Key informant views on potential acceptability and feasibility of long-acting antiretroviral treatment for HIV in Kenya.

BACKGROUND: In 2020, 14% of diagnosed persons living with HIV (PLWH) in Kenya were not taking antiretroviral therapy (ART), and 19% of those on ART had unsuppressed viral loads. Long-acting antiretroviral therapy (LA-ART) may increase viral suppression by promoting ART uptake and adherence. We conducted key informant (KI) interviews with HIV experts in Kenya to identify product and delivery attributes related to the acceptability and feasibility of providing LA-ART to PLWH in Kenya. METHODS: Interviews were conducted via Zoom on potential LA-ART options including intra-muscular (IM) injections, subcutaneous (SC) injections, implants, and LA oral pills. KI were asked to discuss the products they were most and least excited about, as well as barriers and facilitators to LA-ART roll-out. In addition, they were asked about potential delivery locations for LA-ART products such as homes, pharmacies, and clinics. Interviews were recorded and transcribed, and data were analyzed using a combination of inductive and deductive coding. RESULTS: Twelve KI (5 women, 7 men) participated between December 2021 and February 2022. Overall, participants reported that LA-ART would be acceptable and preferable to PLWH because of fatigue with daily oral pills. They viewed IM injections and LA oral pills as the most exciting options to ease pill burden and improve adherence. KI felt that populations who could benefit most were adolescents in boarding schools and stigmatized populations such as sex workers. SC injections and implants were less favored, as they would require new training initiatives for patients or healthcare workers on administration. In addition, SC injections would require refrigeration and needle disposal after use. Some KI thought patients, especially men, might worry that IM injections and implants would impact fertility, given their role in family planning. Pharmacies were perceived by most KI as suboptimal delivery locations; however, given ongoing work in Kenya to include pharmacies in antiretroviral delivery, they recommended asking patients their views. CONCLUSION: There is interest and support for LA-ART in Kenya, especially IM injections and LA oral pills. Identifying patient preferences for modes and delivery locations and addressing misconceptions about specific products as they become available will be important before wide-scale implementation.

Mobile solutions to Empower reproductive life planning for women living with HIV in Kenya (MWACh EMPOWER): Protocol for a cluster randomized controlled trial.

BACKGROUND: Women living with HIV (WLWH) face unique reproductive health (RH) barriers which increase their risks of unmet need for contraception, contraceptive failure, unintended pregnancy, and pregnancy-related morbidity and mortality and may prevent them from achieving their reproductive goals. Patient-centered counseling interventions that support health care workers (HCWs) in providing high-quality RH counseling, tailored to the needs of WLWH, may improve reproductive health outcomes. METHODS AND DESIGN: We are conducting a non-blinded cluster randomized controlled trial (cRCT) of a digital health intervention for WLWH (clinicaltrials.gov #NCT05285670). We will enroll 3,300 WLWH seeking care in 10 HIV care and treatment centers in Nairobi and Western Kenya. WLWH at intervention sites receive the Mobile WACh Empower intervention, a tablet-based RH decision-support counseling tool administered at baseline and SMS support during two years of follow-up. WLWH at control sites receive the standard of care FP counseling. The decision-support tool is a logic-based tool for family planning (FP) counseling that uses branching logic to guide RH questions based on participants' reproductive life plans, tailoring counseling based on the responses. Follow-up SMSs are based in the Information-Motivation-Behavioral (IMB) Skills model of behavioral change and are tailored to participant characteristics and reproductive needs through separate SMS "tracks". Follow-up visits are scheduled quarterly for 2 years to assess plans for pregnancy, pregnancy prevention, and contraceptive use. The primary outcome, FP discontinuation, will be compared using an intent-to-treat analysis. We will also assess the unmet need for FP, dual method use, viral load suppression at conception and unintended pregnancy. DISCUSSION: The Mobile WACh Empower intervention is innovative as it combines a patient-centered counseling tool to support initial reproductive life decisions with longitudinal SMS for continued RH support and may help provide RH care within the context of provision of HIV care.

Implementation and Assessment of the HIV Enhanced Access Testing in the Emergency Department (HEATED) Program in Nairobi, Kenya: A Quasi-Experimental Prospective Study.

