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.

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 .

Links between Household-Level Income-Generating Agricultural Intervention and the Psychological Well-Being of Adolescent Girls in Human Immunodeficiency Virus-Affected Households in Southwestern Kenya: A Qualitative Inquiry.

BACKGROUND: Adolescent girls may experience poor psychological well-being, such as social isolation, shame, anxiety, hopelessness, and despair linked to food insecurity. OBJECTIVES: This study aimed to investigate the experiences with and perceived effects of a household-level income-generating agricultural intervention on the psychological well-being of adolescent girls in human immunodeficiency virus (HIV)-affected households in southwestern Kenya. METHODS: We conducted 62 in-depth interviews with HIV-affected adolescent girls and caregiver dyads in Adolescent Shamba Maisha (NCT03741634), a sub-study of adolescent girls and caregivers with a household member participating in Shamba Maisha (NCT01548599), a multisectoral agricultural and finance intervention trial aimed to improve food security and HIV health indicators. Participants were purposively sampled to ensure diversity in terms of age and location. Data were audiotaped, transcribed, translated, and uploaded into Dedoose (Sociocultural Research Consultants, LLC) software for management. Data were analyzed thematically based on reports from Dedoose. RESULTS: We found evidence that a household-level structural intervention aimed at increasing food and financial security among persons living with HIV can contribute to better psychological well-being among adolescent girls residing in these households. The intervention also affected: 1) reduction of social isolation, 2) reduction of shame and stigma, 3) increased attendance and concentration in school, 4) improved caregiver mental health, and 5) reduced parental aggression and improved household communication. These associations were reported more commonly among those in the intervention arm than the control arm. CONCLUSIONS: This study extends existing research by demonstrating how multisectoral structural interventions delivered at a household level can improve the psychological well-being of adolescents. We recommend that future research test livelihood interventions designed specifically for adolescent girls that integrate food-security interventions with other elements to address the social and psychological consequences of food insecurity holistically. This trial was registered at clinicaltrials.gov as NCT03741634.

Preferences for Multipurpose Technology and Non-oral Methods of Antiretroviral Therapy Among Women Living With HIV in Western Kenya: A Survey Study.

Introduction: Understanding interests in and preferences for multipurpose technology (MPT) for the co-administration of contraception and antiretroviral therapy (ART) and alternative, non-oral ART methods among women living with HIV (WLHIV) is vital to successful implementation of future treatment options, such as long-acting injectable ART. Methods: Between May 2016 and March 2017 we conducted a cross-sectional telephone survey of 1,132 WLHIV of reproductive potential with prior experience using intermediate- or long-acting contraceptive methods in western Kenya. We present descriptive statistics and multinomial logistic regression to evaluate predictors of interest in specific MPT and non-oral ART methods. Results: Two-thirds (67%) reported interest in MPT, with the most common reason for interest being ease of using a single medication for both purposes of HIV treatment and pregnancy prevention (26%). Main reasons for lack of interest in MPT were need to stop/not use contraception while continuing ART (21%) and risk of side effects (16%). Important characteristics of MPT were effectiveness for pregnancy prevention (26%) and HIV treatment (24%) and less than daily dosing (19%). Important characteristics of non-oral ART methods were less than daily dosing (47%), saving time accessing ART (16%), and effectiveness of HIV treatment (15%). The leading preferred methods for both MPT and non-oral ART were injectables (50 and 54%) and implants (32 and 31%). Prior use of a contraceptive implant or injectable predicted interest in similar methods for both MPT and non-oral ART methods, while this relationship did not appear to vary between younger vs. older WLHIV. Discussion: Most WLHIV in western Kenya are interested in MPT for HIV treatment and contraception. Prior exposure to contraceptive implants or injectables appears to predict interest in similar methods of MPT and non-oral ART. Developers of MPT and non-oral ART methods should strongly consider WLHIV's preferences, including their changing reproductive desires.

Efficacy of single-dose HPV vaccination among young African women.

