Computational Microbiome Pharmacology Analysis Elucidates the Anti-Cancer Potential of Vaginal Microbes and Metabolites.

The vaginal microbiome's role in risk, progression, and treatment of female cancers has been widely explored. Yet, there remains a need to develop methods to understand the interaction of microbiome factors with host cells and to characterize their potential therapeutic functions. To address this challenge, we developed a systems biology framework we term the Pharmacobiome for microbiome pharmacology analysis. The Pharmacobiome framework evaluates similarities between microbes and microbial byproducts and known drugs based on their impact on host transcriptomic cellular signatures. Here, we apply our framework to characterization of the Anti-Gynecologic Cancer Vaginal Pharmacobiome. Using published vaginal microbiome multi-omics data from the Partners PrEP clinical trial, we constructed vaginal epithelial gene signatures associated with each profiled vaginal microbe and metabolite. We compared these microbiome-associated host gene signatures to post-drug perturbation host gene signatures associated with 35 FDA-approved anti-cancer drugs from the Library of Integrated Network-based Cellular Signatures database to identify vaginal microbes and metabolites with high statistical and functional similarity to these drugs. We found that Lactobacilli and their metabolites can regulate host gene expression in ways similar to many anti-cancer drugs. Additionally, we experimentally tested our model prediction that taurine, a metabolite produced by L. crispatus, kills cancerous breast and endometrial cancer cells. Our study shows that the Pharmacobiome is a powerful framework for characterizing the anti-cancer therapeutic potential of vaginal microbiome factors with generalizability to other cancers, microbiomes, and diseases.

Acceptability of six-monthly PrEP dispensing supported with interim HIV self-testing to simplify PrEP delivery in Kenya: findings from qualitative research.

BACKGROUND: In Africa, dispensing oral HIV pre-exposure prophylaxis (PrEP) within already strained public health facilities has led to prolonged waiting periods and suboptimal experiences for clients. We sought to explore the acceptability of dispensing PrEP semiannually with interim HIV self-testing (HIVST) versus quarterly PrEP dispensing with clinic-based HIV testing to optimize clinic-delivered PrEP services. METHODS: We conducted a qualitative study within a non-inferiority individual-level randomized controlled trial testing the effect of six-monthly PrEP dispensing with HIVST compared to the standard-of-care three-monthly PrEP dispensing on PrEP clinical outcomes in Kenya (ClinicalTrials.gov: NCT03593629). Eligible participants were ≥ 18 years, refilling PrEP for the first time, and either in an HIV serodifferent relationship (men and women) or singly enrolled (women only). A subset of participants in the intervention group completed serial in-depth interviews (IDIs) at enrollment, six months, and 12 months. We utilized stratified purposive sampling to ensure representation across participant groups. We analyzed our qualitative data thematically using a combination of inductive and deductive approaches, the latter guided by the Theoretical Framework of Acceptability (TFA). RESULTS: Between May 2018 and June 2021, we conducted 120 serial IDIs with 55 participants; 64% (35/55) were in a serodifferent relationship, 64% (35/55) were women, and the median age was 32 years (IQR 27-40). Overall, participants found this novel PrEP delivery model highly acceptable; it was well-liked, private (TFA construct: affective attitude), and less burdensome (TFA construct: burden) compared to standard PrEP delivery. Additionally, participants were confident in their ability to participate in the intervention (TFA construct: self-efficacy). Some participants, however, highlighted model disadvantages, including fewer opportunities for in-person counseling and potentially less accurate HIV testing (TFA construct: opportunity costs). Ultimately, most participants reported that the intervention allowed them to achieve their HIV prevention goals (TFA construct: perceived effectiveness) and that their confidence in at-home HIVST and PrEP continuation increased following each semiannual clinic visit. CONCLUSIONS: Semiannual PrEP clinic visits supported with six-monthly drug dispensing and interim HIVST was acceptable among PrEP users who experienced the intervention in Kenya. More comprehensive pre-intervention counseling and training on HIVST may help alleviate the client concerns presented, which were often resolved over time with intervention experience.

True and false positive HIV point of care test results in a prospective multinational study of at-risk African women: implications for large-scale repeat HIV testing in HIV prevention programs.

