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The Project YES! clinic-based peer mentoring program was a randomized controlled trial (RCT) conducted among 276 youth from four HIV clinics to test the impact of the program on promoting HIV self-management and reducing internalized stigma among youth living with HIV (ages 15–24 years) in Ndola, Zambia. We conducted a qualitative sub-study involving in-depth interviews with 40 intervention youth participants (21 female, 19 male) to explore their experiences with Project YES! which included: an orientation meeting led by a healthcare provider, monthly individual and group counseling sessions over six months, and three optional caregiver group sessions. Using baseline RCT data, we used maximum variation sampling to purposively select youth by sex, age, change in virologic results between baseline and midline, and study clinic. A four-person team conducted thematic coding. Youth described their increased motivation to take their HIV care seriously due to Project YES!, citing examples of improvements in ART adherence and for some, virologic results. Many cited changes in behavior in the context of greater feelings of self-worth and acceptance of their HIV status, resulting in less shame and fear associated with living with HIV. Youth also attributed Project YES! with reducing their sense of isolation and described Project YES! youth peer mentors and peers as their community and "family." Findings highlight that self-worth and personal connections play a critical role in improving youths' HIV outcomes. Peer-led programs can help foster these gains through a combination of individual and group counseling sessions. Greater attention to the context in which youth manage their HIV, beyond medication intake, is needed to reach global HIV targets. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the leading cause of cancer death in Zambia, where HIV prevalence is also high (11.3%). HIV heightens the risk of developing and dying from cervical cancer. The human papillomavirus (HPV) vaccine can prevent 90% of cervical cancers, and in Zambia is recommended for adolescent girls ages 14–15 years, including those with HIV. Currently they mainly deliver HPV vaccination via school-based campaigns, which may exclude the most vulnerable adolescents—those out-of-school or who irregularly attend. Adolescents living with HIV (ALHIV) are more likely to have these vulnerabilities. Further, school-based campaigns are not tailored to the WHO-recommended HPV vaccination schedule for ALHIV (3 versus 2 doses). Integrating HPV vaccination into routine care in adolescent HIV clinics may ensure that ALHIV have access to vaccine at the WHO-recommended schedule. Such integration requires a multilevel approach, stakeholder engagement, and diversified implementation strategies, given known challenges of providing the HPV vaccine in LMICs, including Zambia. Methods: Our study aims to integrate HPV vaccination into routine care in adolescent HIV clinics. To achieve success, we will co-design a package of implementation strategies using a previously successful implementation research approach developed for cervical cancer prevention in LMICs: the Integrative Systems Praxis for Implementation Research (INSPIRE). INSPIRE is a novel, comprehensive approach to develop, implement, and evaluate implementation science efforts. Following key elements of INSPIRE, our specific aims are to: 1) Identify the unique multilevel contextual factors (barriers and facilitators) across HIV settings (rural, urban, peri-urban) that influence HPV vaccine uptake; 2) Use Implementation Mapping to translate stakeholder feedback and findings from Aim 1 into a package of implementation strategies to integrate HPV vaccine into HIV clinics; 3) Conduct a Hybrid Type 3 effectiveness-implementation trial to evaluate the package of multilevel implementation strategies for integrating HPV vaccine into HIV clinics. Discussion: Our research team has strong support, technical expertise, and resources (e.g., vaccines) from the Zambian Ministry of Health; and political will for scale-up. This stakeholder-based implementation model has the potential to be transported to HIV clinics across Zambia and serve as a model to address cancer prevention priorities for those with HIV in other LMICs. Trial registration: To be registered prior to Aim 3, when implementation strategies finalized. [ABSTRACT FROM AUTHOR]

Background: Shigella is a leading cause of bacterial diarrhea morbidity and mortality affecting mainly children under five in the developing world. In Zambia, Shigella has a high prevalence of 34.7% in children with diarrhea and an attributable fraction of 6.7% in Zambian children with moderate to severe diarrhea. Zambian diarrhea management guidelines and the health ministry reporting tool Health Management Information System (HMIS) heavily rely on the WHO clinical classification of dysentery to potentially identify and estimate the burden of Shigella in children. This reliance on clinical dysentery as a proxy to shigellosis in under five children may be resulting in gross under-estimation of shigella disease burden in Zambia. Methods: We used existing laboratory and clinical data to examine the sensitivity and predictive value of dysentery to correctly identify Shigella infection in under five children with PCR confirmed Shigella infection in Lusaka and Ndola districts, Zambia. Results: Clinical dysentery had a sensitivity of 8.5% (34/401) in identifying under five children with Shigella by stool PCR. Dysentery was able to correctly classify Shigella in 34 of 68 bloody stool samples giving a corresponding positive predictive value of 50%. Of the 1087 with non-bloody diarrhea, 720 did not have Shigella giving a negative predictive value of 66.2%. Conclusions: Use of clinical dysentery as a screening symptom for Shigella infection in children under five presenting with moderate to severe diarrhea has low sensitivity and low positive predictive value respectively. Clinical dysentery as a screening symptom for Shigella contributes to gross under diagnosis and reporting of Shigella infection among under five children in Zambia. Further research is required to better inform practice on more accurate methods or tools to use in support of routine diagnosis, particularly in low middle-income settings where laboratory diagnosis remains a challenge. [ABSTRACT FROM AUTHOR]

