The Afya Bora Consortium: An Africa-US Partnership to Train Leaders in Global Health

The Afya Bora Consortium is a partnership of 8 academic health institutions, 4 in Africa and 4 in the United States. The Consortium is developing a Global Health Leadership Fellowship for medical, nursing, and public health professionals, largely drawn from the 4 African partner countries. The fellowship provides trainees with practical skills to prepare them for future positions leading the design, implementation, and evaluation of large, high-impact programs in governmental agencies, nongovernmental organizations, and academic health institutions in their own countries. This article describes a Pilot of the proposed program

Path-Specific Objectives for Safer Agent Incentives

We present a general framework for training safe agents whose naive incentives are unsafe. As an example, manipulative or deceptive behaviour can improve rewards but should be avoided. Most approaches fail here: agents maximize expected return by any means necessary. We formally describe settings with 'delicate' parts of the state which should not be used as a means to an end. We then train agents to maximize the causal effect of actions on the expected return which is not mediated by the delicate parts of state, using Causal Influence Diagram analysis. The resulting agents have no incentive to control the delicate state. We further show how our framework unifies and generalizes existing proposals.Comment: Presented at AAAI 202

Analysis of the TCR Repertoire in HIV-Exposed but Uninfected Infants

Maternal human immunodeficiency virus (HIV) infection has been shown to leave profound and lasting impacts on the HIV-exposed uninfected (HEU) infant, including increased mortality and morbidity, immunological changes, and developmental delays compared to their HIV-unexposed (HU) counterparts. Exposure to HIV or antiretroviral therapy may influence immune development, which could increase morbidity and mortality. However, a direct link between the increased mortality and morbidity and the infant’s immune system has not been identified. To provide a global picture of the neonatal T cell repertoire in HEU versus HU infants, the diversity of the T cell receptor beta chain (TRB) expressed in cord blood samples from HEU infants was determined using next-generation sequencing and compared to healthy (HU) infants collected from the same community. While the TRB repertoire of HU infants was broadly diverse, in line with the expected idea of a naïve T cell repertoire, samples of HEU infants showed a significantly reduced TRB diversity. This study is the first to demonstrate differences in TRB diversity between HEU and HU cord blood samples and provides evidence that maternal HIV, in the absence of transmission, influences the adaptive immune system of the unborn child

Systems analysis and improvement to optimize pMTCT (SAIA): a cluster randomized trial

BACKGROUND: Despite significant increases in global health investment and the availability of low-cost, efficacious interventions to prevent mother-to-child HIV transmission (pMTCT) in low- and middle-income countries with high HIV burden, the translation of scientific advances into effective delivery strategies has been slow, uneven and incomplete. As a result, pediatric HIV infection remains largely uncontrolled. A five-step, facility-level systems analysis and improvement intervention (SAIA) was designed to maximize effectiveness of pMTCT service provision by improving understanding of inefficiencies (step one: cascade analysis), guiding identification and prioritization of low-cost workflow modifications (step two: value stream mapping), and iteratively testing and redesigning these modifications (steps three through five). This protocol describes the SAIA intervention and methods to evaluate the intervention’s impact on reducing drop-offs along the pMTCT cascade. METHODS: This study employs a two-arm, longitudinal cluster randomized trial design. The unit of randomization is the health facility. A total of 90 facilities were identified in Côte d’Ivoire, Kenya and Mozambique (30 per country). A subset was randomly selected and assigned to intervention and comparison arms, stratified by country and service volume, resulting in 18 intervention and 18 comparison facilities across all three countries, with six intervention and six comparison facilities per country. The SAIA intervention will be implemented for six months in the 18 intervention facilities. Primary trial outcomes are designed to assess improvements in the pMTCT service cascade, and include the percentage of pregnant women being tested for HIV at the first antenatal care visit, the percentage of HIV-infected pregnant women receiving adequate prophylaxis or combination antiretroviral therapy in pregnancy, and the percentage of newborns exposed to HIV in pregnancy receiving an HIV diagnosis eight weeks postpartum. The Consolidated Framework for Implementation Research (CFIR) will guide collection and analysis of qualitative data on implementation process. DISCUSSION: This study is a pragmatic trial that has the potential benefit of improving maternal and infant outcomes by reducing drop-offs along the pMTCT cascade. The SAIA intervention is designed to provide simple tools to guide decision-making for pMTCT program staff at the facility level, and to identify low cost, contextually appropriate pMTCT improvement strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT0202365

