Tuberculosis Preventative Therapy Initiation and Completion Among Adolescents and Young Adults Living With HIV in Kenya.

BACKGROUND: Tuberculosis is the leading cause of death among adolescents and young adults living with HIV (YWHIV) and their heightened risk warrants deeper understanding of utilization of tuberculosis-prevention measures within HIV care. SETTING: Retrospective study using clinic surveys and medical record data from 86 Kenyan HIV clinics. METHODS: Clinic surveys obtained information on tuberculosis preventive therapy (TPT) services. Medical records of YWHIV were abstracted. Bivariate and multivariate analyses used generalized linear models to determine individual-level and clinic-level cofactors of TPT initiation and completion. RESULTS: Among 10,328 eligible YWHIV, 4337 (42.0%) initiated TPT. Of 3295 with ≥6 months follow-up, 1774 (53.8%) completed TPT. A lower patient-to-staff ratio was a clinic-level cofactor of TPT initiation ( P = 0.044) and completion ( P = 0.004); designated adolescent areas were associated with TPT initiation {prevalence ratio 2.05 [95% confidence interval (CI): 1.46 to -2.88]}. Individual cofactors of TPT initiation included younger age at HIV-care enrollment [relative risk (RR) 0.85 (95% CI: 0.80 to 0.90)] and antiretroviral therapy (ART) duration [1-2 vs. <1 year RR 1.31 (95% CI: 1.18 to 1.45)]. TPT completion was associated with younger age [RR 0.91 (95% CI: 0.85 to 0.98)] and ART duration [2-5 vs. <1 year RR 1.27 (95% CI: 1.03 to 1.57)]. In multivariate models, TPT initiation was associated with younger age and ART duration [1-2 vs. 1 year; adjusted RR 1.30 (95% CI: 1.16 to 1.46)] and TPT completion with ART duration [2-5 vs. 1 year adjusted RR 1.23 (95% CI: 0.99 to 1.52)]. CONCLUSION: Over half of YWHIV did not initiate and >40% did not complete TPT, with distinct clinic-level and individual-level cofactors. Approaches to enhance adolescent-friendly infrastructure and support older YWHIV are necessary to improve TPT use.

"PrEP Gives the Woman the Control": Healthcare Worker Perspectives on Using pre-Exposure Prophylaxis (PrEP) During Pregnancy and Postpartum in Kenya.

Background: Pregnant and postpartum women in high HIV prevalent regions are at increased HIV risk. Oral pre-exposure prophylaxis (PrEP) can decrease HIV incidence reducing infant HIV infections. Understanding healthcare worker (HCW) beliefs about PrEP prior to national roll-out is critical to supporting PrEP scale-up. Methods: We conducted 45 semi-structured interviews among a range of HCW cadres with and without PrEP provision experience purposively recruited from four clinics in Kenya to compare their views on prescribing PrEP during pregnancy and postpartum. Interviews were analysed using a conventional content analysis approach to identify key influences on PrEP acceptability and feasibility. Results: All HCWs perceived PrEP as an acceptable and feasible HIV prevention strategy for pregnant and postpartum women. They believed PrEP meets women's needs as an on-demand, female-controlled prevention strategy that empowers women to take control of their HIV risk. HCWs highlighted their role in PrEP delivery success while acknowledging how their knowledge gaps, concerns and perceived PrEP implementation challenges may hinder optimal PrEP delivery. Conclusion: HCWs supported PrEP provision to pregnant and postpartum women. However, counseling tools to address risk perceptions in this population and strategies to reduce HCW knowledge gaps, concerns and perceived implementation barriers are required.

"Your status cannot hinder you": the importance of resilience among adolescents engaged in HIV care in Kenya.