BACKGROUND: Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, though false (both negative and positive) results are expected to occur. SETTING: We assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using three contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia. METHODS: HIV serologic testing was conducted quarterly using two parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and ribonucleic acid (RNA). RESULTS: 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (i.e., one negative and one positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing but six (9.7%) had dually-positive rapid results and four (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%. CONCLUSION: Although the majority of rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low.

HIV Self-Testing for Efficient PrEP Delivery Is Highly Acceptable and Feasible in Public Health HIV Clinics in Kenya: A Mixed Methods Study.

HIV self-testing (HIVST) has the potential to reduce barriers associated with clinic-based preexposure prophylaxis (PrEP) delivery. We conducted a substudy nested in a prospective, pilot implementation study evaluating patient-centered differentiated care services. Clients chose either a blood-based or oral fluid HIVST kit at the first refill visit. Data were abstracted from program files and surveys were administered to clients. We purposively sampled a subset of PrEP clients and their providers to participate in in-depth interviews. We surveyed (n = 285). A majority (269/285, 94%) reported HIV risk. Blood-based HIVST was perceived as easy to use (76/140, 54%), and (41/140, 29%) perceived it to be more accurate. Oral fluid-based HIVST was perceived to be easy to use (95/107, 89%), but almost all (106/107, 99%) perceived it as less accurate. HIVST improved privacy, reduced workload, and saved time. HIVST demonstrates the potential to streamline facility-based PrEP care in busy African public health facilities.

Differentiated Service Delivery Models for Maintaining HIV Treatment and Prevention Services During Crisis and Disease Outbreaks: Lessons from the COVID-19 Pandemic.

PURPOSE OF REVIEW: This review summarizes differentiated service delivery (DSD) models for HIV treatment and prevention that have been adapted for maintaining continuity of services during the COVID-19 pandemic and proposes strategies for sustaining their benefits now and during future disruptions. RECENT FINDINGS: The COVID-19 pandemic resulted in an overburdened and disrupted health system, forcing countries to adopt and/or scale up DSD models for HIV services. While initially implemented as emergency measures, these models evolved and were refined over time to fit recipient needs ensuring continued HIV treatment and prevention services with minimal health system impact. Successful models employed task shifting, community-based delivery models, multimonth scripting and dispensing, and telehealth for remote consultation. DSD models enabled HIV services globally to be maintained during the COVID-19 pandemic. Though these models and adaptations were critical in addressing health gaps and disruptions caused by the pandemic, they were beneficial in improving efficiency and access to client-centered services and should be sustained.

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility.

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent in reproductive-age women worldwide. Adverse outcomes associated with BV include an increased risk of sexually acquired Human Immunodeficiency Virus (HIV), yet the immunological mechanisms underlying this association are not well understood. To investigate BV driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and peripheral blood mononuclear cells (PBMC). Immunofluorescence analysis of genital mucosal tissues revealed a reduced density of CD3+CD4+CCR5+ cells in the VT lamina propria of individuals with compared to those without BV (median 243.8 cells/mm2 BV- vs 106.9 cells/mm2 BV+, p=0.043). High-parameter flow cytometry of VT biopsies revealed an increased frequency in individuals with compared to those without BV of dysfunctional CD39+ conventional CD4+ T cells (Tconv) (median frequency 15% BV- vs 30% BV+, padj=0.0331) and tissue-resident CD69+CD103+ Tconv (median frequency 24% BV- vs 38% BV+, padj=0.0061), previously reported to be implicated in HIV acquisition and replication. Our data suggests that BV elicits diverse and complex VT T cell alterations and expands on potential immunological mechanisms that may promote adverse outcomes including HIV susceptibility.

Impact of a point-of-care urine tenofovir assay on adherence to HIV pre-exposure prophylaxis among women in Kenya: a randomised pilot trial.