Male Perspectives on Incorporating Men into Antenatal HIV Counseling and Testing

Male partner involvement in antenatal voluntary HIV counseling and testing (VCT) has been shown to increase uptake of interventions to reduce the risk of HIV transmission in resource-limited settings. We aimed to identify methods for increasing male involvement in antenatal VCT and determine male correlates of accepting couple counseling in these settings.We invited women presenting to a Nairobi antenatal clinic to return with their male partners for individual or couples VCT. Male attitudes towards VCT and correlates of accompanying female partners to antenatal clinic and receiving couple counseling were determined. Of 1,993 women who invited their partner, 313 (16%) returned with their partners to ANC. Men attending antenatal clinic were married (>99%), employed (98%), and unlikely to report prior HIV testing (14%). Wanting an HIV test (87%) or health information (11%) were the most commonly cited reasons for attending. Most (95%) men who came to antenatal clinic accepted HIV testing and 39% elected to receive counseling as a couple. Men who received counseling with partners were younger, had fewer children, and were less knowledgeable about prevention of mother-to-child HIV transmission (PMTCT) than those who received counseling individually (p<0.05). Only 27% of men stated they would prefer HIV testing at a site other than the ANC. There was agreement between male and female reports for sociodemographic characteristics; however, men were more likely to report HIV preventive behaviors and health communication within the partnership than their partners (p<0.05).Offering VCT services to men at antenatal clinic with options for couple and individual counseling is an important opportunity and acceptable strategy for increasing male involvement in PMTCT and promoting male HIV testing

Sexually Transmitted Infections among HIV-1-Discordant Couples

INTRODUCTION:More new HIV-1 infections occur within stable HIV-1-discordant couples than in any other group in Africa, and sexually transmitted infections (STIs) may increase transmission risk among discordant couples, accounting for a large proportion of new HIV-1 infections. Understanding correlates of STIs among discordant couples will aid in optimizing interventions to prevent HIV-1 transmission in these couples. METHODS:HIV-1-discordant couples in which HIV-1-infected partners were HSV-2-seropositive were tested for syphilis, chlamydia, gonorrhea, and trichomoniasis, and HIV-1-uninfected partners were tested for HSV-2. We assessed sociodemographic, behavioral, and biological correlates of a current STI. RESULTS:Of 416 couples enrolled, 16% were affected by a treatable STI, and among these both partners were infected in 17% of couples. A treatable STI was found in 46 (11%) females and 30 (7%) males. The most prevalent infections were trichomoniasis (5.9%) and syphilis (2.6%). Participants were 5.9-fold more likely to have an STI if their partner had an STI (P<0.01), and STIs were more common among those reporting any unprotected sex (OR = 2.43; P<0.01) and those with low education (OR = 3.00; P<0.01). Among HIV-1-uninfected participants with an HSV-2-seropositive partner, females were significantly more likely to be HSV-2-seropositive than males (78% versus 50%, P<0.01). CONCLUSIONS:Treatable STIs were common among HIV-1-discordant couples and the majority of couples affected by an STI were discordant for the STI, with relatively high HSV-2 discordance. Awareness of STI correlates and treatment of both partners may reduce HIV-1 transmission. TRIAL REGISTRATION:ClinicalTrials.gov NCT00194519

Consistency of Mycobacterium tuberculosis-Specific Interferon-Gamma Responses in HIV-1-Infected Women during Pregnancy and Postpartum