BACKGROUND: Approximately 40% of the 110,000 adolescents living with HIV (ALHIV) in Kenya have not achieved viral suppression. Despite the increasing availability of adolescent-friendly services, adolescents face barriers that impact ART adherence. This study aimed to identify key stigma-related barriers to ART adherence and strategies used by adolescents in overcoming these barriers. METHODS: Data were collected by LVCT Health, a Kenyan organization with a programmatic focus on HIV testing, prevention, and care. 122 participants were recruited from 3 clinical sites affiliated with LVCT Health in Nairobi, Kisumu, and Mombasa. In-depth interviews were conducted with ALHIV (n = 12). Focus group discussions were conducted with ALHIV (n = 5), peer leaders (n = 3), and adolescents receiving HIV services in community settings (AIC) irrespective of HIV status (n = 3). Interviews and focus groups were audio recorded, translated, and transcribed. Data were analyzed thematically, with a focus on stigma and resilience. RESULTS: While AIC primarily focused on adherence barriers and stigma, ALHIV and, to some extent, peer leaders, also identified resilience factors that helped overcome stigma. Four major themes emerged: 1) knowledge and future-oriented goals can drive motivation for ALHIV to remain healthy; 2) disclosure to others strengthens support systems for ALHIV; 3) medication-taking strategies and strategic disclosure can overcome adherence challenges in school; and 4) a supportive clinic environment promotes continuous adolescent engagement in HIV care. These concepts were used to develop a conceptual stigma/resilience model depicting how resilience moderates negative effects of stigma among ALHIV. CONCLUSIONS: This study demonstrates the positive effects of ALHIV resilience on ART adherence and illuminates how stigma impacts ALHIV differently depending on their resilience. Strengths-based interventions, focused on increasing resilience among ALHIV in Kenya, and more formal involvement of adolescent peers to bolster adolescent support, have the potential to improve ART adherence among ALHIV.

Integrating PrEP delivery in public health family planning clinics: a protocol for a pragmatic stepped wedge cluster randomized trial in Kenya.

BACKGROUND: Adolescent girls and young women account for a disproportionate fraction of new HIV infections in Africa and are a priority population for HIV prevention, including provision of pre-exposure prophylaxis (PrEP). Anchoring PrEP delivery to care settings like family planning (FP) services that women already access routinely may offer an efficient platform to reach HIV at-risk women. However, context-specific implementation science evaluation is needed. METHODS: The Family Planning Plus Project is a prospective, pragmatic implementation evaluation, designed as a stepped wedge, cluster randomized trial, at 12 clinics in Kenya. In collaboration with the Kenya Ministry of Health and Kisumu County Department of Health, we will introduce integration of HIV risk screening and PrEP delivery in public health FP clinics. The core multifaceted implementation strategies to integrate PrEP in FP clinics will include: (1) PrEP delivery by existing FP clinic staff, (2) health provider training, (3) PrEP technical assistance to coach and mentor providers, (4) joint supervision with Kisumu County health officials, and (5) stakeholder engagement. All core components of PrEP delivery-including screening for HIV risk, HIV testing, dispensing, adherence and risk reduction counseling, assessment of side effects, and provision of refills, or safety assessment-will be conducted by existing FP clinic staff as part of a standard care service package. The goal is to catalyze sustainable scale-up within existing infrastructures beyond the project. We will rigorously evaluate implementation outcomes and impact, using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework, and we will use Organizational Readiness for Implementing Change (ORIC) and the Consolidated Framework for Implementation Science Research (CFIR) to assess readiness to implement and contextual enablers and barriers of implementation, including how clinics innovate efficient delivery systems. DISCUSSION: Anchoring PrEP delivery to existing FP systems and staffing has tremendous potential to address barriers that women face in accessing HIV prevention and PrEP care, including lack of time, cost, and stigma of visiting a facility solely for HIV prevention. The FP Plus Project will initiate preparation for full-scale and sustainable model of integration of comprehensive HIV prevention services, including PrEP implementation, in public health FP clinics in low-income settings. Trial registration Registered with ClinicalTrials.gov on December 14, 2020: NCT04666792.

Women's Autonomy in Infant Feeding Decision-Making: A Qualitative Study in Nairobi, Kenya.

BACKGROUND: Exclusive breastfeeding (EBF) is the optimal way to feed young infants. Guidelines recommend that women living with HIV on antiretroviral therapy should EBF for 6 months and continue breastfeeding for up to 24 months or longer. Parents may face social or logistical barriers creating challenges to EBF. OBJECTIVES: To explore barriers, facilitators and community norms influencing EBF practices in Kenya. METHODS: This qualitative research was nested within a longitudinal study of intensive maternal counseling to increase EBF among HIV-positive mothers. HIV-negative and HIV-positive mothers were recruited from four public clinics in Nairobi. Women participated in focus group discussions (FGDs) that explored beliefs about and experiences with infant feeding. Conventional content analysis was used to describe and compare barriers and facilitators influencing HIV-positive and HIV-negative women's EBF experiences. RESULTS: We conducted 17 FGDs with 80 HIV-positive and 53 HIV-negative women between 2009 and 2012. Overall, women agreed that breastmilk is good for infants. However, early mixed feeding was a common cultural practice. HIV-positive women perceived that infant feeding methods and durations were their decision. In contrast, HIV-negative women reported less autonomy and more mixed feeding, citing peer pressure and lack of HIV transmission concerns. Autonomy in decision-making was facilitated by receiving EBF counseling and family support, especially from male partners. Low milk production was a barrier to EBF, regardless of HIV status, and perceived to represent poor maternal nutrition. CONCLUSIONS: Despite challenges, counseling empowered women living with HIV to advocate for EBF with spouses and family.