Background: Persons seeking emergency injury care are often from underserved key populations (KPs) and priority populations (PPs) for HIV programming. While facility-based HIV Testing Services (HTS) in Kenya are effective, emergency department (ED) delivery is limited, despite the potential to reach underserved persons. Methods: This quasi-experimental prospective study evaluated implementation of the HIV Enhanced Access Testing in Emergency Departments (HEATED) at Kenyatta National Hospital ED in Nairobi, Kenya. The HEATED program was designed using setting specific data and utilizes resource reorganization, services integration and HIV sensitization to promote ED-HTS. KPs included sex workers, gay men, men who have sex with men, transgender persons and persons who inject drugs. PPs included young persons (18-24 years), victims of interpersonal violence, persons with hazardous alcohol use and those never previously HIV tested. Data were obtained from systems-level records, enrolled injured patient participants and healthcare providers. Systems and patient-level data were collected during a pre-implementation period (6 March - 16 April 2023) and post-implementation (period 1, 1 May - 26 June 2023). Additional, systems-level data were collected during a second post-implementation (period 2, 27 June - 20 August 2023). Evaluation analyses were completed across reach, effectiveness, adoption, implementation and maintenance framework domains. Results: All 151 clinical staff were reached through trainings and sensitizations on the HEATED program. Systems-level ED-HTS increased from 16.7% pre-implementation to 23.0% post-implementation periods 1 and 2 (RR=1.31, 95% CI:1.21-1.43; p<0.001) with a 62.9% relative increase in HIV self-test kit provision. Among 605 patient participants, facilities-based HTS increased from 5.7% pre-implementation to 62.3% post-implementation period 1 (RR=11.2, 95%CI:6.9-18.1; p<0.001). There were 440 (72.7%) patient participants identified as KPs (5.6%) and/or PPs (65.3%). For enrolled KPs/PPs, HTS increased from 4.6% pre-implementation to 72.3% post-implementation period 1 (RR=13.8, 95%CI:5.5-28.7, p<0.001). Systems and participant level data demonstrated successful adoption and implementation of the HEATED program. Through 16-weeks post-implementation a significant increase in ED-HTS delivery was maintained as compared to pre-implementation. Conclusions: The HEATED program increased ED-HTS and augmented delivery to KPs/PPs, suggesting that broader implementation could improve HIV services for underserved persons, already in contact with health systems.

Preferences and uptake of home-based HIV self-testing for maternal retesting in Kenya.

Objective: To compare preferences, uptake, and cofactors for unassisted home-based oral self-testing (HB-HIVST) versus clinic-based rapid diagnostic blood tests (CB-RDT) for maternal HIV retesting. Design: Prospective cohort. Methods: Between November 2017 and June 2019, HIV-negative pregnant Kenyan women receiving antenatal care were enrolled and given a choice to retest with HB-HIVST or CB-RDT. Women were asked to retest between 36 weeks gestation and 1 week post-delivery if the last HIV test was <24 weeks gestation or at 6 weeks postpartum if ≥24 weeks gestation, and self-report on retesting at a 14 week postpartum. Results: Overall, 994 women enrolled and 33% (n=330) selected HB-HIVST. HB-HIVST was selected because it was private (68%), convenient (63%), and offered flexibility in timing of retesting (63%), whereas CB-RDT was selected due to trust of providers to administer the test (77%) and convenience of clinic testing (64%). Among 905 women who reported retesting at follow-up, 135 (15%) used HB-HIVST. Most (94%) who selected CB-RDT retested with this strategy, compared to 39% who selected HB-HIVST retesting with HB-HIVST. HB-HIVST retesting was more common among women with higher household income and those who may have been unable to test during pregnancy (both retested postpartum and delivered <37 weeks gestation) and less common among women who were depressed. Most women said they would retest in the future using the test selected at enrollment (99% HB-HIVST; 93% CB-RDT-RDT). Conclusions: While most women preferred CB-RDT for maternal retesting, HB-HIVST was acceptable and feasible and may increase retesting coverage and partner testing.

Mechanical and Microstructural Investigation of Geopolymer Concrete Incorporating Recycled Waste Plastic Aggregate.

The effective use of waste materials is one of the key drivers in ensuring sustainability within the construction industry. This paper investigates the viability and efficacy of sustainably incorporating a polylactic acid-type plastic (WP) as a 10 mm natural coarse aggregate (NA) replacement in geopolymer concrete. Two types of concrete (ordinary Portland cement-OPC and geopolymer) were produced for completeness using a concrete formulation ratio of 1:2:3. The ordinary concrete binder control was prepared using 100% OPC at a water/binder ratio of 0.55, while the geopolymer concrete control used an optimum alkaline activator/precursor-A/P ratio (0.5) and sodium silicate to sodium hydroxide-SS/SH volume ratio (1.2/0.8). Using the same binder quantity as the control, four concrete batches were developed by replacing 10 mm NA with WP at 30 and 70 wt% for ordinary and geopolymer concrete. The mechanical performance of the developed concrete was assessed according to their appropriate standards, while a microstructural investigation was employed after 28 days of curing to identify any morphological changes and hydrated phases. The results illustrate the viability of incorporating WP in geopolymer concrete production at up to 70 wt% replacement despite some negative impacts on concrete performance. From a mechanical perspective, geopolymer concrete indicated a 46.7-58.3% strength development superiority over ordinary concrete with or without WP. The sample composition and texture quantified using automated scanning electron microscopy indicated that adding WP reduced the presence of pores within the microstructure of both concrete types. However, this was detrimental to the ordinary concrete due to the low interfacial zone (ITZ) between calcium silicate hydrate (CSH) gel and WP, resulting in the formation of cracks.

Risk factors of adverse birth outcomes among a cohort of pregnant women in Coastal Kenya, 2017-2019.