Background. We determined the consistency of positive interferon-gamma (IFN-γ) release assays (IGRAs) to detect latent TB infection (LTBI) over one-year postpartum in HIV-1-infected women. Methods. Women with positive IGRAs during pregnancy had four 3-monthly postpartum IGRAs. Postpartum change in magnitude of IFN-γ response was determined using linear mixed models. Results. Among 18 women with positive pregnancy IGRA, 15 (83%) had a subsequent positive IGRA; 9 (50%) were always positive, 3 (17%) were always negative, and 6 (33%) fluctuated between positive and negative IGRAs. Women with pregnancy IGRA IFN-γ>8 spot forming cells (SFCs)/well were more likely to have consistent postpartum IGRA response (odds ratio: 10.0; 95% confidence interval (CI): 0.9–117.0). Change in IFN-γ response over postpartum was 10.2 SFCs/well (95% CI: −1.5–21.8 SFCs/well). Conclusion. Pregnancy positive IGRAs were often maintained postpartum with increased consistency in women with higher baseline responses. There were modest increases in magnitude of IGRA responses postpartum

Distance from Home to Study Clinic and Risk of Follow-Up Interruption in a Cohort of HIV-1-Discordant Couples in Nairobi, Kenya

Background: Longitudinal studies of HIV-1-infected individuals or those at risk of infection are subject to missed study visits that may have negative consequences on the care of participants and can jeopardize study validity due to bias and loss of statistical power. Distance between participant residence and study clinic, as well as other socioeconomic and demographic factors, may contribute to interruptions in patient follow-up. Methods: HIV-1-serodiscordant couples were enrolled between May 2007 and October 2009 and followed for two years in Nairobi, Kenya. At baseline, demographic and home location information was collected and linear distance from each participant’s home to the study clinic was determined. Participants were asked to return to the study clinic for quarterly visits, with follow-up interruptions (FUI) defined as missing two consecutive visits. Cox proportional hazards regression was used to assess crude and adjusted associations between FUI and home-to-clinic distance, and other baseline characteristics. Results: Of 469 enrolled couples, 64% had a female HIV-1-infected partner. Overall incidence of FUI was 13.4 per 100 person-years (PY), with lower incidence of FUI in HIV-1-infected (10.8 per 100 PY) versus -uninfected individuals (16.1 per 100 PY) (hazard ratio [HR] = 0.66; 95% confidence interval [CI]: 0.50, 0.88). Among HIV-1-infected participants, those living between 5 and 10 kilometers (km) from the study clinic had a two-fold increased rate of FUI compared to those living <5 km away (HR = 2.17; 95% CI: 1.09, 4.34). Other factors associated with FUI included paying higher rent (HR = 1.67; 95% CI: 1.05, 2.65), having at least primary school education (HR = 1.96; 95% CI: 1.02, 3.70), and increased HIV-1 viral load (HR = 1.23 per log10 increase; 95% CI: 1.01, 1.51). Conclusions: Home-to-clinic distance, indicators of socioeconomic status, and markers of disease progression may affect compliance with study follow-up schedules. Retention strategies should focus on participants at greatest risk of FUI to ensure study validity

Factors affecting adherence to antiretroviral therapy among children and adolescents living with HIV in the Mbita Sub-County Hospital, Homa Bay- Kenya

