Are violence, harmful alcohol/substance use and poor mental health associated with increased genital inflammation?: A longitudinal cohort study with HIV-negative female sex workers in Nairobi, Kenya.

Violence, alcohol use, substance use and poor mental health have been linked with increased HIV acquisition risk, and genital inflammation enhances HIV susceptibility. We examined whether past 6 month experience of these exposures was associated with increased genital inflammation, thereby providing a biological link between these exposures and HIV acquisition risk. The Maisha Fiti study was a longitudinal mixed-methods study of female sex workers in Nairobi, Kenya. Behavioural-biological surveys were conducted at baseline (June-December 2019) and endline (June 2020-March 2021). Analyses were restricted to HIV-negative women (n = 746). Women with raised levels of at least 5 of 9 genital inflammatory cytokines were defined as having genital inflammation. Multivariable logistic regression models were used to estimate (i) baseline associations between genital inflammation and violence, harmful alcohol/substance use, and poor mental health, and (ii) longitudinal associations between these exposures at different survey rounds, and genital inflammation at follow-up. Inflammation data was available for 711 of 746 (95.3%) women at baseline; 351 (50.1%) had genital inflammation, as did 247 (46.7%) at follow-up. At baseline, 67.8% of women had experienced physical and/or sexual violence in the past 6 months, 33.9% had harmful alcohol use, 26.4% had harmful substance use, 25.5% had moderate/severe depression/anxiety, and 13.9% had post-traumatic stress disorder. In adjusted analyses, there was no evidence that these exposures were associated cross-sectionally or longitudinally with genital inflammation. We report no associations between past 6 month experience of violence, harmful alcohol/substance use, or poor mental health, and immune parameters previously associated with HIV risk. This suggests that the well-described epidemiological associations between these exposures and HIV acquisition do not appear to be mediated by genital immune changes, or that any such changes are relatively short-lived. High prevalences of these exposures suggest an urgent need for sex-worker specific violence, alcohol/substance use and mental health interventions.

Associations of hair cortisol levels with violence, poor mental health, and harmful alcohol and other substance use among female sex workers in Nairobi, Kenya.

Violence, poor mental health, and harmful substance use are commonly experienced by female sex workers (FSWs) in sub-Saharan Africa, all of which are associated with increased HIV susceptibility. We aimed to investigate the associations between violence, poor mental health and harmful alcohol/substance use with hair cortisol concentration (HCC) levels as a potential biological pathway linking the experiences of these stressors and HIV vulnerability. We used the baseline data of the Maisha Fiti study of FSWs in Nairobi, Kenya. Participants reported recent violence, poor mental health, and harmful alcohol/substance use. Hair samples proximal to the scalp were collected to measure cortisol levels determined by ELISA. We analysed the data of 425 HIV-negative respondents who provided at least 2 cm of hair sample. The prevalence of recent violence was 89.3% (physical 54.6%; sexual 49.4%; emotional 77.0% and financial 66.5%), and 29.1% had been arrested due to sex work. 23.7% of participants reported moderate/severe depression, 11.6% moderate/severe anxiety, 13.5% PTSD and 10.8% recent suicidal thoughts and/or attempts. About half of the participants (48.8%) reported recent harmful alcohol and/or other substance use. In multivariable linear regression analyses, both physical and/or sexual violence (adjusted geometric mean ratio (aGMR) = 1.28; 95% CI 1.01-1.62) and harmful alcohol and/or other substance use (aGMR = 1.31; 95% CI 1.03-1.65) were positively and independently associated with increased HCC levels. Findings suggest a role of violence and substance use in elevated HCC levels, which could increase HIV risk due to cortisol-related T cell activation. However, longitudinal and mechanistic studies are needed to confirm this hypothesis.

Impact of antimicrobials on penile HIV susceptibility and immunology in uncircumcised men: A randomized phase 1/2 clinical trial.