BACKGROUND: Adherence challenges with oral tenofovir-based pre-exposure prophylaxis (PrEP) are common. We developed a point-of-care assay to objectively assess tenofovir in urine and conducted a pilot trial examining the impact of counselling informed by use of this urine assay on long-term PrEP adherence. METHODS: This randomised trial enrolled women not in serodiscordant partnerships 3 months after PrEP initiation at the Kenya Medical Research Institute to compare standard-of-care adherence counselling versus counselling informed by the urine assay (urine-test counselling group) every 3 months for 12 months. In the standard of care group, urine samples were stored and tested at study end without participant feedback. Here we report the adherence primary outcome of hair concentrations of tenofovir at 12 months as a long-term metric (undetectable levels defined long-term non-adherence), as well as urine concentrations of tenofovir at each visit as a short-term adherence metric and acceptability of the assay assessed by quantitative surveys. Data were analysed by randomisation group. This completed trial was registered with ClinicalTrials.gov (NCT03935464). FINDINGS: From March 17, 2021 to Jan 18, 2022 we enrolled 49 women in the urine-test counselling group and 51 in the standard of care group; retention was 86 (86%) of 100. Nine (21%) of 42 in the urine-test counselling group had hair samples at 12 months with tenofovir concentrations below the limit of quantification compared with 15 (37%) of 41 in the standard of care group. The relative odds of long-term non-adherence in the standard of care group compared with urine-test counselling were 3·53 (95% CI 1·03-12·03; p=0·044). Pre-intervention, urine tenofovir was detectable in 65% in the urine-test counselling group and 71% in the standard of care group (p=0·68). At 12 months, 31 (72%) of 43 in the intervention group had detectable urine tenofovir compared with 19 (45%) of 42 in the standard of care group (p=0·0015). 40 (93%) of 43 participants liked the test very much and only one disliked the test. One participant in the standard of care group was withdrawn at the 6-month visit due to HIV seroconversion. INTERPRETATION: A low-cost urine tenofovir assay to inform PrEP counselling resulted in improvement in both short-term and long-term metrics of adherence. This urine tenofovir assay could help to improve long-term PrEP adherence. FUNDING: National Institute of Allergy and Infectious Diseases and National Institutes of Health.

Establishing adherence-concentration-efficacy thresholds of TDF-FTC pre-exposure prophylaxis for HIV prevention in African women: a protocol for the Women TDF-FTC Benchmark Study.

Background: Oral pre-exposure prophylaxis (PrEP) using co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) is a potent HIV prevention method for men and women, with its efficacy highly dependent on adherence. A pivotal HIV efficacy study combined with a directly observed pharmacological study defined the thresholds for HIV protection in men who have sex with men (MSM), which are the keys to PrEP promotion and development of new PrEP agents. For African women at risk for HIV and belonging to a priority group considered due to disproportionately high incident HIV infections, the variable adherence in PrEP clinical trials and the limited pharmacologic data have resulted in a lack of clarity about the PrEP adherence required for HIV protection. We propose a study to quantify the adherence-concentration-efficacy thresholds of TDF/FTC PrEP among African cisgender women to inform decisions about optimal PrEP dosing and adherence for HIV protection. Methods: We randomized 45 low-risk HIV-uninfected African women, aged 18-30 years old, to directly observe the TDF/FTC PrEP of two, four, or seven doses per week for 8 weeks. A complementary age-matched pregnant women cohort at high risk of HIV, who will receive seven doses per week, was recruited (N = 15) with the primary aim of establishing benchmark concentrations in dried blood spots and peripheral blood mononuclear cells. Plasma, whole blood (WB), urine, hair, vaginal fluid, and vaginal tissue (non-pregnant women only) were archived for future testing. Drug concentrations were measured using methods validated for each biological matrix. Pharmacokinetic models were fitted to drug concentrations to quantify concentration-adherence thresholds. To define the drug concentrations associated with HIV protection, we applied the newly defined thresholds from the primary pharmacologic trial to the subset of women randomized to TDF/FTC or TDF in the Partners PrEP Study with the drug concentration assessed in plasma and WB samples. Multiple imputation was used to construct a data set with drug concentrations at each visit when an HIV test was performed for the entire cohort, replicating the work for MSM. Discussion: The proposed study generated the first African women-specific TDF-PrEP adherence-concentration-efficacy thresholds essential for guiding the accurate interpretation of TDF/FTC PrEP programs and clinical trials of novel HIV prevention products using TDF/FTC as an active control. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT05057858).

