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Introduction: Several HIV risk scores have been developed to identify individuals for prioritized HIV prevention in sub-Saharan Africa. We systematically reviewed HIV risk scores to: (1) identify factors that consistently predicted incident HIV infection, (2) review inclusion of community-levelHIV risk in predictive models and (3) examine predictive performance. Methods: We searched nine databases from inception until 15 February 2021 for studies developing and/or validating HIV risk scores among the heterosexualadult population in sub-Saharan Africa. Studies not prospectively observing seroconversion or recruiting only key populations were excluded. Record screening, data extraction and critical appraisal were conducted in duplicate. We used random-effects meta-analysis to summarize hazard ratios and the area under the receiver-operating characteristic curve (AUC-ROC). Results: From 1563 initialsearch records, we identified 14 risk scores in 13 studies. Seven studies were among sexually active women using contraceptives enrolled in randomized-controlled trials, three among adolescent girls and young women (AGYW) and three among cohorts enrolling both men and women. Consistently identified HIV prognostic factors among women were younger age (pooled adjusted hazard ratio: 1.62 [95% confidence interval: 1.17, 2.23], compared to above 25), single/not cohabiting with primary partners (2.33 [1.73, 3.13]) and having sexually transmitted infections (STIs) at baseline (HSV-2: 1.67 [1.34, 2.09]; curable STIs: 1.45 [1.17; 1.79]). Among AGYW, only STIs were consistently associated with higher incidence, but studies were limited (n = 3). Community-levelHIV prevalence or unsuppressed viralload strongly predicted incidence but was only considered in 3 of 11 multi-site studies. The AUC-ROC ranged from 0.56 to 0.79 on the model development sets. Only the VOICE score was externally validated by multiple studies, with pooled AUC-ROC 0.626 [0.588, 0.663] ([I.sup.2]: 64.02%). Conclusions: Younger age, non-cohabiting and recent STIs were consistently identified as predicting future HIV infection. Both community HIV burden and individualfactors should be considered to quantify HIV risk. However, HIV risk scores had only low-to-moderate discriminatory ability and uncertain generalizability, limiting their programmatic utility. Further evidence on the relative value of specific risk factors, studies populations not restricted to 'at-risk' individuals and data outside South Africa will improve the evidence base for risk differentiation in HIV prevention programmes. PROSPERO Number: CRD42021236367 Keywords: risk scores; HIV incidence; sub-Saharan Africa; adolescent girls and young women; risk factors for HIV incidence, 1 | INTRODUCTION Efficiently identifying populations and individuals at high risk of HIV infection and linking them to effective HIV prevention is essential for continued progress towards ending HIV as [...]

: Introduction: Sexualized drug use (SDU), the use of psychoactive drugs in the context of sexual intercourse, has been identified as a risk factor for HIV among men who have sex with men (MSM) in Asia. Given the distinct social and cultural context of same‐sex relationships and drug‐using practice in Asia, we aimed to describe the prevalence of SDU in East and South Asian countries and its associations with condomless anal sex (CAI) and HIV status. Synthesizing SDU research in this region, including SDU definitions, prevalence and outcomes, provides insights to inform future research and improved programme planning, resourcing and advocacy. Methods: We systematically searched OVID Medline, OVID EMBASE, OVID Global Health, CINAHL, PsycINFO and SCOPUS publication databases for scientific articles published from 1990 to 2022 measuring SDU among MSM in East and South Asian countries. A narrative synthesis was utilized to describe key study attributes and findings, and meta‐analyses using random pooled effect models were used to estimate SDU prevalence and its associations with CAI and HIV status. Subgroup meta‐analyses, sensitivity analysis and assessment of publication bias examined potential sources of heterogeneity for the pooled SDU prevalence estimates. Results and discussion: Of the 1788 publications screened, 49 publications met the selection criteria and 18 were suitable for meta‐analyses. Findings highlight SDU definitions distinct from other regions but inconsistencies in the definition of SDU between studies that have been highlighted in research elsewhere. The pooled prevalence of recent SDU (past 12 months) was 13% (95% CI = 10–16%; I[sup.2] = 97.6) but higher when studies utilized self‐administered surveys (15%; 95% CI = 12–19%; p Conclusions: SDU is common among MSM in East and South Asian countries, but varying SDU definitions limit between‐study comparisons. Responses to SDU‐related harms should consider local contexts, including specific drug types used and their relative risks., INTRODUCTION The United Nations Office on Drugs and Crimes has recently emphasized the urgency of addressing intersecting drug use and sexual practices by recommending targeted interventions for HIV prevention, particularly [...]