INTRODUCTION: Adverse birth outcomes particularly preterm births and congenital anomalies, are the leading causes of infant mortality globally, and the burden is highest in developing countries. We set out to determine the frequency of adverse birth outcomes and the risk factors associated with such outcomes in a cohort of pregnant women in Kenya. METHODS: From October 2017 to July 2019, pregnant women < 28 weeks gestation were enrolled and followed up until delivery in three hospitals in coastal Kenya. Newborns were examined at delivery. Among women with birth outcome data, we assessed the frequency of congenital anomalies defined as gastroschisis, umbilical hernia, limb abnormalities and Trisomy 21, and adverse birth outcomes, defined as either stillbirth, miscarriage, preterm birth, small for gestational age, or microcephaly. We used log-binomial regression to identify maternal characteristics associated with the presence of at least one adverse outcome. RESULTS: Among the 2312 women enrolled, 1916 (82.9%) had birth outcome data. Overall, 402/1916 (20.9%; 95% confidence interval (CI): 19.1-22.8) pregnancies had adverse birth outcomes. Specifically, 66/1916 (3.4%; 95% CI: 2.7-4.4) were stillbirths, 34/1916 (1.8%; 95% CI: 1.2-2.4) were miscarriages and 23/1816 (1.2%; 95% CI: 0.8-1.9) had congenital anomalies. Among the participants with anthropometric measurements data, 142/1200 (11.8%; 95% CI: 10.1 - 13.8) were small for gestational age and among the participants with ultrasound records, 143/1711 (8.4%; 95% CI: 7.1-9.8) were preterm. Febrile illnesses in current pregnancy (adjusted risk ratio (aRR): 1.7; 95% CI: 1.1-2.8), a history of poor birth outcomes in prior pregnancy (aRR: 1.8; 95% CI: 1.3-2.4) and high blood pressure in pregnancy (aRR: 3.9, 95% CI: (1.7-9.2) were independently associated with adverse birth outcomes in a model that included age, education, human immunodeficiency virus status and high blood pressure at enrolment. CONCLUSION: We found similar rates of overall adverse birth outcomes, congenital anomalies, and small for gestational age but higher rates of stillbirths and lower rates of prematurity compared to the rates that have been reported in the sub-Saharan Africa region. However, the rates of adverse birth outcomes in this study were comparable to other studies conducted in Kenya. Febrile illnesses during the current pregnancy, previous history of poor birth outcomes and high blood pressure in pregnancy are predictive of an increased risk of adverse birth outcomes.

Cofactors of Partner HIV Self-testing and Oral PrEP Acceptance Among Pregnant Women at High Risk of HIV in Kenya.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) and male partner HIV self-testing (HIVST) is being scaled up within antenatal clinics. Few data are available on how co-distribution influences acceptance of both interventions. METHODS: We used data from the PrEP Implementation of Mothers in Antenatal Care (NCT03070600) trial in Kenya. Women included in this analysis were determined to be at high risk of HIV and offered oral PrEP and partner HIVST. Characteristics were compared between women who chose: (1) PrEP and HIVST, (2) HIVST-alone, (3) PrEP-alone, or (4) declined both (reference), excluding women who had partners known to be living with HIV. RESULTS: Among 911 women, median age was 24 years, 87.3% were married, 43.9% perceived themselves to be at high risk of HIV and 13.0% had history of intimate partner violence (IPV). Overall, 68.9% accepted HIVST and 18.4% accepted PrEP, with 54.7% accepting HIVST-alone, 4.2% PrEP-alone, and 14.3% both HIVST and PrEP. Of women accepting HIVST, partner HIV testing increased from 20% to 82% and awareness of partner HIV status increased from 4.7% to 82.0% between pregnancy and 9 months postpartum (P < 0.001). Compared with women who accepted neither, choosing: (1) HIVST-alone was associated with being married, higher level of education, and residing with partner; (2) PrEP-alone was associated with lower social support, IPV, not residing with partner, longer time living with partner, and suspicion of other partners; and (3) PrEP and HIVST was associated with being married, IPV, and suspicion that partner had other partners. CONCLUSIONS: Understanding factors associated with accepting HIVST and PrEP can inform HIV prevention programs for pregnant women. CLINICAL TRIAL NUMBER: NCT03070600.

Prevalence and Predictors of Chlamydia trachomatis and Neisseria gonorrhoeae Among HIV-Negative Pregnant Women in Kenya.

BACKGROUND: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections in pregnancy contribute to adverse perinatal outcomes. We identified predictors of CT and/or NG infection among pregnant Kenyan women. METHODS: Women without HIV were enrolled at 2 antenatal clinics in Western Kenya. Both CT and NG were assessed using endocervical samples for nucleic acid amplification tests. Poisson regression models were used to evaluate potential CT/NG risk factors. Classification and regression trees were generated to evaluate the joint effects of predictors. RESULTS: Overall, 1276 women had both CT and NG assessments. Women enrolled at a median of 26 weeks' gestation (interquartile range, 22-31 weeks), median age was 22 years (interquartile range, 19-27 years), and 78% were married. In total, 98 (7.7%) tested positive for CT/NG: 70 (5.5%) for CT and 32 (2.5%) for NG, 4 of whom (0.3%) had coinfections. Two-thirds (66%) of CT/NG cases were asymptomatic and would have been missed with only syndromic management. Risk factors of CT/NG included age <22 years, crowded living conditions, being unmarried, being in partnerships for <1 year, abnormal vaginal discharge, sexually transmitted infection history, and Trichomonas vaginalis diagnosis ( P < 0.1). Classification and regression tree analyses identified unmarried women <22 years in relationships for <1 year as 6.1 times more likely to have CT/NG compared with women without these characteristics (26% vs. 6%, adjusted prevalence ratio = 6.1, 95% confidence interval = 3.55-10.39, P < 0.001). CONCLUSIONS: Chlamydia trachomatis / Neisseria gonorrhoeae was frequently asymptomatic and common among young unmarried women in newer partnerships in this cohort. Integrating CT/NG testing into routine antenatal care may be beneficial, especially for young women in Kenya.

