Evaluating the performance of a risk assessment score tool to predict HIV acquisition among pregnant and postpartum women in Kenya.

BACKGROUND: Clinical risk score tools require validation in diverse settings and populations before they are widely implemented. We aimed to externally validate an HIV risk assessment tool for predicting HIV acquisition among pregnant and postpartum women. In the context of prevention of mother-to-child transmission programs, risk score tools could be used to prioritize retesting efforts and delivery of pre-exposure prophylaxis (PrEP) to pregnant and postpartum women most at risk for HIV acquisition while minimizing unnecessary perinatal exposure. METHODS: Data from women enrolled in a cross-sectional study of programmatic HIV retesting and/or receiving maternal and child health care services at five facilities in Western Kenya were used to validate the predictive ability of a simplified risk score previously developed for pregnant/postpartum women. Incident HIV infections were defined as new HIV diagnoses following confirmed negative or unknown status during pregnancy. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUC) and Brier score. RESULTS: Among 1266 women with 35 incident HIV infections, we found an AUC for predicting HIV acquisition of 0.60 (95% CI, 0.51, 0.69), with a Brier score of 0.27. A risk score >6 was associated with a 2.9-fold increase in the odds of HIV acquisition (95% CI, 1.48, 5.70; p = 0.002) vs scores ≤6. Women with risk scores >6 were 27% (346/1266) of the population but accounted for 52% of HIV acquisitions. Syphilis, age at sexual debut, and unknown partner HIV status were significantly associated with increased risk of HIV in this cohort. CONCLUSION: The simplified risk score performed moderately at predicting risk of HIV acquisition in this population of pregnant and postpartum women and may be useful to guide PrEP use or counseling.

Using FRAME to characterize provider-identified adaptations to a stepped care intervention for adolescents and youth living with HIV in Kenya: a mixed methods approach.

INTRODUCTION: The Data-informed Stepped Care (DiSC) study is a cluster-randomized trial implemented in 24 HIV care clinics in Kenya, aimed at improving retention in care for adolescents and youth living with HIV (AYLHIV). DiSC is a multi-component intervention that assigns AYLHIV to different intensity (steps) of services according to risk. We used the Framework for Reporting Adaptations and Modifications-Expanded (FRAME) to characterize provider-identified adaptations to the implementation of DiSC to optimize uptake and delivery, and determine the influence on implementation outcomes. METHODS: Between May and December 2022, we conducted continuous quality improvement (CQI) meetings with providers to optimize DiSC implementation at 12 intervention sites. The meetings were guided by plan-do-study-act processes to identify challenges during early phase implementation and propose targeted adaptations. Meetings were audio-recorded and analysed using FRAME to categorize the level, context and content of planned adaptations and determine if adaptations were fidelity consistent. Providers completed surveys to quantify perceptions of DiSC acceptability, appropriateness and feasibility. Mixed effects linear regression models were used to evaluate these implementation outcomes over time. RESULTS: Providers participated in eight CQI meetings per facility over a 6-month period. A total of 65 adaptations were included in the analysis. The majority focused on optimizing the integration of DiSC within the clinic (83%, n = 54), and consisted of improving documentation, addressing scheduling challenges and improving clinic workflow. Primary reasons for adaptation were to align delivery with AYLHIV needs and preferences and to increase reach among AYLHIV: with reminder calls to AYLHIV, collaborating with schools to ensure AYLHIV attended clinic appointments and addressing transportation challenges. All adaptations to optimize DiSC implementation were fidelity-consistent. Provider perceptions of implementation were consistently high throughout the process, and on average, slightly improved each month for intervention acceptability (ß = 0.011, 95% CI: 0.002, 0.020, p = 0.016), appropriateness (ß = 0.012, 95% CI: 0.007, 0.027, p<0.001) and feasibility (ß = 0.013, 95% CI: 0.004, 0.022, p = 0.005). CONCLUSIONS: Provider-identified adaptations targeted improved integration into routine clinic practices and aimed to reduce barriers to service access unique to AYLHIV. Characterizing types of adaptations and adaptation rationale may enrich our understanding of the implementation context and improve abilities to tailor implementation strategies when scaling to new settings.