Background: Adequate adherence to antiretroviral therapy (ART) is key to the successful treatment of children and adolescents living with HIV. Continuous ART Adherence is the key factor for virologic suppression and stability of the immune system and prevents the occurrence of opportunistic infections. Children and adolescents struggle with adherence to ART for various reasons, including a poor psychosocial support system and clinic attendance. Objectives: To describe the uptake of HIV treatment services among children and adolescents in the Mbita Sub-County Hospital, Homa Bay and determine how schooling, clinic attendance, and type of pill/regimen affect adherence to ART and viral suppression. Methods: This retrospective study was conducted at the Mbita Sub-County Hospital. Medical chart data was abstracted from the hospital files of children and adolescents between the ages of 0-19 years on antiretroviral therapy, between the periods of October 2016 and September, 2017. Data was analyzed using measures of central tendency, and cross-tabulations were done to compare schooling, clinic attendance, type of pill/regimen and viral suppression. Univariate and multivariate logistic regression analyses were conducted to determine associations between groups. Results: According to patient files reviewed, majority of patients, 244(91.4%) were enrolled into care within 2 weeks of HIV diagnosis according to guidelines, and 193(73.1 %) remained enrolled in care at end of study period. An overall viral suppression of 74.2 %( 132) was recorded. Of all the files reviewed, 121(74.7%) of patients attending school suppressed against 11(68.8 %) out of school, p=0.280. Suppression among Day and boarding reported at 78.6 %( 11) and 74.8 %( 113) of those out of school, respectively, p=0.533. Participants in primary school, 17(85.0%) suppressed better than those in secondary school, 102(73.4%), p=0.263. Keeping clinic appointments among eligible patient files reviewed decreased from 83.1% at 3 months, p=0.016, to 76.6%, p=0.526 at 6 months and to 52.9% at 12 months, p=0.278. Only 3- month clinic appointment return rates and Enhanced Adherence Counseling (EAC) were significant predictors of viral supression \u3c72 (2) = 0.280, p = 0.869 (&gt; 0.05). Conclusion: The clinic attendance rate within the first 3 months, and Enhanced Adherence Counseling (EAC) were significant predictors of viral suppression, and therefore adherence to antiretroviral therapy

Opportunities and Challenges to Emergency Department-Based HIV Testing Services and Self-Testing Programs: A Qualitative Study of Healthcare Providers and Patients in Kenya

BACKGROUND: Young people in Sub-Saharan Africa, especially males, have been insufficiently engaged through HIV Testing Services (HTS). In Kenya, younger persons are often treated in emergency departments (EDs) for injuries, an interaction where HTS and HIV self-testing (HIVST) can be leveraged. Data from stakeholders on ED-HTS and HIVST is lacking and needed to understand opportunities and barriers for HIV testing and care, and inform program implementation. METHODS: Between December 2021 and March 2022, 32 in-depth interviews (IDIs) were conducted with 16 male and 16 female patients who had been treated in the Kenyatta National Hospital (KNH) ED, half of whom had been HIV-tested. Six focus-group discussions (FGDs) were also conducted with 50 nurses, doctors, HIV testing counselors, and administrators working in the ED. All transcripts were double-coded and thematically analyzed using Dedoose software and a parallel inductive and deductive coding approach which allowed for capture of both a priori and emergent themes. RESULTS: Patients and providers agreed that ED-HTS are facilitated by friendly staff, patient education, high perceived HIV risk, and confidentiality. However, ED-HTS is limited by burdens on staff, resources, time, and space, as well as severity of patient injuries limiting ability to consent to or prioritize HIV testing. These limitations provide opportunities for ED-HIVST: particularly the ability to test at a comfortable time and place, especially when provided alongside sufficient HIV and testing education, contact with healthcare providers, and psychosocial support. Barriers for ED-HIVST where identified and as patients’ concerns about HIVST accuracy and mental health impacts of a positive test, as well providers’ identified barriers on their concerns for loss to follow up and inability to complete confirmatory testing. COM-B Model [Figure: see text] Application of the COM-B Model of Behavior Change to ED-HIVST Acceptability in Kenya CONCLUSION: ED stakeholders are receptive to HTS and HIVST, and patients desire the opportunity to use HIVST. Potential challenges—such as psychological effects of testing positive, worries about access to follow-up care, and confusion about how to self-administer testing, may be addressed through programming designed to promote education, access and ensure follow-up mechanisms. DISCLOSURES: All Authors: No reported disclosures