Introduction: Post-abortion clinics located in regions with high HIV burden may ideal locations to integrate counselling and delivery of HIV pre-exposure prophylaxis (PrEP), aligning with normative goals for integrated delivery of HIV and reproductive health care. The objective of this study was to gauge the degree to which Kenyan women seeking care for a pregnancy loss, including induced abortion, are at risk for HIV and whether women would welcome an introduction to PrEP prior to discharge from post-abortion care. Methods: We conducted a mixed-methods study from August 2019 to February 2020 with women ages 15 to 30 recruited sequentially as they were accessing post-abortion care at public and private facilities in Thika and Kisumu, Kenya. Data collection was through a cross-sectional survey and laboratory testing for common sexually transmitted infections (N = 200), and in-depth interviews (N = 30). Descriptive statistics summarize PrEP knowledge and referrals and a multivariable log-link binomia model estimated correlates of receiving a referral for PrEP. Qualitative data were analysed using inductive and deductive approaches. Results: Among 200 HIV-negative women (median age 21.0, interquartile range 19.0 to 22.0), the prevalence of Chlamydia trachomatis was 18.2% and Neisseria gonorrhoeae was 2.0%. Half of the women scored [greater than or equal to]5 on a validated tool that would correspond to an expected HIV incidence of 9.5% per year. Approximately half (55.8%) of women were familiar with PrEP prior to the study and 33.3% received a referral from study staff to a clinic offering PrEP. In qualitative interviews, women expressed interest in accessing PrEP from the gynaecology ward that provided post-abortion care but they preferred alternative locations for PrEP refills. Conclusions: Kenyan women accessing post-abortion care have substantial HIV risk and were favourable about the idea of receiving support to initiate PrEP as part of care offered during post-abortion care. These settings can be integrated into national PrEP programmes as locations providing PrEP referrals and initiation. Keywords: PrEP; abortion; Kenya; young women; HIV prevention, 1 | INTRODUCTION Young women living in settings with a high HIV burden face intersecting risks for unintended pregnancy, HIV and other sexually transmitted infections. To combat this, a priority [...]

PE28.01 An analysis of gender-based violence and HIV risk among adolescents and youth across 10 countries C. Lenz (1) ; M. Ombija (2) ; R. Van de Ven (3) ; [...]

PE19.01 Population-level correlation between incidence of selected sexually transmitted infections and HIV-1 among women participating in HIV pre-exposure prophylaxis trials in Africa P. Hunidzarira (1) ; E.R. Brown (2) ; [...]

: Introduction: Semen induces mucosal changes in the female reproductive tract to improve pregnancy outcomes. Since semen‐induced alterations are likely short‐lived and genital inflammation is linked to HIV acquisition in women, we investigated the contribution of recent semen exposure on biomarkers of genital inflammation in women at high HIV risk and the persistence of these associations. Methods: We assessed stored genital specimens from 152 HIV‐negative KwaZulu‐Natal women who participated in the CAPRISA 008 trial between November 2012 and October 2014. During the two‐year study period, 651 vaginal specimens were collected biannually (mean five samples per woman). Cervicovaginal lavage (CVL) was screened for prostate‐specific antigen (PSA) by ELISA, whereas Y‐chromosome DNA (YcDNA) detection and quantification were conducted by RT‐PCR, representing semen exposure within 48 hours (PSA+YcDNA+) and semen exposure within three to fifteen days (PSA−YcDNA+). Soluble protein concentrations were measured in CVLs by multiplexed ELISA. T‐cell frequencies were assessed in cytobrushes by flow‐cytometry, and vulvovaginal swabs were used to detect common vaginal microbes by PCR. Linear mixed models adjusting for factors associated with genital inflammation and HIV risk were used to assess the impact of semen exposure on biomarkers of inflammation over multiple visits. Results: Here, 19% (125/651) of CVLs were PSA+YcDNA+, 14% (93/651) were PSA−YcDNA+ and 67% (433/651) were PSA−YcDNA−. Semen exposure was associated with how often women saw their partners, the frequency of vaginal sex in the past month, HSV‐2 antibody detection, current gonorrhoea infection and Nugent Score. Both PSA detection (PSA+YcDNA+) and higher cervicovaginal YcDNA concentrations predicted increases in several cytokines, barrier‐related proteins (MMP‐2, TIMP‐1 and TIMP‐4) and activated CD4+CCR5+HLA‐DR+ T cells (β = 0.050; CI 0.001 to 0.098; p = 0.046) and CD4+HLA‐DR+ T cells (β = 0.177; CI 0.016 to 0.339; p = 0.032) respectively. PSA detection was specifically associated with raised pro‐inflammatory cytokines (including IL‐6, TNF‐α, IP‐10 and RANTES), and with the detection of BVAB2 (OR = 1.755; CI 1.116 to 2.760; p = 0.015), P. bivia (OR = 1.886; CI 1.102 to 3.228; p = 0.021) and Gardnerella vaginalis (OR = 1.815; CI 1.093 to 3.015; p = 0.021). Conclusions: More recent semen exposure was associated with raised levels of inflammatory biomarkers and the detection of BV‐associated microbes, which declined by three to fifteen days of post‐exposure. Although transient, semen‐induced alterations may have implications for HIV susceptibility in women., Introduction Semen induces mucosal alterations at the female reproductive tract to improve pregnancy outcomes [1‐3]. However, the contribution of semen‐associated changes to human immunodeficiency virus (HIV) risk in women remains [...]