Within the penile microbiome, bacteria associated with seroconversion, immunology, and cells (BASIC species) enhance HIV susceptibility in heterosexual uncircumcised men by inducing foreskin inflammation and HIV target cell recruitment. This phase 1/2 clinical trial randomizes HIV-uninfected Ugandan men (n = 125) to either oral tinidazole, topical metronidazole, topical clindamycin, or topical hydrogen peroxide to define impact on ex vivo foreskin HIV susceptibility, penile immunology, and BASIC species density. Antimicrobials are well tolerated, and 116 (93%) participants complete the protocol. Topical metronidazole and oral tinidazole reduce the inner foreskin tissue density of HIV-susceptible CD4+ T cells (predefined primary endpoint). Antimicrobials also have varying but substantial effects on reducing prepuce inflammation and BASIC species density, reducing density of foreskin T cell subsets, and increasing foreskin epithelial integrity. Immune alterations correlate strongly with changes in the abundance of BASIC species. Clinical interventions targeting the penile microbiota, particularly topical metronidazole, may reduce HIV susceptibility in uncircumcised men.

Factors Associated with Usage of Oral-PrEP among Female Sex Workers in Nairobi, Kenya, Assessed by Self-Report and a Point-of-Care Urine Tenofovir Immunoassay.

Pre-exposure prophylaxis (PrEP) is highly effective at reducing HIV acquisition. We aimed to estimate usage of oral-PrEP, and factors associated with adherence among female sex workers (FSWs) in Nairobi, Kenya, using a novel point-of-care urine tenofovir lateral flow assay (LFA). The Maisha Fiti study randomly selected FSWs from Sex Worker Outreach Program clinics in Nairobi. Data were collected from 1003 FSWs from June-October 2019, including surveys on self-reported oral-PrEP adherence. Adherence was also measured using the LFA for HIV-negative FSWs currently taking oral-PrEP. Informed by a social-ecological theoretical framework, we used hierarchical multivariable logistic regression models to estimate associations between individual, interpersonal/community, and structural/institutional-level factors and either self-reported or LFA-assessed adherence. Overall, 746 HIV-negative FSWs aged 18-40 participated in the study, of whom 180 (24.1%) self-reported currently taking oral-PrEP. Of these, 56 (31.1%) were adherent to oral-PrEP as measured by LFA. In the multivariable analyses, associations with currently taking oral-PrEP included having completed secondary education, high alcohol/substance use, feeling empowered to use PrEP, current intimate partner, no recent intimate partner violence, having support from sex worker organisations, experiencing sex work-related stigma, and seeking healthcare services despite stigma. Associations with oral-PrEP LFA-measured adherence measured included having only primary education, experience of childhood emotional violence, belonging to a higher wealth tertile, and being nulliparous. Oral-PrEP adherence, measured by self-report or objectively, is low among FSWs in Nairobi. Programs to improve oral-PrEP usage among FSWs should work to mitigate social and structural barriers and involve collaboration between FSWs, healthcare providers and policymakers.

Vaginal Lactobacillus crispatus persistence following application of a live biotherapeutic product: colonization phenotypes and genital immune impact.

BACKGROUND: Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a live biotherapeutic containing the Lactobacillus crispatus strain CTV-05, reduced BV recurrence and vaginal inflammation; however, 3 months after product cessation, CTV-05 colonization was only sustained in 48% of participants. RESULTS: This nested sub-study in 32 participants receiving LACTIN-V finds that 72% (23/32) demonstrate clinically relevant colonization (CTV-05 absolute abundance > 106 CFU/mL) during at least one visit while 28% (9/32) of women demonstrate colonization resistance, even during product administration. Immediately prior to LACTIN-V administration, the colonization-resistant group exhibited elevated vaginal microbiota diversity. During LACTIN-V administration, colonization resistance was associated with elevated vaginal markers of epithelial disruption and reduced chemokines, possibly due to elevated absolute abundance of BV-associated species and reduced L. crispatus. Colonization permissive women were stratified into sustained and transient colonization groups (31% and 41% of participants, respectively) based on CTV-05 colonization after cessation of product administration. These groups also exhibited distinct genital immune profiles during LACTIN-V administration. CONCLUSIONS: The genital immune impact of LACTIN-V may be contingent on the CTV-05 colonization phenotype, which is in turn partially dependent on the success of BV clearance prior to LACTIN-V administration.