The Effects of the COVID-19 Pandemic on Healthcare Providers' Mental Health: Experiences at Kenyatta National Hospital, Kenya.

BACKGROUND: In 2020, healthcare providers were expected to provide care to individuals with coronavirus disease 2019 (COVID-19), putting them at risk of acquiring COVID-19. The possibility of acquiring poorly understood infectious diseases while providing care may have an impact on the mental health of providers. We conducted a study to explore the effects of COVID-19 on the mental health of healthcare providers. METHODS: Between April and August 2021, we conducted in-depth interviews with 60 healthcare providers in the infectious disease unit (IDU) and other units of the hospital (non-IDU). The healthcare providers completed an online self-administered survey form with demographic data (age, sex, average income, and known contact with a COVID-19 patient). We used semi-structured interview guides to understand the healthcare providers' lived experiences of stress, anxiety, depression, and their associated factors. We transcribed the interviews verbatim and coded and analyzed the transcripts to derive thematic concepts related to mental health experiences. RESULTS: The healthcare providers had a median age of 37 years [IQR 20.0-58.0], and 56.7% were female, 30.0% nurses, 18.3% medical doctors, and 11.7% laboratory technologists. The healthcare providers reported increased stress during the pandemic, attributed to the high demand for patient care, changes in social life, and fear of COVID-19 infection. They also reported experiences of anxiety and depression as a result of limited knowledge at the beginning of the pandemic and the perception that "COVID-19 resulted in death". Testing positive for COVID-19, high exposure to COVID-19 risks, and the death of patients and colleagues reportedly affected the healthcare providers' mental health. Additionally, the healthcare providers reported mental health support through debriefing meetings, peer-to-peer support, and psychological counseling, with privacy and confidentiality concerns. CONCLUSIONS: Healthcare providers faced mental health issues such as stress and anxiety while taking care of COVID-19 patients. An effective mental health response requires institutional practices that address context-specific challenges such as privacy and confidentiality.

Confirmatory Factor Analysis and Validation of the Sexual and Reproductive Empowerment Scale for Adolescents and Young Adults in Kenya.

Understanding the levels of power that adolescent girls and young women exercise in their sexual and reproductive lives is imperative to inform interventions to help them meet their goals. We implemented an adapted version of the Sexual and Reproductive Health Empowerment (SRE) Scale for Adolescents and Young Adults among 500 adolescent girls and young women aged 15-20 in Kisumu, Kenya. We used confirmatory factor analysis (CFA) to assess factor structure, and logistic regression to examine construct validity through the relationship between empowerment scores and ability to mitigate risk of undesired pregnancy through consistent contraceptive use. Participants had a mean age of 17.5, and most were students (61 percent), were currently partnered (94 percent), and reported having sex in the past 3 months (70 percent). The final, 26-item CFA model had acceptable fit. All subscales had Cronbach's alpha scores >0.7, and all items had rotated factor loadings >0.5, indicating good internal consistency and robust factor-variable associations. The total SRE-Kenya (SRE-K) score was associated with increased odds of the consistent method used in the past three months (adjusted odds ratio: 1.98, 95 percent CI: 1.29-3.10). The SRE-K scale is a newly adapted and valid measure of sexual and reproductive empowerment specific to adolescent girls and young women in an East African setting.

Antibodies from chlamydia-infected individuals facilitate phagocytosis via Fc receptors.

Non-neutralizing functions of antibodies, including phagocytosis, may play a role in Chlamydia trachomatis (CT) infection, but these functions have not been studied and assays are lacking. We utilized a flow-cytometry-based assay to determine whether serum samples from a well-characterized cohort of CT-infected and naïve control individuals enhanced phagocytosis via Fc-receptor-expressing THP-1 cells, and whether this activity correlated with antibody titers. Fc-receptor-mediated phagocytosis was detected only in CT+ donors. Phagocytosis generally did not correlate well with antibody titer. In addition, we found that complement from both CT+ and negative individuals enhanced phagocytosis of CT into primary neutrophils. These results suggest that anti-CT antibodies can have functions that are not reflected by titer. This method could be used to quantitively measure Fc-receptor-mediated function of anti-CT antibodies or complement activity and could reveal new immune correlates of protection.