Background Co-infection is frequently seen in critically ill patients with influenza, although the exact rate is unknown. We determined the rate of co-infection, the risk factors and the outcomes associated with co-infection in critically ill patients with influenza over a 7-year period in 148 Spanish intensive care units (ICUs). Methods This was a prospective, observational, multicentre study. Influenza was diagnosed using the polymerase chain reaction. Co-infection had to be confirmed using standard bacteriological tests. The primary endpoint of this analysis was the presence of community-acquired co-infection, with secondary endpoints including ICU, 28-day and hospital mortality. Results Of 2901 ICU patients diagnosed with influenza, 482 (16.6 %) had a co-infection. The proportion of cases of co-infection increased from 11.4 % (110/968) in 2009 to 23.4 % (80/342) in 2015 (P < 0.001). Compared with patients without co-infection, patients with co-infection were older [adjusted odds ratio (aOR) 1.1, 95 % confidence interval 1.1-1.2; P < 0.001] and were more frequently immunosuppressed due to existing HIV infection (aOR 2.6 [1.5-4.5]; P < 0.001) or preceding medication (aOR 1.4 [1.1-1.9]; P = 0.03). Co-infection was an independent risk factor for ICU mortality (aOR 1.4 [1.1-1.8]; P < 0.02), 28-day mortality (aOR 1.3 [1.1-1.7]; P = 0.04) and hospital mortality (aOR 1.9 [1.5-2.5]; P < 0.001). Conclusions Co-infection in critically ill patients with influenza has increased in recent years. In this Spanish cohort, age and immunosuppression were risk factors for co-infection, and co-infection was an independent risk factor for ICU, 28-day and hospital mortality., Author(s): Ignacio Martin-Loeches [sup.1] [sup.2], Marcus J Schultz [sup.3], Jean-Louis Vincent [sup.4], Francisco Alvarez-Lerma [sup.5], Lieuwe D. Bos [sup.3], Jordi Solé-Violán [sup.6], Antoni Torres [sup.7], Alejandro Rodriguez [sup.8] [sup.9] Author [...]

Chronic immune activation, immunosuppression, and T cell exhaustion are hallmarks of HIV infection, yet the mechanisms driving these processes are unclear. Chronic activation can be a driving force in immune exhaustion, and type I interferons (IFN-I) are emerging as critical components underlying ongoing activation in HIV infection. Here, we have tested the effect of blocking IFN-I signaling on T cell responses and virus replication in a murine model of chronic HIV infection. Using HIV-infected humanized mice, we demonstrated that in vivo blockade of IFN-I signaling during chronic HIV infection diminished HIV-driven immune activation, decreased T cell exhaustion marker expression, restored HIV-specific CD8 T cell function, and led to decreased viral replication. Antiretroviral therapy (ART) in combination with IFN-I blockade accelerated viral suppression, further decreased viral loads, and reduced the persistently infected HIV reservoir compared with ART treatment alone. Our data suggest that blocking IFN-I signaling in conjunction with ART treatment can restore immune function and may reduce viral reservoirs during chronic HIV infection, providing validation for IFN-I blockade as a potential therapy for HIV infection., Introduction The HIV-specific T cell response is critical to control HIV replication following infection (1, 2). However, for a variety of reasons, including the insufficient generation and maintenance of functional [...]