A prospective cohort study examining the association between the periconceptual vaginal microbiota and first-trimester miscarriage in Kenyan women.

BACKGROUND: Studies evaluating the association between the vaginal microbiota and miscarriage have produced variable results. OBJECTIVE: This study evaluated the association between periconceptual and first-trimester vaginal microbiota and women's risk for miscarriage. METHODS: At monthly preconception visits and at 9-12 weeks gestation, women collected vaginal swabs for molecular characterisation of the vaginal microbiota. Participants who became pregnant were followed to identify miscarriage versus pregnancy continuing to at least 20 weeks gestation. RESULTS: Forty-five women experienced miscarriage and 144 had pregnancies continuing to ≥20 weeks. A principal component analysis of periconceptual and first-trimester vaginal bacteria identified by 16S rRNA gene PCR with next-generation sequencing did not identify distinct bacterial communities with miscarriage versus continuing pregnancy. Using taxon-directed quantitative PCR assays, increasing concentrations of Megasphaera hutchinsoni, Mageeibacillus indolicus, Mobiluncus mulieris and Sneathia sanguinegens/vaginalis were not associated with miscarriage. In exploratory analyses, these data were examined as a binary exposure to allow for multivariable modelling. Detection of Mobiluncus mulieris in first-trimester samples was associated with miscarriage (adjusted relative risk [aRR] 2.14, 95% confidence interval [CI] 1.08, 4.22). Additional analyses compared women with early first-trimester miscarriage (range 4.7-7.3 weeks) to women with continuing pregnancies. Mobiluncus mulieris was detected in all eight (100%) first-trimester samples from women with early first-trimester miscarriage compared to 101/192 (52.6%) samples from women with continuing pregnancy (model did not converge). Detection of Mageeibacillus indolicus in first-trimester samples was also associated with early first-trimester miscarriage (aRR 4.10, 95% CI 1.17, 14.31). CONCLUSIONS: The primary analyses in this study demonstrated no association between periconceptual or first-trimester vaginal microbiota and miscarriage. Exploratory analyses showing strong associations between first-trimester detection of Mobiluncus mulieris and Mageeibacillus indolicus and early first-trimester miscarriage suggest the need for future studies to determine if these findings are reproducible.

Patient actor training improves preexposure prophylaxis delivery for adolescent girls and young women in Kenya: a cluster randomized trial.

OBJECTIVE: To evaluate effectiveness of a standardized patient actor (SP) training intervention to improve quality of preexposure prophylaxis (PrEP) services for adolescent girls and young women (AGYW) in Kenya. DESIGN: Cluster randomized trial and mystery shopper evaluation. METHODS: Twelve of 24 maternal child health and family planning facilities were randomized to SP training. Providers at intervention facilities participated in 2-day training in adolescent health, PrEP guidelines, values clarification, and communication skills, followed by role-playing and de-briefing with trained actors. Control facilities received standard national training. The primary outcome was quality of care, assessed by unannounced SPs (USPs) or "mystery shoppers" blinded to intervention arm. Quality was measured in two domains: guideline adherence and communication skills. Intent to treat analysis compared postintervention quality scores by randomization arm, clustering on facility, and adjusting for baseline scores and USP. RESULTS: Overall, 232 providers consented to USP visits, and 94 providers completed the training. Following training, USPs posed as AGYW seeking PrEP in 142 encounters (5-6 encounters per site). The mean quality score was 73.6% at intervention sites and 58.4% at control sites [adjusted mean difference = 15.3, 95% confidence interval (CI): 9.4-21.1, P  < 0.001]. Mean guideline adherence scores were 57.2% at intervention sites and 36.2% at control sites (adjusted mean difference = 21.0, 95% CI: 12.5-29.4, P  < 0.001). Mean communication scores were 90.0% at intervention sites and 80.5% at control sites (adjusted mean difference = 9.5, 95% CI: 5.5-13.6, P  < 0.001). CONCLUSIONS: SP training significantly improved quality of PrEP care for AGYW in Kenya. Incorporating SP training and unannounced SP evaluation could improve PrEP uptake among AGYW.