Health Care Providers as Agents of Change: Integrating PrEP With Other Sexual and Reproductive Health Services for Adolescent Girls and Young Women.

Background: Successful integration of pre-exposure prophylaxis (PrEP) with existing reproductive health services will require iterative learning and adaptation. The interaction between the problem-solving required to implement new interventions and health worker motivation has been well-described in the public health literature. This study describes structural and motivational challenges faced by health care providers delivering PrEP to adolescent girls and young women (AGYW) alongside other SRH services, and the strategies used to overcome them. Methods: We conducted in-depth interviews (IDIs) and focus group discussions (FGDs) with HCWs from two demonstration projects delivering PrEP to AGYW alongside other SRH services. The Prevention Options for the Women Evaluation Research (POWER) is an open label PrEP study with a focus on learning about PrEP delivery in Kenyan and South African family planning, youth mobile services, and public clinics at six facilities. PrIYA focused on PrEP delivery to AGYW via maternal and child health (MCH) and family planning (FP) clinics in Kenya across 37 facilities. IDIs and FGDs were transcribed verbatim and analyzed using a combination of inductive and deductive methods. Results: We conducted IDIs with 36 participants and 8 FGDs with 50 participants. HCW described a dynamic process of operationalizing PrEP delivery to better respond to patient needs, including modifying patient flow, pill packaging, and counseling. HCWs believed the biggest challenge to sustained integration and scaling of PrEP for AGYW would be lack of health care worker motivation, primarily due to a misalignment of personal and professional values and expectations. HCWs frequently described concerns of PrEP provision being seen as condoning or promoting unprotected sex among young unmarried, sexually active women. Persuasive techniques used to overcome these reservations included emphasizing the social realities of HIV risk, health care worker professional identities, and vocational commitments to keeping young women healthy. Conclusion: Sustained scale-up of PrEP will require HCWs to value and prioritize its incorporation into daily practice. As with the provision of other SRH services, HCWs may have moral reservations about providing PrEP to AGYW. Strategies that strengthen alignment of HCW personal values with professional goals will be important for strengthening motivation to overcome delivery challenges.

Lessons from PrEP: A Qualitative Study Investigating How Clinical and Policy Experts Weigh Ethics and Evidence When Evaluating Preventive Medications for Use in Pregnant and Breastfeeding Women.

This study explored how multinational HIV experts weigh clinical, evidential, and ethical considerations regarding pre-exposure prophylaxis in pregnant/breastfeeding women. Semi-structured interviews were conducted with experts in HIV policy, research, treatment, and implementation from three global regions. A constant comparative approach identified major themes. Experts noted that exclusion of pregnant women from research limits evidence regarding risks/benefits, emphasizing that underinclusion of pregnant women in RCTs shifts the onus of evidence-building to clinical care. Experts discussed approaches for weighing evidence to make decisions, including triangulating evidence from sources other than RCTs. Likelihood and severity of disease strongly influenced decisions. Less effective interventions with limited fetal risk were preferred over interventions of uncertain safety, unless the disease was serious. Experts resisted the dichotomous choice between protecting maternal and fetal interests, arguing that these interests are intertwined and that more holistic approaches to maternal-fetal balance support greater inclusion of pregnant women in research.

HIV-Uninfected Kenyan Adolescent and Young Women Share Perspectives on Using Pre-Exposure Prophylaxis During Pregnancy.

To optimize scale-up of pre-exposure prophylaxis (PrEP) for pregnant women at risk of HIV in high HIV burden settings, implementation strategies must be developed that account for perceptions of PrEP in this unique population. Semistructured focus group discussions were conducted with 68 HIV-uninfected Kenyan pregnant and postpartum women without prior PrEP knowledge or experience. A qualitative descriptive analysis was performed, using a constant comparison approach, to identify key themes related to the values and rationale impacting potential PrEP use in pregnancy. Median age was 19.5 years and participants were either pregnant or had 1-2 children. Almost all (96%) were married or had a steady partner. Women felt pregnancy was a time of high HIV risk because they desired sex less frequently, which may lead their partners to have outside partnerships. This made PrEP an attractive HIV prevention option for themselves and their infants. Although women believed male partner behaviors influenced their HIV risk, many women perceived that male partners would react negatively, including becoming physically violent, if they discovered that women used PrEP. Clinicians were identified as potential facilitators of PrEP use who could explain PrEP to male partners on behalf of pregnant women. Women said that community-level stigma against HIV and potential for conflating PrEP with antiretroviral therapy (ART) would necessitate that PrEP use be discreet. Our results indicate the importance of addressing risk perception of women, concerns of male partners, HIV stigma, and benefits of PrEP for HIV prevention as programs are developed for pregnant women.