Background: Little is known about youth-led approaches to addressing HIV-related outcomes among adolescents and young adults (AYA) living with HIV. In response, Project YES! hired and trained youth living with HIV as peer mentors (YPMs) in four HIV clinics in Ndola, Zambia to hold meetings with 276 15-24-year-olds living with HIV. Within this randomized controlled trial, a qualitative sub-study was conducted to explore YPMs' implementing experiences. Methods: In-depth interviews were conducted with the eight YPMs (50% female) ages 21–26 years. YPMs were asked about their experiences working with clients, their feedback on program components, and what the experience meant to them personally and professionally. Interviews were audio-recorded, transcribed verbatim, and thematic analysis was performed. Results: YPMs connected with AYA clients by discussing shared struggles, modeling positive health behaviors, and establishing judgement-free environments. YPMs experienced powerful personal transformations in HIV-related health behaviors, conceptions of self, and plans for the future. Many expressed now seeing themselves as community leaders–"ambassadors", "game changers"–and "not just alone in this world." They described newfound commitments to reaching personal and professional goals. YPMs were adamant that Project YES! should expand so other HIV-positive AYA might benefit. Conclusion: Well-trained and compensated YPMs who are integrated into HIV clinics can support AYA in unique and important ways due to their shared experiences. The transformational experience of becoming YPMs empowers youth to see themselves as role models and leaders. Future programs should engage youth living with HIV as partners in efforts to end the HIV epidemic. [ABSTRACT FROM AUTHOR]

Introduction: Adolescents and young adults (AYAs) living with HIV face unique challenges and have poorer health outcomes than adults with HIV. Project YES! was a youth-led initiative to promote HIV self-management and reduce stigma among AYAs in four Ndola, Zambia clinics. Clinic health care providers (HCPs) were involved in multiple intervention aspects, including serving as expert resources during AYA and caregiver group meetings, facilitating resistance test-based AYA antiretroviral drug changes, meeting with participants referred through a safety protocol, and guiding a subset of participants' physical transition from pediatric to adult clinic settings. This study aimed to understand HCP insights on facilitators and barriers to implementing Project YES! and scaling up a clinic-based, youth-focused program. Methods: A trained interviewer conducted ten in-depth interviews with participating HCPs from November–December 2018 and analyzed data, identifying key themes. These themes were examined in terms of two implementation science outcomes–acceptability and feasibility–to inform scalability. Results: HCPs found peer mentoring valuable for AYAs with HIV and the bimonthly caregiver meetings beneficial to AYA caregivers. HCPs voiced a desire for more involvement in specific processes related to patient clinical care, such as drug changes. HCPs' experiences with the study safety protocol, including referrals for youth experiences of violence, shifted their views of AYAs and informed their understanding of key issues youth face. Considering this, many HCPs requested more resources to support AYAs' varied needs. HCPs noted limited time and clinic space as implementation barriers but felt the program was valuable overall. Conclusions: HCPs concluded youth peer mentoring was highly acceptable and feasible, supporting scale-up of youth-led interventions addressing the multi-faceted needs of AYAs living with HIV. Continued provider involvement in resistance test-based antiretroviral drug changes, considered in the context of health system and clinic policy, would enhance long-term success of the program at scale. [ABSTRACT FROM AUTHOR]

Background: HIV drug resistance (HIVDR) poses a threat to the HIV epidemic control in Zambia especially in sub-populations such as the 15–24 years where there is poor virological suppression. Understanding the prevalence and patterns of HIVDR in this population (15–24 years) will contribute to defining effective antiretroviral therapy (ART) regimens, improving clinical decision making, and supporting behavioral change interventions needed to achieve HIV epidemic control. Methods: A cross-sectional analysis of study enrollment data from the Project YES! Youth Engaging for Success randomized controlled trial was conducted. Participants were 15 to 24 years old, who knew their HIV status, and had been on ART for at least 6 months. All participants completed a survey and underwent viral load (VL) testing. Participants with viral failure (VL ≥1,000 copies/mL) underwent HIVDR testing which included analysis of mutations in the protease and reverse transcriptase genes. Results: A total of 99 out of 273 analyzed participants receiving ART had VL failure, of whom 77 had successful HIVDR amplification and analysis. Out of the 77, 75% (58) had at least one drug resistant mutation, among which 83% (48/58) required a drug change. Among the 58 with HIVDR mutations, the prevalence of at least one HIVDR mutation to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 81%, 65.5% and 1.7%. The mutation M184V which confers resistance to NRTI drugs of lamivudine (3TC) and emtricitabine (FTC) was the most common (81%) among NRTI associated mutations followed by K65R (34.5%) which is associated with both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) resistance. Thymidine analogue mutations (TAMs) which confer resistance primarily to zidovudine (AZT), stavudine (d4T) and other NRTIs were observed at 32.8%. Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%). The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP). There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine. Conclusions: There is a high prevalence of HIVDR including TAMs despite majority of these patients (90.48%) being on AZT or d4T sparing first line ART among the youth. Emergence of these mutations including the NNRTI associated mutations (Y181C and Y188C) may compromise future second- and third-line regimens in the absence of routine HIVDR testing. HIVDR monitoring at start of ART or at first-line failure can better inform clinical decision making and ART programing. [ABSTRACT FROM AUTHOR]