Phase 1 randomized trials to assess safety, pharmacokinetics, and vaginal bleeding associated with use of extended duration dapivirine and levonorgestrel vaginal rings.

BACKGROUND: Vaginal rings formulated to deliver two drugs simultaneously have potential as user-controlled, long-acting methods for dual prevention of HIV and pregnancy. METHODS: Two phase 1 randomized trials (MTN-030/IPM 041 and MTN-044/IPM 053/CCN019) respectively enrolled 24 and 25 healthy, HIV-negative participants to evaluate safety, pharmacokinetics, and vaginal bleeding associated with use of a vaginal ring containing 200mg dapivirine (DPV) and 320mg levonorgestrel (LNG) designed for 90-day use. MTN-030/IPM 041 compared the DPV/LNG ring to a DPV-only ring (200mg) over 14 days of use. MTN-044/IPM 053/CCN019 compared continuous or cyclic use of the DPV/LNG ring over 90 days of use. Safety was assessed by recording adverse events (AEs). DPV and LNG concentrations were quantified in plasma, cervicovaginal fluid, and cervical tissue. Vaginal bleeding was self-reported. RESULTS: There were no differences in the proportion of participants with grade ≥2 genitourinary AEs or grade ≥3 AEs with DPV/LNG ring vs. DPV ring use (p = .22), or with DPV/LNG ring continuous vs. cyclic use (p = .67). Higher plasma DPV concentrations were observed in users of DPV/LNG compared to DPV-only rings (Cmax p = 0.049; AUC p = 0.091). Plasma DPV and LNG concentrations were comparable with continuous and cyclic use (Cmax p = 0.74; AUC p = 0.25). With cyclic use, median nadir plasma DPV concentration was approximately 300 pg/mL two days after removal and median t1/2 for cervicovaginal fluid DPV concentration was 5.76 hours (n = 3). Overall bleeding experiences did not differ between continuous and cyclic users (p = 0.12). CONCLUSIONS: The extended duration DPV/ LNG rings were well tolerated and the observed DPV concentrations in plasma and cervicovaginal fluid when used continuously exceeded concentrations observed in previous DPV ring efficacy studies. LNG concentrations in plasma were comparable with other efficacious LNG-based contraceptives. Genital DPV concentrations had a short half-life and were thus not well sustained following ring removal.

Gut virome and microbiome dynamics before and after SARS-CoV-2 infection in women living with HIV and their infants.

Microbiome perturbations can have long-term effects on health. The dynamics of the gut microbiome and virome in women living with HIV (WLHIV) and their newborn infants is poorly understood. Here, we performed metagenomic sequencing analyses on longitudinal stool samples including 23 mothers (13 WLHIV, 10 HIV-negative) and 12 infants that experienced SARS-CoV-2 infection with mild disease, as well as 40 mothers (18 WLHIV, 22 HIV-negative) and 60 infants that remained SARS-CoV-2 seronegative throughout the study follow-up. Regardless of HIV or SARS-CoV-2 status, maternal bacterial and viral profiles were distinct from infants. Using linear mixed effects models, we showed that while the microbiome alpha diversity trajectory was not significantly different between SARS-CoV-2 seropositive and seronegative women. However, seropositive women's positive trajectory while uninfected was abruptly reversed after SARS-CoV-2 infection (p = 0.015). However, gut virome signatures of women were not associated with SARS-CoV-2. Alterations in infant microbiome and virome diversities were generally not impacted by SARS-CoV-2 but were rather driven by development. We did not find statistically significant interactions between HIV and SARS-CoV-2 on the gut microbiome and virome. Overall, our study provides insights into the complex interplay between maternal and infant bacterial microbiome, virome, and the influence of SARS-CoV-2 and HIV status.