The Effect of Stigma on Family Planning and HIV Pre-exposure Prophylaxis Decisions of Young Women Accessing Post-Abortion Care in Kenya.

Adolescent girls and young women (AGYW) in Eastern and Southern Africa face parallel epidemics of unintended pregnancy and HIV. Their sexual health decisions are often dominated by intersecting stigmas. In an implementation science project integrating delivery of daily, oral pre-exposure prophylaxis (PrEP) for HIV prevention into 14 post-abortion care (PAC) clinics in Kenya, we enrolled a subset of PrEP initiating AGYW (aged 15 to 30 years) into a research cohort. Utilizing log binomial models, we estimated the effect of PrEP stigma on PrEP continuation (measured via self-report and urine assay for tenofovir) and abortion stigma on contraceptive initiation. Between April 2022 and February 2023, 401 AGYW were enrolled after initiating PrEP through their PAC provider, of which 120 (29.9%) initiated highly-effective contraception. Overall, abortion and PrEP stigmas were high in this cohort. Abortion stigma was more prevalent among those that were adolescents, unmarried, and reported social harm. Among 114 AGYW returning for the month 1 follow-up visit, 83.5% reported continuing PrEP and 52.5% had tenofovir detected. In this subset, higher levels of PrEP stigma were significantly associated with greater likelihood of PrEP adherence, but not PrEP continuation. For abortion stigma, greater scores in the subdomain of isolation were significantly associated with greater likelihood of initiating a highly-effective contraception, while greater scores in the subdomain of community condemnation were significantly associated with reduced likelihood of initiating a highly-effective contraception. Given the burden of stigma documented by our work, PAC settings are a pivotal space to integrate stigma-informed counseling and to empower young women to optimize contraceptive and PrEP decisions.

Acceptability and feasibility of long-term, real-time electronic adherence monitoring of HIV pre-exposure prophylaxis (PrEP) use among young women in Kenya: A mixed methods study.

Real-time electronic adherence monitoring involves "smart" pill boxes that record and monitor openings as a proxy for pill taking and may be useful in understanding and supporting PrEP use; however, acceptability and/or feasibility for PrEP users is uncertain. We sought to understand the experiences of using a real-time electronic adherence monitor for PrEP delivery among young women in Kisumu and Thika, Kenya. We used the Wisepill device to monitor PrEP use among 18-24-year-old women for two years. Half of the participants were randomized to also receive SMS adherence reminders (daily or as needed for missed doses). We assessed acceptability quantitatively and qualitatively according to the four constructs of Unified Theory of Acceptance and Use of Technology (UTAUT): performance expectancy, effort expectancy, social influence, and facilitating conditions. We assessed feasibility by monitor functionality during periods of PrEP use. We analyzed quantitative data descriptively and compared by site and over time; qualitative data were analyzed inductively and deductively. The median age was 21 years (IQR 19-22), median education was 12 years (IQR 10-13), 182 (53%) had disclosed PrEP use, and 55 (16%) reported recent intimate partner violence. Most participants reported high levels of usefulness and high interest in using the monitor with few problems or worries reported throughout follow-up. Feasibility was high overall with some differences by site (96% functional monitor days in Kisumu vs 88% in Thika). Few monitors were reported lost (N = 29; 8%) or dysfunctional (N = 11; 3%). In qualitative interviews, electronic monitoring was perceived as useful because it supported privacy, confidentiality, easy storage, and PrEP adherence. Effort was generally considered low. Participants expressed some concern for stigma from monitor and/or PrEP use. Facilitating conditions involved the monitor size, color, and battery life. Overall, real-time electronic adherence monitoring was a highly acceptable and feasible approach to understand PrEP adherence among young women in a sub-Saharan African setting.

Effect of differentiated direct-to-pharmacy PrEP refill visits supported with client HIV self-testing on clinic visit time and early PrEP continuation.