"I Did Not Want to Give Birth to a Child Who has HIV": Experiences Using PrEP During Pregnancy Among HIV-Uninfected Kenyan Women in HIV-Serodiscordant Couples.

OBJECTIVES: The perceptions, motivations, and beliefs of HIV-uninfected women about pre-exposure prophylaxis (PrEP) use during pregnancy can influence its uptake and adherence. This study elicited the views of HIV-uninfected women with personal experience taking PrEP during pregnancy. DESIGN: Qualitative interviews were conducted with HIV-uninfected women who had personal experience taking PrEP while pregnant. METHODS: Semistructured interviews were conducted with 21 HIV-uninfected Kenyan women in HIV-serodiscordant couples enrolled in an open-label PrEP demonstration project who became pregnant while using PrEP and continued PrEP through their pregnancy. Interviews were audio-recorded and transcribed into English. A qualitative descriptive analysis was performed, using a constant comparison approach to identify key themes related to PrEP use in pregnancy. RESULTS: Desire to remain HIV uninfected and have an HIV-free infant were strong motivators influencing continued use of PrEP during pregnancy. Supporting HIV-infected partners and childbearing within an HIV-serodiscordant relationship were also motivators. Women had challenges distinguishing normal pregnancy symptoms from PrEP side effects and were concerned that observed side effects could be signs of danger for the infant related to PrEP exposure. Health care providers were important conduits of knowledge about PrEP, and continuity of PrEP providers throughout pregnancy facilitated adherence. CONCLUSIONS: HIV-uninfected women in HIV-serodiscordant couples were motivated to use PrEP during pregnancy to remain HIV uninfected and to have an HIV-free child but had concerns about side effects. Health care providers will be important for PrEP messaging and adherence support in this unique population.

"At our age, we would like to do things the way we want: " a qualitative study of adolescent HIV testing services in Kenya.

OBJECTIVES: Adolescents in Africa have low HIV testing rates. Better understanding of adolescent, provider, and caregiver experiences in high-burden countries such as Kenya could improve adolescent HIV testing programs. DESIGN: We conducted 16 qualitative interviews with HIV-positive and HIV-negative adolescents (13-18 years) and six focus group discussions with Healthcare workers (HCWs) and caregivers of adolescents in Nairobi, Kenya. METHODS: Semi-structured interviews and focus groups were recorded and transcribed. Analysis employed a modified constant comparative approach to triangulate findings and identify themes influencing testing experiences and practices. RESULTS: All groups identified that supportive interactions during testing were essential to the adolescent's positive testing experience. HCWs were a primary source of support during testing. HCWs who acted respectful and informed helped adolescents accept results, link to care, or return for repeat testing, whereas HCWs who acted dismissive or judgmental discouraged adolescent testing. Caregivers universally supported adolescent testing, including testing with the adolescent to demonstrate support. Caregivers relied on HCWs to inform and encourage adolescents. Although peers played less significant roles during testing, all groups agreed that school-based outreach could increase peer demand and counteract stigma. All groups recognized tensions around adolescent autonomy in the absence of clear consent guidelines. Adolescents valued support people during testing but wanted autonomy over testing and disclosure decisions. HCWs felt pressured to defer consent to caregivers. Caregivers wanted to know results regardless of adolescents' wishes. CONCLUSION: Findings indicate that strengthening HCW, caregiver, and peer capacities to support adolescents while respecting their autonomy may facilitate attaining '90-90-90' targets for adolescents.

Pediatric HIV Disclosure Intervention Improves Knowledge and Clinical Outcomes in HIV-Infected Children in Namibia.