Longitudinal dynamics of the nasopharyngal microbiome in response to SARS-CoV-2 Omicron variant and HIV infection in Kenyan women and their infants.

The nasopharynx and its microbiota are implicated in respiratory health and disease. The interplay between viral infection and the nasopharyngeal microbiome is an area of increased interest and of clinical relevance. The impact of SARS-CoV-2, the etiological agent of the Coronavirus Disease 2019 (COVID-19) pandemic, on the nasopharyngeal microbiome, particularly among individuals living with HIV, is not fully characterized. Here we describe the nasopharyngeal microbiome before, during and after SARS-CoV-2 infection in a longitudinal cohort of Kenyan women (21 living with HIV and 14 HIV-uninfected) and their infants (18 HIV-exposed, uninfected and 18 HIV-unexposed, uninfected), followed between September 2021 through March 2022. We show using genomic epidemiology that mother and infant dyads were infected with the same strain of the SARS-CoV-2 Omicron variant that spread rapidly across Kenya. Additionally, we used metagenomic sequencing to characterize the nasopharyngeal microbiome of 20 women and infants infected with SARS-CoV-2, 6 infants negative for SARS-CoV-2 but experiencing respiratory symptoms, and 34 timepoint matched SARS-CoV-2 negative mothers and infants. Since individuals were sampled longitudinally before and after SARS-CoV-2 infection, we could characterize the short- and long-term impact of SARS-CoV-2 infection on the nasopharyngeal microbiome. We found that mothers and infants had significantly different microbiome composition and bacterial load (p-values <.0001). However, in both mothers and infants, the nasopharyngeal microbiome did not differ before and after SARS-CoV-2 infection, regardless of HIV-exposure status. Our results indicate that the nasopharyngeal microbiome is resilient to SARS-CoV-2 infection and was not significantly modified by HIV.

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.

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.

Lower self-reported ART adherence among adolescents in boarding schools compared to day schools.

INTRODUCTION: Adolescents living with HIV (ALH) have poorer adherence to antiretroviral therapy (ART) than adults. Many ALH in sub-Saharan Africa (SSA) are enrolled in boarding schools where stigma is pervasive and may impact adherence. METHODS: We collected sociodemographic data, school information, medical history, and viral load (VL) data from ALH age 14-19 in 25 HIV clinics in 3 counties in Kenya. Using generalized estimating equations, we compared ART adherence in ALH attending day and boarding schools. RESULTS: Of 880 ALH, 798 (91%) were enrolled in school, of whom 189 (24%) were in boarding schools. Of those in school, median age was 16 (IQR: 15, 18), 55% were female, 78% had a parent as a primary caregiver, and 74% were on DTG-based ART. Median age at ART initiation was 6 years (IQR 3, 10).Overall, 227 (29%) ALH self-reported missing ART when school was in session (40% in boarding and 25% in day school). After adjusting for sociodemographic and HIV care characteristics, ALH in boarding schools were significantly more likely to self-report missing ART than those in day schools (adjusted Prevalence Ratio (aPR): 1.47, 95% CI 1.18, 1.83, p=0.001). Among 194 ALH, only 60% had undetectable (<20 copies/ml) HIV viral load (62% day schools and 51% boarding schools)(p=0.097). CONCLUSION: ALH had high self-reported non-adherence overall, with worse adherence among those in boarding schools. Schools remain a critical untapped resource for improving ALH outcomes.

Maternal COVID-19 Vaccination and Prevention of Symptomatic Infection in Infants.