HIV Viral Load Patterns and Risk Factors Among Women in Prevention of Mother-To-Child Transmission Programs to Inform Differentiated Service Delivery.

BACKGROUND: Differentiated service delivery (DSD) approaches decrease frequency of clinic visits for individuals who are stable on antiretroviral therapy. It is unclear how to optimize DSD models for postpartum women living with HIV (PWLH). We evaluated longitudinal HIV viral load (VL) and cofactors, and modelled DSD eligibility with virologic failure (VF) among PWLH in prevention of mother-to-child transmission programs. METHODS: This analysis used programmatic data from participants in the Mobile WAChX trial (NCT02400671). Women were assessed for DSD eligibility using the World Health Organization criteria among general people living with HIV (receiving antiretroviral therapy for ≥6 months and having at least 1 suppressed VL [<1000 copies/mL] within the past 6 months). Longitudinal VL patterns were summarized using group-based trajectory modelling. VF was defined as having a subsequent VL ≥1000 copies/mL after being assessed as DSD-eligible. Predictors of VF were determined using log-binomial models among DSD-eligible PWLH. RESULTS: Among 761 women with 3359 VL results (median 5 VL per woman), a 3-trajectory model optimally summarized longitudinal VL, with most (80.8%) women having sustained low probability of unsuppressed VL. Among women who met DSD criteria at 6 months postpartum, most (83.8%) maintained viral suppression until 24 months. Residence in Western Kenya, depression, reported interpersonal abuse, unintended pregnancy, nevirapine-based antiretroviral therapy, low-level viremia (VL 200-1000 copies/mL), and drug resistance were associated with VF among DSD-eligible PWLH. CONCLUSIONS: Most postpartum women maintained viral suppression from early postpartum to 24 months and may be suitable for DSD referral. Women with depression, drug resistance, and detectable VL need enhanced services.

Maternal HIV Status and Risk of Infant Mycobacterium tuberculosis Infection as Measured by Tuberculin Skin Test.

BACKGROUND: The effect of maternal HIV on infant Mycobacterium tuberculosis (Mtb) infection risk is not well-characterized. METHODS: Pregnant women with/without HIV and their infants were enrolled in a longitudinal cohort in Kenya. Mothers had interferon gamma-release assays (QFT-Plus) and tuberculin skin tests (TST) at enrollment in pregnancy; children underwent TST at 12 and 24 months of age. We estimated the incidence and correlates of infant TST-positivity using Cox proportional hazards regression. RESULTS: Among 322 infants, 170 (53%) were HIV-exposed and 152 (47%) were HIV-unexposed. Median enrollment age was 6.6 weeks [interquartile range (IQR): 6.1-10.0]; most received Bacillus Calmette-Guerin (320, 99%). Thirty-nine (12%) mothers were TST-positive; 102 (32%) were QFT-Plus-positive. Among HIV-exposed infants, 154 (95%) received antiretrovirals for HIV prevention and 141 (83%) of their mothers ever received isoniazid preventive therapy (IPT). Cumulative 24-month infant Mtb infection incidence was 3.6/100 person-years (PY) [95% confidence interval (CI): 2.4-5.5/100 PY]; 5.4/100 PY in HIV-exposed infants (10%, 17/170) versus 1.7/100 PY in HIV-unexposed infants (3.3%, 5/152) [hazard ratio (HR): 3.1 (95% CI: 1.2-8.5)]. More TST conversions occurred in the first versus second year of life [5.8 vs. 2.0/100 PY; HR: 2.9 (95% CI: 1.0-10.1)]. Infant TST-positivity was associated with maternal TST-positivity [HR: 2.9 (95% CI: 1.1-7.4)], but not QFT-Plus-positivity. Among HIV-exposed children, Mtb infection incidence was similar regardless of maternal IPT. CONCLUSIONS: Mtb infection incidence (by TST) by 24 months of age was ~3-fold higher among HIV-exposed children, despite high maternal IPT uptake. Overall, more TST conversions occurred in the first 12 months compared to 12-24 months of age, similar in both HIV-exposed and HIV-unexposed children.

Maternal breastfeeding and education impact infant growth and development more than in-utero HIV/antiretroviral therapy exposure in context of universal antiretroviral therapy.