INTRODUCTION: Delivery of oral pre-exposure prophylaxis (PrEP) is being scaled up in Africa, but clinic-level barriers including lengthy clinic visits may threaten client continuation on PrEP. METHODS: Between January 2020 and January 2022, we conducted a quasi-experimental evaluation of differentiated direct-to-pharmacy PrEP refill visits at four public health HIV clinics in Kenya. Two clinics implemented the intervention package, which included direct-to-pharmacy for PrEP refill, client HIV self-testing (HIVST), client navigator, and pharmacist-led rapid risk assessment and dispensing. Two other clinics with comparable size and client volume served as contemporaneous controls with the usual clinic flow. PrEP continuation was evaluated by visit attendance and pharmacy refill records, and time and motion studies were conducted to determine time spent in the clinics. Dried blood spots were collected to test for tenofovir-diphosphate (TFV-DP) at random visits. We used logistic regression to assess the intervention effect on PrEP continuation and the Wilcoxon rank sum test to assess the effect on clinic time. RESULTS: Overall, 746 clients were enrolled, 366 at control clinics (76 during pre-implementation and 290 during implementation phase), and 380 at direct-to-pharmacy clinics (116 during pre-implementation and 264 during implementation phase). Prior to implementation, the intervention and control clinics were comparable on client characteristics (female: 51% vs. 47%; median age: 33 vs. 33 years) and PrEP continuation (35% vs. 37% at 1 month, and 37% vs. 39% at 3 months). The intervention reduced total time spent at the clinic by 35% (median of 51 minutes at control vs. 33 minutes at intervention clinics; p<0.001), while time spent on HIV testing (20 vs. 20 minutes; p = 0.50) and pharmacy (8 vs. 8 minutes; p = 0.8) was unchanged. PrEP continuation was higher at intervention versus the control clinics: 45% versus 33% at month 1, 34% versus 25% at month 3 and 23% versus 16% at month 6. TFV-DP was detected in 85% (61/72) of samples, similar by the study group (83% vs. 85%). CONCLUSIONS: A client-centred PrEP delivery approach with direct-to-pharmacy PrEP refill visits plus client HIVST significantly reduced clinic visit time by more than one-third and improved PrEP continuation in public health HIV clinics in Kenya.

Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials.

BACKGROUND: The first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed greater than 97% efficacy against persistent HPV16 and HPV18 infection at 36 months among women in Kenya. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), the first randomised trial of the single- dose regimen in girls aged 9-14 years, the target age range for vaccination, with those after one dose of the same vaccine in KEN SHE. METHODS: In the DoRIS trial, 930 girls aged 9-14 years in Tanzania were randomly assigned to one, two, or three doses of the 2-valent vaccine (Cervarix) or the 9-valent vaccine (Gardasil-9). The proportion seroconverting and geometric mean concentrations (GMCs) at month 24 after one dose were compared with those in women aged 15-20 years who were randomly assigned to one dose of the same vaccines at the same timepoint in KEN SHE. Batched samples were tested together by virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial:KEN SHE) was predefined as a lower bound of the 95% CI less than 0·50. FINDINGS: Month 24 HPV16 and HPV18 antibody GMCs in DoRIS were similar or higher than those in KEN SHE. 2-valent GMC ratios were 0·90 (95% CI 0·72-1·14) for HPV16 and 1·02 (0·78-1·33) for HPV18. 9-valent GMC ratios were 1·44 (95% CI 1·14-1·82) and 1·47 (1·13-1·90), respectively. Non-inferiority of antibody GMCs and seropositivity was met for HPV16 and HPV18 for both vaccines. INTERPRETATION: HPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination. FUNDING: The UK Department of Health and Social Care, the Foreign, Commonwealth, & Development Office, the Global Challenges Research Fund, the UK Medical Research Council and Wellcome Trust Joint Global Health Trials scheme, the Bill and Melinda Gates Foundation, the US National Cancer Institute; the US National Institutes of Health, and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases. TRANSLATION: For the KiSwahili translation of the abstract see Supplementary Materials section.

Structural influences on delivery and use of oral HIV PrEP among adolescent girls and young women seeking post abortion care in Kenya.