: Introduction: Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub‐Saharan Africa. Schistosomiasis is hypothesized to increase HIV‐1 acquisition risk, and multiple cross‐sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. Methods: We conducted nested case‐control analyses within three longitudinal cohorts of heterosexual HIV‐1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow‐up from 1993 to 2014. Cases HIV‐1 seroconverted during prospective follow‐up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV‐1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. Results: We included 245 HIV‐1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV‐1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV‐1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species‐specific effects, there was no statistically significant association between HIV‐1 acquisition risk and Schistosoma mansoni (serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) or Schistosoma haematobium (serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. Conclusions: Schistosomiasis was not a strong risk factor for HIV‐1 acquisition in these four prospective studies. S. mansoni was responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis that S. mansoni infection is associated with increased HIV‐1 acquisition risk. S. haematobium infection was associated with a point estimate of elevated HIV‐1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts., Introduction Schistosomiasis, a parasitic disease caused by the schistosome flatworm, affects approximately 200 million people globally [1], over 90% of whom live in sub‐Saharan Africa [2,3]. In Africa, schistosomiasis is [...]

: Introduction: WHO/UNAIDS recommended Voluntary Medical Male Circumcision in 2007 based on systematic review of observational studies prior to 1999 and three randomized controlled trials (RCTs). To inform updated WHO guidance, we conducted a systematic review and meta‐analysis of impact of circumcision on the risk of HIV infection among heterosexual men. Methods: Studies in PubMed of HIV incidence and changes in prevalence in heterosexual men by circumcision status were identified. Pooled incidence rate ratios were computed using fixed‐ and random‐effects meta‐analysis and risk of bias was assessed using the ROBINS‐I tool. Results and Discussion: In three RCTs, the pooled incidence ratio was 0.41 (95% CI 0.30 to 0.56), with risk difference 10 (8 to 12) fewer infections per 1000 person‐years (py). Pooled incidence ratios were 0.34 (0.24 to 0.49) in two post‐RCT follow‐up studies, 0.29 (0.19 to 0.43) in men at high HIV risk (five cohorts), 0.48 (0.33 to 0.70) in four community‐based cohorts before circumcision scale‐up, and 0.56 (0.49 to 0.64) (7 [6 to 8] fewer per 1000 py) in six community‐based cohorts during circumcision and antiretroviral treatment scale‐up. Heterogeneity between studies was low except in men at high HIV risk. We estimated 520,000 (425,000 to 605,000) fewer infections occurred in men by end of 2018 from 22.7 million circumcisions performed since 2008 and increasing by 155,000 (125,000 to 180,000) annually if epidemic conditions remain similar. After exclusion of studies with high risk of bias and those conducted outside Africa, pooled incidence ratios were similar. There was no evidence of confounding nor changes in risk behaviour following circumcision. In post‐hoc exploratory analyses we observed a trend of decreasing effectiveness of circumcision in cohorts with lower HIV incidence. Conclusions: Efficacy of medical male circumcision on HIV incidence from randomized controlled trials was supported by effectiveness from observational studies in populations with diverse HIV risk and changing epidemic contexts. Voluntary Medical Male Circumcision remains an important evidence‐based intervention for control of generalized HIV epidemics., Introduction Data suggesting a potential link between male circumcision and HIV infection at the individual and population levels were published in 1988 [1] and 1989 [2]. A meta‐analysis of observational [...]

: Introduction: Low uptake of HIV testing and services, including pre‐exposure prophylaxis (PrEP), in Thai men who have sex with men (MSM) and transgender women (TGW) may be due to the inaccuracy in self‐risk assessment. This study investigated the discordance between self‐perceived HIV risk and actual risk. Methods: Data were obtained between May 2015 and October 2016 from MSM and TGW enrolled in key population‐led Test and Treat study in six community health centres in Thailand. Eligible participants were at least 18 years old, Thai national, had sex with men, had unprotected sex with a man in the past six months or had at least three male sex partners in the past six months, and were not known to be HIV positive. Baseline demographic behavioural characteristics questionnaires, including self‐perceived HIV risk, were self‐administered. Participants received HIV/STI (syphilis/gonorrhoea/chlamydia) testing at baseline. Participants who self‐perceived to have low risk, but engaged in HIV‐susceptible practices were categorized as having risk discordance (RD). Regression was conducted to assess factors associated with RD among MSM and TGW separately. Results: Of the 882 MSM and 406 TGW participants who perceived themselves as having low HIV risk, over 80% reported at least one of the following: tested HIV positive, engaged in condomless sex, tested positive for a sexually transmitted infection sexually transmitted infection (STI; or used amphetamine‐type stimulants. Logistic regression found that living with a male partner (p = 0.005), having never tested for HIV (p = 0.045), and living in Bangkok (p = 0.01) and Chiang Mai (p < 0.001) were associated with increased risk discordance among MSM. Living with a male partner (p = 0.002), being less than 17 years old at sexual debut (p = 0.001), and having a low knowledge score about HIV transmission (p < 0.001) were associated with increased risk discordance among TGW. However, for TGW, being a sex worker decreased the chance of risk discordance (p = 0.034). Conclusions: Future HIV prevention messages need to fill in the gap between self‐perceived risk and actual risk in order to help HIV‐vulnerable populations understand their risk better and proactively seek HIV prevention services., Introduction Thailand has made remarkable progress in reducing new HIV infections over the past years, and its trajectory is well‐set to achieve UNAIDS' 90‐90‐90 goals. Of all new HIV infections, [...]