Vaginal fungi are associated with treatment-induced shifts in the vaginal microbiota and with a distinct genital immune profile.

Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus-based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans. Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans. Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

Effect of cryopreservation on CD4+ T cell subsets in foreskin tissue.

Voluntary medical male circumcision (VMMC) reduces HIV acquisition by at least 60%, but the determinants of HIV susceptibility in foreskin tissues are incompletely understood. Flow cytometry is a powerful tool that helps us understand tissue immune defenses in mucosal tissue like the inner foreskin, but foreskin flow cytometry has only been validated using fresh tissue samples. This restricts immune analyses to timepoints immediately after surgical acquisition and hinders research in this area. We compared fresh analysis with whole tissue cryopreservation and later thawing and digestion to analyze CD4+ T cell populations relevant to HIV susceptibility (CCR5, CD25, CD127, CCR4, CXCR3, CCR6, CCR10, HLA-DR, and CD38). Eight foreskin samples from HIV-negative males aged >18 years were collected after VMMC. For each sample, half the foreskin was immediately cryopreserved for later digestion and flow cytometry analysis, while the remaining tissues were analyzed fresh. We demonstrate no significant impact of cryopreservation on CD4+ T cell expression of CD25, CCR4, CCR6, HLA-DR, CCR10, or CD127. Although expression levels of CCR5, CD38, and CXCR3 were increased after cryopreservation, the relative ranking of participants was retained. In conclusion, cryopreserved foreskin tissues may be suitable for subsequent digestion and flow cytometry phenotyping of HIV-susceptible T cell populations.

Quantifying the impact of cascade inequalities: a modelling study on the prevention impacts of antiretroviral therapy scale-up in Eswatini.

Background: Inequalities in the antiretroviral therapy (ART) cascade across subpopulations remain an ongoing challenge in the global HIV response. Eswatini achieved the UNAIDS 95-95-95 targets by 2020, with differentiated programs to minimize inequalities across subpopulations, including for female sex workers (FSW) and their clients. We sought to estimate additional HIV infections expected in Eswatini if cascade scale-up had not been equal, and under which epidemic conditions these inequalities could have the largest influence. Methods: Drawing on population-level and FSW-specific surveys in Eswatini, we developed a compartmental model of heterosexual HIV transmission which included eight subpopulations and four sexual partnership types. We calibrated the model to stratified HIV prevalence, incidence, and ART cascade data. Taking observed cascade scale-up in Eswatini as the base-case-reaching 95-95-95 in the overall population by 2020-we defined four counterfactual scenarios in which the population overall reached 80-80-90 by 2020, but where FSW, clients, both, or neither were disproportionately left behind, reaching only 60-40-80. We quantified relative additional cumulative HIV infections by 2030 in counterfactual vs base-case scenarios. We further estimated linear effects of viral suppression gap among FSW and clients on additional infections by 2030, plus effect modification by FSW/client population sizes, rates of turnover, and HIV prevalence ratios. Results: Compared with the base-case scenario, leaving behind neither FSW nor their clients led to the fewest additional infections by 2030: median (95% credible interval) 14.9 (10.4, 18.4)% vs 26.3 (19.7, 33.0)% if both were left behind-a 73 (40, 149)% increase. The effect of lower cascade on additional infections was larger for clients vs FSW, and both effects increased with population size and relative HIV incidence. Conclusions: Inequalities in the ART cascade across subpopulations can undermine the anticipated prevention impacts of cascade scale-up. As Eswatini has shown, addressing inequalities in the ART cascade, particularly those that intersect with high transmission risk, could maximize incidence reductions from cascade scale-up.