BACKGROUND AND OBJECTIVES: Maternal vaccination may prevent infant coronavirus disease 2019 (COVID-19). We aimed to quantify protection against infection from maternally derived vaccine-induced antibodies in the first 6 months of an infant's life. METHODS: Infants born to mothers vaccinated during pregnancy with 2 or 3 doses of a messenger RNA COVID-19 vaccine (nonboosted or boosted, respectively) had full-length spike (Spike) immunoglobulin G (IgG), pseudovirus 614D, and live virus D614G, and omicron BA.1 and BA.5 neutralizing antibody (nAb) titers measured at delivery. Infant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was determined by verified maternal-report and laboratory confirmation through prospective follow-up to 6 months of age between December 2021 and July 2022. The risk reduction for infection by dose group and antibody titer level was estimated in separate models. RESULTS: Infants of boosted mothers (n = 204) had significantly higher Spike IgG, pseudovirus, and live nAb titers at delivery than infants of nonboosted mothers (n = 271), and were 56% less likely to acquire infection in the first 6 months (P = .03). Irrespective of boost, for each 10-fold increase in Spike IgG titer at delivery, the infant's risk of acquiring infection was reduced by 47% (95% confidence interval 8%-70%; P = .02). Similarly, a 10-fold increase in pseudovirus titers against Wuhan Spike, and live virus nAb titers against D614G, and omicron BA.1 and BA.5 at delivery were associated with a 30%, 46%, 56%, and 60% risk reduction, respectively. CONCLUSIONS: Higher transplacental binding and nAb titers substantially reduced the risk of SARS-CoV-2 infection in infants, and a booster dose amplified protection during a period of omicron predominance. Until infants are age-eligible for vaccination, maternal vaccination provides passive protection against symptomatic infection during early infancy.

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.

Effect of tuberculosis-HIV co-treatment on clinical and growth outcomes among hospitalized children newly initiating antiretroviral therapy.

OBJECTIVE: Evaluate effects of tuberculosis (TB)-HIV co-treatment on clinical and growth outcomes in children with HIV (CHIV). DESIGN: Longitudinal study among Kenyan hospitalized ART-naive CHIV in the PUSH trial (NCT02063880). METHODS: CHIV started ART within 2 weeks of enrollment; Anti-TB therapy was initiated based on clinical and TB diagnostics. Children were followed for 6 months with serial viral load, CD4%, and growth assessments [weight-for-age z -score (WAZ), height-for-age z -score (HAZ), and weight-for-height z -score (WHZ)]. TB-ART treated and ART-only groups were compared at 6 months post-ART for undetectable viral load (<40 c/ml), CD4% change, and growth using generalized linear models, linear regression, and linear mixed-effects models, respectively. RESULT: Among 152 CHIV, 40.8% (62) were TB-ART treated. Pre-ART, median age was 2.0 years and growth was significantly lower, and viral load significantly higher in the TB-ART versus ART-only group. After 6 months on ART, 37.2% of CHIV had undetectable viral load and median CD4% increased by 7.2% (IQR 2.0-11.6%) with no difference between groups. The TB-ART group had lower WAZ and HAZ over 6 month follow-up [WAZ -0.81 (95% CI: -1.23 to -0.38], P  < 0.001; HAZ -0.15 (95% CI: -0.29 to -0.01), P  = 0.030] and greater rate of WAZ increase in analyses unadjusted and adjusted for baseline WAZ [unadjusted 0.62 (95% CI: 0.18-1.07, P  = 0.006) or adjusted 0.58 (95% CI: 0.12-1.03, P  = 0.013)]. CONCLUSION: TB-HIV co-treatment did not adversely affect early viral suppression and CD4 + recovery post-ART. TB-ART-treated CHIV had more rapid growth reconstitution, but growth deficits persisted, suggesting need for continued growth monitoring.

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.

Hybrid Immunity to SARS-CoV-2 During Pregnancy Provides More Durable Infant Antibody Responses Compared to Natural Infection Alone.