: Introduction: Socio‐behavioural factors may contribute to the wide variance in HIV prevalence between and within sub‐Saharan African (SSA) countries. We studied the associations between socio‐behavioural variables potentially related to the risk of acquiring HIV. Methods: We used Bayesian network models to study associations between socio‐behavioural variables that may be related to HIV. A Bayesian network consists of nodes representing variables, and edges representing the conditional dependencies between variables. We analysed data from Demographic and Health Surveys conducted in 29 SSA countries between 2010 and 2016. We predefined and dichotomized 12 variables, including factors related to age, literacy, HIV knowledge, HIV testing, domestic violence, sexual activity and women's empowerment. We analysed data on men and women for each country separately and then summarized the results across the countries. We conducted a second analysis including also the individual HIV status in a subset of 23 countries where this information was available. We presented summary graphs showing associations that were present in at least six countries (five in the analysis with HIV status). Results: We analysed data from 190,273 men (range across countries 2295 to 17,359) and 420,198 women (6621 to 38,948). The two variables with the highest total number of edges in the summary graphs were literacy and rural/urban location. Literacy was negatively associated with false beliefs about AIDS and, for women, early sexual initiation, in most countries. Literacy was also positively associated with ever being tested for HIV and the belief that women have the right to ask their husband to use condoms if he has a sexually transmitted infection. Rural location was positively associated with false beliefs about HIV and the belief that beating one's wife is justified, and negatively associated with having been tested for HIV. In the analysis including HIV status, being HIV positive was associated with female‐headed household, older age and rural location among women, and with no variables among men. Conclusions: Literacy and urbanity were strongly associated with several factors that are important for HIV acquisition. Since literacy is one of the few variables that can be improved by interventions, this makes it a promising intervention target., Introduction In sub‐Saharan Africa, about 26 million people were living with HIV in 2018. HIV prevalence is high overall, but very heterogeneous between countries, ranging from under 1% in Senegal [...]

: Introduction: Some studies suggest that use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) may increase susceptibility to HIV infection. We aim to determine the influence that such an association could have had on the HIV epidemic in South Africa. Methods: We simulate the heterosexual adult HIV epidemic in South Africa using a compartmental model stratified by age, behavioural risk group, sex, male circumcision status and contraceptive use. We model two possible scenarios: (1) The “With Effect” scenario assumes that DMPA increases susceptibility to HIV infection by 1.20‐fold (95% confidence interval 1.06 to 1.36) based on a combination of the results of a recent randomised controlled trial (ECHO trial) and a number of observational studies. (2) The “No Effect” scenario assumes that DMPA has no effect on HIV acquisition risk. We calculate the difference in HIV‐related outcomes between the With Effect and No Effect scenarios to determine the potential impact that DMPA use could have had on the HIV epidemic. Results: A causal association between DMPA and HIV acquisition could have caused 430,000 (90% of model runs 160,000 to 960,000) excess HIV infections and 230,000 (90,000 to 470,000) AIDS deaths in South Africa from 1980 to 2017. These figures represent 4.3% (1.6% to 9.6%) and 6.9% (2.6% to 15.2%) of the total modelled estimates of HIV infections and AIDS deaths respectively in South Africa in that period. Of the additional infections, 36% (25% to 48%) would have occurred among men. If DMPA use continues at current levels, a potential causal association could cause an additional 130,000 (50,000 to 270,000) infections between 2018 and 2037. The excess infections would have required an additional 640,000 (190,000 to 1,660,000) years of ART from 1980 to 2017, and a further 2,870,000 (890,000 to 7,270,000) years of ART from 2018 to 2037. Conclusions: If there is a causal association between DMPA use and HIV risk, it could have substantially increased the scale of the HIV epidemic in South Africa, affecting not only the users of DMPA, but also their partners and the wider population. The magnitude of this potential effect demands careful data collection and a careful consideration of policy choices for contraception in settings with large HIV epidemics., Introduction Injectable hormonal contraception (IHC) is used by over 50 million women worldwide, the majority of whom are using depot medroxyprogesterone acetate (DMPA). It is particularly popular in southern and [...]