Association of oral microbiome with oral human papillomavirus infection: a population study of the National Health and Nutrition Examination Survey, 2009-2012.

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

Insertive vaginal sex is associated with altered penile immunology and enrichment of Gardnerella vaginalis in uncircumcised Ugandan men.

PROBLEM: HIV susceptibility is linked to the penile immune milieu (particularly IL-8 levels) and microbiome. The effects of insertive vaginal sex itself on penile immunology and microbiota are not well described. METHOD OF STUDY: We compared the immune milieu and microbiology of the coronal sulcus (CS) and distal urethra in 47 uncircumcised Ugandan men reporting ever (n = 42) or never (n = 5) having had vaginal intercourse. Soluble immune factors were assayed by multiplex ELISA, and penile bacteria abundance by 16S rRNA qPCR and sequencing. Co-primary endpoints were penile levels of IL-8 and soluble E-cadherin. RESULTS: Independent of classical STIs, men reporting prior vaginal sex demonstrated elevated IL-8 levels in both the coronal sulcus (1.78 vs. 0.81 log10 pg/mL, p = .021) and urethra (2.93 vs. 2.30 log10 pg/mL; p = .003), with a strong inverse relationship between urethral IL-8 levels and the time from last vaginal sex (r = -0.436; p = .004). Vaginal sex was also associated with elevated penile IL-1α/ß and soluble E-cadherin (sEcad), a marker of epithelial disruption. Gardnerella vaginalis (Gv) was only present in the penile microbiome of men reporting prior vaginal sex, and urethral Gv absolute abundance was strongly associated with urethral inflammation (r = 0.556; p < .001); corynebacteria were enriched in the CS of men reporting no prior vaginal sex and were associated with reduced CS inflammation. CONCLUSIONS: Sexual intercourse was associated with sustained changes in penile immunology, potentially mediated through microbial alterations, in particular the urethral abundance of G. vaginalis. Future studies should further characterize the effects of sexual debut on penile bacteria and immunology.

The epidemiology of HIV infection among female sex workers in Nairobi, Kenya: A structural determinants and life-course perspective.

High HIV prevalence among female sex workers (FSWs) is heavily influenced by structural determinants (e.g. criminalisation of sex work; violence) and significant life events (e.g. orphanhood, teenage pregnancy). This study aims to understand the epidemiology of HIV among FSWs in Nairobi, Kenya using a structural determinants and life-course perspective. Baseline cross-sectional survey data were collected June-December 2019 for the Maisha Fiti study with 1003 FSWs (aged 18-45 years). Odds ratios and 95% confidence intervals were estimated using multivariable logistic regression with a hierarchical modelling approach. HIV prevalence was 28.0%, and increased with age (<25 years 5.7%, 25-34 years 19.0%, ≥35 years 40.6%). In adjusted analyses, HIV seroprevalence was associated with childhood and adolescence including violence from militia or soldiers (AOR = 1.60; 95%CI:1.00-2.53), young age at sexual debut (≤15 years old vs. ≥18 years AOR = 0.57; 95%CI:0.39-0.84) and teenage pregnancy (AOR = 1.37; 95%CI:1.00-1.88). For adulthood the factors included lower SES score (lowest vs. highest tertile AOR = 0.63; 95%CI:0.40-0.98); reduced housing insecurity (AOR = 0.52; 95%CI:0.54-0.79); lower alcohol/drug use score (AOR = 0.44; 95%CI:0.31-0.61); and a longer duration of selling sex (0-5 years vs. ≥11 years AOR = 2.35; 95%CI:1.44-3.82). Among HIV-negative FSWs, prevalence of HIV risk factors was high (recent hunger 32.3%; internalised 67.7% and experienced 66.0% sex work stigma; recent police arrest 30.1%; recent physical or sexual violence 65.6%, condomless last sex intimate partner 71.1%; harmful alcohol or substance use 49.1%). Only 24.6% of HIV-negative FSWs reported taking PrEP. Taken together, adverse events in childhood and adolescence were associated with increased odds of living with HIV, and were more strongly associated with HIV serostatus than adulthood structural or behavioural risk factors. HIV-negative FSWs remain at high risk of HIV acquisition. This study highlights the importance of addressing adverse events throughout the life course to reduce HIV risk, and the need to continue multi-level HIV prevention and treatment efforts.