Background: Single-dose HPV vaccination, if efficacious, would be tremendously advantageous; simplifying implementation and decreasing costs. Methods: We performed a randomized, multi-center, double-blind, controlled trial of single-dose nonavalent (HPV 16/18/31/33/45/52/58/6/11) or bivalent (HPV 16/18) HPV vaccination compared to meningococcal vaccination among Kenyan women aged 15-20 years. Enrollment and six monthly cervical swabs and a month three vaginal swab were tested for HPV DNA. Enrollment sera were tested for HPV antibodies. The modified intent-to-treat (mITT) cohort comprised participants who tested HPV antibody negative at enrollment and HPV DNA negative at enrollment and month three. The primary outcome was incident persistent vaccine-type HPV infection by month 18. Results: Between December 2018 and June 2021, 2,275 women were randomly assigned and followed; 758 received the nonavalent HPV vaccine, 760 the bivalent HPV vaccine, and 757 the meningococcal vaccine; retention was 98%. Thirty-eight incident persistent infections were detected in the HPV 16/18 mITT cohort: one each among participants assigned to the bivalent and nonavalent groups and 36 among those assigned to the meningococcal group; nonavalent Vaccine Efficacy (VE) was 97.5% (95%CI 81.7-99.7%, p=<0.0001), and bivalent VE was 97.5% (95%CI 81.6-99.7%, p=<0.0001). Thirty-three incident persistent infections were detected in the HPV 16/18/31/33/45/52/58 mITT cohort: four in the nonavalent group and 29 in the meningococcal group; nonavalent VE for HPV 16/18/31/33/45/52/58 was 88.9% (95%CI 68.5-96.1%, p<0.0001). The rate of SAEs was 4.5-5.2% by group. Conclusions: Over the 18 month time-frame we studied, single-dose bivalent and nonavalent HPV vaccines were each highly effective in preventing incident persistent oncogenic HPV infection, similar to multidose regimens.

The role of food security in increasing adolescent girls' agency towards sexual risk taking: qualitative findings from an income generating agricultural intervention in southwestern Kenya.

BACKGROUND: Food insecurity is an important underlying driver of HIV risk and vulnerability among adolescents in sub-Saharan Africa. In this region, adolescents account for 80% of all new HIV infections. The primary purpose of this analysis is to understand perceived mechanisms for how a multisectoral agricultural intervention influenced sexual risk taking among HIV-affected adolescents in southwestern Kenya. METHODS: We conducted semi-structured, individual interviews with 34 adolescent-caregiver dyads who were participants in Adolescent Shamba Maisha (NCT03741634), a sub-study of adolescent girls and caregivers with a household member participating in the Shamba Maisha trial (NCT01548599), a multi-sectoral agricultural and microfinance intervention. Interviews were audiotaped, transcribed, translated, and analyzed using framework and interpretive description analysis methods. RESULTS: Adolescents receiving the Shamba Maisha intervention described no longer needing to engage in transactional sex or have multiple concurrent sexual partners as a way to meet their basic needs, including food. Key mechanisms for these effects include greater sexual agency among adolescent girls, and increased confidence and self-efficacy in overcoming existing reciprocity norms and sexual relationship power inequity; as well as staying in school. The intervention also increased caregiver confidence in talking about adolescent sexual reproductive health issues. In contrast, driven primarily by the need for food and basic needs, girls in the control arms described engaging in transactional sex, having multiple sexual partners, being unable to focus in school, getting pregnant or becoming HIV infected. CONCLUSION: These findings emphasize the need to address food insecurity as a part of structural interventions targeting adolescent HIV risk in low-resource countries. We recommend that future interventions build upon the Shamba Maisha model by combining sustainable agricultural production, with household level interventions that deliberately target gender norms that contribute to unequal power dynamics.

Political prioritization and the competing definitions of adolescent pregnancy in Kenya: An application of the Public Arenas Model.

BACKGROUND: Approximately one in every five adolescent girls in Kenya has either had a live birth or is pregnant with her first child. There is an urgent need to understand the language and symbols used to represent adolescent pregnancy, if the current trend in adolescent pregnancy is to be reversed. Agreement on the definition of a societal problem is an important precursor to a social issue's political prioritization and priority setting. METHODS: We apply the Public Arenas Model to appraise the environments, definitions, competition dynamics, principles of selection and current actors involved in problem-solving and prioritizing adolescent pregnancy as a policy issue. Using a focused ethnographic approach, we undertook semi-structured interviews with 14 members of adolescent sexual reproductive health networks at the national level and conducted thematic analysis of the interviews. FINDINGS: We found that existing definitions center around adolescent pregnancy as a "disease" that needs prevention and treatment, socially deviant behaviour that requires individual agency, and a national social concern that drains public resources and therefore needs to be regulated. These competing definitions contribute to the rarity of the topic achieving traction within the political agenda and contribute to conflicting solutions, such as lowering the legal age of consenting to sex, while limiting access to contraceptive information and services to minors. CONCLUSION: This paper provides a timely theoretical approach to draw attention to the different competing definitions and subsequent divergent interpretations of the problem of adolescent pregnancy in Kenya. Adolescent reproductive health stakeholders need to be familiar with the existing definitions and deliberately reframe this important social problem for better political prioritization and resource allocation. We recommend a definition of adolescent pregnancy that cuts across different arenas, and leverages already existing dominant and concurrent social and economic issues that are already on the agenda table.