BACKGROUND: Exposure to HIV and antiretroviral therapy (ART) in utero may influence infant growth and development. Most available evidence predates adoption of universal ART (Option B+ ART regimens). In a recent cohort, we compared growth and development in HIV-exposed uninfected (HEU) to HIV-unexposed (HUU) infants. DESIGN: Prospective cohort study: data from Impact of Maternal HIV on Mycobacterium Tuberculosis Infection among Peripartum Women and their Infants (MiTIPS) in Western Kenya. METHODS: Women were enrolled during pregnancy. Mother-infant pairs were followed until 24 months postpartum. We used multivariable linear mixed-effects models to compare growth rates [weight-for-age z score (WAZ) and height-for-age z score (HAZ)] and multivariable linear regression to compare overall development between HEU and HUU children. RESULTS: About 51.8% (184/355) of the infants were HEU, 3.9% low birthweight (<2.5 kg), and 8.5% preterm (<37 gestational weeks). During pregnancy, all mothers of HEU received ART; 67.9% started ART prepregnancy, and 87.3% received 3TC/FTC, TDF, and EFV. In longitudinal analyses, HEU children did not differ significantly from HUU in growth or development ( P  > 0.05 for all). In the combined HEU/HUU cohort, higher maternal education was associated with significantly better growth and development: WAZ [ ß â€Š= 0.18 (95% CI 0.01-0.34)], HAZ [ ß â€Š= 0.26 (95% CI 0.04-0.48)], and development [ ß â€Š= 0.24 (95% CI 0.02-0.46)]. Breastfeeding was associated with significantly better HAZ [ ß =0.42 (95% CI 0.19-0.66)] and development [ ß â€Š=0.31 (95% CI 0.08-0.53)]. CONCLUSION: HEU children in the setting of universal maternal ART had a similar growth trajectory and development to HUU children. Breastfeeding and maternal education improved children's weight, height, and overall development irrespective of maternal HIV status.

Biomarker-confirmed suboptimal adherence to isoniazid preventive therapy among children with HIV in western Kenya.

OBJECTIVES: The aim of this study was to assess the level and correlates of biomarker-confirmed adherence to isoniazid (INH) preventive therapy (IPT) among children with HIV (CLHIV). DESIGN: This prospective cohort study assessed adherence among CLHIV on IPT in public sector HIV clinics from 2019 through 2020. METHODS: Adherence was assessed by pill counts or caregiver or self-reports, and urine biomarkers (in-house dipstick and Isoscreen). Both urine biomarker tests detect INH metabolites within 48 h of ingestion. Consistent adherence was defined as having positive results on either biomarker at all visits. Correlates of biomarker-confirmed nonadherence at each visit were evaluated using generalized estimating equations. The in-house dipstick was validated using Isoscreen as the reference. RESULTS: Among 97 CLHIV on IPT with adherence assessments, median age was 10 years (IQR 7-13). All were on ART at IPT initiation (median duration 46 months [IQR 4-89]); 81% were virally suppressed (<1000 copies/ml). At all visits, 59% ( n  = 57) of CLHIV reported taking at least 80% of their doses, while 39% ( n  = 38) had biomarker-confirmed adherence. Viral nonsuppression (adjusted risk ratio [aRR] = 1.65; 95% confidence interval [95% CI] 1.09-2.49) and the sixth month of IPT use (aRR = 2.49; 95% CI 1.34-4.65) were independent correlates of biomarker-confirmed nonadherence at each visit. Sensitivity and specificity of the in-house dipstick were 98.1% ( 94.7 - 99.6%) and 94.7% ( 88.1 - 98.3%) , respectively, versus Isoscreen. CONCLUSION: Biomarker-confirmed adherence to IPT was sub-optimal and was associated with viral nonsuppression and duration of IPT. Urine dipstick testing may be useful in assessing adherence to IPT in clinical care.

An implementation strategy package (video education, HIV self-testing, and co-location) improves PrEP implementation for pregnant women in antenatal care clinics in western Kenya.

Background: Pre-exposure prophylaxis (PrEP) is recommended by the World Health Organization and the Kenyan Ministry of Health for HIV prevention in pregnancy and postpartum for women at risk for HIV. Integration of PrEP into antenatal care is promising, but delivery gaps exist in the face of healthcare provider shortages in resource-limited settings. Methods: Between May and November 2021, we conducted a difference-in-differences study (3 months pre-intervention data collection and 3 months post-intervention data collection) analyzing four intervention facilities, where the strategies were implemented, and four comparison facilities, where no strategies were implemented. We tested a combination of three implementation strategies-video-based PrEP information in the waiting bay, HIV self-testing, and dispensing of PrEP in the antenatal care rooms-to improve PrEP delivery. We compared absolute changes in the proportion of antenatal attendees screened for PrEP (PrEP penetration), the proportion receiving all PrEP-specific steps in a visit (HIV testing, risk screening, and PrEP counseling) (PrEP fidelity), and client PrEP knowledge, client satisfaction, and waiting time and service time (a priori outcomes); post hoc, we compared the proportion offered PrEP (PrEP offer) and completing HIV testing. We measured provider perceptions of the acceptability and appropriateness of the implementation strategies. Results: We observed significant improvements in PrEP penetration, PrEP offer, satisfaction, and knowledge (p < 0.05) and improvements in fidelity that trended towards significance (p = 0.057). PrEP penetration increased 5 percentage points (p = 0.008), PrEP fidelity increased 8 percentage points (p = 0.057), and PrEP offer increased 4 percentage points (p = 0.003) in intervention vs. comparison facilities. Client PrEP knowledge increased by 1.7 out of 6 total points (p < 0.001) and client satisfaction increased by 0.7 out of 24 total points (p = 0.003) in intervention vs. comparison facilities. We observed no changes in service time (0.09-min decrease; p = 0.435) and a small increase in waiting time (0.33-min increase; p = 0.005). HIV testing among those eligible did not change (1.5 percentage point decrease, p = 0.800). Providers felt the implementation strategies were acceptable and appropriate (median acceptability: 20/20; median appropriateness: 19.5/20). However, absolute levels of each step of the PrEP cascade remained suboptimal. Conclusions: An implementation strategy package with video information, HIV self-testing, and co-location of medication dispensing enhanced PrEP delivery across several implementation outcomes and client satisfaction, while not substantially increasing wait time or decreasing provider-client contact time. Clinical trial registration: ClinicalTrials.gov , identifier, NCT04712994.