Childhood and adolescent factors shaping vulnerability to underage entry into sex work: a quantitative hierarchical analysis of female sex workers in Nairobi, Kenya.

OBJECTIVE: To explore factors associated with early age at entry into sex work, among a cohort of female sex workers (FSWs) in Nairobi, Kenya. BACKGROUND: Younger age at sex work initiation increases the risk of HIV acquisition, condom non-use, violence victimisation and alcohol and/or substance use problems. This study aimed to understand factors in childhood and adolescence that shape the vulnerability to underage sex work initiation. DESIGN: Building on previous qualitative research with this cohort, analysis of behavioural-biological cross-sectional data using hierarchical logistic regression. PARTICIPANTS AND MEASURES: FSWs aged 18-45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi, and between June and December 2019, completed a baseline behavioural-biological survey. Measurement tools included WHO Adverse Childhood Experiences, Alcohol, Smoking and Substance Involvement Screening Test and questionnaires on sociodemographic information, sexual risk behaviours and gender-based violence. Descriptive statistics and logistic regression were conducted using hierarchical modelling. RESULTS: Of the 1003 FSWs who participated in the baseline survey (response rate 96%), 176 (17.5%) initiated sex work while underage (<18 years). In the multivariable analysis, factors associated with entering sex work while underage included incomplete secondary school education (aOR=2.82; 95% CI=1.69 to 4.73), experiencing homelessness as a child (aOR=2.20; 95% CI=1.39 to 3.48), experiencing childhood physical or sexual violence (aOR=1.85; 95% CI=1.09 to 3.15), young age of sexual debut (≤15 years) (aOR=5.03; 95% CI=1.83 to 13.79) and being childless at time of sex work initiation (aOR=9.80; 95% CI=3.60 to 26.66). CONCLUSIONS: Lower education level and childhood homelessness, combined with sexual violence and sexual risk behaviours in childhood, create pathways to underage initiation into sex work. Interventions designed for girls and young women at these pivotal points in their lives could help prevent underage sex work initiation and their associated health, social and economic consequences.

Immunogenicity of COVID-19 vaccines and their effect on HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. Our study on 68 PWH and 23 HIV-negative participants aged 55 and older post-three vaccine doses showed equally strong anti-spike IgG responses in serum and saliva through week 48 from baseline, while PWH salivary IgA responses were low. PWH had diminished live-virus neutralization responses after two vaccine doses, which were 'rescued' post-booster. Spike-specific T cell immunity was enhanced in PWH with normal CD4+ T cell count, suggesting Th1 imprinting. The frequency of detectable HIV viremia increased post-vaccination, but vaccines did not affect the size of the HIV reservoir in most PWH, except those with low-level viremia. Thus, older PWH require three doses of COVID-19 vaccine for maximum protection, while individuals with unsuppressed viremia should be monitored for adverse reactions from HIV reservoirs.

Emergency departments as under-utilized venues to provide HIV prevention services to female sex workers in Nairobi, Kenya.