BACKGROUND: Hybrid immunity (infection plus vaccination) may increase maternally derived SARS-CoV-2 antibody responses and durability versus infection alone. METHODS: Prospective cohort of pregnant participants with prior SARS-CoV-2 infection (anti-nucleocapsid IgG, RT-PCR, or antigen positive) and their infants had blood collected in pregnancy, at delivery/birth, and postpartum tested for anti-spike (anti-S) IgG and neutralizing antibodies (neutAb). RESULTS: Among 107 participants at enrollment, 40% were unvaccinated and 60% were vaccinated (received ≥1 dose); 102 had previous SARS-CoV-2 infection in pregnancy (median, 19 weeks' gestation); 5 were diagnosed just prior to pregnancy (median, 8 weeks). At delivery, fewer unvaccinated participants (87% anti-S IgG+, 86% neutAb) and their infants (86% anti-S IgG+, 75% neutAb) had anti-S IgG+ or neutAb compared to vaccinated participants and their infants (100%, P ≤ .01 for all). By 3-6 months postpartum, 50% of infants of unvaccinated participants were anti-S IgG+ and 14% had neutAb, versus 100% among infants of vaccinated participants (all P < .01), with lower median antibody responses (anti-S IgG log10 1.95 vs 3.84 AU/mL, P < .01; neutAb log10 1:1.34 vs 1:3.20, P = .11). CONCLUSIONS: In pregnant people with prior SARS-CoV-2, vaccination before delivery provided more durable maternally derived antibody responses than infection alone in infants through 6 months.

Prevalence and Correlates of Stunting among a High-Risk Population of Kenyan Children Recently Hospitalized for Acute Illnesses.

Stunting (length/height-for-age z-score < -2) is associated with significant morbidity and mortality among children under 5 years of age in sub-Saharan Africa. Children who are stunted and recently hospitalized for acute illness may be at particularly elevated risk for post-discharge mortality. In this cross-sectional analysis, we measured the prevalence of stunting at hospital discharge and identified host, caregiver, and environmental correlates of stunting among children aged 1-59 months in Western Kenya enrolled in the Toto Bora Trial. Child age- and site-adjusted prevalence ratios were estimated using Poisson regression. Of the 1,394 children included in this analysis, 23% were stunted at hospital discharge. Older children (12-23 months and 24-59 months versus 0-5 months) had a higher prevalence of stunting (adjusted prevalence ratio [aPR]: 1.58; 95% CI: 1.04-2.36 and aPR: 1.59; 95% CI: 1.08-2.34, respectively). HIV-exposed, uninfected children (aPR: 1.94; 95% CI: 1.39-2.70), children with HIV infection (aPR: 2.73; 95% CI: 1.45-5.15), and those who were never exclusively breastfed in early life (aPR 2.51; 95% CI: 1.35-4.67) were more likely to be stunted. Caregiver education (primary school or less) and unimproved sanitation (pit latrine without slab floor or open defecation) were associated with increased risk of stunting (aPR: 1.94; 95% CI: 1.54-2.44; aPR: 1.99; 95% CI: 1.20-3.31; aPR: 3.57; 95% CI: 1.77-7.21, respectively). Hospital discharge represents an important opportunity for both identifying and delivering targeted interventions for nutrition-associated poor outcomes among a high-risk population of children.

Adolescent experiences, perceptions, and preferences for the process of HIV status disclosure in Kenya.