Isoniazid preventive therapy during infancy does not adversely effect growth among HIV-exposed uninfected children: secondary analysis of data from a randomized controlled trial.

Background: Isoniazid preventive therapy (IPT) decreases risk of tuberculosis (TB) disease; impact on long-term infant growth is unknown. In a recent randomized trial (RCT), we assessed IPT effects on infant growth without known TB exposure. Methods: The infant TB Infection Prevention Study (iTIPS) trial was a non-blinded RCT among HIV-exposed uninfected (HEU) infants in Kenya. Inclusion criteria included age 6-10 weeks, birthweight ≥2.5 kg, and gestation ≥37 weeks. Infants in the IPT arm received 10 mg/kg isoniazid daily for 12 months, while the control trial received no intervention; post-trial observational follow-up continued through 24 months of age. We used intent-to-treat linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) between trial arms. Results: Among 298 infants, 150 were randomized to IPT, 47.6% were females, median birthweight was 3.4 kg (interquartile range [IQR] 3.0-3.7), and 98.3% were breastfed. During the 12-month intervention period and 12-month post-RCT follow-up, WAZ and HAZ declined significantly in all children, with more HAZ decline in male infants. There were no growth differences between trial arms, including in sex-stratified analyses. In longitudinal linear analysis, mean WAZ (ß=0.04 [95% CI:-0.14, 0.22]), HAZ (ß=0.14 [95% CI:-0.06, 0.34]), and WHZ [ß=-0.07 [95% CI: -0.26, 0.11]) z-scores were similar between arms as were WAZ and HAZ growth trajectories. Infants randomized to IPT had higher monthly WHZ increase (ß to 24 months 0.02 [95% CI:0.01, 0.04]) than the no-IPT arm. Conclusion: IPT administered to HEU infants did not significantly impact growth outcomes in the first two years of life.

Implementation determinants and strategies in integration of PrEP into maternal and child health and family planning services: experiences of frontline healthcare workers in Kenya.

Background: Delivery of PrEP to adolescent girls and young women (AGYW) and to pregnant women through maternal and child health (MCH) and family planning (FP) clinics is scaling up in Kenya. Evaluation of implementation challenges and strategies is critical to optimize delivery. Methods: We conducted focus group discussions (FGDs) with healthcare workers (HCWs) in MCH and FP clinics offering PrEP in a large implementation project in Kisumu, Kenya. Discussion guides were based on the Consolidated Framework for Implementation Research (CFIR). FGDs were audio recorded and transcribed. Directed content analysis was used to identify implementation challenges and strategies to overcome them. Results: Fifty HCWs from 26 facilities participated in 8 FGDs. HCWs believed PrEP integration was appropriate because it met the needs of AGYW and pregnant women by providing a female-controlled prevention strategy and aligned with policy priorities of elimination of vertical HIV transmission. They were universally accepting of PrEP provision, especially through MCH clinics, noting the relative advantage of this approach because it: (1) enabled high coverage, (2) harmonized PrEP and MCH visits, and (3) minimized stigma compared to PrEP offered through HIV care clinics. However, HCWs noted implementation challenges affecting feasibility and adoption including: (1) increased workload and documentation burden amid workforce shortages, (2) insufficient health care worker knowledge (3) multiple implementing partners with competing priorities (4) drug and documentation form stockouts. HCWs employed various implementation strategies to overcome challenges, including task shifting from nurses to HIV testing providers, patient flow modifications (e.g., fast-tracking PrEP clients to reduce wait times), PrEP demand generation and myth clarification during health talks, provider education, dedicated PrEP delivery rooms, and coordination with adolescent-friendly services. Additional suggested strategies to improve PrEP integration included community education to increase broader PrEP awareness and enable shorter counseling sessions, and task-shifting data entry and client risk assessments. Conclusions: HCWs were enthusiastic about the appropriateness and acceptability of integrating PrEP services into MCH and FP clinics but noted challenges to adoption and feasibility. Strategies to address challenges focused on improving provider time and space constraints, and increasing provider and client knowledge.

Impact of Human Immunodeficiency Virus and Peripartum Period on Mycobacterium tuberculosis Infection Detection.