BACKGROUND: Female sex workers (FSW) in sub-Saharan Africa are disproportionately affected by HIV and remain a key target population for efforts to reduce transmission. While HIV prevention tools such as PEP and PrEP are available through outpatient FSW clinics, these services are underused. Emergency medicine is a rapidly expanding field in Kenya and may provide a novel venue for initiating or optimizing HIV prevention services. This study examined the characteristics of FSW from Nairobi, Kenya, who had utilized an emergency department (ED) during the past year to broaden our understanding of the patient factors related to usage. METHODS: An anonymous questionnaire was administered to a convenience sample of 220 Nairobi FSW attending dedicated clinics from June to July 2019. The participants were categorized into those who attended an ED over the past year (acute care users) and clinic-only users (control). A modified version of the WHO Violence Against Women Instrument assessed gender-based violence. Multivariable negative binomial logistic regressions evaluated predictors of health care use among these populations. RESULTS: Of the total 220 women (median [IQR] age 32 [27-39]), 101 and 116 were acute care and control populations, respectively. Acute care users had 12.7 ± 8.5 healthcare visits over a 12-month period, and the control population had 9.1 ± 7.0 (p < 0.05). ED attendance did not improve the PrEP usage, with 48.5%, and 51% of acute care and clinic users indicated appropriate PrEP use. Patient factors that correlated with health care utilization among acute care users included client sexual violence (OR 2.2 [1.64-2.94], p < 0.01), PrEP use (OR 1.54 (1.25-1.91), < 0.01), and client HIV status (OR 1.35 (1.02-1.69), p < 0.01). CONCLUSIONS: Many FSW at high risk for HIV were not accessing HIV prevention tools despite attending a dedicated FSW clinic offering such services. FSW who had attended an ED over the past year had a higher prevalence of HIV risk factors, demonstrating that emergency departments may be important acute intervention venues to prevent HIV transmission in this population. These results can guide policy design, health care provider training, and facility preparedness to support strategies aimed at improving HIV prevention strategies for FSW in Kenyan ED's.

Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV). We measured total and neutralizing Ab responses to SARS-CoV-2 spike and RBD in sera, total anti-spike Abs in saliva, frequency of anti-RBD/NTD B cells, changes in frequency of anti-spike, HIV gag/nef-specific T cells, and HIV reservoirs in peripheral CD4 + T cells. The resulting datasets were used to create a mathematical model for within-host immunization. Various regimens of BNT162b2, mRNA-1273, and ChAdOx1 vaccines elicited equally strong anti-spike IgG responses in PWH and HIV - participants in serum and saliva at all timepoints. These responses had similar kinetics in both cohorts and peaked at 4 weeks post-booster (third dose), while half-lives of plasma IgG also dramatically increased post-booster in both groups. Salivary spike IgA responses were low, especially in INRs. PWH had diminished live virus neutralizing titers after two vaccine doses which were 'rescued' after a booster. Anti-spike T cell immunity was enhanced in IRs even in comparison to HIV - participants, suggesting Th1 imprinting from HIV, while in INRs it was the lowest. Increased frequency of viral 'blips' in PWH were seen post-vaccination, but vaccines did not affect the size of the intact HIV reservoir in CD4 + T cells in most PWH, except in LLVs. Thus, older PWH require three doses of COVID-19 vaccine to maximize neutralizing responses against SARS-CoV-2, although vaccines may increase HIV reservoirs in PWH with persistent viremia.

Conducting Violence and Mental Health Research with Female Sex Workers during the COVID-19 Pandemic: Ethical Considerations, Challenges, and Lessons Learned from the Maisha Fiti Study in Nairobi, Kenya.

Conducting violence and mental health research during the COVID-19 pandemic with vulnerable groups such as female sex workers (FSWs) required care to ensure that participants and the research team were not harmed. Potential risks and harm avoidance needed to be considered as well as ensuring data reliability. In March 2020, COVID-19 restrictions were imposed in Kenya during follow-up data collection for the Maisha Fiti study (n = 1003); hence data collection was paused. In June 2020, the study clinic was re-opened after consultations with violence and mental health experts and the FSW community. Between June 2020 and January 2021, data were collected in person and remotely following ethical procedures. A total of 885/1003 (88.2%) FSWs participated in the follow-up behavioural-biological survey and 47/47 (100%) participated in the qualitative in-depth interviews. A total of 26/885 (2.9%) quantitative surveys and 3/47 (6.4%) qualitative interviews were conducted remotely. Researching sensitive topics like sex work, violence, and mental health must guarantee study participants' safety and privacy. Collecting data at the height of COVID-19 was crucial in understanding the relationships between the COVID-19 pandemic, violence against women, and mental health. Relationships established with study participants during the baseline survey-before the pandemic-enabled us to complete data collection. In this paper, we discuss key issues involved in undertaking violence and mental health research with a vulnerable population such as FSWs during a pandemic. Lessons learned could be useful to others researching sensitive topics such as violence and mental health with vulnerable populations.