Introduction: Disclosure of HIV status to adolescents living with HIV has been associated with improved treatment outcomes. However, there are limited data regarding the experiences of, perceptions of, and preferences for the process of disclosure of HIV status among adolescents and young adults living with HIV (AYLH), especially in sub-Saharan Africa. Methods: Young adults living with HIV from 20 HIV clinics in Kenya who participated in a clinical trial evaluating the effectiveness of a disclosure and transition package completed an anonymous survey in 2019. We described their experiences and preferences using counts and proportions and assessed factors associated with satisfaction with the disclosure process using linear regression, reporting age-adjusted mean differences (aMD), and 95% confidence intervals (95%CIs). Results: Of the 375 enrolled AYLH, 265 (71%) had perinatally acquired HIV, of whom 162 (61%) were female. The median age of the enrolled AYLH was 16 years (IQR: 14-19 years), and all of them were on antiretroviral therapy (ART). For over half (55%) of the participants, caregivers disclosed their HIV status, and 57% preferred that their caregivers disclose the status to them. Most (78%) of the participants preferred full disclosure by 12 years of age. The majority (69%) believed the disclosure was planned, and 11% suspected being HIV positive before the disclosure. Overall, 198 (75%) AYLH reported that they were ready for disclosure when it happened, and 86% were satisfied with the process. During both pre-disclosure (67 and 70%, respectively) and post-disclosure (>75% for each), AYLH felt supported by the clinic and caregivers. Factors associated with higher satisfaction with the disclosure process were pre-disclosure clinic support (aMD: 0.19 [95%CI: 0.05-0.33]) and pre-disclosure (aMD: 0.19 [0.06-0.31]) and post-disclosure (aMD: 0.17 [0.03-0.31]) caregiver support. AYLH who suspected they were HIV positive before they were disclosed to tended to have lower satisfaction when compared to those who never suspected (aMD: -0.37 [-0.74-(-0.01)]). Overall, they reported that disclosure positively influenced their ART adherence (78%), clinic attendance (45%), and communication with caregivers (20%), and 40% reported being happier after disclosure. Conclusion: Young adults living with HIV advocated for an appropriately timed disclosure process with the involvement of caregivers and healthcare workers (HCWs). Support from caregivers and HCWs before and during disclosure is key to improving their disclosure experience.

Results of a cluster randomized trial testing the Systems Analysis and Improvement Approach to increase cervical cancer screening in family planning clinics in Mombasa County, Kenya.

BACKGROUND: Cervical cancer is the leading cause of cancer death in Kenyan women. Integrating cervical cancer screening into family planning (FP) clinics is a promising strategy to improve health for reproductive-aged women. The objective of this cluster randomized trial was to test the efficacy of an implementation strategy, the Systems Analysis and Improvement Approach (SAIA), as a tool to increase cervical cancer screening in FP clinics in Mombasa County, Kenya. METHODS: Twenty FP clinics in Mombasa County were randomized 1:1 to SAIA versus usual procedures. SAIA has five steps: (1) cascade analysis tool to understand the cascade and identify inefficiencies, (2) sequential process flow mapping to identify bottlenecks, (3) develop and implement workflow modifications (micro-interventions) to address identified bottlenecks, (4) assess the micro-intervention in the cascade analysis tool, and (5) repeat the cycle. Prevalence ratios were calculated using Poisson regression with robust standard errors to compare the proportion of visits where women were screened for cervical cancer in SAIA clinics compared to control clinics. RESULTS: In the primary intent-to-treat analysis in the last quarter of the trial, 2.5% (37/1507) of visits with eligible FP clients at intervention facilities included cervical cancer screening compared to 3.7% (66/1793) in control clinics (prevalence ratio [PR] 0.67, 95% CI 0.45-1.00). When adjusted for having at least one provider trained to perform cervical cancer screening at baseline, there was no significant difference between screening in intervention clinics compared to control clinics (adjusted PR 1.14, 95% CI 0.74-1.75). CONCLUSIONS: The primary analysis did not show an effect on cervical cancer screening. However, the COVID-19 pandemic and a healthcare worker strike likely impacted SAIA's implementation with significant disruptions in FP care delivery during the trial. While SAIA's data-informed decision-making and clinic-derived solutions are likely important, future work should directly study the mechanisms through which SAIA operates and the influence of contextual factors on implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03514459. Registered on April 19, 2018.