Background: AIDS-related illness is a leading cause of death globally in women aged 15 to 49. Increased susceptibility to HIV or SHIV infection has been proposed to occur during the luteal phase of the menstrual cycle when levels of the immunosuppressive sex-hormone progesterone are fluctuating. We sought to better define the contribution of the menstrual cycle to HIV susceptibility through studying longitudinal immune properties. Methods: Immune properties were defined throughout the menstrual cycle in 9 pigtail macaques with standard cycles (average length: 32.8 days). Plasma progesterone and cytokines levels were measured by enzyme or bead-based immunoassay. CD38, CCR5, CXCR3, PD-1, FoxP3, IFNg and TNFa from CD4 T cells in PBMC were measured using fluorochrome-conjugated antibody recognition. Power spectral analysis by Lomb-Scargle algorithms was used to detect molecular oscillations in progesterone and CCR5 expression over reproductive cycles. Relationships between SHIV susceptibility and phase of the menstrual cycle were defined in macaques infected during repeated exposures to low ([50TCID.sub.50]) doses of [SHIV.sub.162p3]. PBMCs from 10 healthy women were used to define inflammatory behaviors during the cycle. Statistical modeling to evaluate pairwise comparisons of means were fit using generalized estimating equations. Results: Menstrual cycle phase was associated with variations in circulating adaptive cellular characteristics, including CD4 T cell expression of CCR5, activation-associated molecules PD-1, CD38, and CXCR3, and functional responses defined by IFNg and TNFa. Comprehensive innate immune characterizations corroborated T cell variations and identified elevated type-1 inflammatory properties predominantly occurring in the late luteal phase. Using power spectral analysis, we identified sinusoidal expression patterns of CCR5 that synchronized with reproductive cycles. [SHIV.sub.163P3] infection in macaques was linked to challenges during periods of increasing inflammatory properties, while expression abundance or cycle phase alone was not strongly correlated. Analogous fluctuations in T cell inflammatory properties were found in healthy menstruating women. Conclusions: We demonstrate that periodic shifts in the immune landscape under menstrual cycle regulation drives type-1 inflammatory properties and dictates infection opportunities. We posit that novel prevention strategies that reduce local inflammation events in the FRT, such as occurs under menstrual cycle regulation, may help prevent HIV transmission events in women., OA22.04 A. Kohlmeier (1); J. Brody (2); A. Sheth (3); F. Hardnett (4); S. Sharma (4); I. Ofotokun (5); I. Massud (4) and G. Garcia-Lerma (4) (1) CDC, DHAP, Atlanta, [...]

: Introduction: Globally, sexually transmitted infections (STI) affect >300 million people annually, and are a major cause of sexual and reproductive health complications in women. In this commentary, we describe how STIs interact with the immune and non‐immune cells, both within and below the cervicovaginal mucosal barrier, to cause inflammation, which in turn has been associated with increased HIV acquisition risk. Discussion: STIs have a major impact on the female genital mucosa, which is an important biological and physical barrier that forms the first line of defence against invading microorganisms such as HIV. Pattern recognition of STI pathogens, by receptors expressed either on the cell surface or inside the cell, typically triggers inflammation at the mucosal barrier. The types of mucosal responses vary by STI, and can be asymptomatic or culminate in the formation of discharge, ulcers and/or warts. While the aim of this response is to clear the invading microbes, in many cases these responses are either evaded or cause pathology that impairs barrier integrity and increases HIV access to target cells in the sub‐mucosa. In addition, innate responses to STIs can result in an increased number of immune cells, including those that are the primary targets of HIV, and may contribute to the association between STIs and increased susceptibility to HIV acquisition. Many of these cells are mediators of adaptive immunity, including tissue‐resident cells that may also display innate‐like functions. Bacterial vaginosis (BV) is another common cause of inflammation, and evidence for multiple interactions between BV, STIs and HIV suggest that susceptibility to these conditions should be considered in concert. Conclusions: STIs and other microbes can induce inflammation in the genital tract, perturbing the normal robust function of the mucosal barrier against HIV. While the impact of STIs on the mucosal immune system and HIV acquisition is often under‐appreciated, understanding their interactions of the infections with the immune responses play an important role in improving treatment and reducing the risk of HIV acquisition. The frequent sub‐clinical inflammation associated with STIs underscores the need for better STI diagnostics to reverse the immunological consequences of infection., Introduction There are over 50 types of viruses, bacteria and parasites that can be sexually transmitted, eight of which are most widely recognized as sexually transmitted infections (STIs). These include [...]