Violence across the Life Course and Implications for Intervention Design: Findings from the Maisha Fiti Study with Female Sex Workers in Nairobi, Kenya.

We examined violence experiences among Female Sex Workers (FSWs) in Nairobi, Kenya, and how these relate to HIV risk using a life course perspective. Baseline behavioural-biological surveys were conducted with 1003 FSWs June-December 2019. Multivariable logistic regression models were used to estimate the adjusted odds ratio (AOR) and 95% confidence intervals (CI) for associations of life course factors with reported experience of physical or sexual violence in the past 6 months. We found substantial overlap between violence in childhood, and recent intimate and non-intimate partner violence in adulthood, with 86.9% reporting one or more types of violence and 18.7% reporting all three. Recent physical or sexual violence (64.9%) was independently associated with life course factors, including a high WHO Adverse Childhood Experiences (ACE) score (AOR = 7.92; 95% CI:4.93-12.74) and forced sexual debut (AOR = 1.97; 95% CI:1.18-3.29), as well as having an intimate partner (AOR = 1.67; 95% CI:1.25-2.23), not having an additional income to sex work (AOR = 1.54; 95% CI:1.15-2.05), having four or more dependents (AOR = 1.52; 95% CI:0.98-2.34), recent hunger (AOR = 1.39; 95% CI:1.01-1.92), police arrest in the past 6 months (AOR = 2.40; 95% CI:1.71-3.39), condomless last sex (AOR = 1.46; 95% CI:1.02-2.09), and harmful alcohol use (AOR = 3.34; 95% CI:1.74-6.42). Interventions that focus on violence prevention during childhood and adolescence should help prevent future adverse trajectories, including violence experience and HIV acquisition.

Syndemic of factors that shape the early lives of women who enter into sex work: a qualitative methods study from Nairobi, Kenya.

OBJECTIVE: To explore the structural and social co-factors that shape the early lives of women who enter sex work in Nairobi, Kenya. DESIGN: Thematic analysis of qualitative data collected as part of the Maisha Fiti study among female sex workers (FSWs) in Nairobi. PARTICIPANTS AND MEASURES: FSWs aged 18-45 years were randomly selected from seven Sex Workers Outreach Programme clinics in Nairobi and participated in baseline behavioural-biological surveys. Participants in this qualitative study were randomly selected from the Maisha Fiti study cohort and were interviewed between October 2019 and July 2020. Women described their lives from childhood, covering topics including sex work, violence and financial management. RESULTS: 48 out of 1003 Maisha Fiti participants participated in the in-depth qualitative interviews. FSWs described how physical and sexual violence, poverty and incomplete education in their childhood and adolescence intertwined with early pregnancy, marriage, intimate partner violence and relationship breakdown in their adolescence and early adulthood. The data analysis found clear syndemic relationships between these risk factors, particularly childhood violence, poverty and incomplete education and highlighted pathways leading to financial desperation and caring for dependents, and subsequent entry into sex work. Women perceived sex work as risky and most would prefer alternative work if possible, but it provided them with some financial independence and agency. CONCLUSIONS: This is the first study in Kenya to qualitatively explore the early lives of sex workers from a syndemic perspective. This method identified the pivotal points of (1) leaving school early due to poverty or pregnancy, (2) breakdown of early intimate relationships and (3) women caring for dependents on their own. Complex, multi-component structural interventions before these points could help increase school retention, reduce teenage pregnancy, tackle violence, support young mothers and reduce entry into sex work and the risk that it entails by expanding livelihood options.