OBJECTIVES: Using routinely collected data, we evaluated a nationally implemented intervention to assist health care workers and caregivers with HIV disclosure to children. We assessed the impact of the intervention on child's knowledge and health outcomes. METHODS: Data were abstracted from national databases and patient charts for HIV-infected children aged 7-15 years attending 4 high-volume HIV clinics in Namibia. Disclosure rates, time to disclosure, and HIV knowledge in 314 children participating in the intervention were analyzed. Logistic regression was used to identify correlates of partial vs. full disclosure. Paired t-tests and McNemar tests were used to compare adherence and viral load (VL) before versus after intervention enrollment. RESULTS: Among children who participated in the disclosure intervention, 11% knew their HIV status at enrollment and an additional 38% reached full disclosure after enrollment. The average time to full disclosure was 2.5 years (interquartile range: 1.2-3 years). Children who achieved full disclosure were more likely to be older, have lower VLs, and have been enrolled in the intervention longer. Among children who reported incorrect knowledge regarding why they take their medicine, 83% showed improved knowledge after the intervention, defined as knowledge of HIV status or adopting intervention-specific language. On comparing 0-12 months before vs. 12-24 months after enrollment in the intervention, VL decreased by 0.5 log10 copies per milliliter (N = 42, P = 0.004), whereas mean adherence scores increased by 10% (N = 88, P value < 0.001). CONCLUSIONS: This HIV disclosure intervention demonstrated improved viral suppression, adherence, and HIV knowledge and should be considered for translation to other settings.

Toll-like receptor variants are associated with infant HIV-1 acquisition and peak plasma HIV-1 RNA level.

OBJECTIVE: We evaluated the association of single nucleotide polymorphisms (SNPs) in TLRs with infant HIV-1 acquisition and viral control. DESIGN: Infant HIV-1 outcomes were assessed in a Kenyan perinatal HIV-1 cohort. METHODS: Infants were genotyped for six candidate and 118 haplotype-tagging polymorphisms in TLRs 2, 3, 4, 7, 8, and 9, MYD88 and TIRAP. Cox proportional hazards and linear regression were performed to assess associations with time to HIV-1 acquisition, time to infant mortality, and peak viral load. RESULTS: Among 368 infants, 56 (15%) acquired HIV-1 by month 1 and 17 (4.6%) between 1 and 12 months. Infants with the TLR9 1635A (rs352140) variant were more likely to acquire HIV-1 by 1 month [hazard ratio = 1.81, 95% confidence interval (CI) = 1.05-3.14, P = 0.033] and by 12 months (hazard ratio = 1.62, CI = 1.01-2.60, P = 0.044) in dominant models adjusted for maternal plasma HIV-1 RNA level and genetic ancestry. Among 56 infants infected at 1 month of age or less, at least one copy of the TLR9 1635A allele was associated with a 0.58 log10 copies/ml lower peak viral load (P = 0.002). Female infants with at least one copy of the TLR8 1G (rs3764880) variant had a 0.78 log10 copies/ml higher peak viral load (P = 0.0009) and having at least one copy of the C allele for a haplotype tagging TLR7 variant (rs1634319) was associated with a 0.80 log10 copies/ml higher peak viral load in female infants (P = 0.0003). CONCLUSION: In this African perinatal cohort, we found several TLR polymorphisms associated with HIV-1 acquisition and progression. Defining mechanisms for these TLR associations may inform HIV-1 prevention strategies that leverage innate responses.

Prevalence, perceptions, and correlates of pediatric HIV disclosure in an HIV treatment program in Kenya.

Disclosure to HIV-infected children regarding their diagnosis is important as expanding numbers of HIV-infected children attain adolescence and may become sexually active. In order to define correlates of pediatric disclosure and facilitate development of models for disclosure, we conducted a cross-sectional survey of primary caregivers of HIV-1 infected children aged 6-16 years attending a pediatric HIV treatment program in Nairobi, Kenya. We conducted focus group discussions with a subset of caregivers to further refine perceptions of disclosure. Among 271 caregiver/child dyads in the cross-sectional survey, median child age was 9 years (interquartile range: 7-12 years). Although 79% of caregivers believed children should know their HIV status, the prevalence of disclosure to the child was only 19%. Disclosure had been done primarily by health workers (52%) and caregivers (33%). Caregivers reported that 5 of the 52 (10%) who knew their status were accidentally disclosed to. Caregivers of older children (13 vs. 8 years; p<0.001), who were HIV-infected and had disclosed their own HIV status to the child (36% vs. 4%; p=0.003), or who traveled frequently (29% vs. 16%, p=0.03) were more likely to have disclosed. Children who had been recently hospitalized (25% vs. 44%, p=0.03) were less likely to know their status, and caregivers with HIV were less likely to have disclosed (p=0.03). Reasons for disclosure included medication adherence, curiosity or illness while reasons for nondisclosure included age and fear of inadvertent disclosure. Our study found that disclosure rates in this Kenyan setting are lower than observed rates in the USA and Europe but consistent with rates from other resource-limited settings. Given these low rates of disclosure and the potential benefits of disclosure, strategies promoting health worker trainings and caregiver support systems for disclosure may benefit children with HIV.