OBJECTIVES: Indigenous leaders and child and family advocates are deeply concerned about the health impacts of the child welfare system, including HIV vulnerability. The objectives of this study were to describe the prevalence of having been apprehended into the child welfare system and associated HIV vulnerabilities among young Indigenous people who use drugs. METHODS: The Cedar Project is a cohort of young Indigenous people ages 14-30 years who use illicit drugs in Vancouver and Prince George, British Columbia. Multivariable logistic regression modeling determined associations between a history of involvement in the child welfare system and vulnerability to HIV infection. RESULTS: Of 605 participants, 65% had been taken from their biological parents. Median age of first apprehension was 4 years old. Having been sexually abused, having a parent who attended residential school and being HIV-positive were all independently associated with having been involved in the child welfare system. Participants who had been involved in the child welfare system were also more likely to have been homeless, paid for sex, diagnosed and hospitalized with mental illness, self-harmed, thought about suicide, and attempted suicide. Among participants who used injection drugs, those who had been involved in child welfare were more likely to have shared needles and overdosed. CONCLUSION: This study has found compelling evidence that young Indigenous people who use drugs in two cities in BC are experiencing several distressing health outcomes associated with child welfare involvement, including HIV infection. Jurisdictional reforms and trauma-informed programs that use culture as intervention are urgently needed. KEYWORDS: Child welfare; HIV; substance-related disorders; Indians; North American La traduction du resume se trouve a la fin de l'article. OBJECTIFS: Les dirigeants autochtones et les defenseurs des enfants et des familles sont profondement preoccupes par les effets du systeme de protection de la jeunesse sur la sante, notamment sur la vulnerabilite au VIH. Notre etude vise a decrire la prevalence de la prise en charge par un organisme de protection de la jeunesse et des vulnerabilites au VIH connexes chez les jeunes autochtones qui consomment de la drogue. METHODE: Le Cedar Project est une cohorte de jeunes autochtones de 14 a 30 ans consommant de la drogue a Vancouver et a Prince George (Colombie-Britannique). Un modele de regression logistique multivariee a determine les associations entre les antecedents de prise en charge par un organisme de protection de la jeunesse et la vulnerabilite a l'infection a VIH. RESULTATS: Sur 605 participants, 65 % avaient ete retires a leurs parents biologiques. L'age median a la premiere prise en charge etait de 4 ans. Le fait d'avoir ete victime d'agression sexuelle, d'avoir un parent ayant frequente un pensionnat et d'etre seropositif pour le VIH etaient trois variables independamment associees a la prise en charge par un organisme de protection de la jeunesse. Les participants ayant ete pris en charge par un organisme de protection de la jeunesse etaient aussi plus susceptibles d'avoir ete sans abri, d'avoir ete payes pour un rapport sexuel, d'avoir ete diagnostiques et hospitalises pour une maladie mentale, de s'etre automutiles, d'avoir songe au suicide et d'avoir fait une tentative de suicide. Parmi les participants utilisant des drogues par injection, ceux ayant ete pris en charge par un organisme de protection de l'enfance etaient plus susceptibles d'avoir partage des aiguilles et fait une surdose. CONCLUSION: Nous avons des preuves convaincantes que dans deux villes de la C.-B., les jeunes autochtones qui consomment de la drogue presentent plusieurs resultats de sante troublants, notamment l'infection a VIH, associes a la prise en charge par des organismes de protection de la jeunesse. Il existe un besoin urgent d'amorcer des reformes du systeme judiciaire et d'etablir des programmes eclaires par les traumatismes en utilisant la culture comme outil d'intervention. MOTS CLES: protection de l'enfance; VIH; troubles lies a une substance; Indiens d'Amerique Nord doi: 10.17269/CJPH.106.5026, Prior to the arrival of European missionaries and settlers, Indigenous families and communities supported healthy, independent children through spiritual connection to lands, traditions, language and culture. (1) However, traditional styles [...]