Secondary infections in critically ill patients with viral pneumonia due to COVID-19 and influenza: a historical cohort study.

PURPOSE: To compare the incidence and nature of secondary infections (SI) between critically ill patients with viral pneumonia due to COVID-19 and seasonal influenza and explore the association between SI and clinical outcomes. METHODS: We conducted a historical cohort study of patients admitted to the intensive care unit (ICU) at two tertiary care centers during the first wave of the COVID-19 pandemic and patients admitted with influenza during the 2018-2019 season. The primary outcome was the rate of SI. Secondary outcomes included rates of ICU and in-hospital mortality, organ-support-dependent disease, and length of ICU and hospital stay. RESULTS: Secondary infections developed in 55% of 95 COVID-19 patients and 51% of 47 influenza patients (unadjusted odds ratio [OR], 1.16; 95% confidence interval [CI], 0.57 to 2.33). After adjusting for baseline differences between cohorts, there were no significant differences between the COVID-19 cohort and the influenza cohort (adjusted OR, 1.00; 95% CI, 0.41 to 2.44). COVID-19 patients with SI had longer ICU and hospital stays and duration of mechanical ventilation. The SI incidence was higher in COVID-19 patients treated with steroids than in those not treated with steroids (15/20, 75% vs 37/75, 49%). CONCLUSION: Secondary infections were common among critically ill patients with viral pneumonia including COVID-19. We found no difference in the incidence of SI between COVID-19 and influenza in our cohort study, but SI in patients with COVID-19 were associated with worse clinical outcomes and increased healthcare resource use. The small cohort size precludes any causal inferences but may provide a basis for future research.

RéSUMé: OBJECTIF: Comparer l'incidence et la nature des infections secondaires entre les patients gravement malades atteints de pneumonie virale due à la COVID-19 et ceux atteints de la grippe saisonnière et explorer l'association entre les infections secondaires et les issues cliniques. MéTHODE: Nous avons réalisé une étude de cohorte historique de patients admis à l'unité de soins intensifs (USI) dans deux centres de soins tertiaires pendant la première vague de la pandémie de COVID-19 et de patients admis pour la grippe au cours de la saison 2018-2019. Le critère d'évaluation principal était le taux d'infections secondaires. Les critères d'évaluation secondaires comprenaient les taux de mortalité à l'USI et à l'hôpital, les maladies nécessitant un support d'organes et la durée du séjour à l'USI et à l'hôpital. RéSULTATS: Des infections secondaires se sont développées chez 55 % des 95 patients atteints de COVID-19 et 51 % des 47 patients grippaux (rapport des cotes [RC] non ajusté, 1,16; intervalle de confiance [IC] à 95 %, 0,57 à 2,33). Après ajustement pour tenir compte des différences initiales entre les cohortes, aucune différence significative n'a été observée entre la cohorte de COVID-19 et la cohorte de grippe (RC ajusté, 1,00; IC 95 %, 0,41 à 2,44). Les patients atteints de COVID-19 atteints d'infections secondaires ont séjourné plus longtemps aux soins intensifs et à l'hôpital et la durée de la ventilation mécanique était plus longue pour ces patients. L'incidence d'infections secondaires était plus élevée chez les patients atteints de COVID-19 traités par stéroïdes que chez ceux non traités par stéroïdes (15/20, 75 % vs 37/75, 49 %). CONCLUSION: Les infections secondaires étaient fréquentes chez les patients gravement malades atteints de pneumonie virale, y compris de COVID-19. Nous n'avons observé aucune différence dans l'incidence d'infections secondaires entre les patients atteints de COVID-19 et ceux atteints de grippe dans notre étude de cohorte, mais les infections secondaires chez les patients atteints de COVID-19 étaient associées à de moins bonnes issues cliniques et à une utilisation accrue des ressources de soins de santé. La petite taille de la cohorte exclut toute inférence causale, mais peut fournir une base pour les recherches futures.