Background: Little is known about violence against HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. This analysis examines experiences of violence victimization, and the perpetrators of this violence, among AYA living with HIV, aged 15–24 years, in Zambia. Methods: We analyzed baseline data from 272 AYA (60.1% female, 71.0% perinatally infected) enrolled in Project YES! (Youth Engaging for Success), a randomized controlled trial conducted in four HIV clinics in Ndola, Zambia. Violence measures were adapted from the ICAST-C and the WHO Multi-Country Study on Women's Health and Domestic Violence. Youth could report up to 12 perpetrator types for past-year experiences of violence. We estimated lifetime and past-year prevalence of physical violence, psychological abuse, and forced sex, disaggregated by sex and age group. Estimates were weighted using sex and age data from the 2013–14 Zambian Demographic and Health Survey to be representative of HIV-positive AYA in Zambia. Results: Estimated lifetime prevalence of any violence victimization was 78.2%. Past-year prevalence was 72.0% among males and 74.5% among females. Almost half of AYA (46.1%) had ever experienced polyvictimization (2+ types of violence). Psychological abuse was most common (70.4% lifetime, 65.3% past-year), followed by physical violence (50.8% lifetime, 44.7% past-year) and forced sex (10.4% lifetime, 4.7% past-year). Among past-year victims, males experienced more violence than females from a friend/peer (74.3% vs. 45.1%, p<0.001); females experienced more violence than males from a romantic partner (33.3% vs. 5.0%, p<0.001), parent/caregiver (32.4% vs. 17.6%, p = 0.02), and stranger (19.7% vs. 5.2%, p<0.001). Conclusion: The widespread and overlapping prevalence of multiple types of violence highlights the critical need for prevention and response efforts that are tailored to youths' sex and the perpetrator type. Future research should explore violence victimization and HIV outcomes, and the measurement of psychological abuse and sexual violence, among HIV-positive AYA in the region. [ABSTRACT FROM AUTHOR]

Background: Youth-led strategies remain untested in clinic-based programs to improve viral suppression (VS) and reduce stigma among HIV-positive adolescents and young adults (AYA) in sub-Saharan Africa. In response, Project YES! placed paid HIV-positive youth peer mentors (YPM) in four HIV clinics in Ndola, Zambia including a Children's Hospital (pediatric setting), an adult Hospital and two primary care facilities (adult settings). Methods: A randomized controlled trial was conducted from December 2017 to February 2019. Consecutively recruited 15 to 24-year-olds were randomly assigned to an intervention arm with monthly YPM one-on-one and group sessions and optional caregiver support groups, or a usual care comparison arm. Survey data and blood samples were collected at baseline and at the six-month midline. Generalized estimating equation models evaluated the effect of study arm over time on VS, antiretroviral treatment (ART) adherence gap, and internalized stigma. Results: Out of 276 randomized youth, 273 were included in the analysis (Intervention n = 137, Comparison n = 136). VS significantly improved in both arms (I:63.5% to 73.0%; C:63.7% to 71.3.0%) [OR:1.49, 95% CI:1.08, 2.07]. In a stratified analysis intervention (I:37.5% to 70.5%) versus the comparison (C:60.3% to 59.4%) participants from the pediatric clinic experienced a relative increase in the odds of VS by a factor of 4.7 [interaction term OR:4.66, 95% CI:1.84, 11.78]. There was no evidence of a study arm difference in VS among AYA in adult clinics, or in ART adherence gaps across clinics. Internalized stigma significantly reduced by a factor of 0.39 [interaction term OR:0.39, 95% CI:0.21,0.73] in the intervention (50.4% to 25.4%) relative to the comparison arm (45.2% to 39.7%) Conclusions: Project YES! engaged AYA, improving VS in the pediatric clinic and internalized stigma in the pediatric and adult clinics. Further research is needed to understand the intersection of VS and internalized stigma among AYA attending adult HIV clinics. Trial registration: ClinicalTrials.gov NCT04115813. [ABSTRACT FROM AUTHOR]