Introduction: We previously showed that the rectal mucosal immune environment among men who have sex with men (MSM) engaging in condomless receptive anal intercourse (CRAI) is immunologically distinct from that of men who do not engage in anal intercourse (AI). Here, we further examined these differences with quantitative immunohistochemistry to better understand the geographic distribution of immune markers of interest. Methods: We enrolled a cohort of MSM engaging in CRAI (n = 41) and men who do not engage in AI (n = 21) between October 2013 and April2015. Participants were healthy, HIV-negative men aged 18-45 from the metro Atlanta area. We performed rectal mucosal sampling via rigid sigmoidoscopy during two study visits separated by a median of nine weeks and timed with sexual activity for MSM engaging in CRAI. We used standardized, automated immunohistochemistry and quantitative image analysis to investigate the rectal mucosal distribution of neutrophils (MPO), IL-17-producing cells (IL-17) and [T.sub.regs] (FOXP3) in the lamina propria, and cellular proliferation (Ki67) and adherens junction protein (E-cadherin) in the epithelium. We examined associations between biomarker expression and the rectal mucosal microbiota composition by 16s rRNA sequencing. Results: Relative to the colonic crypt base, IL-17, FOXP3, and MPO expression increased towards the rectallumen, while Ki67 decreased and E-cadherin was more uniformly distributed. Throughout the rectal mucosa distribution examined, MSM engaging in CRAI had higher mean lamina propria MPO expression (p = 0.04) and epithelialKi67 (p = 0.04) compared to controls. There were no significant differences in IL-17, FOXP3 or E-cadherin expression. We found no significant associations of the five biomarkers with the global rectal microbiota composition or the individual taxa examined. Conclusions: Understanding the mucosal distribution of inflammatory mediators can enhance our knowledge of the earliest events in HIV transmission. Neutrophil enrichment and crypt epithelial cell proliferation likely represent sub-clinical inflam-mation in response to CRAI in the rectal mucosa of MSM, which could increase the risk for HIV acquisition. However, the contributory role of the microbiota in mucosal inflammation among MSM remains unclear. HIV prevention may be enhanced by interventions that reduce inflammation or capitalize on the presence of specific inflammatory mechanisms during HIV exposure. Keywords: men who have sex with men; rectal mucosa; HIV transmission; receptive anal intercourse; mucosal immunology; microbiome, 1 | INTRODUCTION From 2013 to 2017 in the United States, 72% of new HIV infections occurred among men who have sex with men (MSM), with approximately 70% attributed to [...]

: Introduction: Evidence has shown that the experience of violence by a partner has important influences on women's risk of HIV acquisition. Using a randomized experiment in northeast South Africa, we found that a conditional cash transfer (CCT) targeted to poor girls in high school reduced the risk of physical intimate partner violence (IPV) in the past 12 months by 34%. The purpose of this analysis is to understand the pathways through which the CCT affects IPV. Methods: HPTN 068 was a phase 3, randomized controlled trial in rural Mpumalanga province, South Africa. Eligible young women (aged 13–20) and their parents or guardians were randomly assigned (1:1) to either receive a monthly cash transfer conditional on monthly high school attendance or no cash transfer. Between 2011 and 2015, participants (N = 2,448) were interviewed at baseline, then at annual follow‐up visits at 12, 24 and 36 months. The total effect of the CCT on IPV was estimated using a GEE log‐binomial regression model. We then estimated controlled direct effects to examine mediation of direct effects through intermediate pathways. Mediators include sexual partnership measures, the sexual relationship power scale, and household consumption measures. Results: We found evidence that the CCT works in part through delaying sexual debut or reducing the number of sexual partners. The intervention interacts with these mediators leading to larger reductions in IPV risk compared to the total effect of the CCT on any physical IPV [RR 0.66, CI(95%):0.59–0.74]. The largest reductions are seen when we estimate the controlled direct effect under no sexual debut [RR 0.57, CI(95%):0.48–0.65] or under no sexual partner in the last 12 months [RR 0.53, CI(95%):0.46–0.60]. Conclusions: Results indicate that a CCT for high school girls has protective effects on their experience of IPV and that the effect is due in part to girls choosing not to engage in sexual partnerships, thereby reducing the opportunity for IPV. As a lower exposure to IPV and safer sexual behaviours also protect against HIV acquisition, this study adds to the growing body of evidence on how cash transfers may reduce young women's HIV risk., Introduction Violence against women, and specifically intimate partner violence (IPV), is a major global public health problem, causing significant morbidity and mortality worldwide. Around a third of women globally have [...]