Acceptability, adherence, and clinical outcomes, of amoxicillin dispersible tablets versus oral suspension in treatment of children aged 2-59 Months with pneumonia, Kenya: A cluster randomized controlled trial.

Amoxicillin dispersible tablet (DT) is now recommended by the WHO as a first-line drug for the treatment of pneumonia in children below 5 years. The study aim was to compare acceptability, adherence and clinical outcome of amoxicillin DT and amoxicillin oral suspension (OS) in the treatment of children aged 2-59 months with pneumonia in Kenya. We conducted a two-arm cluster randomized controlled trial and utilized quantitative methods. The community unit was the unit of randomization. Children aged 2-59 months with pneumonia were enrolled and treated with either amoxicillin DT or OS. Acceptability was defined as the perception of taste of medication as the same or better compared to other medicines and expression of willingness of caregivers to use DT/OS in future, adherence was measured based on the dose, frequency, and duration of treatment, and clinical outcome as complete resolution of symptoms without change of antibiotic treatment. Equivalence was defined as a difference of ≤8% between study arms. We found high levels of acceptability among both DT (93.9%) and OS (96.1%) arms (difference 2.3%, 90% CI -2.6-7.3). The objective measure of adherence on day four and the overall objective measure were significantly higher among children on DT compared to children on OS (88.7% vs. 41.5% (difference 47.2%, 90% CI 31.0-63.3) & 83.5% vs. 39% (difference 44.5%, 90% CI 27.9-60.9), respectively). Cure rates were high in both arms (DT (99.5%), OS (98.1%), difference 1.4%, 90% CI -0.2-3.2). There is reported better adherence to Amoxicillin DT compared to OS and equivalence in acceptability and clinical outcomes.

HIV serostatus and disclosure: implications for infant feeding practice in rural south Nyanza, Kenya.

BACKGROUND: The World Health Organization (WHO) recommends that HIV-infected women practice exclusive breastfeeding (EBF) for the first 6 months postpartum to reduce HIV transmission. The aim of this study was to determine the effects of HIV/AIDS knowledge and other psychosocial factors on EBF practice among pregnant and postpartum women in rural Nyanza, Kenya, an area with a high prevalence of HIV. METHODS: Data on baseline characteristics and knowledge during pregnancy, as well as infant feeding practices 4-8 weeks after the birth were obtained from 281 pregnant women recruited from nine antenatal clinics. Factors examined included: fear of HIV/AIDS stigma, male partner reactions, lack of disclosure to family members, knowledge of prevention of mother-to-child transmission (PMTCT) and mental health. In the analysis, comparisons were made using chi-squared and t-test methods as well as logistic multivariate regression models. RESULTS: There were high levels of anticipated stigma 171(61.2%), intimate partner violence 57(20.4%) and postpartum depression 29(10.1%) and low levels of disclosure among HIV positive women 30(31.3%). The most significant factors determining EBF practice were hospital delivery (aOR = 2.1 95% CI 1.14-3.95) HIV positive serostatus (aOR 2.5 95% CI 1.23-5.27), and disclosure of HIV-positive serostatus (aOR 2.9 95% CI 1.31-6.79). Postpartum depression and PMTCT knowledge were not associated with EBF (aOR 1.1 95% CI 0.47-2.62 and aOR 1.2 95% CI 0.64-2.24) respectively. CONCLUSIONS: Health care workers and counselors need to receive support in order to improve skills required for diagnosing, monitoring and managing psychosocial aspects of the care of pregnant and HIV positive women including facilitating disclosure to male partners in order to improve both maternal and child health outcomes.

Patient satisfaction with integrated HIV and antenatal care services in rural Kenya.

A cluster randomized controlled trial was initiated in Kenya to determine if full integration (FI) of HIV care, including HAART, into antenatal care (ANC) clinics improves health outcomes among HIV-infected women and exposed infants, compared to a non-integrated (NI) model. This article examines ANC clients' satisfaction with and preferences regarding HIV-integrated services. In this cross-sectional study, pregnant women attending five FI clinics (n=185) and four NI clinics (n=141) completed an interviewer-administered questionnaire following an ANC visit. By self-report, 55 women (17%) were HIV(+), 230 (71%) were HIV(-), and 40 (12%) did not know their HIV status. Among HIV-infected women, 79% attending FI clinics were very satisfied with their clinic visit compared to 54% of women attending NI clinics (P=0.044); no such difference was found among HIV-uninfected women. In multivariate analysis, overall satisfaction was also independently associated with satisfaction with administrative staff, satisfaction with health care providers, positive evaluation of wait time, and having encountered a receptionist. Full integration of HIV care into antenatal clinics can significantly increase overall satisfaction with care for HIV-infected women, with no significant decrease in satisfaction for HIV-uninfected women served in the same clinics.