; and curable sexually transmitted infections (STI), herpes simplex virus type 2 (HSV-2), human immunodeficiency virus (HIV) and unintended pregnancies remain persistently high in this population. Evidence based strategies are urgently needed to improve these outcomes. The aim of this systematic review was to synthesize the evidence from randomized controlled trials (RCT) to determine whether school-based interventions promote safe sex behaviors, reduce sexual risk behaviors and risk of curable STIs, HSV-2, HIV and unintended pregnancies among young adolescents aged 9 to 19 years in SSA. Electronic databases were searched for published studies and manual searches were conducted through reviewing of references of cited literature in the English language up to December 2019. Two independent reviewers screened and abstracted the data. We identified 428 articles and data from nine RCTs (N=14,426 secondary school students) that fulfilled the selection criteria were analysed. Two studies measured pregnancy as an outcome and showed significant declines in unintended pregnancies. Of the five studies that measured HIV/AIDS related-knowledge, condom-use outcomes (normative beliefs, knowledge, and self-efficacy) and attitudes to HIV testing, four showed significant improvements. Of the six studies that measured sexual debut, four reported moderate but non-significant declines and in two studies sexual debut information was either incomplete or unreliable. One study measured curable STIs and found no significant declines; whilst the second study that measured HSV-2 and HIV, no significant declines were observed. This review highlights the need to undertake well-designed research studies to provide evidence on the impact of interventions on curable STIs, HSV-2 and HIV, critical to improving the health of young adolescents.

There is an urgent need to identify immunological markers of tuberculosis (TB) risk in HIV co-infected individuals. Previously we have shown that TB recurrence in HIV co-infected individuals on ART was associated with markers of systemic inflammation (IL-6, IL1β and IL-1Rα). Here we examined the effect of additional acute inflammation and microbial translocation marker expression on risk of TB recurrence. Stored plasma samples were drawn from the TB Recurrence upon Treatment with HAART (TRuTH) study, in which individuals with previously treated pulmonary TB were screened for recurrence quarterly for up to 4 years. Recurrent TB cases (n = 37) were matched to controls (n = 102) by original trial study arm assignment and ART start date. Additional subsets of HIV infected (n = 41) and HIV uninfected (n = 37) individuals from Improving Recurrence Success (IMPRESS) study were sampled at active TB and post successful treatment completion. Plasma concentrations of soluble adhesion molecules (sMAdCAM, sICAM and sVCAM), lipopolysaccharide binding protein (LBP) and transforming growth factor-beta (TGF-β1, TGF-β2, TGF-β3) were measured by multiplex immunoassays and ELISA. Cytokine data was square root transformed in order to reduce variability. Multivariable analysis adjusted for a number of potential confounders measured at sample time-point: age, BMI, CD4 count, viral load (VL) and measured at baseline: presence or absence of lung cavities, previous history of TB, and WHO disease stage (4 vs 3). The following analytes were associated with increased risk of TB recurrence in the multivariable model: sICAM (aOR 1.06, 95% CI: 1.02-1.12, p = 0.009), LBP (aOR 8.78, 95% CI: 1.23-62.66, p = 0.030) and TGF-β3 (aOR 1.44, 95% CI 1.01-2.05, p = 0.044). Additionally, we observed a positive correlation between LBP and sICAM (r= 0.347, p

PROBLEM Injectable hormonal contraceptives (IHC) have been associated with altered mucosal and systemic milieu which might increase HIV risk, but most studies have focused on DMPA and not NET-EN, despite the growing popularity and lower HIV risk associated with the latter in observational studies. METHOD OF STUDY We used high-performance liquid chromatography in combination with tandem triple quadrupole mass spectrometry (HPLC-LC-MS/MS) to measure steroid hormones in plasma samples of CAPRISA004 study participants. Concentrations of 48 cytokines were measured in the cervicovaginal lavage (CVL) and plasma, and their expression was compared between participants with detectable NET-EN (n = 201) versus non-detectable IHC (n = 90). Each log10 cytokine concentration was tested as an outcome in linear-mixed models, with NET-EN detection as the main explanatory variable. Multivariable models were adjusted for potential confounders. RESULTS In bivariate analysis, detectable NET-EN was associated with reduced cervicovaginal M-CSF (P = 0.008), GM-CSF (P = 0.025) and G-CSF (P = 0.039), and elevated levels MIF (P = 0.008), IL-18 (P = 0.011), RANTES (P = 0.005) and IL-1Rα (P