Background: Adolescent girls and young women (AGYW) in East and southern Africa experience a disproportionate burden of HIV incidence. Integrating HIV pre-exposure prophylaxis (PrEP) within existing programs is a key component of addressing this disparity. Methods: We evaluated an oral PrEP program integrated into post-abortion care (PAC) in Kenya from March 2021 to November 2022. Technical advisors trained staff at PAC clinics on PrEP delivery, abstracted program data from each clinic, and collected data on structural characteristics. Utilizing a modified Poisson regression, we estimated the effect of structural factors on the probability of PrEP offer and uptake. Findings: We abstracted data on 6877 AGYW, aged 15-30 years, across 14 PAC clinics. PrEP offers were made to 57.4% of PAC clients and 14.1% initiated PrEP. Offers were associated with an increased probability at clinics that had consistent supply of PrEP (relative risk (RR):1.81, 95% CI: 1.1-2.95), inconsistent HIV testing commodities (RR: 1.89, 95% CI: 1.29-2.78), had all providers trained (RR: 1.65, 95% CI: 1.01, 2.68), and were public (RR: 1.89, 95% CI: 1.29-2.78). These same factors were associated with PrEP uptake: consistent supply of PrEP (RR: 2.71, 95% CI: 1.44-5.09), inconsistent HIV testing commodities (RR: 2.55, 95% CI: 1.39-4.67), all providers trained (RR: 2.61, 95% CI: 1.38-4.92), and were public (RR: 2.55, 95% CI: 1.39-4.67). Interpretation: Greater success with integration of HIV prevention into reproductive health services will likely require investments in systems, such as human resources and PrEP and HIV testing commodities, to create stable availability and ensure consistent access. Funding: PrEDIRA 2 was supported by funding from Children's Investment Fund Foundation (R-2001-04433). Ms. Zia was funded by the NIH Ruth L. Kirchstein pre-doctoral award (5F31HD105494-02) and Dr. Heffron was funded by National Institute of Mental Health (K24MH123371).

Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results.

Cervical cancer burden is high where prophylactic vaccination and screening coverage are low. We demonstrated in a multicenter randomized, double-blind, controlled trial that single-dose human papillomavirus (HPV) vaccination had high vaccine efficacy (VE) against persistent infection at 18 months in Kenyan women. Here, we report findings of this trial through 3 years of follow-up. Overall, 2,275 healthy women aged 15-20 years were recruited and randomly assigned to receive bivalent (n = 760), nonavalent (n = 758) or control (n = 757) vaccine. The primary outcome was incident-persistent vaccine type-specific cervical HPV infection. The primary evaluation was superiority analysis in the modified intention-to-treat (mITT) HPV 16/18 and HPV 16/18/31/33/45/52/58 cohorts. The trial met its prespecified end points of vaccine type-specific persistent HPV infection. A total of 75 incident-persistent infections were detected in the HPV 16/18 mITT cohort: 2 in the bivalent group, 1 in the nonavalent group and 72 in the control group. Nonavalent VE was 98.8% (95% CI 91.3-99.8%, P < 0.0001) and bivalent VE was 97.5% (95% CI 90.0-99.4%, P < 0.0001). Overall, 89 persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: 5 in the nonavalent group and 84 in the control group; nonavalent VE was 95.5% (95% CI 89.0-98.2%, P < 0.0001). There were no vaccine-related severe adverse events. Three years after vaccination, single-dose HPV vaccination was highly efficacious, safe and conferred durable protection. ClinicalTrials.gov no. NCT03675256 .

The Acceptability of Pharmacy-Based HPV Vaccination in Western Kenya among Pharmacy Clients and Providers.

Vaccine coverage for the human papillomavirus (HPV) remains low globally, and differentiated models of vaccine delivery are needed to expand access. Pharmacy-based models of the HPV vaccination may engage women who could benefit. We assessed the acceptability of such a model among pharmacy clients and providers at 20 private pharmacies in Kisumu County, Kenya. In questionnaires, participants (≥18 years) were asked the extent they agreed (5-point scale) with statements that assessed different acceptability component constructs outlined in the Theoretical Framework of Acceptability (TFA). From March to June 2022, 1500 pharmacy clients and 40 providers were enrolled and completed questionnaires. Most clients liked the intervention (TFA: affective attitude; 96%, 1435/1500) and did not think it would be hard to obtain (TFA: burden; 93%, 1399/1500). All providers agreed the intervention could reduce HPV infection (TFA: perceived effectiveness) and felt confident they could deliver it (TFA: self-efficacy). Among the clients who had received or were planning to receive the HPV vaccine in the future, half (50%, 178/358) preferred a pharmacy-based HPV vaccination. In this study, most Kenyan pharmacy clients and providers perceived a pharmacy-delivered HPV vaccination as highly acceptable; however, more research is needed to test the feasibility and effectiveness of this novel vaccine delivery model in Africa.