BACKGROUND: Pregnancy and human immunodeficiency virus (HIV) may influence tuberculosis infection detection using interferon (IFN)-γ release assay (QFT-Plus; Qiagen) and tuberculin skin test (TST). METHODS: Participants in Western Kenya underwent QFT-Plus and TST in pregnancy, 6 weeks postpartum (6wkPP) and 12 months postpartum (12moPP). RESULTS: 400 participants (200 with HIV [WHIV], 200 HIV-negative) enrolled during pregnancy (median 28 weeks' gestation [interquartile range, 24-30]). QFT-Plus positivity prevalence was higher than TST in pregnancy (32.5% vs 11.6%) and through 12moPP (6wkPP, 30.9% for QFT-Plus vs 18.0% for TST; 12moPP, 29.5% vs 17.1%; all P < .001), driven primarily by QFT-Plus-positive/TST-negative discordance among HIV-negative women. Tuberculosis infection test conversion incidence was 28.4/100 person-years (PY) and higher in WHIV than HIV-negative women (35.5 vs 20.9/100 PY; hazard ratio, 1.73 [95% confidence interval, 1.04-2.88]), mostly owing to early postpartum TST conversion among WHIV. Among QFT-Plus-positive participants in pregnancy, Mycobacterium tuberculosis  (Mtb)-specific IFN-γ responses were dynamic through 12moPP and lower among WHIV than HIV-negative women with tuberculosis infection at all time points. CONCLUSIONS: QFT-Plus had higher diagnostic yield than TST in peripartum women. Peripartum QFT-Plus positivity was stable and less influenced by HIV than TST. Mtb-specific IFN-γ responses were dynamic and lower among WHIV. Tuberculosis infection test conversion incidence was high between pregnancy and early postpartum, potentially owing to postpartum immune recovery.

A prospective preconception cohort study of the association between Mycoplasma genitalium and fecundability in Kenyan women trying to conceive.

STUDY QUESTION: Is Mycoplasma genitalium-infection associated with reduced fecundability? SUMMARY ANSWER: Preconception M. genitalium-infection was associated with 27% lower fecundability though confidence intervals were wide, and the association between M. genitalium and fecundability may be dependent on concurrent bacterial vaginosis (BV). WHAT IS KNOWN ALREADY: M. genitalium has been associated with cervicitis, pelvic inflammatory disease, infertility, and preterm birth, but the extent to which M. genitalium is causally related to adverse reproductive sequelae in women is debated. STUDY DESIGN, SIZE, DURATION: Kenyan women enrolled in a prospective preconception cohort provided vaginal fluid specimens and underwent monthly pregnancy testing. Stored samples from 407 women who had been trying to conceive for ≤6 months were tested for M. genitalium using a nucleic acid amplification test. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on first day of last menstrual period, sexual behavior, pregnancy status, and vaginal specimens were collected at monthly preconception visits. The association between M. genitalium detected at the visit prior to each pregnancy test and fecundability was estimated using discrete time proportional probabilities models. Secondary analyses explored the influence of concurrent BV on the association between M. genitalium and fecundability. MAIN RESULTS AND THE ROLE OF CHANCE: The 407 participants experienced 1220 menstrual cycles and 213 pregnancies. The prevalence of M. genitalium at enrollment was 7.7%. After adjustment for age, frequency of condomless sex in the last 4 weeks, and study site, M. genitalium was associated with a 27% lower fecundability, but confidence intervals were wide (adjusted fecundability ratio (aFR) 0.73, 95% CI 0.44, 1.23). In secondary analyses, when compared to cycles without M. genitalium or BV at the visit prior, women with both M. genitalium and BV at the visit prior had a 51% lower fecundability (aFR = 0.49, 95% CI 0.22, 1.09) whereas there was no association of M. genitalium alone (aFR = 0.98 (95% CI 0.54, 1.76)), and a smaller reduction in fecundability for women with BV only (aFR = 0.80 (95% CI 0.60, 1.07)). LIMITATIONS, REASONS FOR CAUTION: Results should be interpreted cautiously given the relatively low prevalence of M. genitalium and wide confidence intervals. WIDER IMPLICATIONS OF THE FINDINGS: In this cohort of Kenyan women trying to conceive, the association between M. genitalium and fecundability was influenced by concurrent BV status, suggesting there may be a synergistic effect of M. genitalium and BV on fecundability. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a National Institutes of Health grant (NICHD R01 HD087346-RSM). R.S.M. received additional support for mentoring (NICHD K24 HD88229). E.M.L. was supported by pre- and post-doctoral fellowships (NIAID T32 AI07140, NICHD F32 HD100202). Data collection and management were completed using REDCap electronic data capture tools hosted at the University of Washington's Institute of Translational Health Science supported by grants from NCATS/NIH (UL1 TR002319). The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. R.S.M. receives research funding, paid to the University of Washington, from Hologic Corporation and consulting fees from Lupin Pharmaceuticals. L.E.M. receives research funding and material for research studies, paid to the University of Washington, from Hologic Corporation and Nabriva Therapeutics, travel support from Hologic, and consulting fees from Health Advances. E.M.L.'s contributions to this study primarily occurred while affiliated with the University of Washington; at the time of submission, E.M.L. was an employee of and holds stock or stock grants for AbbVie, Inc. The other authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Selecting implementation strategies to improve implementation of integrated PrEP for pregnant and postpartum populations in Kenya: a sequential explanatory mixed methods analysis.