Longitudinal assessment of bacterial vaginosis prior to and during incident pregnancy: an observational study in Kenyan adolescent girls and young women.

OBJECTIVE: To determine bacterial vaginosis (BV) status at multiple time points among adolescent girls and young women (AGYW) and assess the impact of pregnancy on their BV status. DESIGN: Longitudinal cohort study. SETTING: Thika, Kenya. PARTICIPANTS: AGYW aged 16-20 years enrolled prior to first sex or reporting only a single lifetime partner. MAIN OUTCOME MEASURES: The primary outcome was relative risk (RR) of BV during pregnancy compared with before pregnancy by analysing longitudinal trends in BV over time. BV risk was estimated using Poisson regression models. RESULTS: A total of 121 AGYW became pregnant in the parent cohort and had BV results before, during or after pregnancy. Point prevalence of BV was 11.0% at visits >12 months pre-pregnancy, 13.0% at 3-12 months pre-pregnancy, 22.1% at <3 months pre-pregnancy and 13.4% during pregnancy. Compared with visits during pregnancy, RR of BV was 1.65 (95% CI: 1.00 to 2.71; p=0.05) at visits <3 months pre-pregnancy, 0.97 (95% CI: 0.62 to 1.52; p=0.90) at visits 3-12 months pre-pregnancy and 0.82 (95% CI: 0.44 to 1.53; p=0.53) at visits 12 months pre-pregnancy. An adjusted analysis including age, income, residence, date of first sex, recent sexual activity and positive sexually transmitted infection test resulted in small changes in risk estimates, with adjusted RR of BV of 1.66 (95% CI: 1.04 to 2.67; p=0.04) at visits <3 months pre-pregnancy compared with visits during pregnancy. CONCLUSIONS: BV risk during pregnancy was lower than during the immediate pre-pregnancy period. Hormonal changes in pregnancy may reduce BV.

Adaptation of the sexual and reproductive empowerment scale for adolescents and young adults in Kenya.

Measuring empowerment is critical to understanding the level of control adolescents and young adults (AYA) have over their sexual and reproductive health (SRH) behaviors, and could provide a key window into addressing their unique SRH needs. We adapted the Sexual and Reproductive Empowerment (SRE) scale for AYA for use in an East African context. This multi-method qualitative study sampled 15-23 year-old female adolescents and young adults in Kisumu, Kenya. We conducted in-depth interviews (n = 30) and analyzed transcripts with an inductive, constant comparison approach. Empowerment domains were integrated with Kabeer's (1999) framework in a conceptual model, which we referenced to revise the original and develop new scale items. Items underwent expert review, and were condensed and translated through team-based consensus-building. We evaluated content validity in cognitive interviews (n = 25), during which item phrasing and word choice were revised to generate an adapted SRE scale. Participants (n = 55) had a median age of 18 (range 16-23), and 75% were under 19 years. We categorize three types of adaptations to the SRE scale: new item generation, item revision, and translation/linguistic considerations. We developed nine new items reflecting AYA's experiences and new domains of empowerment that emerged from the data; new domains relate to self-efficacy in accessing sexual and reproductive health care, and how material needs are met. All items were revised and translated to echo concepts and language relevant to participants, navigating the multilingualism common in many African countries. Centering the voices of female Kenyan AYA, this study provides insight into measuring the latent construct of adolescent sexual and reproductive empowerment in an East African setting, and supports the adapted SRE scale's content validity for Kenya. We detail our multi-method, theory-driven approach, contributing to limited methods guidance for measure adaptation across contexts and among diverse adolescent populations.