BACKGROUND: There is a higher risk for HIV acquisition during pregnancy and postpartum. Pre-exposure prophylaxis (PrEP) is recommended during this period for those at high risk of infection; integrated delivery in maternal and child health (MCH) clinics is feasible and acceptable but requires implementation optimization. METHODS: The PrEP in Pregnancy, Accelerating Reach and Efficiency study (PrEPARE; NCT04712994) engaged stakeholders to prioritize determinants of PrEP delivery (using Likert scores) and prioritize PrEP delivery implementation strategies. Using a sequential explanatory mixed methods design, we conducted quantitative surveys with healthcare workers at 55 facilities in Western Kenya and a stakeholder workshop (including nurses, pharmacists, counselors, and county and national policymakers), yielding visual plots of stakeholders' perceived feasibility and effectiveness of the strategies. A stepwise elimination process was used to identify seven strategies for empirical testing. Facilitator debriefing reports from the workshop were used to qualitatively assess the decision-making process. RESULTS: Among 146 healthcare workers, the strongest reported barriers to PrEP delivery were insufficient providers and inadequate training, insufficient space, and high volume of patients. Sixteen strategies were assessed, 14 of which were included in the final analysis. Among rankings from 182 healthcare workers and 44 PrEP policymakers and implementers, seven strategies were eliminated based on low post-workshop ranking scores (bottom 50th percentile) or being perceived as low feasibility or low effectiveness for at least 50% of the workshop groups. The top seven strategies included delivering PrEP within MCH clinics instead of pharmacies, fast-tracking PrEP clients to reduce waiting time, delivering PrEP-related health talks in waiting bays, task shifting PrEP counseling, task shifting PrEP risk assessments, training different providers to deliver PrEP, and retraining providers on PrEP delivery. All top seven ranked strategies were grouped into bundles for subsequent testing. Facilitator debriefing reports generally aligned with rankings but noted how stakeholders' decision-making changed when considering the impact of strategies on facility staff and non-PrEP clients. CONCLUSIONS: The most impactful barriers to integrated PrEP delivery in MCH clinics were insufficient staffing and space. Implementation strategies prioritized through multiple methods of stakeholder input focused on co-location of services and increasing clinic efficiency. Future testing of these stakeholder-prioritized strategy bundles will be conducted to assess the effectiveness and implementation outcomes.

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers.

Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. Here, we characterize antibody binding and functionality against Wuhan-Hu-1 (B lineage) strain SARS-CoV-2 in convalescent plasma from 36 postpartum women and 14 of their infants infected with SARS-CoV-2 from a vaccine-naïve prospective cohort in Nairobi, Kenya. We find significantly higher antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels in infants versus mothers. Plasma antibodies from mothers and infants bind to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants display higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants have significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, Spike pseudovirus neutralization titers between infants and mothers are similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody activities and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.

Integrating PrEP in maternal and child health clinics in Kenya: analysis of a service availability and readiness assessment (SARA) survey.

Background: Risk of HIV acquisition is high during pregnancy and postpartum, and pre-exposure prophylaxis (PrEP) is recommended for peripartum populations. Integrating PrEP into maternal and child health (MCH) clinics is feasible and acceptable. Understanding clinics' service availability and readiness is essential for effective scale up. Methods: The PrEP in Pregnancy, Accelerating Reach and Efficiency study (PrEPARE; NCT04712994) engaged PrEP-experienced facilities previously linked to a programmatic or research study in Western Kenya to document available services and commodities via a modified service availability and readiness assessment (SARA) survey with 20 PrEP tracer items covering: staffing/guidelines, services/equipment, and medicines/commodities. Facilities' prior study engagement occurred between 2017 and 2019; SARA survey data was collected between April 2020 and June 2021. Descriptive statistics were stratified by prior study engagement. ANOVA tests assessed associations between facility characteristics and gaps. Fisher's tests assessed differences in commodity availability and stockouts. Results: Of the 55 facilities surveyed, 60% had received PrEP training in the last two years, 95% offered PrEP integrated into MCH, and 64% and 78% had both auditory and visual privacy in PrEP and HIV testing service (HTS) delivery spaces, respectively. Supervision frequency was heterogeneous, but 82% had received a supervision visit within 3 months. Availability of commodities was variable and the most commonly unavailable commodities were PrEP in MCH (71% available) and risk assessment screening tool (RAST) and PrEP cards (60% and 75% available, respectively). The number of service and commodity gaps per facility ranged from zero to eight (median: 3; IQR: 2, 5). The most frequent gaps were: PrEP training and risk assessment cards (40% each), lack of privacy in PrEP (36%) and HIV testing services (31%) spaces, PrEP pills in MCH (29%), and PrEP cards (25%). There were no differences in mean number of gaps by county, previous study engagement, or public vs. private status. Level 4 facilities had fewer gaps (mean 2.2) than level 2, 3, and 5 facilities (mean 5.7, 4.5, and 5.3 respectively; p < 0.001). Conclusions: PrEP service availability and readiness was generally high across MCH facilities. However, there is a need for increased frequency of provider training and supportive supervision focused on fidelity. To address key commodity stockouts such as PrEP pills, implementation of electronic logistics management information systems may be needed. Targeting these gaps is essential to effectively scale up integrated PrEP delivery, especially among facilities with limited infrastructure.